Q2 2024 Vertex Pharmaceuticals Inc Earnings Call

August 1, 2024

Operator: There will be an opportunity to ask questions. Please note this event is being recorded, I would now like to turn the conference over to Ms, Susie Lisa, please go ahead.

Susie Lisa: Good evening, all my name is Susie Lisa and as the senior Vice President of Investor Relations, it is my pleasure to welcome you to our second quarter 2024 financial results conference call. On Tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President Stuart Arbuckle, Chief Operating Officer, and Charlie Wagner, Chief Financial Officer. We recommend that you access the webcast slides as you listen to this call, the call is being recorded and a replay will be available on our website. We will be making forward looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements including without.

Susie Lisa: Good evening, all my name is Susie Lisa and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our second quarter 2024 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Stuart Arbuckle, Chief Operating Officer, and Charlie Wagner, Chief Financial Officer. We recommend that you access the webcast slides as you listen to this call. The call is being recorded and a replay will be available on our website.

Speaker Change: <unk> Chief Financial Officer.

Speaker Change: We recommend that you access the webcast slides as you listen to this call. The call is being recorded and a replay will be available on our website, we will be making forward looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission these statements including without.

Susie Lisa: We will be making forward looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release, and in our filings with the Securities and Exchange Commission. These statements including without limitations those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease, and Beta Thalassemia. Our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF, and SUZETRIGINE in moderate to severe acute pain, and vertex is future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call. This evening are presented on a non-GAAP basis I will now turn the call over to Ray Smith.

Susie Lisa: We will be making forward looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release, and in our filings with the Securities and Exchange Commission. These statements including without limitations those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease, and Beta Thalassemia. Our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF, and SUZETRIGINE in moderate to severe acute pain, and Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially.

Speaker Change: Patients those regarding vertex is marketed medicines for cystic fibrosis, sickle cell disease, and beta thalassemia, our pipeline, including the potential near term launches of the vans the captor triple in CF and Xetra gene in moderate to severe acute pain and vertex is future financial performance are based on management's current is.

Speaker Change: Good day and welcome to the Vertex Pharmaceuticals second quarter 2024 earnings call. All participants will be in a listen-only mode. Should you need assistance, please signal conference specialists by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions.

Operator: Earnings call, all participants will be in a listen-only mode, should you need assistance, please signal conference specialists by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded, I will now like to turn the conference over to Susie Lisa, please go ahead. Good evening now, my name is Susie Lisa and as the Senior Vice President of Investor Relations it is my pleasure to welcome you to ur second quarter 2024 financial results conference call. On tonight's call, making prepared remarksLastly, on the mid and late stage pipeline, I am very pleased with our continued rapid progress. I'll call out three specific programs.

Speaker Change: <unk> actual outcomes and events could differ materially I would also note that the select financial results and guidance that we will review on the call. This evening are presented on a non-GAAP basis I will now turn the call over to Ray Smith.

Susie Lisa: I would also note that the select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. I will now turn the call over to Reshma.

Speaker Change: Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

Susie Lisa: Good evening, all. My name is Susie Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our second quarter 2024 Financial Results Conference Call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Stuart Arbuckle, Chief Operating Officer, and Charlie Wagner, Chief Financial Officer. Transcribed by https://otter.ai

Reshma Kewalramani: Thanks, Susie good evening, all and thank you for joining us on the call today, we've continued our momentum from Q1 with another quarter of excellent performance across the board, including outstanding commercial execution in both CF and the early launch of CASGEVY. Our preparedness for the potential near term launches of the VANZACAFTOR triple in CF and SUZETRIGINE in acute pain as well as the rapid advancement of our broad and deep pipeline.

Speaker Change: We recommend that you access the webcast slides as you listen to this call. The call is being recorded and a replay will be available on our website.

Ray Smith: Vance the captor triple in CF as this sector gene in acute pain as well as the rapid advancement of our broad and deep pipeline.

Speaker Change: We will be making forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission.

Ray Smith: In CF, we continue to reach more patients, delivering $2.65 billion in revenue in Q2, and based on this result, and our outlook, we are increasing our full year product revenue guidance to $10.65 to $10.85 billion, which at the midpoint represents 9% growth versus 2023. In Sickle Cell Disease, and Beta Thalassemia, we are pleased with the reception from patients, physicians and payers as we continue the ongoing launch of CASGEVY, to bring this potentially transformative medicine to patients across multiple regions. And we are very excited about the multiple near term opportunities.

Reshma Kewalramani: In CF, we continue to reach more patients, delivering $2.65 billion in revenue in Q2, and based on this result, and our outlook, we are increasing our full year product revenue guidance to $10.65 to $10.85 billion, which at the midpoint represents 9% growth versus 2023. In Sickle Cell Disease, and Beta Thalassemia, we are pleased with the reception from patients, physicians and payers as we continue the ongoing launch of CASGEVY, to bring this potentially transformative medicine to patients across multiple regions. And we are very excited about the multiple near term opportunities. To reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions the vans or capture triple in patients with cystic fibrosis, six years and older which has been given priority <unk>. View designation and VX 548, or Susceptor gene in moderate to severe acute pain, which has also been granted priority review by the FDA.

Speaker Change: These statements, including, without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, and beta thalassemia, our pipeline, including the potential near-term launches of the Vanzacaptor triple in CF and Suzetra gene in moderate to severe acute pain.

Ray Smith: 2023.

Ray Smith: In sickle cell disease, and beta thalassemia, we are pleased with the reception from patients physicians and payers as we continue the ongoing launch of cash JV to bring this potentially transformative medicine to patients across multiple regions and we are very excited about the multiple near term opportunities.

Speaker Change: and Vertex's Future Financial Performance.

Speaker Change: are based on management's current assumptions.

Speaker Change: Actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. I will now turn the call over to Reshma.

Reshma Kewalramani: And we are very excited about the multiple near term opportunities. To reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions the vans or capture triple in patients with cystic fibrosis, six years and older which has been given priority <unk>. View designation and VX 548, or Susceptor gene in moderate to severe acute pain, which has also been granted priority review by the FDA. Lastly on the mid and late stage pipeline I am very pleased with our continued rapid progress I'll call out three specific programs first the Susceptor regime LFR phase II study has significantly accelerated and we now expect phase two results by the end of this year.

Reshma Kewalramani: And we are very excited about the multiple near term opportunities to reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions. The VANZACAFTOR triple in patients with Cystic Fibrosis, six years and older which has been given priority review designation and VX-548, or SUZETRIGINE in moderate to severe acute pain, which has also been granted priority review by the FDA.

And we are very excited about the multiple near term opportunities. To reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions the vans or capture triple in patients with cystic fibrosis, six years and older which has been given priority <unk>. View designation and VX 548, or Susceptor gene in moderate to severe acute pain, which has also been granted priority review by the FDA.

Susie Lisa: Good evening now, my name is Susie Lisa and as the Senior Vice President of Investor Relations it is my pleasure to welcome you to ur second quarter 2024 financial results conference call. On tonight's call, making prepared remarks we have Dr. Reshma Kewalramani, Vertex's CEO and President, Stuart Arbuckle, Chief Operating Officer and Charlie Wagner, Chief Financial Officer, we recommend that you access the webcast [inaudible] listen to this call, the call is being recorded and a replay will be available on our website. We will be making forward-looking statements on this call that are subject to the risk and uncertainties discussed in detail in today's press release and in our filing for the Securities and Exchange Commission. These statements including, without limitation, those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease and Beta Thalassemia, our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF. And SUZETRIGINE in moderate to severe acute pain, and Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma.

Ray Smith: To reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions the vans or capture triple in patients with cystic fibrosis, six years and older which has been given priority <unk>.

Reshma: Thanks Susie. Good evening all and thank you for joining us on the call today. We've continued our momentum from Q1 with another quarter of excellent performance across the board, including outstanding commercial execution in both CF and the early launch of Cachevi.

Speaker Change: Our preparedness for the potential near-term launches of the Vanzacaptor triple in CF and Ciceptrogene in acute pain, as well as the rapid advancement of our broad and deep pipeline.

Ray Smith: View designation and VX 548, or Susceptor gene in moderate to severe acute pain, which has also been granted priority review by the FDA.

Susie Lisa: We will be making forward-looking statements on this call that are subject to the risk and uncertainties discussed in detail in today's press release and in our filing for the Securities and Exchange Commission. These statements including, without limitation, those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease and Beta Thalassemia, our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF. And SUZETRIGINE in moderate to severe acute pain, and Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma.

Susie Lisa: We will be making forward-looking statements on this call that are subject to the risk and uncertainties discussed in detail in today's press release and in our filing for the Securities and Exchange Commission. These statements including, without limitation, those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease and Beta Thalassemia, our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF, and SUZETRIGINE in moderate to severe acute pain. And Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma.

Reshma Kewalramani: Lastly on the mid and late stage pipeline, I am very pleased with our continued rapid progress, I'll call out three specific programs. First the SUZETRIGINE LSR Phase II study has significantly accelerated and we now expect Phase II results by the end of this year. Second in the VX-880 Phase 1/2 trial in type one diabetes, we have completed enrollment and dosing in the original 17 patient study, and we have secured regulatory endorsement to expand the study the 37 patients in total as we advance towards pivotal development. And third in the POVETACICEPT program, having completed successful end of Phase II regulatory meetings, we will initiate the Phase III pivotal trial in IgA Nephropathy later this month. with those highlights let me now turn to an R&D review limiting my comments this quarter.

Reshma Kewalramani: Lastly on the mid and late stage pipeline, I am very pleased with our continued rapid progress, I'll call out three specific programs. First the SUZETRIGINE LSR Phase II study has significantly accelerated and we now expect Phase II results by the end of this year. Second in the VX-880 Phase 1/2 trial in type one diabetes, we have completed enrollment and dosing in the original 17 patient study, and we have secured regulatory endorsement to expand the study to 37 patients in total as we advance towards pivotal development. And third in the POVETACICEPT program, having completed successful end of Phase II regulatory meetings, we will initiate the Phase III pivotal trial in IgA Nephropathy later this month.

Speaker Change: In CF, we continue to reach more patients, delivering $2.65 billion in revenue in Q2, and based on this result and our outlook, we are increasing our full year product revenue guidance to $10.65 to $10.85 billion, which at the midpoint represents 9% growth versus 2023.

Ray Smith: Lastly on the mid and late stage pipeline I am very pleased with our continued rapid progress I'll call out three specific programs first the Susceptor regime LFR phase II study has significantly accelerated and we now expect phase two results by the end of this year.

Susie Lisa: These statements including, without limitation, those regarding Vertex's marketed medicines for Cystic Fibrosis, Sickle Cell Disease and Beta Thalassemia, our pipeline, including the potential near term launches of the VANZACAFTOR triple in CF. And SUZETRIGINE in moderate to severe acute pain, and Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma.

Susie Lisa: And Vertex's future financial performance are based on management's current assumptions, actual outcomes and events could differ materially. I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma. Thanks Susie, Good evening all, and thank you for joining us on the call today, we continued our momentum from

Susie Lisa: I would also note that the select financial results and guidance that we will review on the call this evening are presented on a Non-GAAP basis. I will now turn the call over to Reshma.

Ray Smith: Second in the VX 880 phase one two trial in type one diabetes, we have completed enrollment and dosing in the original 17 patient study and we have secured regulatory endorsement to expand the study the 37 patients in total as we advance towards pivotal development.

Speaker Change: In sickle cell disease and beta thalassemia, we are pleased with the reception from patients, physicians, and payers as we continue the ongoing launch of CASGEVI to bring this potentially transformative medicine to patients across multiple regions.

Reshma Kewalramani: Thanks Susie, Good evening all, and thank you for joining us on the call today, we continued our momentum from Q1 with another quarter of excellent performance across the board. Including outstanding commercial execution in both CF and the early launch of CASGEVY, our preparedness for the potential near-term launches of the VANZACAFTOR triple in CF and SUZETRIGINE in acute pain, as well as the rapid advancement of our broad R&D pipeline. In CF we continue to reach more patients, delivering $2.65 billion in revenue in Q2, and based on this result, and our outlook, we're increasing our full-year product revenue guidance to $10.65 to $10.85 billion, which as to midpoint represents 9% growth vs 2023. In Sickle Cell Disease and Beta Thalassemia, we are pleased with the reception from patients, physicians and payers, as we continue the ongoing launch of CASGEVY, to bring this potentially transformative medicine to patients across multiple regions. And we are very excited about the multiple near-term oPportunities to reach more patients and deliver additional revenue growth from our programs that have completed clinical development, including the completion and acceptance of two significant regulatory submissions. The VANZACAFTOR triple in patients with Cystic Fibrosis, six years and older, which has been given priority review designation, and VX-548, or SUZETRIGINE in moderate to severe acute pain, which gas also been granted priority review by the FDA.

Reshma Kewalramani: In Sickle Cell Disease and Beta Thalassemia, we are pleased with the reception from patients, physicians and payers, as we continue the ongoing launch of CASGEVY, to bring this potentially transformative medicine to patients across multiple regions. And we are very excited about the multiple near-term oPportunities to reach more patients and deliver additional revenue growth from our programs that have completed clinical development, including the completion and acceptance of two significant regulatory submissions. The VANZACAFTOR triple in patients with Cystic Fibrosis, six years and older, which has been given priority review designation, and VX-548, or SUZETRIGINE in moderate to severe acute pain, which gas also been granted priority review by the FDA.

Reshma Kewalramani: Lastly, on the mid and late stage pipeline, I am very pleased with our continued rapid progress, I'll call out three specific programs. First, the SUZETRIGINE LSR Phase II study has significantly accelerated, and we now expect Phase II results by the end of this year. Second, in the VX-880 Phase 1/2 trial in Type 1 diabetes, we have completed enrollment and dosing in the original 17-patient study, and we have secured regulatory endorsement to expand the study to 37 patients in total as we advance towards pivotal development. And third, in the POVETACICEPT program, having completed successful end of Phase II regulatory meetings, we will initiate the Phase III pivotal trial in IgA nephropathy later this month.

Operator: on the mid and late stage pipeline, I am very pleased with our continued rapid progress. I'll call out three specific programs.

Speaker Change: And we are very excited about the multiple, near-term opportunities to reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions, the Vanzikaft to triple in patients with cystic fibrosis,

Reshma Kewalramani: And third in the POVETACICEPT program, having completed successful end of Phase II regulatory meetings, we will initiate the Phase III pivotal trial in IgA Nephropathy later this month. With those highlights let me now turn to an R&D review limiting my comments this quarter to the programs with the most significant recent updates: Cystic Fibrosis, Pain, type one diabetes and IgA Nephropathy. Starting with CF, we are very pleased with the Phase III results from the VANZACAFTOR Triple program we announced in early February, as we continue to drive towards our ultimate goal of bringing all eligible patients to carrier levels, indeed to normal levels of CFTR our function as measured by sweat chloride. The vans the captor triple demonstrated an even greater reduction in sweat chloride than try CAFTA, a very high bar to have crested and thus sets the stage for the potential to have a new standard in the treatment of CF the.

Ray Smith: And third in the poll the task the CEP program, having completed successful end of phase II regulatory meetings, we will initiate the phase III pivotal trial in Iga Nephropathy. Later this month with those highlights let me now turn to an R&D review limiting my comments this quarter.

Reshma Kewalramani: With those highlights let me now turn to an R&D review limiting my comments this quarter to the programs with the most significant recent updates: Cystic Fibrosis, Pain, type one diabetes and IgA Nephropathy. Starting with CF, we are very pleased with the Phase III results from the VANZACAFTOR Triple program we announced in early February, as we continue to drive towards our ultimate goal of bringing all eligible patients to carrier levels, indeed to normal levels of CFTR function as measured by sweat chloride.

Speaker Change: 6 years and older, which has been given priority review designation and VX548 or sucetra gene in moderate to severe acute pain, which has also been granted priority review by the FDA.

Ray Smith: To the programs with the most significant recent updates cystic fibrosis pain type, one diabetes and Iga nephropathy.

Unknown Executive: First, the Cicetrogene LSR Phase 2 study has significantly accelerated, and we now expect Phase 2 results by the end of this year. Second, in the VX880 Phase 1-2 trial in Type 1 diabetes, we have completed enrollment and dosing in the original 17-patient study, and we have secured regulatory endorsement to expand the study to 37 patients in total as we advance towards pivotal development. And third, in the POVITASISEP program, having completed successful end of phase 2 regulatory meetings, we will initiate the Phase 3 pivotal trial in IgA nephropathy later this month.

Ray Smith: Starting with CF, we are very pleased with the phase III results from the vans. The captor Triple program, we announced in early February as we continue to drive towards our ultimate goal of bringing all eligible patients to carrier levels, indeed to normal levels of CFT, our function as measured by sweat.

Speaker Change: Lastly, on the mid- and late-stage pipeline, I am very pleased with our continued rapid progress.

Speaker Change: I'll call out three specific programs. First, the Cicetrogene LSR Phase 2 study has significantly accelerated and we now expect Phase 2 results by the end of this year.

Reshma Kewalramani: The VANZACAFTOR triple demonstrated an even greater reduction in sweat chloride than TRIKAFTA, a very high bar to have crested and thus sets the stage for the potential to have a new standard in the treatment of CF, the VANZACAFTOR Triple also offers the convenience of once daily dosing, and a substantially lower royalty burden. With regard to the VANZA Global regulatory submissions, in addition to the US acceptance, our filings have also been validated by the EMA in the EU and the MHRA in the UK. With regard to VX five two to our Ctr mrna therapy in development with our partners at Madonna. It has completed the single sending dose portion of the phase one two study and continues in the multiple sending dose portion as a reminder, VX 522 seeks to provide treatment for <unk>.

Ray Smith: Alright.

Ray Smith: The vans the captor triple demonstrated an even greater reduction in sweat chloride than try CAFTA, a very high bar to have crested and thus sets the stage for the potential to have a new standard in the treatment of CF the.

Speaker Change: Second, in the VX880 Phase 1-2 trial in Type 1 Diabetes, we have completed enrollment and dosing in the original 17 patient study.

Speaker Change: And we have secured regulatory endorsement to expand the study to 37 patients in total as we advance towards pivotal development.

Ray Smith: The vans the captor Triple also offers the convenience of once daily dosing and substantially lower royalty burden. With regard to the Vancouver Global regulatory submissions. In addition to the U S acceptance our filings have also been validated by the EMA in the EU and the MH or a in the U K.

Speaker Change: And third, in the Povitacicep program, having completed successful end of phase 2 regulatory meetings, we will initiate the phase 3 pivotal trial in IgA nephropathy later this month.

Speaker Change: With regard to the Vancouver Global regulatory submissions. In addition to the U S acceptance our filings have also been validated by the EMA in the EU and the MH or a in the U K.

Reshma Kewalramani: With those highlights, let me now turn to an R&D review, limiting my comments this quarter to the programs with the most significant recent updates, Cystic Fibrosis, pain, Type 1 diabetes, and IgA nephropathy. Starting with CF, we are very pleased with the Phase III results from the VANZACAFTOR Triple Program we announced in early February, as we continue to drive towards our ultimate goal of bringing all eligible patients to carrier levels, indeed to normal levels of CFTR function as measured by sweat chloride. The VANZACAFTOR triple demonstrated an even greater reduction in sweat chloride than TRIKAFTA, a very high bar to [inaudible], and thus sets the stage for the potential to having new standards in the treatment of CF, the VANZACAFTOR triple also offers the convenience of once-daily dosing at a substantially lower royalty burden. With regard to the VANZA global regulatory submission, in addition to the US acceptance, our filings have also been validated by the EMA in the EU, and the MHRA in the UK. With regard to VX522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion. As a reminder, VX522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025, starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need for LSR therapy. In the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Reshma Kewalramani: With regard to VX-522 our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1/2 study, and continues in the multiple sending dose portion, as a reminder, VX-522 seeks to provide treatment for the more than 5000 people with CF, who do not make any CFTR protein, and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025. Moving now to the pain program and our portfolio of novel highly selective NAV 1.8, and NAV, one seven pain signal inhibitors in acute pain, a few points to highlight first we are very pleased that the sector gene submission has been accepted.

Speaker Change: With those highlights, let me now turn to an R&D review, limiting my comments this quarter to the programs with the most significant recent updates, Cystic Fibrosis, Pain, Type 1 Diabetes and IgA Nephropathy.

Speaker Change: With regard to VX five two to our Ctr mrna therapy in development with our partners at Madonna. It has completed the single sending dose portion of the phase one two study and continues in the multiple sending dose portion as a reminder, VX 522 seeks to provide treatment for <unk>.

Speaker Change: Starting with CF.

Speaker Change: We are very pleased with the Phase 3 results from the Vantacaptor Triple Program we announced in early February , as we continue to drive towards our ultimate goal of bringing all eligible patients to carrier levels, indeed, to normal levels of CFTR function as measured by sweat chloride.

More than 5000 people with CF, who do not make any see FTR protein and therefore cannot benefit from CF GR modulators based on the pace of enrollment and study dynamics. Our current expectation is to complete the study and share both efficacy and safety results from the.

Speaker Change: The Vanzikafta triple demonstrated an even greater reduction in sweat chloride than Trikafta, a very high bar to have crested, and thus sets the stage for the potential to have a new standard in the treatment of CF.

Speaker Change: A study in the first half of 2025.

Reshma Kewalramani: Moving now to the pain program and our portfolio of novel highly selective Nav1.8, and Nav1.7 pain signal inhibitors, in acute pain, a few points to highlight. First, we are very pleased that the SUZETRIGINE submission has been accepted, and granted priority review by the FDA with a PDUFA target action date of January 30th 2025. Second, our next in class Nav 1,8 pain signal inhibitor VX-993 is in the clinic in a Phase I trial with the IV formulation, and is currently enrolling and dosing healthy volunteers. Third VX-993 will soon enter a Phase II study with the oral formulation in acute pain, following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav1.8 inhibitors.

Speaker Change: Moving now to the pain program and our portfolio of novel highly selective NAV 1.8, and NAV, one seven pain signal inhibitors in acute pain, a few points to highlight first we are very pleased that the sector gene submission has been accepted.

Speaker Change: The Vancicaptor Triple also offers the convenience of once-daily dosing and a substantially lower royalty burden.

Reshma Kewalramani: The VANZACAFTOR triple demonstrated an even greater reduction in sweat chloride than TRIKAFTA, a very high bar to [inaudible], and thus sets the stage for the potential to having new standards in the treatment of CF, the VANZACAFTOR triple also offers the convenience of once-daily dosing at a substantially lower royalty burden. With regard to the VANZA global regulatory submission, in addition to the US acceptance, our filings have also been validated by the EMA in the EU, and the MHRA in the UK. With regard to VX-522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion. As a reminder, VX-522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025. Moving out to the pain program and our portfolio of novel, highly selective Nav 1.8 and Nav 1.7 pain signal inhibitors, in acute pain, a few points to highlight. First, we are very pleased that the SUZETRIGINE submission has been accepted and granted priority review by the FDA, with a PDUFA target action date of January 30th 2025. Second, our next-in-class Nav 1.8 pain signal inhibitor, VX-993 is in the clinic in a Phase I trial with the IV formulation and is currently enrolling and dosing healthy volunteers. Third, VX-993 will soon enter a Phase II study with the oral formulation in acute pain following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav 1.8 inhibitors. Just as in acute pain, we have multiple programs moving rapidly through development in lstarting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need for LSR therapy. In the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Speaker Change: With regard to the VANSA Global Regulatory Submissions, in addition to the U.S. acceptance, our filings have also been validated by the EMA in the EU and the MHRA in the UK.

Speaker Change: And granted priority review by the FDA with a producer a target action date of January 30th 2025 second our next in class NAV, one eight pain signal inhibitor VX 993 is in the clinic in a phase one trial with the IV formulation. And is currently enrolling and dosing healthy volunteers third VX 993 will soon enter a phase two study with the oral formulation in acute pain. Following bunionectomy surgery. This study is on track to begin later this quarter. And lastly, we continue to make strong progress pre clinically with our NAV one seven pain signal inhibitor program that may be used alone or in combination with Nab 1.8 inhibitors.

Unknown Executive: With regard to VX522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion. As a reminder, VX522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025, starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need for LSR therapy. In the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Speaker Change: With regard to VX522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion.

Speaker Change: And is currently enrolling and dosing healthy volunteers third VX 993 will soon enter a phase two study with the oral formulation in acute pain. Following bunionectomy surgery. This study is on track to begin later this quarter. And lastly, we continue to make strong progress pre clinically with our NAV one seven pain signal inhibitor program that may be used alone or in combination with Nab 1.8 inhibitors.

Reshma Kewalramani: Third VX-993 will soon enter a Phase II study with the oral formulation in acute pain, following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav1.8 inhibitors. Just as an acute pain, we have multiple programs moving rapidly through development in Peripheral Neuropathic Pain or PNP, starting with painful lumbosacral radiculopathy or LSR, a condition that impacts more than 4 million Americans, there is a high unmet need in LSR. In the U S. There are no medicines approved specifically for the treatment of pain from L. A S R. As.

Reshma Kewalramani: Third VX-993 will soon enter a Phase II study with the oral formulation in acute pain, following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav1.8 inhibitors. Just as an acute pain, we have multiple programs moving rapidly through development in Peripheral Neuropathic Pain or PNP, starting with painful lumbosacral radiculopathy or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need in LSR. In the US, there are no medicines approved specifically for the treatment of pain from LSR.

Reshma Kewalramani: With regard to VX-522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion. As a reminder, VX-522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025. Moving out to the pain program and our portfolio of novel, highly selective Nav 1.8 and Nav 1.7 pain signal inhibitors, in acute pain, a few points to highlight. First, we are very pleased that the SUZETRIGINE submission has been accepted and granted priority review by the FDA, with a PDUFA target action date of January 30th 2025. Second, our next-in-class Nav 1.8 pain signal inhibitor, VX-993 is in the clinic in a Phase I trial with the IV formulation and is currently enrolling and dosing healthy volunteers. Third, VX-993 will soon enter a Phase II study with the oral formulation in acute pain following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav 1.8 inhibitors. Just as in acute pain, we have multiple programs moving rapidly through development in lstarting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need for LSR therapy. In the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Speaker Change: As a reminder, VX522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators.

Speaker Change: And lastly, we continue to make strong progress pre clinically with our NAV one seven pain signal inhibitor program that may be used alone or in combination with Nab 1.8 inhibitors.

Speaker Change: Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025.

Reshma Kewalramani: With regard to VX522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase 1-2 study and continues in the multiple ascending dose portion. As a reminder, VX522 seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025, starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need for LSR therapy. In the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Speaker Change: Just as an acute pain, we have multiple programs moving rapidly through development in peripheral neuropathic pain or P. N P. Starting with painful lumbosacral radiculopathy or LFR, a condition that impacts more than 4 million Americans. There is a high unmet need in L. A S. R.

Speaker Change: Moving now to the pain program and our portfolio of novel, highly selective NAV1.8 and NAV1.7 pain signal inhibitors.

Speaker Change: In acute pain, a few points to highlight. First, we are very pleased that the Sucetra gene submission has been accepted and granted priority review by the FDA with a PDUFA target action date of January 30th, 2025.

Reshma Kewalramani: Moving out to the pain program and our portfolio of novel, highly selective Nav 1.8 and Nav 1.7 pain signal inhibitors, in acute pain, a few points to highlight. First, we are very pleased that the SUZETRIGINE submission has been accepted and granted priority review by the FDA, with a PDUFA target action date of January 30th 2025. Second, our next-in-class Nav 1.8 pain signal inhibitor, VX-993 is in the clinic in a Phase I trial with the IV formulation and is currently enrolling and dosing healthy volunteers. Third, VX-993 will soon enter a Phase II study with the oral formulation in acute pain following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav 1.8 inhibitors. Just as in acute pain, we have multiple programs moving rapidly through development in Peripheral Neuropathic pain or PNP, starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need in LSR, in the U.S., there are no medicines approved specifically for the treatment of pain from LSR. As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase 2 LSR results by the end of this year. Also, in Peripheral Neuropathic Pain, we are excited to begin the Phase 3 Pivotal Program for SucetraGene in Painful Diabetic Peripheral Neuropathy, or DPN, later this quarter. The DPN Pivotal Program consists of two identical randomized control trials of approximately 1,100 patients each, with SucetraGene at a dose of 70 mg once daily and evaluating the change from baseline to Week 12 in NPRS pain scores relative to placebo.

Reshma Kewalramani: In the U S. There are no medicines approved specifically for the treatment of pain from L. A S R. As. As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections study enrollment is now complete and we anticipate sharing phase two <unk> results by the end of this year.

Reshma Kewalramani: In the U S. There are no medicines approved specifically for the treatment of pain from L. A S R. As.

Speaker Change: In the U S. There are no medicines approved specifically for the treatment of pain from L. A S R. As.

Reshma Kewalramani: As mentioned in my opening remarks, the pace of enrollment in this study has been rapid, and significantly exceeded our projections, study enrollment is now complete, and we anticipate sharing Phase II LSR results by the end of this year. Also in peripheral neuropathic pain, we are excited to begin the Phase III pivotal program for SUZETRIGINE in painful diabetic peripheral neuropathy, or DPN, later this quarter. The DPN Pivotal program consists of two identical, randomized controlled trials of approximately 1,100 patients each, with SUZETRIGINE at a dose of 70 milligrams, once-daily and evaluating the change from baseline to week 12 in NPRS pain scores relative to placebo. The [inaudible] also include an active comparator arm of PREGABALIN, a key secondary endpoint is changed from baseline at week 12 in NPRS score for SUZETRIGINE versus PREGABALIN, assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus PREGABALIN. Lastly in P. M. P. I am pleased to share that we will soon initiate a phase II study with the oral formulation of VX 993 in diabetic peripheral neuropathy designed similarly to the sector gene Phase II <unk> study. This trial is also on track to begin.

Speaker Change: As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections study enrollment is now complete and we anticipate sharing phase two <unk> results by the end of this year.

Speaker Change: Second, our next in class NAV1.8 pain signal inhibitor VX993 is in the clinic in a phase one trial with the IV formulation and is currently enrolling and dosing healthy volunteers.

Speaker Change: Third, VX993 will soon enter a Phase 2 study with the oral formulation in acute pain following bunionectomy surgery. This study is on track to begin later this quarter.

Speaker Change: Also in peripheral neuropathic pain, we are excited to begin the phase III pivotal program for Susceptor gene in painful diabetic peripheral neuropathy or D. P. M. Later this quarter. The D. P. N. Pivotal program consists of two identical randomized controlled trials of approximately 1100 patients each with two <unk>.

Reshma Kewalramani: Third, VX-993 will soon enter a Phase II study with the oral formulation in acute pain following bunionectomy surgery, this study is on track to begin later this quarter. And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav 1.8 inhibitors. Just as in acute pain, we have multiple programs moving rapidly through development in Peripheral Neuropathic pain or PNP. Starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans, there is a high unmet need in LSR, in the U.S., there are no medicines approved specifically for the treatment of pain from LSR.

Speaker Change: And lastly, we continue to make strong progress preclinically with our NAV 1.7 pain signal inhibitor program that may be used alone or in combination with NAV 1.8 inhibitors.

Reshma Kewalramani: And lastly, we continue to make strong progress pre-clinically with our Nav 1.7 pain signal inhibitor program that may be used alone or in combination with Nav 1.8 inhibitors. Just as in acute pain, we have multiple programs moving rapidly through development in Peripheral Neuropathic pain or PNP.

Speaker Change: After gene at a dose of 70 milligrams once daily and evaluating the change from baseline to week 12 in N. P. R. S pain scores relative to placebo.

Speaker Change: Just as in acute pain, we have multiple programs moving rapidly through development in peripheral neuropathic pain or PNP.

Reshma Kewalramani: The [inaudible] also include an active comparator arm of PREGABALIN, a key secondary endpoint is changed from baseline at week 12 in NPRS score for SUZETRIGINE versus PREGABALIN, assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus PREGABALIN. Lastly in PNP I am pleased to share that we will soon initiate a Phase II study with the oral formulation of VX-993, in diabetic peripheral neuropathy, designed similarly to the SUZETRIGINE Phase II DPN study. This trial is also on track to begin this quarter. Turning now to type one diabetes VX eight eighties, our stem cell derived fully differentiated islet cell therapy for people with T. One D and impaired hypoglycemic awareness, who experience severe hypoglycemic events, despite optimal medical care.

Reshma Kewalramani: The [inaudible] also include an active comparator arm of PREGABALIN, a key secondary endpoint is changed from baseline at week 12 in NPRS score for SUZETRIGINE versus PREGABALIN, assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus PREGABALIN. Lastly in PNP, I am pleased to share that we will soon initiate a Phase II study with the oral formulation of VX-993, in diabetic peripheral neuropathy, designed similarly to the SUZETRIGINE Phase II DPN study, this trial is also on track to begin this quarter.

Speaker Change: <unk> also include an active comparator arm of Pregabalin, a key secondary endpoint is changed from baseline at week 12 in N. P. R. S score forces cetera gene versus Pregabalin assessed for non inferiority and if we meet non inferiority then we will test for superiority versus pre.

Reshma Kewalramani: Starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans, there is a high unmet need in LSR, in the U.S., there are no medicines approved specifically for the treatment of pain from LSR. As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase 2 LSR results by the end of this year. Also, in Peripheral Neuropathic Pain, we are excited to begin the Phase 3 Pivotal Program for SucetraGene in Painful Diabetic Peripheral Neuropathy, or DPN, later this quarter. The DPN Pivotal Program consists of two identical randomized control trials of approximately 1,100 patients each, with SucetraGene at a dose of 70 mg once daily and evaluating the change from baseline to Week 12 in NPRS pain scores relative to placebo.

Speaker Change: Starting with painful lumbosacral radiculopathy, or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need in LSR. In the US, there are no medicines approved specifically for the treatment of pain from LSR.

Reshma Kewalramani: There is a high unmet need in LSR, in the U.S., there are no medicines approved specifically for the treatment of pain from LSR. As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase 2 LSR results by the end of this year. Also, in Peripheral Neuropathic Pain, we are excited to begin the Phase 3 Pivotal Program for SucetraGene in Painful Diabetic Peripheral Neuropathy, or DPN, later this quarter. The DPN Pivotal Program consists of two identical randomized control trials of approximately 1,100 patients each, with SucetraGene at a dose of 70 mg once daily and evaluating the change from baseline to Week 12 in NPRS pain scores relative to placebo.

Reshma Kewalramani: As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase 2 LSR results by the end of this year. Also, in Peripheral Neuropathic Pain, we are excited to begin the Phase III Pivotal Program for SUZETRIGINE in Painful Diabetic Peripheral Neuropathy, or DPN, later this quarter. The DPN Pivotal Program consists of two identical randomized control trials of approximately 1,100 patients each, with SUZETRIGINE at a dose of 70 mg, once-daily and evaluating the change from baseline to Week 12 in NPRS pain scores relative to placebo, the RCTs also include an active comparator arm of pregabalin.

Unknown Executive: As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase 2 LSR results by the end of this year. Also, in Peripheral Neuropathic Pain, we are excited to begin the Phase 3 Pivotal Program for SucetraGene in Painful Diabetic Peripheral Neuropathy, or DPN, later this quarter. The DPN Pivotal Program consists of two identical randomized control trials of approximately 1,100 patients each, with SucetraGene at a dose of 70 mg once daily and evaluating the change from baseline to Week 12 in NPRS pain scores relative to placebo.

Reshma Kewalramani: Lastly in P. M. P. I am pleased to share that we will soon initiate a phase II study with the oral formulation of VX 993 in diabetic peripheral neuropathy designed similarly to the sector gene Phase II <unk> study. This trial is also on track to begin.

<unk>.

Speaker Change: Lastly in P. M. P. I am pleased to share that we will soon initiate a phase II study with the oral formulation of VX 993 in diabetic peripheral neuropathy designed similarly to the sector gene Phase II <unk> study. This trial is also on track to begin.

Speaker Change: As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections.

Speaker Change: Study enrollment is now complete and we anticipate sharing Phase 2 LSR results by the end of this year.

Speaker Change: Also in peripheral neuropathic pain, we are excited to begin the phase 3 pivotal program for suscetra gene in painful diabetic peripheral neuropathy or DPN later this quarter.

Speaker Change: In this quarter.

Reshma Kewalramani: Turning now to type one diabetes VX-880, our stem cell derived fully differentiated islet cell therapy for people with T1D and impaired hypoglycemic awareness, who experience severe hypoglycemic events, despite optimal medical care. At the ADA meeting in June an oral presentation from the ongoing Phase 1/2 study included updated data with more patients and longer duration of follow up, and continued to demonstrate the potential of VX-880, as a functional cure for patients with T1D. The data reflected 12 patients from parts B and C of the study who received a full dose of VX 880, as a single infusion and had at least three months of follow up the results are remarkable specifically all patients demonstrated islet cell and <unk>.

Speaker Change: Turning now to type one diabetes VX eight eighties, our stem cell derived fully differentiated islet cell therapy for people with T. One D and impaired hypoglycemic awareness, who experience severe hypoglycemic events, despite optimal medical care.

Speaker Change: The DPN Pivotal Program consists of two identical, randomized control trials of approximately 1,100 patients each.

Speaker Change: with SucetraGene at a dose of 70 mg once daily and evaluating the change from baseline to week 12 in NPRS pain scores relative to placebo.

Reshma Kewalramani: The RCTs also include an active comparator arm of pregabalin. A key secondary endpoint is change from baseline at Week 12 in NPRS score for SucetraGene versus pregabalin assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus pregabalin.

Reshma Kewalramani: The RCTs also include an active comparator arm of pregabalin.

Speaker Change: At the Ada meeting in June and oral presentation from the ongoing phase. One two study included updated data with more patients and longer duration of follow up and continued to demonstrate the potential of VX 880, as a functional cure for patients with T. One D.

Speaker Change: The RCTs also include an active comparator arm of Pregabalin.

Speaker Change: A key secondary endpoint is change from baseline at week 12 in NPRS score for suscetragene versus pregabalin assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus pregabalin.

Reshma Kewalramani: The data reflected 12 patients from parts B and C of the study who received a full dose of VX-880, as a single infusion and had at least three months of follow up, the results are remarkable, specifically all patients demonstrated islet cell engraftment, and glucose responses insulin production by day 90. All 12 patients achieved hemoglobin, A1c levels less than 7%, and all 12 patients also had a time in range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use. The three patients with 12 months of follow up and therefore evaluable for the primary endpoint each met the primary endpoint of elimination of severe hypoglycemic events with a hemoglobin a one C level below seven as well as the secondary endpoint of insulin.

Speaker Change: The data reflected 12 patients from parts B and C of the study who received a full dose of VX 880, as a single infusion and had at least three months of follow up the results are remarkable specifically all patients demonstrated islet cell and <unk>.

Reshma Kewalramani: A key secondary endpoint is change from baseline at Week 12 in NPRS score for SUZETRIGINE versus pregabalin, assessed for non-inferiority, and if we meet non-inferiority, then we will test for superiority versus pregabalin. Lastly in PNP, I'm pleased to share that we will soon initiate a Phase II study with the oral formulation of VX-993 in Diabetic Peripheral Neuropathy, designed similarly to the SUZETRIGINE stage 2 DPN study, this trial is also on track to begin this quarter. Turning now to type 1 Diabetes, VX-880 is our stem cell-derived, fully differentiated islet cell therapy for people with T1D, and impaired hypoglycemic awareness who experience severe hypoglycemic events despite optimal medical care. At the ADA meeting in June, an oral presentation of the ongoing Phase 1/2 study included updated data with more patients and longer duration of follow-up, and continue to demonstrate the potential of VX-880 as a functional cure for patients with T1D. The data reflected 12 patients from parts B and C of the study who received a full dose of VX-880 as a single infusion and had at least 3 months of follow-up. The results are remarkable, specifically, all patients demonstrated islet cell engraftment and glucose-responsive, insulin production by day 90, all 12 patients achieved hemoglobin A1c levels les that 7%, and all 12 patients also had a timing range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use, and the three patients with 12 months of follow-up, and therefore, evaluable for the primary endpoint, each met the primary endpoint of elimination of severe hypoglycemic events, with a hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. With these results we're planning forward towards the next phase of development for VX-880, to that end we're very pleased to have secured regulatory approvals to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880, our CellsPlus device, or VX-264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Speaker Change: Lastly, in PNP, I am pleased to share that we will soon initiate a Phase 2 study with the oral formulation of VX993 in diabetic peripheral neuropathy, designed similarly to the SucetraGene Phase 2 DPN study. This trial is also on track to begin this quarter.

Speaker Change: <unk> and glucose responses insulin production by day 90. All 12 patients achieved hemoglobin, a one C levels less than 7% and all 12 patients also had a time in range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exaggerates insulin use.

Speaker Change: All 12 patients achieved hemoglobin, a one C levels less than 7% and all 12 patients also had a time in range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exaggerates insulin use.

Speaker Change: Turning now to type 1 diabetes. VX880s are stem cell derived, fully differentiated islet cell therapy for people with T1D and impaired hypoglycemic awareness who experience severe hypoglycemic events despite optimal medical care.

Speaker Change: 11 of the 12 patients greatly reduced or completely eliminated exaggerates insulin use.

Reshma Kewalramani: Turning now to type 1 Diabetes, VX-880 is our stem cell-derived, fully differentiated islet cell therapy for people with T1D, and impaired hypoglycemic awareness who experience severe hypoglycemic events despite optimal medical care. At the ADA meeting in June, an oral presentation of the ongoing Phase 1/2 study included updated data with more patients and longer duration of follow-up, and continue to demonstrate the potential of VX-880 as a functional cure for patients with T1D. The data reflected 12 patients from parts B and C of the study who received a full dose of VX-880 as a single infusion and had at least 3 months of follow-up. The results are remarkable, specifically, all patients demonstrated islet cell engraftment and glucose-responsive, insulin production by day 90, all 12 patients achieved hemoglobin A1c levels les that 7%, and all 12 patients also had a timing range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use, and the three patients with 12 months of follow-up, and therefore, evaluable for the primary endpoint, each met the primary endpoint of elimination of severe hypoglycemic events, with a hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. With these results we're planning forward towards the next phase of development for VX-880, to that end we're very pleased to have secured regulatory approvals to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880, our CellsPlus device, or VX-264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Reshma Kewalramani: The three patients with 12 months of follow up and therefore evaluable for the primary endpoint each met the primary endpoint of elimination of severe hypoglycemic events with a Hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. With these results we are planning forward towards the next phase of development for VX-880, to that end, we are very pleased to have secured regulatory approval to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continue.

Speaker Change: The three patients with 12 months of follow up and therefore evaluable for the primary endpoint each met the primary endpoint of elimination of severe hypoglycemic events with a hemoglobin a one C level below seven as well as the secondary endpoint of insulin.

Speaker Change: At the ADA meeting in June , an oral presentation from the ongoing Phase 1-2 study included updated data with more patients and longer duration of follow-up.

Speaker Change: and continue to demonstrate the potential of VX880 as a functional cure for patients with T1D.

Speaker Change: With these results we are planning forward towards the next phase of development for VX 882 that and we are very pleased to have secured regulatory approval to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants we look forward to continue.

Speaker Change: The data reflected 12 patients from Parts B and C of the study who received a full dose of VX880 as a single infusion and had at least 3 months of follow-up.

Reshma Kewalramani: The data reflected 12 patients from parts B and C of the study who received a full dose of VX-880 as a single infusion and had at least 3 months of follow-up. The results are remarkable, specifically, all patients demonstrated islet cell engraftment and glucose-responsive, insulin production by day 90, all 12 patients achieved hemoglobin A1c levels les that 7%, and all 12 patients also had a timing range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use, and the three patients with 12 months of follow-up, and therefore, evaluable for the primary endpoint, each met the primary endpoint of elimination of severe hypoglycemic events, with a hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. With these results we're planning forward towards the next phase of development for VX-880, to that end we're very pleased to have secured regulatory approvals to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880, our CellsPlus device, or VX-264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Reshma Kewalramani: We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880 our cells + device or VX-264 program encapsulates the same the VX-880 cells in a proprietary device designed to eliminate the need for immunosuppressants, VX-264 is in a Phase 1/2 multipart global study. We have completed part A of the study at an initial dose with a stagger between patients, we are currently enrolling and dosing patients in part B, which is at the full target dose, also with a stagger between patients. As a reminder, part C of the trial is that the full target dose with no stagger between patients. The last major R&D update pertains to POVETACICEPT, the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high. As a reminder, Pove holds the promise of being a pipeline in a product and has best.

Speaker Change: The results are remarkable. Specifically, all patients demonstrated islet cell engraftment and glucose-responsive insulin production by day 90.

Speaker Change: During the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX 880 ourselves plus device or VX two six floor program encapsulates the same the X 80 cells in a proprietary device designed to eliminate the need for Immunosuppressants. The X to six floors in a phase one two multipart global study. We have completed part a of the study at an initial dose with a stagger between patients. We are currently enrolling and dosing patients in part B, which is at the full target dose also with a stagger between patients as a reminder, part C of the trial is that the full target dose with no staff. <unk> between patients. The last major R&D update pertains to protests, except the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high as a reminder, povey holds the promise of being a pipeline in a product and has best.

Speaker Change: Beyond VX 880 ourselves plus device or VX two six floor program encapsulates the same the X 80 cells in a proprietary device designed to eliminate the need for Immunosuppressants. The X to six floors in a phase one two multipart global study. We have completed part a of the study at an initial dose with a stagger between patients. We are currently enrolling and dosing patients in part B, which is at the full target dose also with a stagger between patients as a reminder, part C of the trial is that the full target dose with no staff. <unk> between patients. The last major R&D update pertains to protests, except the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high as a reminder, povey holds the promise of being a pipeline in a product and has best.

Speaker Change: All 12 patients achieved hemoglobin A1C levels less than 7% and all 12 patients also had a time and range for glucose levels of 70% or greater.

Unknown Executive: 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use, and the three patients with 12 months of follow-up and, therefore, evaluable for the primary endpoint, each met the primary endpoint of elimination of severe hypoglycemic events with a hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. Beyond VX880, our CellsPlus device, or VX264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Reshma Kewalramani: 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use, and the three patients with 12 months of follow-up, and therefore, evaluable for the primary endpoint, each met the primary endpoint of elimination of severe hypoglycemic events, with a hemoglobin A1c level below seven, as well as the secondary endpoint of insulin independence. With these results we're planning forward towards the next phase of development for VX-880, to that end we're very pleased to have secured regulatory approvals to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880, our CellsPlus device, or VX-264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Speaker Change: 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use.

Speaker Change: We have completed part a of the study at an initial dose with a stagger between patients. We are currently enrolling and dosing patients in part B, which is at the full target dose also with a stagger between patients as a reminder, part C of the trial is that the full target dose with no staff. <unk> between patients. The last major R&D update pertains to protests, except the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high as a reminder, povey holds the promise of being a pipeline in a product and has best.

Speaker Change: and the three patients with 12 months of follow-up and therefore evaluable for the primary endpoint.

Speaker Change: Each met the primary endpoint of elimination of severe hypoglycemic events with a hemoglobin A1c level below 7, as well as the secondary endpoint of insulin independence.

Reshma Kewalramani: As a reminder, part C of the trial is that the full target dose with no stagger between patients. The last major R&D update pertains to POVETACICEPT, the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high. As a reminder, Pove holds the promise of being a pipeline in a product and has best. In class potential for the lead indication in IgA Nephropathy, given it's mechanism of action, with dual inhibition of both APRIL and BAFF, it's preclinical profile and the clinical data through Phase II in proteinuria, hematuria and GFR. These attributes plus Pove's once-monthly dose frequency and small volume, subcutaneous route of administration give us high confidence in it's potential to be a transformative medicine for patients with IgAN. I am pleased to share that we are on track to initiate the global Phase III RAINIER study of POVETACICEPT in patients with IgA Nephropathy this month. To recap, we had successful end of Phase II meetings with the FDA and global regulatory authorities and we're very pleased to have reached agreement on the following important elements. The pivotal program is designed as a single, global, randomized double-blind, placebo-controlled trial of approximately 480 patients with biopsy proven IgAN and proteinuria.

Speaker Change: <unk> between patients. The last major R&D update pertains to protests, except the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high as a reminder, povey holds the promise of being a pipeline in a product and has best.

Reshma Kewalramani: With these results we're planning forward towards the next phase of development for VX-880, to that end we're very pleased to have secured regulatory approvals to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions. Beyond VX-880, our CellsPlus device, or VX-264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants.

Speaker Change: The last major R&D update pertains to protests, except the lead asset from our recently closed acquisition of Alpine immune sciences, where enthusiasm for both the acquisition and Toby remains high as a reminder, povey holds the promise of being a pipeline in a product and has best.

Speaker Change: With these results, we are planning forward towards the next phase of development for VX880.

Speaker Change: To that end, we are very pleased to have secured regulatory approval to expand the original 17 patient study, which is fully enrolled and dose to include an additional 20 participants.

In class potential for the lead indication in Iga nephropathy, given its mechanism of action with dual inhibition of both April and Bath.

Speaker Change: We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions.

Speaker Change: Its preclinical profile and the clinical data through phase two in proteinuria hematuria and GFR.

Speaker Change: Beyond VX880, our Cells Plus device, or VX264 program, encapsulates the same VX880 cells in a proprietary device designed to eliminate the need for immunosuppressants. VX264 is in a phase 1-2 multi-part global study.

Unknown Executive: VX264 is in a Phase I-II multi-part global study. These attributes, plus POVI's once-monthly dose frequency and small-volume subcutaneous route of administration, give us high confidence in its potential to be a transformative medicine for patients with IgAN. I am pleased to share that we are on track to initiate the global Phase III Renier study of povitacicept in patients with IgA nephropathy this month. To recap, we had successful end-of-Phase II meetings with the FDA and global regulatory authorities and were very pleased to have reached agreement on the following important elements. The pivotal program is designed as a single, global, randomized, double-blind, placebo-controlled trial of approximately 480 patients with biopsy-proven IgAN and proteinuria.

Speaker Change: These attributes plus Pove's once-monthly dose frequency and small volume, subcutaneous route of administration give us high confidence in it's potential to be a transformative medicine for patients with IgAN. I am pleased to share that we are on track to initiate the global Phase III RAINIER study of POVETACICEPT in patients with IgA Nephropathy this month. To recap, we had successful end of Phase II meetings with the FDA and global regulatory authorities and we're very pleased to have reached agreement on the following important elements. The pivotal program is designed as a single, global, randomized double-blind, placebo-controlled trial of approximately 480 patients with biopsy proven IgAN and proteinuria.

Reshma Kewalramani: These attributes plus Pove's once-monthly dose frequency and small volume, subcutaneous route of administration give us high confidence in it's potential to be a transformative medicine for patients with IgAN. I am pleased to share that we are on track to initiate the global Phase III RAINIER study of POVETACICEPT in patients with IgA Nephropathy this month. To recap, we had successful end of Phase II meetings with the FDA and global regulatory authorities and we're very pleased to have reached agreement on the following important elements. The pivotal program is designed as a single, global, randomized double-blind, placebo-controlled trial of approximately 480 patients with biopsy proven IgAN and proteinuria. Patients will be randomized to receive either Pove or placebo on top of standard of care. In the US, the Phase III design affords us the opportunity to submit for an accelerated approval, a pre-planned interim analysis will take place when a certain number of patients reaches 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104, and an assessment of GFR.

Speaker Change: We have completed Part A of the study at an initial dose with a stagger between patients.

Speaker Change: I am pleased to share that we are on track to initiate the global phase III Reni Air study of Covid task receptor in patients with Iga nephropathy. This month to recap we had successful end of phase two meetings with the FDA and global regulatory authorities and we're very pleased. To have reached agreement on the following important elements. The pivotal program is designed as a single global randomized double blind placebo controlled trial of approximately 480 patients with biopsy proven ICANN and proteinuria.

Speaker Change: We are currently enrolling and dosing patients in Part B, which is at the full target dose, also with a stagger between patients. As a reminder, Part C of the trial is at the full target dose with no stagger between patients.

Speaker Change: The last major R&D update pertains to Povitacicept, the lead asset from our recently closed acquisition of Alpine Immune Sciences, where enthusiasm for both the acquisition and POVI remains high.

Speaker Change: To have reached agreement on the following important elements. The pivotal program is designed as a single global randomized double blind placebo controlled trial of approximately 480 patients with biopsy proven ICANN and proteinuria.

Speaker Change: As a reminder, POVI holds the promise of being a pipeline and a product and has best-in-class potential for the lead indication in IgA nephropathy, given its mechanism of action with dual inhibition of both April and BASC,

Reshma Kewalramani: Patients will be randomized to receive either Pove or placebo on top of standard of care. In the US, the Phase III design affords us the opportunity to submit for an accelerated approval, a pre-planned interim analysis will take place when a certain number of patients reaches 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104, and an assessment of GFR. Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal diseases termed RUBY-3 and a second in B-cell-mediated cytopenias termed RUBY-4. We look forward to read outs from some cohorts in these studies later this year and into next.

Speaker Change: Patients will be randomized to receive either Pove or placebo on top of standard of care. In the US, the Phase III design affords us the opportunity to submit for an accelerated approval, a pre-planned interim analysis will take place when a certain number of patients reaches 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104, and an assessment of GFR. Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal.

Patients will be randomized to receive either Pove or placebo on top of standard of care. In the US, the Phase III design affords us the opportunity to submit for an accelerated approval, a pre-planned interim analysis will take place when a certain number of patients reaches 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104, and an assessment of GFR. Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal diseases termed RUBY-3 and a second in B-cell-mediated cytopenias termed RUBY-4. We look forward to read outs from some cohorts in these studies later this year and into next.

Speaker Change: It's preclinical profile and the clinical data through phase 2 in proteinuria, hematuria and GFR.

Speaker Change: These attributes, plus POVI's once-monthly dose frequency and small-volume subcutaneous route of administration, give us high confidence in its potential to be a transformative medicine for patients with IgAN.

Speaker Change: Ordinary here from baseline to week 36 for full approval. The study will continue through week 104, and an assessment of GFR beyond the phase III study in Iga Nephropathy. Tobey is also being evaluated in two phase II basket trials one in renal.

Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal.

Reshma Kewalramani: Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal diseases termed RUBY-3 and a second in B-cell-mediated cytopenias termed RUBY-4. We look forward to read outs from some cohorts in these studies later this year and into next. To close the pipeline review a brief update on VX, six three or four and VX 668 in Alpha one antitrypsin deficiency or a a T D. Safety was demonstrated in the phase one studies of both VX 634, and 668, however, based on the phase one biomarker analyses, we have determined that neither VX 634, nor VX 668 would deliver transformative efficacy for people with AA. T D and therefore, we have decided to discontinue development of both molecules with these learnings our research efforts in a a T D will continue. I'll now turn it over to Stuart for a commercial update.

Beyond the phase III study in IgA Nephropathy, Pove is also being evaluated in two Phase II basket trials, one in renal diseases termed RUBY-3 and a second in B-cell-mediated cytopenias termed RUBY-4. We look forward to read outs from some cohorts in these studies later this year and into next.

Speaker Change: I am pleased to share that we are on track to initiate the Global Phase 3 Renier Study of Povitacicept in patients with IgA nephropathy this month.

Speaker Change: Diseases termed Ruby three and a second in B cell mediated cytopenia is termed Ruby for we look forward to read outs from some cohorts in these studies later this year and into next.

Reshma Kewalramani: We look forward to read outs from some cohorts in these studies later this year and into next. To close the pipeline review, a brief update on VX-634 and VX-668 in Alpha-1 antitrypsin deficiency, or AATD. Safety was demonstrated in the Phase I studies of both VX-634, and 668, however, based on the Phase I biomarker analyses, we have determined that neither VX-634, nor VX-668 would deliver transformative efficacy for people with AATD, and therefore, we have decided to discontinue development of both molecules. With these learnings, our research efforts in AATD will continue. I'll now turn it over to Stuart for a commercial update.

Reshma Kewalramani: We look forward to read outs from some cohorts in these studies later this year and into next.

Speaker Change: To recap, we had successful end of phase two meetings with the FDA and global regulatory authorities, and we're very pleased to have reached agreement on the following important elements.

Speaker Change: To close the pipeline review a brief update on VX, six three or four and VX 668 in Alpha one antitrypsin deficiency or a a T D.

Reshma Kewalramani: To close the pipeline review, a brief update on VX-634 and VX-668 in Alpha-1 antitrypsin deficiency, or AATD. Safety was demonstrated in the Phase I studies of both VX-634, and 668, however, based on the Phase I biomarker analyses, we have determined that neither VX-634, nor VX-668 would deliver transformative efficacy for people with AATD, and therefore, we have decided to discontinue development of both molecules. With these learnings, our research efforts in AATD will continue. I'll now turn it over to Stuart for a commercial update.

Speaker Change: The pivotal program is designed as a single, global, randomized, double-blind, placebo-controlled trial of approximately 480 patients with biopsy-proven IgAN and proteinuria.

Speaker Change: Safety was demonstrated in the phase one studies of both VX 634, and 668, however, based on the phase one biomarker analyses, we have determined that neither VX 634, nor VX 668 would deliver transformative efficacy for people with AA.

Unknown Executive: Patients will be randomized to receive either POVI or placebo on top of standard of care. In the U.S., the Phase III design affords us the opportunity to submit for an accelerated approval. A pre-planned interim analysis will take place when a certain number of patients reach 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104 and an assessment of GFR. Beyond the Phase III study in IgA nephropathy, POVI is also being evaluated in two Phase II basket trials, one in renal diseases, termed RUBY3, and a second in B-cell-mediated cytopenias, termed RUBY4.

Speaker Change: Patients will be randomized to receive either POVI or placebo on top of standard of care.

Speaker Change: In the US, the Phase 3 design affords us the opportunity to submit for an accelerated approval. A pre-planned interim analysis will take place when a certain number of patients reaches 36 weeks of treatment to evaluate the change in pertinuria from baseline to week 36.

Speaker Change: T D and therefore, we have decided to discontinue development of both molecules with these learnings our research efforts in a a T D will continue. I'll now turn it over to Stuart for a commercial update.

Speaker Change: For full approval, the study will continue through week 104 and an assessment of GFR.

Speaker Change: I'll now turn it over to Stuart for a commercial update.

Stuart Arbuckle: Thanks, Reshma, I'll first discuss CF, then provide some highlights of the ongoing CASGEVY launch, and the outlook for SUZETRIGINE in acute pain. As Reshma noted, we once again delivered strong results in CF, as we grew the number of eligible patients taking our CFTR modulators, and we continue to expect sustained growth in CF over the near, medium, and long term. In the near term we continue to focus on reaching more eligible patients, including younger age groups as with the ongoing KAFTRIO launches in the two to five age group in Europe. With anticipated global approvals for additional rare mutations later this year, and through additional geographies, such as Brazil, where we now have national reimbursement for TRIKAFTA, patients ages six and above.

Speaker Change: Beyond the Phase 3 study in IgA nephropathy, POVI is also being evaluated in two Phase 2 basket trials, one in renal diseases, termed Ruby 3, and a second in B-cell mediated cytopenias, termed Ruby 4.

Stuart: Retro noted we once again delivered strong results in CF as we grew the number of eligible patients taking I'll see FTR modulators and we continue to expect sustained growth in CF over the near medium and long term in the near term we continue to focus on reaching more eligible patients, including younger age groups as with the ongoing Caf trio launches. In the two to five age group in Europe. With anticipated global approvals for additional rare mutations later this year. And through additional geographies, such as Brazil, where we now have national reimbursement for truck after for patients ages six and above.

Speaker Change: We look forward to readouts from some cohorts in these studies later this year and into next.

Speaker Change: To close the pipeline review, a brief update on VX634 and VX668 in Alpha-1 antitrypsin deficiency or AATD.

Stuart: In the two to five age group in Europe. With anticipated global approvals for additional rare mutations later this year. And through additional geographies, such as Brazil, where we now have national reimbursement for truck after for patients ages six and above.

Stuart: With anticipated global approvals for additional rare mutations later this year. And through additional geographies, such as Brazil, where we now have national reimbursement for truck after for patients ages six and above.

Stuart Arbuckle: With anticipated global approvals for additional rare mutations later this year, and through additional geographies, such as Brazil, where we now have national reimbursement for TRIKAFTA, patients ages six and above. We were also pleased to have announced in June an extended long term reimbursement agreement with NHS, England, which ensures access to our CFTR modulators for all existing and future eligible CF patients in England. Comparable arrangements have subsequently been entered into in Scotland, Wales, and Northern Ireland, the agreements are a result of positive recommendations for NICE and SMC for our CFTR modulators. In the medium term, we anticipate growth will be driven by the launch of our fifth see FTR modulator therapy, the VANZACAFTOR triple combination.

Stuart: And through additional geographies, such as Brazil, where we now have national reimbursement for truck after for patients ages six and above.

Speaker Change: Safety was demonstrated in the Phase 1 studies of both VX634 and 668.

Speaker Change: However, based on the Phase 1 biomarker analyses, we have determined that neither VX634 nor VX668 would deliver transformative efficacy for people with AATD, and therefore, we have decided to discontinue development of both molecules.

Speaker Change: We were also pleased to have announced in June an extended long term reimbursement agreement with NHS, England, which ensures access to Aussie FTR modulators for all existing and future eligible CF patients in England.

Speaker Change: Comparable arrangements have subsequently been entered into in Scotland, Wales, and Northern Ireland the.

Speaker Change: The agreements are a result of positive recommendations for nice and that's M. C. Four Aussie FTR modulators.

Speaker Change: With these learnings, our research efforts in AATD will continue. I'll now turn it over to Stuart for a commercial update.

Unknown Executive: We look forward to readouts from some cohorts in these studies later this year and into next. Thanks, Reshma. I'll first discuss CF, then provide some highlights of the ongoing Kaschevi launch and the outlook for cizetrogene in acute pain, with anticipated global approvals for additional rare mutations later this year and through additional geographies such as Brazil, where we now have national reimbursement for Trikafta for patients We were also pleased to have announced in June an extended long-term reimbursement agreement with NHS England which ensures access to our CFDR modulators for all existing and future eligible CF patients in England. The agreements are a result of positive recommendations from NICE and SMC for our CFTR modulator.

Stuart Arbuckle: In the medium term, we anticipate growth will be driven by the launch of our fifth see FTR modulator therapy, the VANZACAFTOR triple combination. We believe many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function and the added convenience of once daily dosing, and there are also more than 6000 patients who have discontinued one of our current CFTR modulators, who also maybe interested in a new treatment option. We continue to execute our VANZA prelaunch activities, including pre-approval information exchange with payers, and are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to CFTR modulators, which is the focus of our mRNA program VX-522. Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia.

Stuart Arbuckle: In the medium term, we anticipate growth will be driven by the launch of our fifth CFTR modulator therapy, the VANZACAFTOR triple combination. We believe many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function and the added convenience of once daily dosing, and there are also more than 6000 patients who have discontinued one of our current CFTR modulators, who also maybe interested in a new treatment option. We continue to execute our VANZA prelaunch activities, including pre-approval information exchange with payers, and are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to CFTR modulators, which is the focus of our mRNA program VX-522.

Speaker Change: In the medium term, we anticipate growth will be driven by the launch of our fifth see FTR modulator therapy. The vans are capped a triple combination.

Stuart: Thanks, Reshma. I'll first discuss CF, then provide some highlights of the ongoing Kasjevi launch and the outlook for cizetrogene in acute pain.

Speaker Change: We believe many existing try to half the patients may seek to achieve even greater levels of CFT, our function and the added convenience of once daily dosing. And there are also more than 6000 patients who have discontinued one of our current see FTR modulators, who also maybe interested in a new treatment option. We continue to execute our vans, a prelaunch activities, including Preapproval information exchange with payers and are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to see FTR modulators, which is the focus of our mrna program VX 522. Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Stuart: As Reshma noted, we once again delivered strong results in CF as we grew the number of eligible patients taking our CFTR modulators.

Speaker Change: And there are also more than 6000 patients who have discontinued one of our current see FTR modulators, who also maybe interested in a new treatment option. We continue to execute our vans, a prelaunch activities, including Preapproval information exchange with payers and are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to see FTR modulators, which is the focus of our mrna program VX 522. Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Stuart: And we continue to expect sustained growth in CF over the near, medium and long term. In the near term, we continue to focus on reaching more eligible patients, including younger age groups, as with the ongoing CAF TRIO launches in the two to five age group in Europe .

Speaker Change: We continue to execute our vans, a prelaunch activities, including Preapproval information exchange with payers and are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to see FTR modulators, which is the focus of our mrna program VX 522. Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Stuart: with anticipated global approvals for additional rare mutations later this year and through additional geographies such as Brazil where we now have national reimbursement for Trikafta for patients ages six and above.

Speaker Change: And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to see FTR modulators, which is the focus of our mrna program VX 522. Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Stuart Arbuckle: And longer term, we expect continued growth in CF from developing medicines for the more than 5000 people with CF, who do not respond to CFTR modulators, which is the focus of our mRNA program VX-522. Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia. We continue to make strong progress with ATC activation as well as physician, patient and payer engagement, as we work to bring this potentially curative therapy to patients around the globe. CASGEVY represents an enormous advancement for the estimated 35,000 people living with severe sickle cell disease, and transfusion-dependent beta thalassemia in the US and Europe, as well as the estimated 23,000 eligible patients in the kingdom of Saudi Arabia and Bahrain.

Stuart: We were also pleased to have announced in June an extended long-term reimbursement agreement with NHS England, which ensures access to our CFDR modulators for all existing and future eligible CF patients in England.

Stuart Arbuckle: Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia. We continue to make strong progress with ATC activation as well as physician, patient and payer engagement, as we work to bring this potentially curative therapy to patients around the globe. CASGEVY represents an enormous advancement for the estimated 35,000 people living with severe sickle cell disease, and transfusion-dependent beta thalassemia in the US and Europe, as well as the estimated 23,000 eligible patients in the kingdom of Saudi Arabia and Bahrain.

Speaker Change: Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Speaker Change: We continue to make strong progress with ATC activation as well as physician patient and payer engagement as we work to bring this potentially curative therapy to patients around the globe.

Stuart: Comparable arrangements have subsequently been entered into in Scotland, Wales and Northern Ireland.

Stuart: The agreements are a result of positive recommendations for NICE and SMC for RC-FTR modulators.

Speaker Change: Cast. Your every represents an enormous advancement for the estimated 35000 people living with severe sickle cell disease, and transfusion dependent beta thalassemia in the U S and Europe as well as the estimated 23000 eligible patients in the kingdom of Saudi Arabia and Bahrain.

Stuart Arbuckle: CASGEVY represents an enormous advancement for the estimated 35,000 people living with severe sickle cell disease, and transfusion-dependent beta thalassemia in the US and Europe, as well as the estimated 23,000 eligible patients in the kingdom of Saudi Arabia and Bahrain.

Stuart: In the medium term we anticipate growth will be driven by the launch of our fifth CFTR modulator therapy the Vanzikavter triple combination.

Stuart: We believe many existing Trikafta patients may seek to achieve even greater levels of CFTR function and the added convenience of once-daily dosing.

Stuart Arbuckle: To update you on the two key metrics, we are sharing externally as important markers of our early launch progress. Firstly, ATC activation, we're pleased with our progress as we now have more than 35 activated centers, up from 25 last quarter and nine at launch, we continue to expect to activate approximately 75 total ATC's globally. Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected. As mentioned last quarter, patients are initiating the treatment journey in every region where CASGEVY is approved, the US, Europe and the Middle East, and we are pleased to report gross.

Stuart Arbuckle: To update you on the two key metrics, we are sharing externally as important markers of our early launch progress. Firstly, ATC activation, we're pleased with our progress as we now have more than 35 activated centers, up from 25 last quarter and nine at launch. We continue to expect to activate approximately 75 total ATC's globally. Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected.

Speaker Change: To update you on the two key metrics, we are sharing externally as important markers of our early launch progress.

Stuart: and there are also more than 6,000 patients who have discontinued one of our current CFTR modulators who also may be interested in a new treatment option.

Speaker Change: Firstly, a T C activation. We're pleased with our progress as we now have more than 35 activated centers up from 25 last quarter and nine that launch. We continue to expect to activate approximately 75 total atc's globally. Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected as mentioned last quarter. Our patients are initiating the treatment journey in every region, where cash Jerry has approved the U S Europe and the Middle East and we are pleased to report gross.

Unknown Executive: We continue to execute our Vanza pre-launch activities, including pre-approval information exchange with payers, and are encouraged by the Outlook. We continue to make strong progress with ATC activation as well as physician, patient, and payer engagement. To update you on the two key metrics we are sharing externally as important markers of our early launch program, firstly, ATC activation.

Speaker Change: We're pleased with our progress as we now have more than 35 activated centers up from 25 last quarter and nine that launch. We continue to expect to activate approximately 75 total atc's globally. Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected as mentioned last quarter. Our patients are initiating the treatment journey in every region, where cash Jerry has approved the U S Europe and the Middle East and we are pleased to report gross.

Stuart: We continue to execute our VANSA pre-launch activities, including pre-approval information exchange with payers, and are encouraged by the Outlook.

Speaker Change: We continue to expect to activate approximately 75 total atc's globally. Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected as mentioned last quarter. Our patients are initiating the treatment journey in every region, where cash Jerry has approved the U S Europe and the Middle East and we are pleased to report gross.

Stuart: And longer term, we expect continued growth in CF from developing medicines for the more than 5,000 people with CF who do not respond to CFTR modulators, which is the focus of our mRNA program VX522.

Speaker Change: Secondly, patient cell collections, we continue to see a growing number of patients beginning the treatment journey approximately 20 patients have already had cells collected as mentioned last quarter. Our patients are initiating the treatment journey in every region, where cash Jerry has approved the U S Europe and the Middle East and we are pleased to report gross.

Stuart Arbuckle: As mentioned last quarter, patients are initiating the treatment journey in every region where CASGEVY is approved, the US, Europe and the Middle East, and we are pleased to report growth in patient cell collections across all of these regions this quarter. We also continue to make strong progress with payers in all regions, who recognize the transformative clinical benefits of CASGEVY, and are moving quickly to provide rapid and equitable access. Outside the US, we are building upon our early successes such as the early access program in France for TDT, and we now have an early access program approved there for sickle cell disease as well as reimbursement in Austria, Bahrain in KSA. In the U S. Given payer support across all market segments commercial Medicaid and Medicare.

Stuart: Now turning to Kastjevi and our launches in sickle cell disease and beta thalassemia.

Speaker Change: Inpatient sell collections across all of these regions this quarter.

Stuart: We continue to make strong progress with ATC activation, as well as physician, patient and payer engagement, as we work to bring this potentially curative therapy to patients around the globe.

Speaker Change: We also continue to make strong progress with payers and all regions, who recognize the transformative clinical benefits of cash JV and are moving quickly to provide rapid and equitable access.

Stuart: Castievi represents an enormous advancement for the estimated 35,000 people living with severe sickle cell disease and transfusion dependent beta-thalassemia in the US and Europe , as well as the estimated 23,000 eligible patients in the Kingdom of Saudi Arabia and Bahrain.

Stuart Arbuckle: Outside the US, we are building upon our early successes such as the early access program in France for TDT, and we now have an early access program approved there for sickle cell disease as well as reimbursement in Austria, Bahrain in KSA. In the US, given payer support across all market segments, commercial, Medicaid and Medicare, I'm pleased to report that we do not see coverage as a significant obstacle to patient access. We have always known that CASGEVY offers an enormous advancement for patients, we've also consistently communicated that the patient journey, that is the process to go from patient interest all the way to infusion of edited cells is long and complex. Whilst it's still early in the launch we have gained many learnings, interest level is high among patients, physicians, governments and other stakeholders, the value of CASGEVY has been widely recognized, leading to broad access and reimbursement by payers. The patient opportunity in the Middle East is particularly significant, given the high prevalence of these hemoglobinopathies and Government's clear focus on elevating the health of their citizens. And lastly, the treatment process does take time, but we are now even more confident in our view that CASGEVY will help large numbers of patients around the world and represents a multibillion dollar opportunity. Shifting now twosies estrogen we believe this novel highly.

Speaker Change: Outside the U S. We are building upon our early successes such as the early access program in France for TD T and we now have an early access program approved there for sickle cell disease as well as reimbursement in Austria, Bahrain in KSA in the U S. Given payer support across all market segments commercial Medicaid and Medicare.

Stuart: To update you on the two key metrics we are sharing externally as important markers of our early launch progress.

Stuart Arbuckle: In the U S. Given payer support across all market segments commercial Medicaid and Medicare. I'm pleased to report that we do not see coverage as a significant obstacle to patient access we have always known that cast JV offers an enormous advancement for patients. We've also consistently communicated that the patient journey that is the process to go from patient interest all the way to infusion of edited cells is long and complex whilst it's. Still early in the launch we have gained many learnings interest level is high among patients physicians governments and other stakeholders the value of cash JV has been widely recognized leading to broad access and reimbursement by payers the patient opportunity in the middle East is particularly significant given the high prevalence of these haemoglobinopathy. Governments clear focus on elevating the health of our citizens and lastly, the treatment process does take time, but we are now even more confident in our view that cash JV will help large numbers of patients around the world and represents a multibillion dollar opportunity shifting now twosies estrogen we believe this novel highly.

Unknown Executive: We're pleased with our progress as we now have more than 35 activated centers, up from 25 last quarter and 9 at launch. We continue to see a growing number of patients beginning the treatment journey. Approximately 20 patients have already had cells collected. As mentioned last quarter, patients are initiating the treatment journey in every region where Castievi is approved, that is, the US, Europe, and the Middle East.

Speaker Change: I'm pleased to report that we do not see coverage as a significant obstacle to patient access we have always known that cast JV offers an enormous advancement for patients. We've also consistently communicated that the patient journey that is the process to go from patient interest all the way to infusion of edited cells is long and complex whilst it's. Still early in the launch we have gained many learnings interest level is high among patients physicians governments and other stakeholders the value of cash JV has been widely recognized leading to broad access and reimbursement by payers the patient opportunity in the middle East is particularly significant given the high prevalence of these haemoglobinopathy. Governments clear focus on elevating the health of our citizens and lastly, the treatment process does take time, but we are now even more confident in our view that cash JV will help large numbers of patients around the world and represents a multibillion dollar opportunity shifting now twosies estrogen we believe this novel highly.

Stuart: Firstly, ATC activation.

Speaker Change: We're pleased with our progress as we now have more than 35 activated centres, up from 25 last quarter and 9 at launch.

Stuart: We continue to expect to activate approximately 75 total ATCs globally.

Stuart: Secondly, patient cell collections.

Stuart: We continue to see a growing number of patients beginning the treatment journey. Approximately 20 patients have already had cells collected. As mentioned last quarter, patients are initiating the treatment journey in every region where Castievi is approved. The US, Europe , and the Middle East.

Speaker Change: Still early in the launch we have gained many learnings interest level is high among patients physicians governments and other stakeholders the value of cash JV has been widely recognized leading to broad access and reimbursement by payers the patient opportunity in the middle East is particularly significant given the high prevalence of these haemoglobinopathy. Governments clear focus on elevating the health of our citizens and lastly, the treatment process does take time, but we are now even more confident in our view that cash JV will help large numbers of patients around the world and represents a multibillion dollar opportunity shifting now twosies estrogen we believe this novel highly.

Stuart Arbuckle: Whilst it's still early in the launch we have gained many learnings, interest level is high among patients, physicians, governments and other stakeholders, the value of CASGEVY has been widely recognized, leading to broad access and reimbursement by payers. The patient opportunity in the Middle East is particularly significant, given the high prevalence of these hemoglobinopathies and Government's clear focus on elevating the health of their citizens. And lastly, the treatment process does take time, but we are now even more confident in our view that CASGEVY will help large numbers of patients around the world and represents a multibillion dollar opportunity. Shifting now twosies estrogen we believe this novel highly.

Stuart Arbuckle: Whilst it's still early in the launch we have gained many learnings, interest level is high among patients, physicians, governments and other stakeholders. The value of CASGEVY has been widely recognized, leading to broad access and reimbursement by payers. The patient opportunity in the Middle East is particularly significant, given the high prevalence of these hemoglobinopathies and Government's clear focus on elevating the health of their citizens. And lastly, the treatment process does take time, but we are now even more confident in our view that CASGEVY will help large numbers of patients around the world and represents a multibillion dollar opportunity.

Stuart: and we are pleased to report growth in patient cell collections across all of these regions this quarter.

Speaker Change: Governments clear focus on elevating the health of our citizens and lastly, the treatment process does take time, but we are now even more confident in our view that cash JV will help large numbers of patients around the world and represents a multibillion dollar opportunity shifting now twosies estrogen we believe this novel highly.

Stuart: We also continue to make strong progress with payers in all regions who recognize the transformative clinical benefits of Castievi and are moving quickly to provide rapid and equitable access.

Stuart: Outside the US, we are building upon our early successes, such as the Early Access Program in France for TDT.

Stuart Arbuckle: Shifting now to SUZETRIGINE, we believe this novel highly-selective, Nav1.8 pain signal inhibitor has the potential to provide a transformative treatment option for the 19 million patients suffering from acute and peripheral neuropathic pain in the US. This quarter I'll limit my commercial comments to the opportunity in acute pain. We have continued to make significant progress building out our commercial team, we've now completed hiring of our strategic account leads, who will primarily focus on the leadership and formulary decision makers with IDMs, as well as our pain territory account managers, who post-approval will call on hospitals and other large treatment sites, such as ambulatory surgical centers. Recall that approximately $80 million.

Stuart: and we now have an early access program approved there for sickle cell disease as well as reimbursement in Austria, Bahrain and KSA.

Speaker Change: If NAV one eight pane single inhibitor has the potential to provide a transformative treatment option for the 19 million patients suffering from acute and peripheral neuropathic pain in the U S. This quarter I'll limit my commercial comments to the opportunity in acute pain. We have continued to make significant progress building out our commercial team. We've now completed hiring of our strategic account leads who will primarily focus on the leadership and formulary decision makers with idms as well as our pain territory account managers, who post approval will call on hospitals and other large treatment sites, such as ambulatory surgical centers recall that approximately $80 million.

Stuart: In the U.S., given payer support across all market segments, commercial, Medicaid, and Medicare, I'm pleased to report that we do not see coverage as a significant obstacle to patient access.

Unknown Executive: We have always known that Castievi offers an enormous advancement for patients. But we've also consistently communicated that the patient journey, that is, the process to go from patient interest all the way to the infusion of edited cells, is long and complex. Whilst it's still early in the launch, we have gained many learnings. Recall that approximately 80 million patients are prescribed a medicine for moderate to severe acute pain each year in the U.S., with approximately two-thirds of patients treated in the institutional setting. As a result, our field force will primarily focus on this institutional setting.

Stuart: We have always known that CASGEV offers an enormous advancement for patients. We've also consistently communicated that the patient journey, that is the process to go from patient interest all the way to infusion of edited cells, is long and complex.

Speaker Change: We've now completed hiring of our strategic account leads who will primarily focus on the leadership and formulary decision makers with idms as well as our pain territory account managers, who post approval will call on hospitals and other large treatment sites, such as ambulatory surgical centers recall that approximately $80 million.

Stuart: Whilst it's still early in the launch, we have gained many learnings.

Stuart: Interest level is high among patients, physicians, governments, and other stakeholders. The value of Castievi has been widely recognized, leading to broad access and reimbursement by payers.

Stuart Arbuckle: Recall that approximately $80 million patients are prescribed the medicine for moderate to severe acute pain each year in the US, with approximately two thirds of patients treated in the institutional setting as a result, our field force will primarily focus on this institutional setting. We have begun engaging in pre-approval information exchanges in those institutional settings with IDM leadership and formulary decision makers, who have responsibility for formularies that enable use in both the inpatient and discharge settings. We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well tolerated pain medication that does not possess addictive properties by way of its mechanism of action. Hospital formulary and payer processes are well defined, and we are engaging appropriately to encourage and support swift reviews by the relevant bodies like PMT committees, including by providing key clinical and economic information, depending on the institution or organization is can take up to 12 months post approval for hospital formulary and payer decisions to be finalized, but we are working to accelerate these timelines.

Stuart Arbuckle: Recall that approximately 80 million patients are prescribed the medicine for moderate to severe acute pain each year in the US, with approximately two thirds of patients treated in the institutional setting. As a result, our field force will primarily focus on this institutional setting. We have begun engaging in pre-approval information exchanges in those institutional settings with IDM leadership and formulary decision makers, who have responsibility for formularies that enable use in both the inpatient and discharge settings.

Speaker Change: Patients are prescribed the medicine for moderate to severe acute pain each year in the U S with approximately two thirds of patients treated in the institutional setting as a result, our field force will primarily focus on this institutional setting we have begun engaging in preapproval information exchanges in those institutional settings with IV and <unk>. The ship and formulary decision makers, who have responsibility for formularies that enable use in both the inpatient and discharge settings. We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well tolerated pain medication that does not possess addictive properties by way of its mechanism of action hospital formulary and payer processes are well defined and we are engaging appropriately to encourage and support swift reviews by the <unk>.

Stuart: The patient opportunity in the Middle East is particularly significant given the high prevalence of these haemoglobinopathies and government's clear focus on elevating the health of their citizens.

Stuart: And lastly, the treatment process does take time, but we are now even more confident in our view that CASGEVY will help large numbers of patients around the world and represents a multi-billion dollar opportunity.

Speaker Change: The ship and formulary decision makers, who have responsibility for formularies that enable use in both the inpatient and discharge settings. We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well tolerated pain medication that does not possess addictive properties by way of its mechanism of action hospital formulary and payer processes are well defined and we are engaging appropriately to encourage and support swift reviews by the <unk>.

Stuart Arbuckle: We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well tolerated pain medication that does not possess addictive properties by way of its mechanism of action. Hospital formulary and payer processes are well defined, and we are engaging appropriately to encourage and support swift reviews by the relevant bodies like PMT committees, including by providing key clinical and economic information, depending on the institution or organization is can take up to 12 months post approval for hospital formulary and payer decisions to be finalized, but we are working to accelerate these timelines. We anticipate engaging in contracting discussions in the latter half of 2024 with the goal of building formulary and payer coverage. During 2025. We also continue to be engaged with federal and state policymakers, including state Governors, who have expressed strong interest in a novel highly effective and well tolerated treatment for pain.

We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well tolerated pain medication that does not possess addictive properties by way of its mechanism of action hospital formulary and payer processes are well defined and we are engaging appropriately to encourage and support swift reviews by the <unk>.

Stuart: Shifting now to cizetrogene, we believe this novel, highly selective NAV1.8 pain signal inhibitor has the potential to provide a transformative treatment option for the 90 million patients suffering from acute and peripheral neuropathic pain in the U.S.

Speaker Change: This quarter, I'll limit my commercial comments to the opportunity and acute pain. We have continued to make significant progress building out our commercial team. We've now completed hiring of our strategic account leads, who will primarily focus on the leadership and formulary decision makers at IDNs.

Speaker Change: Haven't bodies like PMT committees, including by providing key clinical and economic information, depending on the institution or organization that can take up to 12 months post approval for hospital formulary and payer decisions to be finalized, but we are working to accelerate these timelines.

Stuart: as well as our Payne Territory account managers who, post-approval, will call on hospitals and other large treatment sites such as ambulatory surgical centres.

Speaker Change: We anticipate engaging in contracting discussions in the latter half of 2024 with the goal of building formulary and payer coverage. During 2025. We also continue to be engaged with federal and state policymakers, including state Governors, who have expressed strong interest in a novel highly effective and well tolerated treatment for pain.

Stuart Arbuckle: We anticipate engaging in contracting discussions in the latter half of 2024 with the goal of building formulary and payer coverage during 2025. We also continue to be engaged with federal and state policymakers, including state Governors, who have expressed strong interest in a novel, highly-effective and well tolerated treatment for pain, without the addictive potential of opioids. Federally in December 2022, Congress passed the no pain act, in which non opioid therapies are eligible for separate payment for Medicare patients in the outpatient and ACS settings, beginning in January 2025. It is promising to see CMS continuing the process of implementation, as the annual outpatient prospective payment system or OPPS proposed rule was released for public comment last month. Because SUZETRIGINE is still investigational, it is not currently included in the list of seven drugs in the proposed rule, but we fully expect SUZETRIGINE will be eligible for separate payment once it is FDA approved. We view the no pain act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level that can provide a meaningful tailwind to <unk> adoption.

Stuart: Recall that approximately 80 million patients are prescribed a medicine for moderate to severe acute pain each year in the US, with approximately two-thirds of patients treated in the institutional setting. As a result, our field force will primarily focus on this institutional setting.

Speaker Change: Without the addictive potential of opioids federally in December 2022 Congress passed the no pain act in which non opioid therapies are eligible for separate payment for Medicare patients in the outpatient and Acs settings. Beginning in January 2025, it is promising to see CMS continuing the process of.

Speaker Change: We have begun engaging in pre-approval information exchanges in those institutional settings with IDN leadership and formulary decision makers who have responsibility for formularies that enable use in both the inpatient and discharge settings.

Stuart Arbuckle: It is promising to see CMS continuing the process of implementation, as the annual outpatient prospective payment system or OPPS proposed rule was released for public comment last month. Because SUZETRIGINE is still investigational, it is not currently included in the list of seven drugs in the proposed rule, but we fully expect SUZETRIGINE will be eligible for separate payment once it is FDA approved. We view the No Pain Act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level that can provide a meaningful tailwind to SUZETRIGINE adoption. We are also encouraged by the progress of the alternatives to paint Act, which aims to level the playing field for access to non opioids for Medicare part D patients in the discharge or outpatient pharmacy setting it's important to understand that patients who receive a prescription must be able to access their acute pain medication immediately unlike patient.

Unknown Executive: Specifically, for an effective and well-tolerated pain medication that does not possess addictive properties by way of its mechanism of action. Hospital formulary and payer processes are well-defined, and we are engaging appropriately to encourage and support swift reviews by the relevant bodies like P&T committees, including by providing key clinical and economic information. Depending on the institution or organization, it can take up to 12 months post-approval for hospital formulary and payer decisions to be finalized, but we are working to accelerate these timelines.

Stuart: We've encountered High Levels of Enthusiasm for a New Class of Treatment for Pain.

Speaker Change: Implementation as the annual outpatient prospective payment system or PPS proposed rule was released for public comment last month, because that Eugene is still investigational. It is not currently included in the list of seven drugs in the proposed rule, but we fully expect says that Eugene will be eligible for separate payment once it is FDA.

Speaker Change: Specifically for an effective and well-tolerated pain medication that does not possess addictive properties by way of its mechanism of action.

Stuart: Hospital formulary and payer processes are well-defined, and we are engaging appropriately to encourage and support swift reviews by the relevant bodies like P&T committees,

Speaker Change: including by providing key clinical and economic information. Depending on the institution or organisation, it can take up to 12 months post-approval for hospital formulary and payer decisions to be finalised, but we are working to accelerate these timelines.

Stuart Arbuckle: We view the no pain act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level that can provide a meaningful tailwind to <unk> adoption.

Speaker Change: Proved we view the no pain act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level that can provide a meaningful tailwind to <unk> adoption.

Stuart Arbuckle: We are also encouraged by the progress of the Alternatives to Paint Act, which aims to level the playing field for access to non-opioids for Medicare part D patients. In the discharge or outpatient pharmacy setting it's important to understand that patients who receive a prescription must be able to access their acute pain medication immediately, unlike patient with asymptomatic or chronic conditions, patients in acute pain cannot wait for another day or another week to have their prescription filled. We are therefore, working with key pharmacy retail organizations to ensure broad availability of SUZETRIGINE nationally. In addition, we are planning a range of initiatives for the first year of launch, including co-pay assistance, other financial assistance programs to enable patients at the pharmacy to access their prescribed SUZETRIGINE prior to payer coverage decisions. We are very enthusiastic about the potential launch of SUZETRIGINE for patients with moderate to severe acute pain, and the impact we believe it will have on society, we recognize that even in the <unk>.

Speaker Change: We anticipate engaging in contracting discussions in the latter half of 2024 with the goal of building formulary and payer coverage during 2025. We also continue to be engaged with federal and state policymakers, including state governors.

Speaker Change: We are also encouraged by the progress of the alternatives to paint Act, which aims to level the playing field for access to non opioids for Medicare part D patients in the discharge or outpatient pharmacy setting it's important to understand that patients who receive a prescription must be able to access their acute pain medication immediately unlike patient.

Stuart: Who have expressed strong interest in a novel, highly effective, and well-tolerated treatment for pain without the addictive potential of opioids.

Speaker Change: With asymptomatic or chronic conditions patients in acute pain cannot wait for another day or another week to have their prescription filled we are therefore, working with key pharmacy retail organizations to ensure broad availability of <unk> nationally. In addition, we are planning a range of initiatives for the first year of launch including co pay assistance.

Stuart: Federally, in December 2022, Congress passed the No Pain Act, in which non-opioid therapies are eligible for separate payment for Medicare patients in the outpatient and ACS settings, beginning in January 2025. It is promising to see CMS continuing the process of implementation.

Stuart Arbuckle: In addition, we are planning a range of initiatives for the first year of launch, including co-pay assistance, other financial assistance programs to enable patients at the pharmacy to access their prescribed SUZETRIGINE prior to payer coverage decisions. We are very enthusiastic about the potential launch of SUZETRIGINE for patients with moderate to severe acute pain, and the impact we believe it will have on society. We recognize that even in the case of significant unmet need, it can take time for some components of our health care system to adopt new technologies and we are working to accelerate these processes. Ultimately our goal is to fundamentally and forever changed the way pain is treated, and we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025. In conclusion, it's an exciting time to be at Vertex, we continue to treat more CF patients around the world and are well advanced in planning for the launch of the VANZACAFTOR triple combination. We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe, and the Middle East, and our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to redefine the treatment of pain, and drive further diversified revenue growth. I will now turn the call over to Charlie to review the financials.

Other financial assistance programs to enable patients at the pharmacy to access their prescribed so that gene prior to payer coverage decisions. We are very enthusiastic about the potential launch of <unk> for patients with moderate to severe acute pain and the impact. We believe it will have on society, we recognize that even in the <unk>.

Speaker Change: as the Annual Outpatient Prospective Payment System, or OPPS, proposed rule was released for public comment last month. Because cizetrogene is still investigational, it is not currently included in the list of seven drugs in the proposed rule.

Speaker Change: But we fully expect Sazetujine will be eligible for separate payment once it is FDA approved. We view the No Pain Act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level, that can provide a meaningful tailwind to Sazetujine adoption.

Stuart Arbuckle: We recognize that even in the case of significant unmet need, it can take time for some components of our health care system to adopt new technologies and we are working to accelerate these processes. Ultimately our goal is to fundamentally and forever changed the way pain is treated, and we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025. In conclusion, it's an exciting time to be at Vertex, we continue to treat more CF patients around the world and are well advanced in planning for the launch of the VANZACAFTOR triple combination. We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe, and the Middle East, and our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to redefine the treatment of pain, and drive further diversified revenue growth. I will now turn the call over to Charlie to review the financials.

Case, a significant unmet need it can take time for some components of our health care system to adopt new technologies and we are working to accelerate these processes. Ultimately our goal is to fundamentally and forever changed the way pain is treated and we look forward to delivering on the first part of this vision for patients with moderate to.

Stuart Arbuckle: Ultimately our goal is to fundamentally and forever changed the way pain is treated, and we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025. In conclusion, it's an exciting time to be at Vertex, we continue to treat more CF patients around the world and are well advanced in planning for the launch of the VANZACAFTOR triple combination. We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe, and the Middle East, and our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to redefine the treatment of pain, and drive further diversified revenue growth. I will now turn the call over to Charlie to review the financials.

Stuart Arbuckle: Ultimately our goal is to fundamentally and forever changed the way pain is treated, and we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025. In conclusion, it's an exciting time to be at Vertex, we continue to treat more CF patients around the world and are well advanced in planning for the launch of the VANZACAFTOR triple combination. We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe, and the Middle East. And our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to redefine the treatment of pain, and drive further diversified revenue growth.

Speaker Change: We are also encouraged by the progress of the Alternatives to Pain Act, which aims to level the playing field for access to non-opioids for Medicare Part D patients.

Acute pain in early 2025 in conclusion, it's an exciting time to be at vertex. We continue to treat more CF patients around the world and are well advanced in planning for the launch of the vans a catheter triple combination we are entering a new era of commercial diversification with the launch of cash JV in the <unk>.

Stuart: In the discharge or outpatient pharmacy setting, it's important to understand that patients who receive a prescription must be able to access their acute pain medication immediately.

Stuart: Unlike patients with asymptomatic or chronic conditions, patients in acute pain cannot wait for another day or another week to have their prescription filled.

Speaker Change: U S Europe, and the middle East and our launch preparations for <unk> in acute pain are well underway as we seek to redefine the treatment of pain and drive further diversified revenue growth I will now turn the call over to Charlie to review the financials.

Speaker Change: We are therefore working with key pharmacy retail organizations to ensure broad availability of cizetrogene nationally. In addition, we are planning a range of initiatives for the first year of launch.

Stuart Arbuckle: And our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to redefine the treatment of pain, and drive further diversified revenue growth. I will now turn the call over to Charlie to review the financials.

Stuart: Including copay assistance and other financial assistance programs.

Stuart Arbuckle: I will now turn the call over to Charlie to review the financials.

Stuart: to enable patients at the pharmacy to access their prescribed Zetrogene prior to payer coverage decisions.

Charlie Wagner: Thanks, Stuart. Vertex's excellent Q2 results demonstrate once again, our consistent strong performance and attractive growth profile. Second quarter, 2024 revenue increased 6% year over year to $2.65 billion with solid growth of 7% in the US and 5% outside the US. The drivers of this strong quarter were in line with our expectations, including an anticipated reduction in channel inventories in select international markets. Second quarter US growth was driven by continued strong patient demand for TRIKAFTA, outside the US growth was also driven by strong demand with continued uptake from the KAFTRIO launches in children's ages, two to five, partially offset by the reversal of the first quarter channel inventory build. On the expense front Q2, 'twenty four combined non <unk>.

Charlie Wagner: Thanks, Stuart. Vertex's excellent Q2 results demonstrate once again, our consistent strong performance and attractive growth profile. Second quarter, 2024 revenue increased 6% year over year to $2.65 billion with solid growth of 7% in the US and 5% outside the US. The drivers of this strong quarter were in line with our expectations, including an anticipated reduction in channel inventories in select international markets. Second quarter US growth was driven by continued strong patient demand for TRIKAFTA. Outside the US growth was also driven by strong demand with continued uptake from the KAFTRIO launches in children's ages, two to five, partially offset by the reversal of the first quarter channel inventory build.

Stuart: We are very enthusiastic about the potential launch of cizetrogene for patients with moderate to severe acute pain.

Charlie: Second quarter, 2024 revenue increased 6% year over year to $2 65 billion with solid growth of 7% in the U S and 5% outside the U S. The drivers of this strong quarter were in line with our expectations, including an anticipated reduction in channel inventories in select international markets.

Stuart: and the impact we believe it will have on society. We recognize that even in the case of significant unmet need, it can take time for some components of our healthcare system to adopt new technologies, and we are working to accelerate these processes.

Unknown Executive: Ultimately, our goal is to fundamentally and forever change the way pain is treated, and we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025. In conclusion, it's an exciting time to be at Vertex. We are entering a new era of commercial diversification with the launch of CASGEVY in the U.S., Europe, and the Middle East. Thanks, Stuart.

Charlie Wagner: Second quarter US growth was driven by continued strong patient demand for TRIKAFTA, outside the US growth was also driven by strong demand with continued uptake from the KAFTRIO launches in children's ages, two to five, partially offset by the reversal of the first quarter channel inventory build. On the expense front Q2, 'twenty four combined non <unk>.

Stuart: Ultimately, our goal is to fundamentally and forever change the way pain is treated.

Charlie: Second quarter U S growth was driven by continued strong patient demand for Tri CAFTA outside the U S growth was also driven by strong demand with continued uptake from the Caf trio launches in children's ages, two to five partially offset by the reversal of the first quarter channel inventory build on the expense front Q2, 'twenty four combined non <unk>.

Stuart: And we look forward to delivering on the first part of this vision for patients with moderate to severe acute pain in early 2025.

Stuart: In conclusion, it's an exciting time to be at Vertex.

Speaker Change: We continue to treat more CF patients around the world and are well advanced in planning for the launch of the Vanzikafta triple combination.

Charlie Wagner: On the expense front Q2, '24 combined non-GAAP R&D, acquired IP R&D, and as G&A expenses were $5.43 billion, compared to $1.04 billion in the second quarter of 2023. Q2 '24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition. This compares to just $111 million of AIP R&D charges in Q2 of '23, Q2 24, non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio, offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory. Q2, 24, non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for cast JV and prelaunch activities forces after gene in acute pain.

Charlie Wagner: On the expense front Q2, '24 combined non-GAAP R&D, acquired IP R&D, and as G&A expenses were $5.43 billion, compared to $1.04 billion in the second quarter of 2023. Q2 '24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition. This compares to just $111 million of AIP R&D charges in Q2 of '23, Q2 24, non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio. Offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory.

Charlie Wagner: On the expense front Q2, '24 combined non-GAAP R&D, acquired IP R&D, and as G&A expenses were $5.43 billion, compared to $1.04 billion in the second quarter of 2023. Q2 '24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition. This compares to just $111 million of AIP R&D charges in Q2 of '23. Q2 24, non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory.

Speaker Change: GAAP R&D acquired IP, R&D and SG&A expenses were $5 four 3 billion compared to 1.04 billion in the second quarter of 2023 Q2 24 operating expenses include over $4 4 billion in AIP R&D charges, primarily as a result of the alpine acquisition, which we previously disclosed.

Stuart: We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe and the Middle East.

Charlie: And our launch preparations for cizetrogene in acute pain are well underway, as we seek to redefine the treatment of pain and drive further diversified revenue growth. I will now turn the call over to Charlie to review the financials.

Unknown Executive: Vertex's excellent Q2 results demonstrate once again our consistent strong performance and attractive growth profile. Outside the U.S., growth was also driven by strong demand, with continued uptake from the caf trio launches in children ages 2 to 5, partially offset by the reversal of the first quarter channel inventory build. On the expense front, Q2-24 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $5.43 billion, compared to $1.04 billion in the second quarter of 2023.

Speaker Change: Is being accounted for as an asset acquisition. This compares to just $111 million of AIP R&D charges in Q2 of twenty-three Q2, 24, non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio offset by reduced costs from the <unk>.

Charlie: Thanks Stuart. Vertex's excellent Q2 results demonstrate once again our consistent, strong performance and attractive growth profile.

Charlie: Second quarter 2024 revenue increased 6% year over year to $2.65 billion with solid growth of 7% in the U.S. and 5% outside the U.S.

Charlie Wagner: Offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory. Q2, 24, non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for CASGEVY and prelaunch activities forces SUZETRIGINE in acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 within our guidance, as we advanced multiple studies, including SUZETRIGINE, POVE and INAXAPLIN in Phase III programs, VX-993 in acute and peripheral neuropathic pain studies, and the expansion of the VX-880 trial in T1D. In addition. We continue to invest in preparation for upcoming potential new launches, including the further build out of our commercial capabilities in acute pain Q2, 24 results reflected strong revenue and underlying operating results, though due to the $4 4 billion AIP R&D charge from Alpine transaction accounting, we reported a second quarter 2024 non-GAAP op.

Charlie Wagner: offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory. Q2, 24, non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for CASGEVY and prelaunch activities forces SUZETRIGINE in acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 within our guidance, as we advanced multiple studies, including SUZETRIGINE, POVE and INAXAPLIN in Phase III programs, VX-993 in acute and peripheral neuropathic pain studies, and the expansion of the VX-880 trial in T1D.

Charlie Wagner: offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to Cogs in inventory.

Speaker Change: <unk> completed clinical trials as well as the associated transition of certain costs from R&D to Cogs in inventory.

Charlie: The drivers of this strong quarter were in line with our expectations, including an anticipated reduction in channel inventories in select international markets. Second quarter U.S. growth was driven by continued strong patient demand for Trikafta.

Charlie Wagner: Q2, 24, non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for CASGEVY and prelaunch activities forces SUZETRIGINE in acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 within our guidance, as we advanced multiple studies, including SUZETRIGINE, POVE and INAXAPLIN in Phase III programs, VX-993 in acute and peripheral neuropathic pain studies, and the expansion of the VX-880 trial in T1D.

Speaker Change: Q2, 24, non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for cast JV and prelaunch activities forces after gene in acute pain.

Charlie: Outside the U.S., growth was also driven by strong demand, with continued uptake from the Caftreo launches in children's ages 2 to 5.

Speaker Change: We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 within our guidance as we advanced multiple studies, including Suzette regime, Povey and an excellent in phase III programs VX 993 in acute and peripheral neuropathic pain studies and the expansion of the VX 880 <unk>.

Charlie: Partially offset by the reversal of the first quarter channel inventory build. On the expense front, Q2'24 combined non-GAAP R&D acquired IP R&D and SG&A expenses were $5.43 billion compared to $1.04 billion in the second quarter of 2023.

Unknown Executive: Q2-24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition. This compares to just $111 million in AIP R&D charges in Q2 of 2023. Q2-24 non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio, offset by reduced costs from the recently completed clinical trials, as well as the associated transition of certain costs from R&D to COGS and inventory.

Charlie Wagner: In addition, we continue to invest in preparation for upcoming potential new launches, including the further build out of our commercial capabilities in acute pain. Q2, '24 results reflected strong revenue and underlying operating results, though due to the $4.4 billion AIP R&D charge from Alpine transaction accounting, we reported a second quarter 2024 non-GAAP operating loss of $3.1 billion, in the second quarter of 2023, we reported $1.15 billion in non-GAAP operating income. Our tax rate for the quarter was also impacted by the onetime non-deductible Alpine AIP R&D charge, leading to a reported non-GAAP tax rate for the second quarter of 2024 of -10%, compared to a tax rate of 21% in Q2 of '23, aside from the effects of the nondeductible Alpine charge. There were no material changes in vertex is non-GAAP tax rate for the quarter, which would've been approximately 21%, the $4.4 billion AIP R&D charge for the alpine acquisition equates to an impact of approximately $17 per share on Q2, GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83. In Q2, 24 compared to non-GAAP earnings per share of $3.89 in the second quarter of 2023.

Charlie: Q2'24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition.

Speaker Change: While in tier one day in addition.

Speaker Change: We continue to invest in preparation for upcoming potential new launches, including the further build out of our commercial capabilities in acute pain Q2, 24 results reflected strong revenue and underlying operating results, though due to the $4 4 billion AIP R&D charge from Alpine transaction accounting, we reported a second quarter 2024 non-GAAP op.

Charlie: This compares to just 111 million of AIPR&D charges in Q2 of 23.

Charlie: Q224 non-GAAP R&D expenses of $697 million were roughly flat year-over-year, reflecting ongoing investment in the advancement of our broad R&D portfolio, upset by reduced costs from the recently completed clinical trials.

Speaker Change: <unk> loss of $3 1 billion in the second quarter of 2023, we reported 1.15 billion and non-GAAP operating income our tax rate for the quarter was also impacted by the onetime nondeductible Alpine AIP R&D charge, leading to a reported non-GAAP tax rate for the second quarter of 2024 of negative 10.

Charlie Wagner: Our tax rate for the quarter was also impacted by the onetime non-deductible Alpine AIP R&D charge, leading to a reported non-GAAP tax rate for the second quarter of 2024 of -10%, compared to a tax rate of 21% in Q2 of '23, aside from the effects of the nondeductible Alpine charge. There were no material changes in vertex is non-GAAP tax rate for the quarter, which would've been approximately 21%, the $4.4 billion AIP R&D charge for the alpine acquisition equates to an impact of approximately $17 per share on Q2, GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83. In Q2, 24 compared to non-GAAP earnings per share of $3.89 in the second quarter of 2023.

Charlie: as well as the associated transition of certain costs from R&D to COGS and inventory.

Charlie: Q2-24 non-GAAP SG&A expenses of $280 million increased 28% versus prior year, primarily as a result of investments in the commercial organization, including launch activities for Casjevi and pre-launch activities for susetragine in acute pain.

Speaker Change: <unk> percent compared to a tax rate of 21% in Q2 of twenty-three aside from the effects of the nondeductible Alpine charge. There were no material changes in vertex is non-GAAP tax rate for the quarter, which would've been approximately 21% the $4 4 billion AIP R&D charge for the alpine acquisition equates to an impact of approximately.

Charlie Wagner: Compared to a tax rate of 21% in Q2 of '23, aside from the effects of the nondeductible Alpine charge, there were no material changes in vertex is non-GAAP tax rate for the quarter, which would've been approximately 21%. The $4.4 billion AIP R&D charge for the alpine acquisition equates to an impact of approximately $17 per share on Q2, GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83 in Q2, 24 compared to non-GAAP earnings per share of $3.89 in the second quarter of 2023. We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences, additionally, we deployed over $300 million of cash in the second quarter to repurchase more than 700,000 shares now. Now switching to guidance, we are raising our 2024 total product revenue guidance to a range of $10.65 to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients including younger one.

Charlie Wagner: There were no material changes in vertex is non-GAAP tax rate for the quarter, which would've been approximately 21%, the $4.4 billion AIP R&D charge for the alpine acquisition equates to an impact of approximately $17 per share on Q2, GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83. In Q2, 24 compared to non-GAAP earnings per share of $3.89 in the second quarter of 2023.

Charlie: We anticipate that quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024, within our guidance, as we advance multiple studies, including susetragine, POVI, and anaxipline in Phase III programs, VX993 in acute and peripheral neuropathic pain studies, and the expansion of the VX880 trial in T1D.

Speaker Change: Similarly, $17 per share on Q2, GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83. In Q2, 24 compared to non-GAAP earnings per share of $3 89 in the second quarter of 2023.

Charlie: In addition, we continue to invest in preparation for upcoming potential new launches, including the further build-out of our commercial capabilities in acute pain.

Charlie Wagner: We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences, additionally, we deployed over $300 million of cash in the second quarter to repurchase more than 700,000 shares now. Now switching to guidance, we are raising our 2024 total product revenue guidance to a range of $10.65 to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients including younger ones in core markets and select other countries. Guidance also continues to include a contribution in the second half of the year from the commercial launch of cast JV for vertex operating expenses. Our non-GAAP guidance continues to include a range of $4 two to $4 3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance.

Charlie Wagner: We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences. Additionally, we deployed over $300 million of cash in the second quarter to repurchase more than 700,000 shares now. Now switching to guidance, we are raising our 2024 total product revenue guidance to a range of $10.65 to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients including younger ones in core markets and select other countries.

Speaker Change: We ended the quarter with $10 2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine immune Sciences. Additionally, we deployed over $300 million of cash in the second quarter to repurchase more than 700000 shares now.

Charlie: Q2 2024 results reflected strong revenue and underlying operating results, though due to the $4.4 billion AIP R&D charge from Alpine Transaction Accounting, we reported a second quarter 2024 non-GAAP operating loss of $3.1 billion.

Charlie Wagner: Now switching to guidance, we are raising our 2024 total product revenue guidance to a range of $10.65 to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients including younger ones in core markets and select other countries.

Speaker Change: Now switching to guidance, we are raising our 2024 total product revenue guidance to a range of $10 65 to 10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients including younger one.

Charlie: In the second quarter of 2023, we reported $1.15 billion in non-GAAP operating income.

Charlie: Our tax rate for the quarter was also impacted by the one-time non-deductible Alpine AIPR&D charge.

Charlie: Leading to a reported non-gap tax rate for the second quarter of 2024 of negative 10% compared to a tax rate of 21% in Q2 of 23.

Speaker Change: <unk> and core markets and select other countries guidance also continues to include a contribution in the second half of the year from the commercial launch of cast JV for vertex operating expenses. Our non-GAAP guidance continues to include a range of $4 two to $4 3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance.

Charlie Wagner: Guidance also continues to include a contribution in the second half of the year from the commercial launch of CASGEVY, for vertex operating expenses, our non-GAAP guidance continues to include a range of $4.2 to $4.3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance provided in our last earnings call. As previously communicated we absorbing Alpine is projected non-GAAP operating expenses for the remainder of 2024 within our guidance range for R&D and SG&A. For acquired IP R&D, we now expect approximately $4.6 billion for the year, including the Alpine asset acquisition charge recorded in the second quarter. Given that the alpine AIP R&D charge is not deductible for tax purposes, we expect a non-GAAP full year 2024 tax rate of approximately 100% note that the anticipated percentage tax rate is highly sensitive to projected pretax income aside from the impact of the non deductible alpine AIP R&D charge our underlying.

Charlie Wagner: Guidance also continues to include a contribution in the second half of the year from the commercial launch of CASGEVY, for Vertex operating expenses, our non-GAAP guidance continues to include a range of $4.2 to $4.3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance provided in our last earnings call. As previously communicated we absorbing Alpine is projected non-GAAP operating expenses for the remainder of 2024 within our guidance range for R&D and SG&A. For acquired IP R&D, we now expect approximately $4.6 billion for the year, including the Alpine asset acquisition charge recorded in the second quarter.

Charlie: Aside from the effects of the non-deductible Alpine charge, there were no material changes in Vertex's non-GAAP tax rate for the quarter, which would have been approximately 21%.

Charlie: The $4.4 billion AIP R&D charge for the Alpine acquisition equates to an impact of approximately $17 per share on Q2 GAAP and non-GAAP results.

Speaker Change: On our last earnings call as previously communicated we are absorbing alpine is projected non-GAAP operating expenses for the remainder of 2024 within our guidance range for R&D and SG&A.

Charlie: and drove a non-gap loss per share of $12.83 in Q2'24 compared to non-gap earnings per share of $3.89 in the second quarter of 2023.

Speaker Change: For acquired IP R&D, we now expect approximately $4 6 billion for the year, including the Alpine asset acquisition charge recorded in the second quarter.

Unknown Executive: We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences. Additionally, we deployed over $300 million of cash in the second quarter to purchase more than 700,000 shares. Given that the Alpine AIP R&D charge is not deductible for tax purposes, we expect a non-gap full-year 2024 tax rate of approximately 100%. However, note that the anticipated percentage tax rate is highly sensitive to projected pre-tax income.

Charlie: We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences. Additionally, we deployed over $300 million of cash in the second quarter to have purchased more than 700,000 shares.

Charlie Wagner: Given that the Alpine AIP R&D charge is not deductible for tax purposes, we expect a non-GAAP full year 2024 tax rate of approximately 100%, note that the anticipated percentage tax rate is highly sensitive to projected pretax income, aside from the impact of the non deductible alpine AIP R&D charge, our underlying full-year 2024, non-GAAP effective tax rate would have remained in the range of 20% to 21%. In closing, Vertex posted excellent results yet again, as we delivered strong revenue growth, advance our CASGEVY launch, and secured important regulatory approvals. We also strengthened our capabilities in preparation for additional near term launches, progressed our pipeline and made rapid progress closing and integrating Alpine, a compelling fit with Vertex's R&D strategy with significant potential as a pipeline in a product. We are already leveraging Vertex's clinical regulatory and commercial capabilities to accelerate development in IgAN with Phase III set to begin this month. We're targeting US accelerated approval in IgAN in late 2027, and a contribution to Vertex's revenue growth and diversification, beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our Phase II data readout with SUZETRIGINE in LSR, Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to begin the Q&A period.

Speaker Change: Given that the alpine AIP R&D charge is not deductible for tax purposes, we expect a non-GAAP full year 2024 tax rate of approximately 100% note that the anticipated percentage tax rate is highly sensitive to projected pretax income aside from the impact of the non deductible alpine AIP R&D charge our underlying.

Charlie: Now switching to guidance.

Charlie: We are raising our 2024 total product revenue guidance to a range of $10.65 to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates.

Speaker Change: Full year 2024, non-GAAP effective tax rate would have remained in the range of 20% to 21% and closing vertex posted excellent results yet again as we delivered strong revenue growth advanced our cast JV launch and secured important regulatory approvals. We also strengthened our capabilities in preparation for additional near term launches. Progressed, our pipeline and made rapid progress closing and integrating alpine a compelling fit with vertex is R&D strategy with significant potential as a pipeline in a product we are already leveraging vertex as clinical regulatory and commercial capabilities to accelerate development in again with phase III set to begin this month we're. Getting U S accelerated approval and I again in late 2027, and a contribution to vertex as revenue growth and diversification beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our phase two data readout with sues after gene in L. A S R. Phase II initiation of VX 993 studies in acute pain and in diabetic peripheral neuropathy as well as progress towards pivotal development in tier one day. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to.

Charlie: We continue to have high visibility into this revenue outlook as we expect continued growth in CF as we reach more patients, including younger ones, in core markets and select other countries. Guidance also continues to include a contribution in the second half of the year from the commercial launch of Casjevi.

Charlie Wagner: In closing, Vertex posted excellent results yet again, as we delivered strong revenue growth, advance our CASGEVY launch, and secured important regulatory approvals. We also strengthened our capabilities in preparation for additional near term launches, progressed our pipeline and made rapid progress closing and integrating Alpine, a compelling fit with Vertex's R&D strategy with significant potential as a pipeline in a product. We are already leveraging Vertex's clinical regulatory and commercial capabilities to accelerate development in IgAN with Phase III set to begin this month. We're targeting US accelerated approval in IgAN in late 2027, and a contribution to Vertex's revenue growth and diversification, beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our Phase II data readout with SUZETRIGINE in LSR, Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to begin the Q&A period.

Speaker Change: Progressed, our pipeline and made rapid progress closing and integrating alpine a compelling fit with vertex is R&D strategy with significant potential as a pipeline in a product we are already leveraging vertex as clinical regulatory and commercial capabilities to accelerate development in again with phase III set to begin this month we're. Getting U S accelerated approval and I again in late 2027, and a contribution to vertex as revenue growth and diversification beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our phase two data readout with sues after gene in L. A S R. Phase II initiation of VX 993 studies in acute pain and in diabetic peripheral neuropathy as well as progress towards pivotal development in tier one day. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to.

Charlie: For Vertex operating expenses, our non-GAAP guidance continues to include a range of $4.2 to $4.3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance provided on our last earnings call.

Charlie Wagner: We are already leveraging Vertex's clinical regulatory and commercial capabilities to accelerate development in IgAN with Phase III set to begin this month. We're targeting US accelerated approval in IgAN in late 2027, and a contribution to Vertex's revenue growth and diversification, beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our Phase II data readout with SUZETRIGINE in LSR, Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to begin the Q&A period.

Charlie Wagner: We are already leveraging Vertex's clinical regulatory and commercial capabilities to accelerate development in IgAN with Phase III set to begin this month.

Charlie: As previously communicated, we are absorbing Alpine's projected non-GAAP operating expenses for the remainder of 2024 within our guidance range for R&D and SG&A.

Charlie Wagner: We're targeting US accelerated approval in IgAN in late 2027, and a contribution to Vertex's revenue growth and diversification, beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our Phase II data readout with SUZETRIGINE in LSR, Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to begin the Q&A period.

Charlie Wagner: We're targeting US accelerated approval in IgAN in late 2027, and a contribution to Vertex's revenue growth and diversification, beginning in 2028.

Speaker Change: Getting U S accelerated approval and I again in late 2027, and a contribution to vertex as revenue growth and diversification beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our phase two data readout with sues after gene in L. A S R. Phase II initiation of VX 993 studies in acute pain and in diabetic peripheral neuropathy as well as progress towards pivotal development in tier one day. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to.

Charlie: For acquired IPR&D, we now expect approximately $4.6 billion for the year, including the Alpine Asset Acquisition Charge recorded in the second quarter.

Charlie Wagner: In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio such as our Phase II data readout with SUZETRIGINE in LSR, Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls and I'll ask Susie to begin the Q&A period.

Charlie: Given that the Alpine AIPR&D charge is not deductible for tax purposes, we expect a non-GAAP full year 2024 tax rate of approximately 100%. Note that the anticipated percentage tax rate is highly sensitive to projected pre-tax income.

Susie Lisa: Phase II initiation of VX 993 studies in acute pain and in diabetic peripheral neuropathy as well as progress towards pivotal development in tier one day. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17, we look forward to updating you on our progress on future calls and I'll ask Susie to.

Unknown Executive: Aside from the impact of the non-deductible Alpine AIP R&D charge, our underlying full-year 2024 non-gap effective tax rate would have remained in the range of 20 to 21%. In closing, Vertex posted excellent results yet again as we delivered strong revenue growth, advanced our Cast Jevy launch, and secured important regulatory approvals. We also strengthened our capabilities in preparation for additional near-term launches, progressed our pipeline, and made rapid progress closing and integrating Alpine, a compelling fit with Vertex's R&D strategy with significant potential as a pipeline in a product.

Charlie: Aside from the impact of the non-deductible Alpine AIPIA R&D charge, our underlying full-year 2024 non-GAAP effective tax rate would have remained in the range of 20 to 21 percent.

Charlie: In closing, Vertex posted excellent results yet again as we delivered strong revenue growth, advanced our Cast Jevy launch, and secured important regulatory approvals.

Susie Lisa: The Q&A period.

Operator: We will now begin the question and answer session. To ask a question you may press star then one on your touchtone phone, if you're using a speakerphone please pick up your handset before pressing the keys, and to withdraw your question, please press Star then two. And at this time, well pause momentarily to assemble our roster. And the first question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Charlie: We also strengthened our capabilities in preparation for additional near-term launches, progressed our pipeline, and made rapid progress closing and integrating Alpine, a compelling fit with Vertex's R&D strategy with significant potential as a pipeline in a product.

Susie Lisa: To ask a question you May Press Star then one on your Touchtone phone. If you're using a speakerphone please pick up your handset before pressing the keys. And to withdraw your question. Please press Star then two. And at this time, well pause momentarily to assemble our roster. And the first question will come from Selvey enrich their with Goldman Sachs. Please go ahead.

Speaker Change: If you're using a speakerphone please pick up your handset before pressing the keys. And to withdraw your question. Please press Star then two. And at this time, well pause momentarily to assemble our roster. And the first question will come from Selvey enrich their with Goldman Sachs. Please go ahead.

Speaker Change: And to withdraw your question. Please press Star then two. And at this time, well pause momentarily to assemble our roster. And the first question will come from Selvey enrich their with Goldman Sachs. Please go ahead.

Unknown Executive: We are already leveraging Vertex's clinical, regulatory, and commercial capabilities to accelerate development of IGAN, with Phase 3 set to begin this month. We are targeting U.S. accelerated approval for IGAN in late 2027 and a contribution to Vertex's revenue growth and diversification beginning in 2028. In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio, such as a Phase 2 data readout with Suzetra gene in LSR, phase 2 initiation of VX993 studies in acute pain and diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D.

Speaker Change: And at this time, well pause momentarily to assemble our roster. And the first question will come from Selvey enrich their with Goldman Sachs. Please go ahead.

Charlie: We are already leveraging Vertex's clinical, regulatory, and commercial capabilities to accelerate development in IGAN, with Phase 3 set to begin this month.

Speaker Change: And the first question will come from Selvey enrich their with Goldman Sachs. Please go ahead.

Charlie: We are targeting U.S. accelerated approval in IGAN in late 2027 and a contribution to Vertex's revenue growth and diversification beginning in 2028.

Salveen Richter: Good afternoon, thanks for taking my question. Noting that around 6,000 patients have discontinued CFTR modulators, as we think about uptake for VANZACAFTOR Triple, can you help us understand what the early launch dynamics could look like? And whether they can be a significant bolus of early adopters? And then just a second question, if I may, what is the relative contribution of CASGEVY to the updated product revenue guidance? Thank you.

Selvey enrich: Noting that around 6000 patients have discontinued CFT, our modulators as we think about uptake for <unk> to capture Triple can you help us understand what the early launch dynamics could look like and whether they can be a significant bolus of early adopters. Then just a second question if I may what is the relative contribution of cash JV to the updated product revenue guidance. Thank you.

Charlie: In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio, such as a Phase II data readout with susetra gene in LSR, Phase II initiation of VX993 studies in acute pain and in diabetic peripheral neuropathy, as well as progress towards pivotal development in T1D.

Then just a second question if I may what is the relative contribution of cash JV to the updated product revenue guidance. Thank you.

Unknown Executive: These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls, and I'll ask Susie to begin the Q&A period. Hey, thanks, Salveen. We won't be breaking down the revenue for the CF franchise versus cash Chevy.

Susie Lisa: These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls, and I'll ask Susie to begin the Q&A period.

Speaker Change: Hey, Thanks, Salveen, we won't be breaking down the revenue for the CF franchise versus CASGEVY, and I'll turn it over to Stuart to tell you a little bit more about the VANZACAFTOR launch dynamics. <unk> thanks for the question. I don't think theres going to be a single bolus of patients based on our research with physicians. That they are considering for the Venza caf the triple combination I would say that they are excited about the prospects for vans a captive both for their existing patients who are honestly FTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased see FTR function. And also being the fact that it's once a day and then as you say there are also patients who are not currently on our see FTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think theres going to be a broad interest in the vans a catheter triple across both patients who are persistent today on those who have discontinued. Previously.

Susie Lisa: Hey, Thanks, Salveen. We won't be breaking down the revenue for the CF franchise versus CASGEVY, and I'll turn it over to Stuart to tell you a little bit more about the VANZACAFTOR launch dynamics.

Stuart Arbuckle: Yeah Salveen, thanks for the question. I don't think there's going to be a single bolus of patients based on our research with physicians, that they are considering for the VANZACAFTOR triple combination. I would say that they are excited about the prospects for VANZACAFTOR both for their existing patients who are on a CFTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased CFTR function. And also being the fact that it's once a day, and then as you say there are also patients who are not currently on our CFTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think there's going to be a broad interest in the vVANZACAFTOR triple across both patients who are persistent today on those who have discontinued previously.

Stuart: <unk> thanks for the question. I don't think theres going to be a single bolus of patients based on our research with physicians. That they are considering for the Venza caf the triple combination I would say that they are excited about the prospects for vans a captive both for their existing patients who are honestly FTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased see FTR function. And also being the fact that it's once a day and then as you say there are also patients who are not currently on our see FTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think theres going to be a broad interest in the vans a catheter triple across both patients who are persistent today on those who have discontinued. Previously.

Susie Lisa: To ask a question, you may press star then 1 on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. And to withdraw your question, please press star then 2. And at this time, we'll pause momentarily to assemble our roster.

Stuart: I don't think theres going to be a single bolus of patients based on our research with physicians. That they are considering for the Venza caf the triple combination I would say that they are excited about the prospects for vans a captive both for their existing patients who are honestly FTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased see FTR function. And also being the fact that it's once a day and then as you say there are also patients who are not currently on our see FTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think theres going to be a broad interest in the vans a catheter triple across both patients who are persistent today on those who have discontinued. Previously.

Stuart: That they are considering for the Venza caf the triple combination I would say that they are excited about the prospects for vans a captive both for their existing patients who are honestly FTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased see FTR function. And also being the fact that it's once a day and then as you say there are also patients who are not currently on our see FTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think theres going to be a broad interest in the vans a catheter triple across both patients who are persistent today on those who have discontinued. Previously.

Speaker Change: Any first question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Stuart Arbuckle: And also being the fact that it's once a day, and then as you say there are also patients who are not currently on our CFTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think there's going to be a broad interest in the VANZACAFTOR triple across both patients who are persistent today on those who have discontinued previously.

Stuart: And also being the fact that it's once a day and then as you say there are also patients who are not currently on our see FTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think its going to be one or the other I think theres going to be a broad interest in the vans a catheter triple across both patients who are persistent today on those who have discontinued. Previously.

Stuart Arbuckle: So I don't think its going to be one or the other I think there's going to be a broad interest in the vVANZACAFTOR triple across both patients who are persistent today on those who have discontinued previously.

Salveen Richter: And then just a second question, if I may, what is the relative contribution of KES-GEVI to the updated product revenue guidance? Thank you.

Stuart: Previously.

Stuart Arbuckle: And I'll turn it over to Stuart to tell you a little bit more about the Vanzacafter launch dynamics. Yes, Salveen, thanks for the question. I don't think there's going to be a single bolus of patients based on our research with physicians that they are considering for the vanzikafta triple combination. I'd say that they are excited about the prospects for vanzikafta, both for their existing patients who are on a CFTR modulator, many of whom I think are going to be very interested in a treatment option that promises the potential for increased CF And also the fact that it's once a day.

Operator: The next question will come from David Risinger with Leerink Partners. Please go ahead.

Stuart: Please go ahead.

David Risinger: And congrats on the strong execution, I have two questions, first, can you just discuss the potential to develop VX-548 ex US for neuropathic pain, and the second, could you provide the latest on your preclinical development efforts for Nav 1.7 inhibitors? Thanks very much.

David Risinger: I have two questions first can you just discuss the potential to develop VX 548 ex U S for neuropathic pain. And a second could you provide the latest on your preclinical development efforts for NAV, one seven inhibitors. Thanks very much.

Speaker Change: I don't think there's going to be a single bolus of patients based on our research with physicians.

Speaker Change: And a second could you provide the latest on your preclinical development efforts for NAV, one seven inhibitors. Thanks very much.

Speaker Change: that they are considering for the VanZaKafta triple combination. I'd say that they are excited about the prospects for VanZaKafta both for their existing patients who are on a CFTR modulator, many of whom I think are going to be very interested in a treatment option which promises the potential for increased CFTR function.

Reshma Kewalramani: Sure thing Hey, Dave This is Reshma, let me break that into two parts and let me take the preclinical Nav 1.7 first, and then I'll turn it over to Stuart to talk about our goals ex-US. So, we are making really strong progress on the Nav 1.7 inhibitors. They are still in preclinical development, but I would characterize it Dave as it's in late preclinical development. And to contextualize this a little bit more for everybody else, we expect that the Nav 1.7 could be used alone in acute pain or neuropathic pain, or that they could be used in combination with our Nav 1.8 inhibitors VX-548 or 993, or any in our portfolio. with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Reshma Kewalramani: Sure thing. Hey, Dave This is Reshma, let me break that into two parts and let me take the preclinical Nav 1.7 first, and then I'll turn it over to Stuart to talk about our goals ex-US. So, we are making really strong progress on the Nav 1.7 inhibitors. They are still in preclinical development, but I would characterize it Dave as it's in late preclinical development.

Reshma Kewalramani: And then, as you say, there are also patients who are not currently on a CFTR modulator who I think are going to welcome the opportunity for a new treatment option. So I don't think it's going to be one or the other. I think there's going to be a broad interest in the vanzikafta triple across both patients who are persistent today and those who've discontinued previously. Thanks very much. Sure thing. Hey Dave, this is Reshma.

Speaker Change: So. We are making really strong progress on the NAV 1.7 inhibitors. They are still in preclinical development, but I would characterize it Dave is it's in late preclinical development and to contextualize. This a little bit more for everybody else we expect. The NAV one seven could be used alone. In acute pain or neuropathic pain or they could be used in combination with our NAV one eight inhibitors be at 548 or 99 three. Or any in our portfolio with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Speaker Change: We are making really strong progress on the NAV 1.7 inhibitors. They are still in preclinical development, but I would characterize it Dave is it's in late preclinical development and to contextualize. This a little bit more for everybody else we expect. The NAV one seven could be used alone. In acute pain or neuropathic pain or they could be used in combination with our NAV one eight inhibitors be at 548 or 99 three. Or any in our portfolio with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Reshma Kewalramani: And to contextualize this a little bit more for everybody else, we expect that the Nav 1.7 could be used alone in acute pain or neuropathic pain, or that they could be used in combination with our Nav 1.8 inhibitors VX-548 or 993, or any in our portfolio. With that I'll turn it over to Stuart for a little bit on ex-US ambitions.

Speaker Change: The NAV one seven could be used alone. In acute pain or neuropathic pain or they could be used in combination with our NAV one eight inhibitors be at 548 or 99 three. Or any in our portfolio with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Dave: In acute pain or neuropathic pain or they could be used in combination with our NAV one eight inhibitors be at 548 or 99 three. Or any in our portfolio with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Speaker Change: Please go ahead.

Speaker Change: I have two questions. First, can you just discuss the potential to develop VX548-XUS for neuropathic pain, and second,

Stuart: Or any in our portfolio with that I'll turn it over to Stuart for a little bit on ex U S ambitions.

Stuart Arbuckle: Yes, Hi, David, thanks for the question. So I would say that the clinical landscape, and by that I mean, the kind of the treatment options in the way that they used is very similar outside the US, as it is here in the US with things like [inaudible], the acetaminophen in neuropathic pain, things like Pregabalin, Gabapentin, and then obviously opioids. And that's true in both acute pain and neuropathic pain, and I know, you're asking specifically about neuropathic. There are differences, I think it's fair to say that the the level of abuse and misuse of opioids is less, it's not zero, but it's less outside of the US. But in addition, the pricing dynamics in the value recognition of healthcare and innovation by health care systems outside the US is very different, and as such our focus at this time is very much on the unmet need and opportunity to serve patients here in the US first, and ex US is something that we will consider later on.

Stuart Arbuckle: Yes, Hi, David thanks for the question, so I would say that the clinical landscape and by that I mean, the kind of the treatment options in the way that they used is very similar outside the US. As it is here in the US with things like [inaudible], the acetaminophen in neuropathic pain, things like Pregabalin, Gabapentin, and then obviously opioids. And that's true for both acute pain, neuropathic pain, and I know, you're asking specifically about neuropathic. There are differences I think it's fair to say that the the level of abuse and misuse of opioids is less it's not zero, but it's less outside of the US.

Stuart Arbuckle: Let me break that into two parts, and let me take the preclinical MAV 1.7 first, and then I'll turn it over to Stuart to talk about our goals outside the US. So we are making really strong progress on the NAV1.7 inhibitors. They are still in preclinical development, but I would characterize it, Dave, as it's in late preclinical development. And to contextualize this a little bit more for everybody else, we expect that the NAV1.7s could be used alone in acute pain or neuropathic pain, or they could be used in combination with our NAV1.8 inhibitors, be it 548 or 993 or any in our portfolio. With that, I'll turn it over to Stuart for a little bit on ex-U.S. ambitions.

Stuart: In neuropathy pain things like Pregabalin Gabapentin, and then obviously opioids. Australian both acute pain, neuropathic pain, and I know, you're asking specifically about neuropathic. There are differences I think it's fair to say that the the level of abuse and misuse of opioids is less it's not zero, but it's less outside of the U S. But in addition, the pricing dynamics in the value recognition of healthcare and innovation by health care systems outside the U S is very different and as such our focus at this time is very much on the unmet need and opportunity to serve patients here in the U S first and ex U S is something that we will consider later on.

Speaker Change: Australian both acute pain, neuropathic pain, and I know, you're asking specifically about neuropathic. There are differences I think it's fair to say that the the level of abuse and misuse of opioids is less it's not zero, but it's less outside of the U S. But in addition, the pricing dynamics in the value recognition of healthcare and innovation by health care systems outside the U S is very different and as such our focus at this time is very much on the unmet need and opportunity to serve patients here in the U S first and ex U S is something that we will consider later on.

Stuart Arbuckle: But in addition, the pricing dynamics and the value recognition of healthcare and innovation by health care systems outside the US is very different, and as such our focus at this time is very much on the unmet need and opportunity to serve patients here in the US first, and ex US is something that we will consider later on.

Speaker Change: But in addition, the pricing dynamics in the value recognition of healthcare and innovation by health care systems outside the U S is very different and as such our focus at this time is very much on the unmet need and opportunity to serve patients here in the U S first and ex U S is something that we will consider later on.

David Risinger: Thank you.

Operator: The next question will come from Jessica Fye with J P. Morgan. Please go ahead.

Jessica Fye: Hey, there, thanks for taking my question, I wanted to ask about your type one diabetes effort, how do you envision the regulatory path for VX-880? And for VX-264, the encapsulated cells product, I believe you completed Part A with the low dose patients. Is there anything you can share with respect to kind of what you're seeing so far with that one? Thank you.

Speaker Change: With that, I'll turn it over to Stuart for a little bit on ex-U.S. ambitions.

Stuart Arbuckle: Yeah, Dave, thanks for the question. So I would say that the clinical landscape, and by that I mean the kind of treatment options and the way that they're used, is very similar outside the U.S. as it is here in the U.S. With things like NSAIDs, acetaminophen, for neuropathic pain, things like pregabalin, gabapentin, and then obviously opioids. And that's true in both acute pain and neuropathic pain, and I know you were asking specifically about neuropathic pain. But there are differences. I think it's fair to say that the level of abuse and misuse of opioids is lower. It's not zero, but it's less outside of the U.S.

Stuart: Yeah, hi Dave, thanks for the question.

Speaker Change: <unk>. For VX 600 for the encapsulated sells product I believe you completed a with the low dose patients is there anything you can share with respect to kind of what you're seeing so far with that one thank you.

Jessica Fye: For VX 600 for the encapsulated sells product I believe you completed a with the low dose patients is there anything you can share with respect to kind of what you're seeing so far with that one thank you.

Reshma Kewalramani: Yeah, Hi, Jess It's Reshma, let me take those two questions. Maybe it will go with two six for first and then we'll go to VX 880. So on VX 264. This is the southworth device programming, you're exactly right about the stage of the program were in part B, which is the full dose. It's a full dose with a stagger period between patients I would say that our reserve. <unk> are a 2025. Time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880 on VX 880. This is the naked cell programs of cells alone. This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X. Spectation I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a cash Chevy program that our small molecule program, you'll remember that the cash Chevy programming. Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Reshma Kewalramani: Yeah, Hi, Jess It's Reshma, let me take those two questions, aaybe it we'll go with 264 first, and then we'll go to VX-880. So on VX-264, this is the cells + device program, you're exactly right about the stage of the program, were in part B, which is the full dose. It's a full dose with a stagger period between patients, I would say that our results are a 2025 time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880. On VX-880, this is the naked cell programs, or cells alone. This is the one that has now completed, which is obviously a big milestone, enrollment and dosing in the original 17 patient study, we are in the phase of development where we're in full dose, with patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients, so an additional 20 patients. And with regard to your direct question on how should we think about the path forward with regard to regulatory expectations? I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a cash Chevy program that our small molecule program, you'll remember that the cash Chevy programming. Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Ron: Maybe it will go with two six for first and then we'll go to VX 880. So on VX 264. This is the southworth device programming, you're exactly right about the stage of the program were in part B, which is the full dose. It's a full dose with a stagger period between patients I would say that our reserve. <unk> are a 2025. Time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880 on VX 880. This is the naked cell programs of cells alone. This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Speaker Change: <unk> are a 2025. Time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880 on VX 880. This is the naked cell programs of cells alone. This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Ron: Time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880 on VX 880. This is the naked cell programs of cells alone. This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Ron: We're making progress and I'm really happy to be in the clinic with both 264 and 880 on VX 880. This is the naked cell programs of cells alone. This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Speaker Change: XUS is something that we will consider later on.

Ron: This is the one that has now completed which is obviously a big milestone. Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Reshma Kewalramani: This is the one that has now completed, which is obviously a big milestone, enrollment and dosing in the original 17 patient study, we are in the phase of development where we're in full dose, with patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients, so an additional 20 patients. And with regard to your direct question on how should we think about the path forward with regard to regulatory expectations? I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a cash Chevy program that our small molecule program, you'll remember that the cash Chevy programming. Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Speaker Change: The next question will come from Jessica Fye with J.P. Morgan. Please go ahead.

Unknown Attendee: Thanks for taking my question. For VX264, the encapsulated cells product, I believe you've completed Part A with the low-dose patients. Is there anything you can share with respect to kind of what you're seeing so far with that one? Yeah. Hi Jess.

Ron: Enrollment and dosing in the original 17 patient study we are in the phase of development, where we're in full dose. With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Ron: With patients who don't have a stagger. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Jessica Fye: For VX264, the encapsulated cells product, I believe you've completed Part A with the LODOS patients. Is there anything you can share with respect to kind of what you're seeing so far with that one?

Ron: I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients saw an additional 20 patients and with regard to your direct question on how should we think about the path forward with regard to regulatory X.

Reshma Kewalramani: It's Reshma. Let me take those two questions. Maybe we'll go with 264 first, and then we'll go to VX880. So, on VX264, this is the selfless device program.

Stuart: Yeah. Hi, Jess. It's Reshma. Let me take those two questions.

Speaker Change: Maybe we'll go with 264 first, and then we'll go to VX880. So on VX264, this is the selfless device program. You're exactly right about the stage of the program. We're in Part B, which is the full dose.

Reshma Kewalramani: I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a CASGEVY program than a small molecule program. You'll remember that the CASGEVY programming in either TVT or in a, Sickle cell disease was a very efficient sample size, and what we did in the case of CASGEVY is convert it from our Phase1/2 to a Phase 1/2/3 trial. Exactly what it will look like for VX-880, I'll look forward to keeping you updated as we complete the discussions with regulators.

Reshma Kewalramani: Spectation I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a cash Chevy program that our small molecule program, you'll remember that the cash Chevy programming. Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Speaker Change: Spectation I don't have an answer for you today, because that's exactly the conversations that we're going to complete in the coming months, but I would think about the type one diabetes program more like a cash Chevy program that our small molecule program, you'll remember that the cash Chevy programming. Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Reshma Kewalramani: You're exactly right about the stage of the program. We're in Part B, which is the full dose. It's a full dose with a stagger period between patients. I would say that results are in the 2025 timeframe. We're making progress, and I'm really happy to be in the clinic with both 264 and 880. For VX880, this is the naked cell program.

Speaker Change: It's a full dose with a staggered period between patients. I would say that results are a 2025 time frame. We're making progress and I'm really happy to be in the clinic with both 264 and 880.

Ron: Either TVT or in a. Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Reshma Kewalramani: So cells alone. This is the one that has now completed enrollment and dosing in the original 17 patient study, which is obviously a big milestone. We are in the phase of development where we're in full dose. I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients, so an additional 20 patients. And with regard to your direct question on how we should think about the path forward with regard to regulatory expectations, I don't have an answer for you today, because that's exactly the conversation that we're going to have in the coming months.

Ron: Sickle cell disease was a very efficient sample size and what we did in the case of cash JV is converted from our phase one two to a phase 123 trial exactly what it will look like for VX 880. I'll look forward to keeping you updated as we complete the discussions with regulators.

Speaker Change: On VX880, this is the naked cell program, so cells alone. This is the one that has now completed, which is obviously a big milestone, enrollment and dosing in the original 17 patient study.

Ron: I'll look forward to keeping you updated as we complete the discussions with regulators.

Operator: The next question will come from Evan Seigerman with BMO capital markets. Please go ahead.

Speaker Change: with patients who don't have a stagger.

Speaker Change: I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study.

Evan Seigerman: Hi, guys, thank you so much for taking my question, I think Stuart in your prepared remarks, you suggested that the launch of SUZETRIGINE might be more gradual than some other launches. Maybe once approved can you walk me through some of the gating factors to really get this into the hands of patients to have a [inaudible] impact on our health care system? Kind of what you have to do once approved to really get it to this patient? Thank you.

Speaker Change: to a total of 37 patients, so an additional 20 patients. And with regard to your direct question on how should we think about the path forward with regard to regulatory expectations,

Speaker Change: Patient thank you.

Speaker Change: I don't have an answer for you today because that's exactly the conversations that we're going to complete in the coming months.

Unknown: Hello, Evan thanks for the question and just to be absolutely crystal clear, our enthusiasm for SUZETRIGINE is growing as we get closer to the launch, not diminishing, and that's due to the benefit we got from market research, and also our interactions and discussions with physicians, post the Phase III data and the filing. But there are practical realities that we are going to have to face, they are things like, obviously the majority of patients with acute pain are treated in the institutional setting, that means we're going to have to go through formulary and MT processes with those institutions. We're going to have to work with with payers, and work through their formulary and other policy adoption processes. And so whilst those policies are very well defined they do take time, and obviously, we're going to do everything we can to accelerate those timelines, and that's why we're already engaging for instance, with GPOs and IVN leadership to support institutional use.

Reshma Kewalramani: But I would think about the Type 1 Diabetes program more like a CASH-GEVI program than a small molecule program. You'll remember that the CASH-GEVI program in either TDT or in sickle cell disease was a very efficient sample size, and what we did in the case of CASH-GEVI was convert it from a Phase 1-2 to a Phase 1-2-3 trial. Exactly what it will look like for VX-880, I'll look forward to keeping you updated as we complete the discussions with regulators. The next question will come from Evan Seigerman with BMO Capital Markets. Please go ahead.

Speaker Change: You'll remember that the cash chevy program in either TDT or.

Speaker Change: <unk>. But there are practical realities that we are going to have to face it. They are things like <unk>. The majority of patients with acute pain are treated in the institutional setting that means we're going to have to go through formulary in PMT processes with those institutions. We're going to have to work with with Payors. And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Speaker Change: But there are practical realities that we are going to have to face it. They are things like <unk>. The majority of patients with acute pain are treated in the institutional setting that means we're going to have to go through formulary in PMT processes with those institutions. We're going to have to work with with Payors. And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Speaker Change: They are things like <unk>. The majority of patients with acute pain are treated in the institutional setting that means we're going to have to go through formulary in PMT processes with those institutions. We're going to have to work with with Payors. And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Speaker Change: The majority of patients with acute pain are treated in the institutional setting that means we're going to have to go through formulary in PMT processes with those institutions. We're going to have to work with with Payors. And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Unknown: We're going to have to work with with payers, and work through their formulary and other policy adoption processes. And so whilst those policies are very well defined they do take time, and obviously, we're going to do everything we can to accelerate those timelines, and that's why we're already engaging for instance, with GPOs and [inaudible] leadership to support institutional use, we're talking with payers and PBMs to support rapid policy adoption. In addition, we are going to want SUZETRIGINE to be broadly available at retail pharmacies across America, and so we're also engaging with the major retail pharmacy organizations as well. And lastly, because we know that these processes can take time, despite the fact, we're going to do everything we can to accelerate them, we are also looking at deploying a range of initiatives, including things like co-pay assistance and financial assistance program, so that if a physician and patient decided that SUZETRIGINE is right for them, that patient can access the product without delay, and isn't forced to kind of abandon the prescription, because that particular plan or payer is not finalized their medical policy yet. So those are some of the challenges we're going to be facing, they're not unique to Vertex, they are relatively well defined and we are going to do everything we can to accelerate them, so that SUZETRIGINE can become the multibillion dollar drug we know it's going to become.

Speaker Change: We're going to have to work with with Payors. And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Speaker Change: And work through their formulary and other policy adoption processes and so whilst those policies are very well defined they do take time and obviously, we're going to do everything we can to accelerate those timelines and that's why we're already engaging for instance, with <unk> and IV in leadership to support it.

Speaker Change: The next question will come from Evan Seigerman with BMO Capital Markets. Please go ahead.

Unknown: And so whilst those policies are very well defined they do take time, and obviously, we're going to do everything we can to accelerate those timelines, and that's why we're already engaging for instance, with GPOs and IVN leadership to support institutional use.

Evan Saigerman: Hi, guys. Thank you so much for taking my question. I think, Stuart, in your prepared remarks, you suggested that the launch of SuzetraGene might be more gradual than some other launches. Maybe once approved, can you walk me through some of the gating factors to really get this into the hands of patients to, you know, have the maximum impact on a healthcare system, kind of what you have to do once approved to really get it to these patients? Thank you.

Speaker Change: Institutional use we're talking with payers and Pbms to support rapid policy adoption in. In addition, we are going to want <unk> to be broadly available at retail pharmacies across America. So we're also engaging with the major retail pharmacy organizations as well. Lastly, because we know that these processes can take time. Despite the fact, we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co pay assistance and financial assistance program. So that if a physician and patient decided that says that gene is right for them. That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Institutional use

we're talking with payers and Pbms to support rapid policy adoption in. In addition, we are going to want <unk> to be broadly available at retail pharmacies across America. So we're also engaging with the major retail pharmacy organizations as well. Lastly, because we know that these processes can take time. Despite the fact, we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co pay assistance and financial assistance program. So that if a physician and patient decided that says that gene is right for them. That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Unknown: In addition, we are going to want SUZETRIGINE to be broadly available at retail pharmacies across America, and so we're also engaging with the major retail pharmacy organizations as well. And lastly, because we know that these processes can take time, despite the fact, we're going to do everything we can to accelerate them, we are also looking at deploying a range of initiatives, including things like co-pay assistance and financial assistance program. So that if a physician and patient decided that SUZETRIGINE is right for them, that patient can access the product without delay, and isn't forced to kind of abandon the prescription, because that particular plan or payer is not finalized their medical policy yet. So those are some of the challenges we're going to be facing, they're not unique to Vertex, they are relatively well defined and we are going to do everything we can to accelerate them, so that SUZETRIGINE can become the multibillion dollar drug we know it's going to become.

Unknown Executive: Sure, Evan, thanks for the question. And just to be absolutely crystal clear, our enthusiasm for cizetrogene is growing as we get closer to launch, not diminishing. And that's due to the benefit we've got from, you know, market research and also our interactions and discussions with physicians following the phase three data and the filing. But there are, you know, practical realities that we are going to have to face.

Speaker Change: In addition, we are going to want <unk> to be broadly available at retail pharmacies across America. So we're also engaging with the major retail pharmacy organizations as well. Lastly, because we know that these processes can take time. Despite the fact, we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co pay assistance and financial assistance program. So that if a physician and patient decided that says that gene is right for them. That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Speaker Change: So we're also engaging with the major retail pharmacy organizations as well. Lastly, because we know that these processes can take time. Despite the fact, we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co pay assistance and financial assistance program. So that if a physician and patient decided that says that gene is right for them. That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Speaker Change: Lastly, because we know that these processes can take time. Despite the fact, we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co pay assistance and financial assistance program. So that if a physician and patient decided that says that gene is right for them. That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Speaker Change: And that's due to the benefit we've got from market research and also our interactions and discussions with physicians post the phase three data and the filing. But there are practical realities that we are going to have to face.

Unknown: So that if a physician and patient decided that SUZETRIGINE is right for them, that patient can access the product without delay, and isn't forced to kind of abandon the prescription, because that particular plan or payer is not finalized their medical policy yet. So those are some of the challenges we're going to be facing, they're not unique to Vertex, they are relatively well defined and we are going to do everything we can to accelerate them, so that SUZETRIGINE can become the multibillion dollar drug we know it's going to become.

Unknown Executive: And they are things like, obviously, the majority of patients with acute pain are treated in the institutional setting. That means we're going to have to go through formulary and P&T processes with those institutions. We're going to have to work with payers and work through their formulary and other policy adoption processes. And so, whilst those policies are very well defined, they do take time.

Speaker Change: They are things like, obviously, the majority of patients with acute pain are treated in the institutional setting. That means we're going to have to go through formulary and P&T processes with those institutions.

Speaker Change: That patient can access the product without delay and is enforced kind of abandon the prescription because that particular plan or payer is not finalized their medical policy. Yet. So those are some of the challenges we're going to be facing theyre not unique to vertex. They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Speaker Change: and work through their formulary and other policy adoption processes. And so whilst those policies are very well defined, they do take time. And obviously we're gonna do everything we can to accelerate.

Speaker Change: They are relatively well defined and we are going to do everything we can to accelerate them. So that <unk> can become the multibillion dollar drug we know it's going to become.

Evan Seigerman: Great. Thank you.

Unknown Executive: And obviously, we're going to do everything we can to accelerate those timelines. And that's why we're already engaging, for instance, with GPOs and IDN leadership to support institutional use. We're talking with payers and PBMs to support rapid policy adoption. In addition, you know, we are going to want cizetrogene to be broadly available at retail pharmacies across America. And lastly, because we know that these processes can take time, despite the fact we're going to do everything we can to accelerate them, we are also looking at deploying a range of initiatives, including things like copay assistance and financial assistance programs, so that if a physician and patient decide that cizetrogene is right for them, that patient can access the product without delay and isn't forced to kind of abandon the prescription because their So those are some of the challenges we're going to be facing. They're not unique to Virtex.

Speaker Change: Those timelines, and that's why we're already engaging, for instance, with GPOs and IDN leadership to support institutional use. We're talking with payers and PBMs to support rapid policy adoption.

Operator: The next question will come from Chris Raymond with Piper Sandler. Please go ahead.

Christopher Raymond: Hey, thanks, maybe two questions, first maybe on POVE, just a competitive question is IgAN seems to be getting a little bit more crowded. Biogen just got access to Felzartamab, which I think had a pretty interesting Phase II data. Just maybe talk a little bit about, you know, how you view the sort of match up to that, and maybe how does anti-CD38, compared [inaudible] inhibition. And then maybe a CASGEVY commercial question, just on the HHS suit around fertility treatments for patients. getting CASGEVY. Can you maybe talk about the overall timelines there with that case? And maybe also talk about how much of an impact it is to not have this reimbursement for fertility in place during the early stage of the launch? Thank you.

Chris Raymond: Maybe two questions first maybe on Kobe. Just a competitive question is I guess, it seems to be getting a little bit more crowded. Biogen just got access to. Those are the Mab, which I think had a pretty interesting phase two data. Just maybe talk a little bit about. How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Chris Raymond: Just a competitive question is I guess, it seems to be getting a little bit more crowded. Biogen just got access to. Those are the Mab, which I think had a pretty interesting phase two data. Just maybe talk a little bit about. How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: In addition, you know, we are going to want susetra gene to be broadly available at retail pharmacies across America.

Speaker Change: Biogen just got access to. Those are the Mab, which I think had a pretty interesting phase two data. Just maybe talk a little bit about. How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: And so we're also engaging with the major retail pharmacy organizations as well.

Speaker Change: Those are the Mab, which I think had a pretty interesting phase two data. Just maybe talk a little bit about. How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: And lastly, because we know that these processes can take time, despite the fact that we're going to do everything we can to accelerate them.

Speaker Change: Just maybe talk a little bit about. How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Unknown Executive: They are, you know, relatively well defined, and we're going to do everything we can to accelerate them so that cizetrogene can become the multibillion-dollar drug we know it's going to become. Great, thank you, not to have this reimbursement for fertility, you know, in place during that early stage of the launch. Thank you. Great, thank you very much for taking my question. Maybe one question on the LS-SAR trial. If you could help set some expectations there,

Speaker Change: How you view the sort of match up to that and maybe how does. Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: We are also looking at deploying a range of initiatives, including things like co-pay assistance and financial assistance programs, so that if a physician and patient decide that Sozetogene is right for them,

Speaker Change: Anti CD 38, comparative Bath April inhibition. And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Christopher Raymond: And then maybe a CASGEVY commercial question, just on the HHS suit around fertility treatments for patients. getting CASGEVY. Can you maybe talk about the overall timelines there with that case? And maybe also talk about how much of an impact it is to not have this reimbursement for fertility in place during the early stage of the launch? Thank you.

Speaker Change: And then maybe a cash Debbie commercial question just on the HHS. Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: Suit around fertility treatments for patients. Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: that patient can access the product without delay and isn't forced to kind of abandon the prescription because their particular plan or payer has not finalized their medical policy yet. So those are some of the challenges we're going to be facing. They're not unique to Virtex.

Speaker Change: Didn't catch JV. Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: Can you maybe talk about the overall timelines there with that case and maybe also talk about how much of an impact it has to. To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: To not have this reimbursement for fertility in place during the early stage of the launch thank you.

Speaker Change: They are, you know, relatively well-defined and we're going to do everything we can to accelerate them so that Cezettegine can become the multi-billion dollar drug we know it's going to become.

Reshma Kewalramani: Sure hey, this is Reshma, let me take the first question first and then I'll turn it over to Stuart to talk about CASGEVY, and how that's going. So, important things to know about Iga Nephropathy, it is a rare disease, but it is one of the more common rare diseases, there's more than 130,000 with Iga Nephropathy in the US alone. And it's actually the most common primary glomerulonephritis, so there are lots of patients that are waiting to be served. To date, there is no specific therapy that treats the underlying cause of this disease, and the reason for our enthusiasm, and after a Iga Nephropathy has been in our sandbox as it were a disease area of interest for a long time. And after, there has been some activity in this space, and a full analysis bias of everything available out there, our enthusiasm for Alpine and the that the POVETACICEPT, which is a dual APRIL/BAFF inhibitor, comes from the fact that it is the agent that works directly on the underlying cause of the disease. To put it in a short way, the disease is caused by B-cells, it is the activation of these B-Cells, it is about auto-antibodies, and this drug APRIL/BAFF directly inhibits B-Cell proliferation, maturation, and proliferation. And what we have seen by way of mechanism of action, this dual APRIL/BAFF inhibition, all of the preclinical data potency affinity, as well as the clinical data, it is through it's phase two development, so we're talking about proteinuria, hematuria, GFR, and also the biomarker of what's called GBA Iga, that's the Aberrantly glycosylated Iga, which is the underlying problem. Not to mention Q monthly dosing it's subcutaneous and small volume, you put that all together, POVE has the most transformational profile, and holds the potential to be best in class for IgAN, but also holds the potential to have effect, transformative effect in a whole host of other B-Cell mediated kidney diseases, like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like IPP, cold agglutinin disease, warm hemolytic anemia. So I couldnt be more excited about this molecule getting to it's first Phase III program, which is Iga Nephropathy.

Speaker Change: Great, thank you.

Speaker Change: It is a rare disease, but it is one of the more common rare diseases, there's more than 130000 with Iga nephropathy and the U S alone. And it's actually the most common primary glomerulonephritis. So there are lots of patients that are waiting to be served to date. There is no specific therapy that treats the underlying cause of this disease. And the reason for our enthusiasm and after a Iga nephropathy has been in our sandbox as it were in a disease area of interest for a long time. And after. There has been some activity. In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: Hey, thanks. Just maybe two questions. First, maybe on POVI, just a competitive question as IGAN seems to be getting a little bit more crowded.

Stuart: And it's actually the most common primary glomerulonephritis. So there are lots of patients that are waiting to be served to date. There is no specific therapy that treats the underlying cause of this disease. And the reason for our enthusiasm and after a Iga nephropathy has been in our sandbox as it were in a disease area of interest for a long time. And after. There has been some activity. In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: Biogen just got access to Fasartimab, which I think had pretty interesting phase 2 data. Just maybe talk a little bit about, you know,

Speaker Change: how you view the sort of match-up to that, and maybe how does anti-CD38 compare to BAF, April, and Addition? And then maybe a Cass Javie commercial question, just on the HHS.

Reshma Kewalramani: To date, there is no specific therapy that treats the underlying cause of this disease, and the reason for our enthusiasm, and after a Iga Nephropathy has been in our sandbox as it were a disease area of interest for a long time. And after, there has been some activity in this space, and a full analysis bias of everything available out there, our enthusiasm for Alpine and the that the POVETACICEPT, which is a dual APRIL/BAFF inhibitor, comes from the fact that it is the agent that works directly on the underlying cause of the disease. To put it in a short way, the disease is caused by B-cells, it is the activation of these B-Cells, it is about auto-antibodies, and this drug APRIL/BAFF directly inhibits B-Cell proliferation, maturation, and proliferation. And what we have seen by way of mechanism of action, this dual APRIL/BAFF inhibition, all of the preclinical data potency affinity, as well as the clinical data, it is through it's phase two development, so we're talking about proteinuria, hematuria, GFR, and also the biomarker of what's called GBA Iga, that's the Aberrantly glycosylated Iga, which is the underlying problem. Not to mention Q monthly dosing it's subcutaneous and small volume, you put that all together, POVE has the most transformational profile, and holds the potential to be best in class for IgAN, but also holds the potential to have effect, transformative effect in a whole host of other B-Cell mediated kidney diseases, like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like IPP, cold agglutinin disease, warm hemolytic anemia. So I couldnt be more excited about this molecule getting to it's first Phase III program, which is Iga Nephropathy.

Stuart: And the reason for our enthusiasm and after a Iga nephropathy has been in our sandbox as it were in a disease area of interest for a long time. And after. There has been some activity. In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: suit around fertility treatments for patients getting CAST-CoV-2.

And after. There has been some activity. In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Stuart: There has been some activity. In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: Can you maybe talk about the overall timelines there with that case?

Stuart: In this space and a full analysis. Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: and maybe also talk about how much of an impact it is to not have this reimbursement for fertility in place during that early stage of the launch. Thank you.

Speaker Change: Bias of everything available out there our enthusiasm for alpine and Theyre, probably taxes that the which is a dual April back inhibitor. Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: Sure. Hey, this is Reshma. Let me take the first question first and then I'll turn it over to Stuart to talk about cash chevy and how that's going.

Comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way the diseases caused by B cells is the activation of these b cells. It is about auto antibodies. And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: So, important things to know about IgA nephropathy.

Speaker Change: It is a rare disease, but it is one of the more common rare diseases. There's more than 130,000 with IgG nephropathy in the U.S. alone.

Reshma Kewalramani: To put it in a short way, the disease is caused by B-cells, it is the activation of these B-Cells, it is about auto-antibodies, and this drug APRIL/BAFF directly inhibits B-Cell proliferation, maturation, and proliferation. And what we have seen by way of mechanism of action, this dual APRIL/BAFF inhibition, all of the preclinical data potency affinity, as well as the clinical data, it is through it's phase two development, so we're talking about proteinuria, hematuria, GFR, and also the biomarker of what's called GBA Iga, that's the Aberrantly glycosylated Iga, which is the underlying problem. Not to mention Q monthly dosing it's subcutaneous and small volume, you put that all together, POVE has the most transformational profile, and holds the potential to be best in class for IgAN, but also holds the potential to have effect, transformative effect in a whole host of other B-Cell mediated kidney diseases, like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like IPP, cold agglutinin disease, warm hemolytic anemia. So I couldnt be more excited about this molecule getting to it's first Phase III program, which is Iga Nephropathy.

Speaker Change: And this drug April Bath directly inhibits b cell proliferation maturation. And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Stuart: And it's actually the most common primary glomerulonephritis. So there are lots of patients that are waiting to be served. To date, there is no specific therapy that treats the underlying cause of this disease.

Speaker Change: And proliferation and what we have seen by way of mechanism of action. This dual April back inhibition all of the preclinical data potency affinity as well as the clinical data. It is through its phase two development. So we're talking about proteinuria key mature. GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: And the reason for our enthusiasm and after a IgA nephropathy has been in our sandbox, as it were, a disease area of interest for a long time.

Speaker Change: GFR and also the biomarker of what's called GBA Iga, that's the Aberrantly Glycocholate Iga, which is the underlying problem not to mention Q monthly dosing. It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: by us of everything available out there. Our enthusiasm for Alpine and their Pobitasacet, which is a dual April bath inhibitor.

Reshma Kewalramani: Not to mention Q monthly dosing it's subcutaneous and small volume, you put that all together, POVE has the most transformational profile, and holds the potential to be best in class for IgAN, but also holds the potential to have effect, transformative effect in a whole host of other B-Cell mediated kidney diseases, like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like IPP, cold agglutinin disease, warm hemolytic anemia. So I couldnt be more excited about this molecule getting to it's first Phase III program, which is Iga Nephropathy.

Speaker Change: It's subcutaneous and some small volume you put that all together. <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: <unk> has the most transformational profile and holds the potential to be best in class for ICANN, but also holds the potential to have a. Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

Speaker Change: To put it in a short way, the disease is caused by B cells.

Speaker Change: Effect transformative effect in a whole host of other b cell mediated kidney diseases like lupus nephritis membranous anchor associated and a host of B cell mediated heme diseases like T. P cold agglutinin disease warm hemolytic anemia. So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

It is the activation of these B-cells, it is about autoantibodies, and this drug, APRIL-BAF, directly inhibits B-cell proliferation, maturation, and proliferation.

Speaker Change: What we have seen by way of mechanism of action, this dual April bath inhibition,

Speaker Change: So I couldnt be more excited about this molecule getting to its first phase III program, which is Iga nephropathy.

All of the preclinical data, potency, affinity, as well as the clinical data, it is...

Multiple: [inaudible]

through its phase two development.

Stuart Arbuckle: Let me just rake a step back before I talk specifically about fertility preservation, so because of the treatment journey to get CASGEVY, which requires multiple trips to the, activated an authorized treatment centers, and because there's only a certain number of sites in the United States. And in addition, because of the B cell [inaudible] conditioning regiments, whether fertility risk comes in, we have sought to try and provide support to patients in two particular areas. One is travel and lodging, and the other one is in fertility preservation, and we want to provide those support services to patients equitably, no matter what their payer is. We are able to provide both of those services to commercially insured patients, and we are able to provide travel and lodging support to government-insured patients because that has previously been ruled on by the body <unk>, while they have not given us an affirmative decision on his own fertility preservation and Thats why we have launched a. Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Speaker Change: So we're talking about proteinuria, hematuria, GFR, and also the biomarker of what's called GDA, IGA, that's the aberrantly glycosylated IGA, which is the underlying

Speaker Change: In the United States and in addition, because of the B cell phone conditioning regiments, whether fertility risk comes in we have sought to try and provide. Support to patients in two particular areas one is travel and lodging. On the other one is in fertility preservation and we want to provide those support services to patients equitably no matter what there. Bayer is we are able to provide both of those services to commercially insured patients and we are able to provide travel and lodging support the government insured patients because that has previously been ruled on by the body <unk>, while they have not given us an affirmative decision on his own fertility preservation and Thats why we have launched a. Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Speaker Change: Support to patients in two particular areas one is travel and lodging. On the other one is in fertility preservation and we want to provide those support services to patients equitably no matter what there. Bayer is we are able to provide both of those services to commercially insured patients and we are able to provide travel and lodging support the government insured patients because that has previously been ruled on by the body <unk>, while they have not given us an affirmative decision on his own fertility preservation and Thats why we have launched a. Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Speaker Change: On the other one is in fertility preservation and we want to provide those support services to patients equitably no matter what there. Bayer is we are able to provide both of those services to commercially insured patients and we are able to provide travel and lodging support the government insured patients because that has previously been ruled on by the body <unk>, while they have not given us an affirmative decision on his own fertility preservation and Thats why we have launched a. Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Stuart Arbuckle: We are able to provide both of those services to commercially insured patients, and we are able to provide travel and lodging support to government-insured patients because that has previously been ruled on by the OIG. While they have not given us an affirmative decision on his own fertility preservation and that's why we have launched [inaudible] to try and get fertility preservation approved with government-insured patients as well. It's impossible to speculate exactly on the timing of when that suite will be heard and resolved, in the short term, I don't see it as being rate limiting to a successful launch of CASGEVY and I think we're already seeing that in the number of patients who are beginning the treatment journey, and in the number of cell collections. Having said that we are completely committed to the sickle cell and TET communities and we are going to fight for their rights to get equitable access, whatever that payer.

Speaker Change: Bayer is we are able to provide both of those services to commercially insured patients and we are able to provide travel and lodging support the government insured patients because that has previously been ruled on by the body <unk>, while they have not given us an affirmative decision on his own fertility preservation and Thats why we have launched a. Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Speaker Change: transformative effect in a whole host of other B-cell mediated kidney diseases like lupus nephritis, membranous

Speaker Change: Anka Associated, and a host of B-cell mediated heme diseases like ITP, cold agglutinin disease, warm hemolytic anemia. So I couldn't be more excited about this molecule getting to its first phase 3 program which is IgA nephropathy.

Speaker Change: Suite to try and get fertility preservation approved with government insured patients as well, it's impossible to speculate exactly on the timing of when that suite will be heard and resolved. In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Stuart Arbuckle: It's impossible to speculate exactly on the timing of when that suite will be heard and resolved, in the short term, I don't see it as being rate limiting to a successful launch of CASGEVY and I think we're already seeing that in the number of patients who are beginning the treatment journey, and in the number of cell collections. Having said that we are completely committed to the sickle cell and TET communities and we are going to fight for their rights to get equitable access, whatever that payer.

Yeah, let me just take a step back before I talk specifically about fertility preservation. So, because of the treatment journey to get Castievi, which requires multiple trips to the activated and authorized treatment centers, and because there's only a certain number of sites,

In the short term I don't see it as being rate limiting to a successful launch of <unk> and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of cell collections, having said that we are completely committed to the sickle cell and <unk> communities and we are going to fight for their rights to get equitable access. Whatever that payer.

Stuart Arbuckle: Having said that we are completely committed to the sickle cell and TET communities and we are going to fight for their rights to get equitable access, whatever that payer.

In the United States.

And in addition, because of the bucellophane conditioning regimen, which is where the fertility risk comes in, we have sought to try and provide support to patients in two particular areas. One is travel and lodging.

Speaker Change: Whatever that payer.

Operator: And the next question will come from Terence Flynn with Morgan Stanley. Please go ahead.

Terence Flynn: Hi, thanks for taking the question, maybe two for me. Stuart you discussed at a high level your confidence in VANZACAFTOR pricing. Maybe just, I know you're not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision next year? And then any update on where we might see the full phase III data for VX548, plus fall. Thank you.

Speaker Change: Stuart you discussed at a high level. Your confidence and fans of catheter pricing. Maybe just I know youre not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision next year and then any update on where we might see the full phase III data for VX 548, plus fall. Thank you.

Speaker Change: Your confidence and fans of catheter pricing. Maybe just I know youre not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision next year and then any update on where we might see the full phase III data for VX 548, plus fall. Thank you.

Terence Flynn: Maybe just I know youre not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision next year and then any update on where we might see the full phase III data for VX 548, plus fall. Thank you.

We are able to provide travel and lodging support to government-insured patients because that has previously been ruled on by the OIG. What they have not given us an affirmative decision on is on fertility preservation, and that's why we've launched...

Reshma Kewalramani: Hey, Terrence let me take the second question first. I think it's now been released the VX-548 SUZETRIGINE data have been accepted at the ASA fall conference, and it has been accepted in the best abstract category, so you can expect to see it there. I'm sure the teams are also going to be working on whole manuscripts, probably in the fall-winter timeframe, but the Congress acceptance of SUZETRIGINE as best in class abstract has already been announced. Stuart over to you, yes, it's Arizona on vans, a catheter, we're going to approach the pricing advantage of catheter as we have with all of our medicines, which is we're going to base. It on. The clinical benefits and the value it provides to patients and as you know we're very positive about the vans a catheter profile. It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

Our suit to try and get fertility preservation approved for government insured patients as well.

Speaker Change: I think it's now been released the VX five for rates. This extra gene data have been accepted at the a safe all conference. And it has been accepted in the best abstract category. So you can expect to see it there I'm sure. The teams are also going to be working on. Manuscripts, probably in the fall winter timeframe, but the Congress acceptance of sector gene as best in class abstract has already been announced Stuart over to you, yes, it's Arizona on vans, a catheter, we're going to approach the pricing advantage of catheter as we have with all of our medicines, which is we're going to base. It on. The clinical benefits and the value it provides to patients and as you know we're very positive about the vans a catheter profile. It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

It's impossible to speculate exactly on the timing of when that suit will be heard and resolved.

In the short term, I don't see it as being rate limiting to a successful launch of Castievi, and I think we're already seeing that.

Speaker Change: And it has been accepted in the best abstract category. So you can expect to see it there I'm sure. The teams are also going to be working on. Manuscripts, probably in the fall winter timeframe, but the Congress acceptance of sector gene as best in class abstract has already been announced Stuart over to you, yes, it's Arizona on vans, a catheter, we're going to approach the pricing advantage of catheter as we have with all of our medicines, which is we're going to base. It on. The clinical benefits and the value it provides to patients and as you know we're very positive about the vans a catheter profile. It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

In the number of patients who are beginning the treatment journey and in the number of cell collections. Having said that, we are completely committed to the sickle cell and TET communities, and we are going to fight for their rights to get equitable access, whatever their payer.

Stuart: Manuscripts, probably in the fall winter timeframe, but the Congress acceptance of sector gene as best in class abstract has already been announced Stuart over to you, yes, it's Arizona on vans, a catheter, we're going to approach the pricing advantage of catheter as we have with all of our medicines, which is we're going to base. It on. The clinical benefits and the value it provides to patients and as you know we're very positive about the vans a catheter profile. It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

Reshma Kewalramani: Yes, Terence on VANZACAFTOR, we're going to approach the pricing of VANZACAFTOR as we have with all of our medicines, which is we're going to base is on the clinical benefits, and the value it provides to patients, and as you know we're very positive about the VANZACAFTOR profile. It performed brilliantly in the Phase III program, non inferior as anticipated to TRIKAFTA [inaudible], but demonstrated superior restoration of CFTR function, as measured by sweat chloride, and of course it has the convenience of being once daily. So we're going to take all those factors into consideration when thinking of the pricing, which is obviously a decision we'll make much closer to the launch.

And the next question will come from Terence Flynn with Morgan Stanley . Please go ahead.

Hi, thanks for taking the question, maybe two for me. Stuart, you discussed at a high level,

Stuart: The clinical benefits and the value it provides to patients and as you know we're very positive about the vans a catheter profile. It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

your confidence in, you know, Vanzikafter pricing. Maybe just, I know you're not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision next year? And then any update on where we might see the full phase three data for VX548 this fall. Thank you.

Speaker Change: It performed brilliantly in the phase III program non inferior as anticipated to try catheter on SB, one, but demonstrated superior restoration of CFT, our function as measured by sweat chloride and of course it has the convenience of being once daily So we're going to take all those factors into consideration. Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

Hey Terence, let me take the second question first.

Speaker Change: Asian, when thinking of the pricing, which is obviously a decision we'll make. And much closer to the launch.

Speaker Change: And much closer to the launch.

Operator: The next question will come from Mohit Bansal with Wells Fargo. Please go ahead.

Mohit Bansal: Great, thank you very much for taking my question, maybe question on LSR trial, if you could help set some expectations there? It's a placebo-controlled trial so if we think a two point improvement just like a VPN trial would be good enough here? And then the other is that, are you expecting any AD com for the pain, acute pain program at this point? Thank you.

Speaker Change: Maybe a. One question on I'll, let Todd trial, if you could help that. <unk> set some expectations there. Well controlled trials so it. We think a two point improvement just like a VPN trial would be good enough here. And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: One question on I'll, let Todd trial, if you could help that. <unk> set some expectations there. Well controlled trials so it. We think a two point improvement just like a VPN trial would be good enough here. And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: <unk> set some expectations there. Well controlled trials so it. We think a two point improvement just like a VPN trial would be good enough here. And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: Well controlled trials so it. We think a two point improvement just like a VPN trial would be good enough here. And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: We think a two point improvement just like a VPN trial would be good enough here. And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: And then the other the other one is that. Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Yeah, Terence, on vanzikafta, we're going to approach the pricing of vanzikafta as we have with all of our medicines, which is we're going to base it on the clinical benefits and the value it provides to patients. And as you know, we're very

Speaker Change: Are you expecting any AD com for the fall. The pain. It's been a program at this point thank you.

Speaker Change: The pain. It's been a program at this point thank you.

Speaker Change: It's been a program at this point thank you.

Reshma Kewalramani: Sure, Mohit, let me take the second question first. As I said in my prepared remarks, we are thrilled that SUZETRIGINE, the submission was not only accepted but granted priority review. The agency has let us know that they do not plan to hold an AD com as it stands today, but also as you know, the agency can let us know that they wish to have one at anytime between the acceptance of the filing and the actual approval. On the LSR, so that's also a VX-548 trial, that's a trial that has significantly honestly, far significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year, and for us to be able to share results this year. So with regard to this study and how you can think about it, it uses the high dose for the 69 milligrams from the Phase III study of DPN. The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain. And so our Phase II trial in LSR is a within group, so it's within arm change of the NPRS score for the LSR sorry for the VX-548 group, and equally we'll have the placebo group within group change. And the goal for the LSR study, which frankly was the same goal as the DPN study is to get a magnitude of the treatment effect, so that we can appropriately power the Phase III study, and the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPM. This study LSR as a placebo arm because there is no specifically approved therapy for the treatment of LSR. I hope that helps.

Positive about the Vantacaptor profile.

Speaker Change: Let me take the second question first. As I said in my prepared remarks, we are thrilled that this sector gene. The submission was not only accepted but granted priority review. The agency has let us know that they do not plan to hold an AD com as it stands today, but also as you know I'm. The agency can let us know that they wish to have one at anytime between the acceptance of the filing and the actual approval. On the <unk>. So that's also a VX 548 trial, that's a trial that has significantly honestly. <unk> significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year and for us to be able to share results. This year. With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: As I said in my prepared remarks, we are thrilled that this sector gene. The submission was not only accepted but granted priority review. The agency has let us know that they do not plan to hold an AD com as it stands today, but also as you know I'm. The agency can let us know that they wish to have one at anytime between the acceptance of the filing and the actual approval. On the <unk>. So that's also a VX 548 trial, that's a trial that has significantly honestly. <unk> significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year and for us to be able to share results. This year. With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: The agency has let us know that they do not plan to hold an AD com as it stands today, but also as you know I'm. The agency can let us know that they wish to have one at anytime between the acceptance of the filing and the actual approval. On the <unk>. So that's also a VX 548 trial, that's a trial that has significantly honestly. <unk> significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year and for us to be able to share results. This year. With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: On the <unk>. So that's also a VX 548 trial, that's a trial that has significantly honestly. <unk> significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year and for us to be able to share results. This year. With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Reshma Kewalramani: On the LSR, so that's also a VX-548 trial, that's a trial that has significantly honestly, far significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year, and for us to be able to share results this year. So with regard to this study and how you can think about it, it uses the high dose for the 69 milligrams from the Phase III study of DPN. The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain. And so our Phase II trial in LSR is a within group, so it's within arm change of the NPRS score for the LSR sorry for the VX-548 group, and equally we'll have the placebo group within group change. And the goal for the LSR study, which frankly was the same goal as the DPN study is to get a magnitude of the treatment effect, so that we can appropriately power the Phase III study, and the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPM. This study LSR as a placebo arm because there is no specifically approved therapy for the treatment of LSR. I hope that helps.

The next question will come from Mohit Bansal with Wells Fargo. Please go ahead.

Speaker Change: <unk> significantly exceeded our projections in terms of enrollment and study completion, we're now expecting that study to finish this year and for us to be able to share results. This year. With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Unknown Executive: It's a placebo-controlled trial, so do we think a two-point improvement just like a DPN trial would be good enough here? And then the other question is, are you expecting any outcome for the pain, acute pain program at this point? Sure. Mohit, let me take the second question first. As I said in my prepared remarks, we are thrilled that the SucetraGene submission was not only accepted but granted priority review. The agency has let us know that they do not plan to hold an ad comp, as it stands today.

Speaker Change: With regard to this study and how you can think about it it uses the high dose for. So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: So the 69 milligrams from the Phase III study of D. P M. The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: The big difference between D. P. N N. LFR is that LFR has no specific therapy approved for the treatment of this kind of ridiculous policy pain. So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Reshma Kewalramani: The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain. And so our Phase II trial in LSR is a within group, so it's within arm change of the NPRS score for the LSR sorry for the VX-548 group, and equally we'll have the placebo group within group change. And the goal for the LSR study, which frankly was the same goal as the DPN study is to get a magnitude of the treatment effect, so that we can appropriately power the Phase III study, and the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPM. This study LSR as a placebo arm because there is no specifically approved therapy for the treatment of LSR. I hope that helps.

Reshma Kewalramani: The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain.

Sure. Mohit, let me take the second question first.

Speaker Change: So our phase II trial in LFR is a within group. So it's within arm change of the NPS score for the LFR sorry for the VX 548 group and equally we'll have the placebo group. In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Reshma Kewalramani: And so our Phase II trial in LSR is a within group, so it's within arm change of the NPRS score for the LSR sorry for the VX-548 group, and equally we'll have the placebo group within group change. And the goal for the LSR study, which frankly was the same goal as the DPN study is to get a magnitude of the treatment effect, so that we can appropriately power the Phase III study, and the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPM. This study LSR as a placebo arm because there is no specifically approved therapy for the treatment of LSR. I hope that helps.

Unknown Executive: But also, as you know, the agency can let us know that they wish to have one at any time between the acceptance of the filing and the actual approval. Chuck, we'll take two more questions, please. Yes, ma'am. The next question will come from Liisa Bayko with Evercore ISI. Please go ahead.

Speaker Change: In group change and the goal for the <unk> study, which frankly was the same goal as the D. P. M study is to get a magnitude of the treatment effect. So that we can appropriately power the phase III study and the reason the D. P. N study had a pregabalin arm was big. Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Speaker Change: Cause pregabalin isn't available therapy for the treatment of DPM. This study LFR as a placebo arm because there is no specifically approved therapy for the treatment of <unk> I hope that helps.

Mohit Bansal: Thank you.

Chuck: [inaudible] can we take two more questions, please? yes, ma'am. The next question will come from Lisa <unk> with Evercore ISI. Please go ahead.

Susie Lisa: [inaudible] can we take two more questions, please?

The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain.

Operator: Yes, ma'am. The next question will come from Liisa Bayko with Evercore ISI. Please go ahead.

Liisa Bayko: Hi, thanks for taking my question, just to follow up on VANZACAFTOR, maybe you can talk about how you're expecting the rollout there? In terms of patient uptake, it's not quite as much [inaudible] some of your other therapies are, but nevertheless, like I you know the the value there is obvious, you know do you expect like quite quick conversion will happen slowly over time? Do you think the vast majority of patients will switch over? Just curious about what the feedback has been there? Thanks. Stuart, any additional comments to make?

Speaker Change: Just to follow up on Panther catheter, maybe you can talk about. How youre expecting the rollout are there in terms of patient uptake. It's not quite as much but some of your other therapies are but nevertheless, like I you know the the value. There is obvious you know do you expect like quite quick conversion will happen slowly over time do you think the <unk>. The majority of patients will will switch over just curious about what the feedbacks been there. Any additional comments to make

And so our phase two trial in LSR is a within group, so it's within arm change.

Speaker Change: How youre expecting the rollout are there in terms of patient uptake. It's not quite as much but some of your other therapies are but nevertheless, like I you know the the value. There is obvious you know do you expect like quite quick conversion will happen slowly over time do you think the <unk>. The majority of patients will will switch over just curious about what the feedbacks been there. Any additional comments to make

Speaker Change: It's not quite as much but some of your other therapies are but nevertheless, like I you know the the value. There is obvious you know do you expect like quite quick conversion will happen slowly over time do you think the <unk>. The majority of patients will will switch over just curious about what the feedbacks been there. Any additional comments to make

of the NPRS score for the LSR, sorry, for the VX548 group and equally we'll have the placebo group within group change.

Speaker Change: The majority of patients will will switch over just curious about what the feedbacks been there. Any additional comments to make

And the goal for the LSR study, which frankly was the same goal as the DPN study, is to get a magnitude of the treatment effect.

Reshma Kewalramani: Stuart, any additional comments to make?

Speaker Change: Any additional comments to make yes, just that we are we're as excited about the vantage a catheter launches of any of our other <unk> modulators for the reasons I think you were referring to Liza or it's got a great.

Any additional comments to make

Stuart Arbuckle: Yes, just that we are we're as excited about the VANZACAFTOR launch as of any of our other CFTR modulators for the reasons I think you were referring to Lisa, it's got a great benefit-risk profile. And I think it is going to, as I said earlier, I think it's going to be equally all interest to patients who are on a CFTR modulator today, but would like to increase CFTR function as demonstrated by sweat chloride, because these patients know that is important for their health and wellbeing, but I think it's also going to be of value to those who discontinued. So as I said earlier on, I really don't think there's going to have one group or another, we're going to be more interested than others. I do think it's something that's going to be broadly of appeal to people. And as I also mentioned, not to forget the fact that it has the benefit of being once-daily which again, is an attractive part of a chronic medication. So as I said, we're as excited about our launch of VANZA as we have been about any of our other CFTR modulators. I was just trying to get a sense of the [inaudible] like how quickly people might convert over you're thinking? Do you think it would be a test flow and study or, you know, [inaudible]

Stuart Arbuckle: Yes, just that we are we're as excited about the VANZACAFTOR launch as of any of our other CFTR modulators for the reasons I think you were referring to Liisa, it's got a great benefit-risk profile. And I think it is going to, as I said earlier, I think it's going to be equally all interest to patients who are on a CFTR modulator today, but would like to increase CFTR function as demonstrated by sweat chloride, because these patients know that is important for their health and wellbeing, but I think it's also going to be of value to those who discontinued. So as I said earlier on, I really don't think there's going to have one group or another, we're going to be more interested than others. I do think it's something that's going to be broadly of appeal to people. And as I also mentioned, not to forget the fact that it has the benefit of being once-daily which again, is an attractive part of a chronic medication. So as I said, we're as excited about our launch of VANZA as we have been about any of our other CFTR modulators.

And the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPN. This study, LSR, has a placebo arm because there is no.

Speaker Change: Benefit risk profile and I think it is going to as I said earlier I think it's going to be equally all interest to patients who are honestly FTR modulator today, but would like increase the FTR function as demonstrated by sweat chloride because these patients no.

Specifically Approved Therapy for the Treatment of LSR. I hope that helps.

Chuck, we'll take two more questions, please. Yes, ma'am. The next question will come from Liisa Bayko with Evercore ISI. Please go ahead.

Speaker Change: That is important for their health and wellbeing, but I think it's also going to be all.

Speaker Change: Our value to those who discontinued so as I said earlier on I really don't think there's going to have one group or another we're going to be more interested than than others. I do think it's something that's going to be broadly all of appeal to people and as I also mentioned not to forget the fact that it has the benefit of being once daily which again.

Speaker Change: <unk> is an attractive part of a chronic medication. So as I said, we're as excited about our launch of vendors, we have been about any of our other <unk> modulators.

The vast majority of patients will switch over. Just curious about what the feedback's been there. Thanks.

Liisa Bayko: I was just trying to get a sense of the [inaudible] like how quickly people might convert over you're thinking? Do you think it would be a test flow and study or, you know, [inaudible]

Speaker Change: I was just trying to get a sense of their repeat it like how quickly people might convert over just thinking do you think it would be a test flow and study or not.

Speaker Change: Pretty rock.

Stuart Arbuckle: Yes, I mean, certainly the reaction we've had from physicians and patients, the profile has been very enthusiastic, I'm not going to speculate exactly on how much of the, how rapidly we're going to get the transitions and people restarted Lisa. Lisa maybe I'll just add one thing if you want to think through it. Patients with CF, usually visit their doctors once a quarter. As Stuart said the patients are very aware of drug development and vans a character in particular as are their physicians and patients have consistently. Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Benefit Risk Profile, and I think it is going to, as I said earlier, I think it's going to be equally of interest.

Speaker Change: How rapidly we're going to get the transitions and people restarted Lisa. Lisa maybe I'll just add one thing if you want to think through it. Patients with CF, usually visit their doctors once a quarter. As Stuart said the patients are very aware of drug development and vans a character in particular as are their physicians and patients have consistently. Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Speaker Change: Lisa maybe I'll just add one thing if you want to think through it. Patients with CF, usually visit their doctors once a quarter. As Stuart said the patients are very aware of drug development and vans a character in particular as are their physicians and patients have consistently. Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Reshma Kewalramani: Liisa maybe I'll just add one thing if you want to think through it, patients with CF, usually visit their doctors once a quarter. As Stuart said, the patients are very aware of drug development and VANZACAFTOR in particular, as are their physicians. And patients have consistently expressed interest in thinking about medicines that may bring them the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

To patients who are on a CFTR modulator today. But would like increased CFTR function as demonstrated by sweat chloride because

Lisa: Patients with CF, usually visit their doctors once a quarter. As Stuart said the patients are very aware of drug development and vans a character in particular as are their physicians and patients have consistently. Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Speaker Change: As Stuart said the patients are very aware of drug development and vans a character in particular as are their physicians and patients have consistently. Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

that that is important for their kind of health and well-being, but I think it's also going to be of value to those who've discontinued.

Expressed interest in thinking about medicines that may bring them are the potential for higher efficacy. I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

As I said earlier on, I really don't think there's one group or another who are going to be more interested than others. I do think it's something that's going to be broadly of appeal to people, and as I also mentioned, not to forget the fact that it has the benefit of being once daily, which again, is an attractive part of a chronic medication.

Speaker Change: I think that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Liisa Bayko: Thanks.

Operator: The next question will come from Michael Yee with Jefferies. Please go ahead.

As I said, we're as excited about the launch of Banzer as we have been about any of our other CFTR modulators.

Michael Yee: Hey, guys, thank you, great, two questions for us, on the alpine product, can you just remind me, I know you guys think it's best-in-class, but how to think about greater reduction in proteinuria versus an apparent program that will have data in first half '25. And is it your idea that you'll have greater reductions and therefore, better stabilization of EGFR or that it also will just be shining through in lupus and other autoimmune diseases for which we'll have to wait for Ruby-3 data? So just maybe talk about and remind us how you think the benefits will be seen on that product? And then, really quickly on the acute pain launch can you just remind me on the comments on the no pain Act? You believe you'll eventually get reimbursement there, but that's more of a CMS exposure population to take that in consideration. On the commercial that's more about blocking and tackling on formularies and commercial plans? Thank you.

Speaker Change: On the alpine product.

Michael Yee: Can you just remind me I know you guys think it's best in class, but how to think about greater reduction in proteinuria versus say a bear on a program that walk data in first half 'twenty five and.

Speaker Change: Is it your idea that youll have greater reductions and therefore, better stabilization of Egfr or that it also will just be shining through in lupus and other autoimmune diseases for which we will have to wait for Ruby <unk> III data. So just maybe talk about and remind us how you think the benefits will be seen on that product and then.

Michael Yee: So just maybe talk about and remind us how you think the benefits will be seen on that product? And then, really quickly on the acute pain launch can you just remind me on the comments on the no pain Act? You believe you'll eventually get reimbursement there, but that's more of a CMS exposure population to take that in consideration. On the commercial that's more about blocking and tackling on formularies and commercial plans? Thank you.

As Stuart said, the patients are very aware of drug development and vanzikaftor in particular, as are their physicians, and patients have consistently expressed interest in thinking about medicines.

Speaker Change: Really quickly on the acute pain launch can you just remind me on the comments on the no pain Act you believe you'll eventually get reimbursement there, but that's more of a CMS exposure.

Speaker Change: Our population.

Speaker Change: You take that in consideration.

that may bring them the potential for higher efficacy. I think that that's as far as we can go with regard to timing, but maybe those are pieces of information that are helpful to you.

Speaker Change: Commercial that's more about blocking and tackling on formularies and commercial plans. Thank you.

Reshma Kewalramani: Yeah, Mike I'm going to ask Stuart to comment on no pain first, I think, it was a little hard to hear you, Mike, but I think Stuart, Mike's question is does the no pain Act pertain to government pain patients? And how are you thinking about commercial? And then I'll come back for POVE.

Mike: Mike I'm going to ask Stuart to comment on no pain first I think it was a little hard to hear you, Mike, but I think Stuart. My question is does the no pain Act pertain to government paid.

Thanks.

The next question will come from Michael Yee with Jeffries. Please go ahead.

Speaker Change: Pain patients and how are you thinking about commercial and then I'll come back for <unk>.

Stuart Arbuckle: Yes, so, no pain, Mike is looking at the add on payment to patients who are treated in the outpatient ambulatory surgical center setting. As you said, we were not listed as one of the products, so that is because we are not approved, and so yes, we do anticipate being added to that list once SUZETRIGINE is approved. In terms of, in the Medicare area, maybe you're also thinking of the alternatives to Pain Act, which is looking to level the playing field in terms of things like step therapy, and not aligned with things like that, and utilization management in part D, and also making sure that there is parity in terms of the copay, for patients between opioids and non-opioids. In terms of all commercial, as you said, these are less relevant because that business is really sort of as you said, blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Stuart: No pain. <unk> is looking at the add on payment to patients who are treated in the ER. Outpatient ambulatory surgical center setting. As you said, we were not listed as one of the products. So that is because we are not approved and so yes, we do anticipate being added to that list once. <unk> is approved in terms of in the Medicare area, maybe Youre also thinking of the alternatives to pay an act, which is lucky to level the playing field in terms of things like step therapy, and not aligned with things like that and utilization management in part D. And also making sure that there is parity in terms of the copay. For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Speaker Change #100: <unk> is looking at the add on payment to patients who are treated in the ER. Outpatient ambulatory surgical center setting. As you said, we were not listed as one of the products. So that is because we are not approved and so yes, we do anticipate being added to that list once. <unk> is approved in terms of in the Medicare area, maybe Youre also thinking of the alternatives to pay an act, which is lucky to level the playing field in terms of things like step therapy, and not aligned with things like that and utilization management in part D. And also making sure that there is parity in terms of the copay. For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Speaker Change #101: Outpatient ambulatory surgical center setting. As you said, we were not listed as one of the products. So that is because we are not approved and so yes, we do anticipate being added to that list once. <unk> is approved in terms of in the Medicare area, maybe Youre also thinking of the alternatives to pay an act, which is lucky to level the playing field in terms of things like step therapy, and not aligned with things like that and utilization management in part D. And also making sure that there is parity in terms of the copay. For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

and is it your idea that you have greater reductions and therefore...

Speaker Change #102: As you said, we were not listed as one of the products. So that is because we are not approved and so yes, we do anticipate being added to that list once. <unk> is approved in terms of in the Medicare area, maybe Youre also thinking of the alternatives to pay an act, which is lucky to level the playing field in terms of things like step therapy, and not aligned with things like that and utilization management in part D. And also making sure that there is parity in terms of the copay. For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Stabilization of EGFR, or that it also will just be shining through in lupus and other autoimmune diseases for which we will have to wait for RWBY 3 data. So, just maybe talk about

Stuart Arbuckle: In terms of, in the Medicare area, maybe you're also thinking of the alternatives to Pain Act, which is looking to level the playing field in terms of things like step therapy, and not aligned with things like that, and utilization management in part D, and also making sure that there is parity in terms of the copay, for patients between opioids and non-opioids. In terms of all commercial, as you said, these are less relevant because that business is really sort of as you said, blocking and tackling is what we'll be doing in talking to commercial plans.

Speaker Change #103: <unk> is approved in terms of in the Medicare area, maybe Youre also thinking of the alternatives to pay an act, which is lucky to level the playing field in terms of things like step therapy, and not aligned with things like that and utilization management in part D. And also making sure that there is parity in terms of the copay. For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

and remind us how you think the benefits will be seen on that product.

And then, really quickly on the acute pain launch, can you just remind me, on the comments on the No Pain Act, you believe you will eventually get reimbursement there, but that's more of a CMS exposure population to take that into consideration.

Speaker Change #104: For patients between opioids and non opioids in terms of all commercial as you said these are less relevant because that business is really so as you said blocking and tackling is what we'll be doing in talking to commercial plans. And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

And for commercial, that's more about blocking and tackling on formularies and commercial plans. Thank you.

Stuart Arbuckle: In terms of all commercial, as you said, these are less relevant because that business is really sort of as you said, blocking and tackling is what we'll be doing in talking to commercial plans.

Yep.

Mike, I'm going to ask Stuart to comment on no pain first. I think it was a little hard to hear you, Mike, but I think Stuart, Mike's question is, does the no pain act pertain to government paid patients? And how are you thinking about commercial? And then I'll come back for Toby.

Speaker Change #103: And Mike on the question on Tobey I think the question was how should we think about <unk> in Iga nephropathy, and then how should we think about it. In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Stuart Arbuckle: And Mike on the question on POVE, I think the question was how should we think about POVE in Iga Nephropathy, and then how should we think about it in the other studies? Is it all about proteinuria? So the way I would think about it is, underlying cause of disease and B-Cell mediated diseases. We have two Phase III studies going on, is a very clever design by Alpine scientists, theres, a Ruby-3, which is a basket of B-Cell mediated renal diseases, Iga Nephropathy, which is now going to Phase III this month. It has lupus nephritis in there, anchor associated nephritis, as well as membranous, all of these diseases are B-Cell mediated diseases, in many of these diseases proteinuria is important. But I'll tell you for example in membranous PLA2R is a very important biomarker, and in some of the nephritities, as you may know, hematuria is very very important. So I think protein is, proteinuria is clearly very important in Iga Nephropathy, and it's prominence is elevated because of the FDA's acceptance of proteinuria in Iga Nephropathy, as an accelerated approval endpoint, but hematuria is important and some looking at biomarkers like PLA2R is important in others. And in the Ruby-4 basket, these are B-Cell mediated heme diseases, it's really not about proteinuria, it's about other markers of interest like, it could be something like hemoglobin, or in the case of ITP it would be platelets. But the way, the way I would look at it, and my enthusiasm for POVETACICEPT is because it is such a good B-Cell, it's such a good medicine to tamped down the B-Cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Reshma Kewalramani: And Mike on the question on POVE, I think the question was how should we think about POVE in Iga Nephropathy, and then how should we think about it in the other studies? Is it all about proteinuria? So the way I would think about it is, underlying cause of disease and B-Cell mediated diseases.

Speaker Change #104: In the other studies visit all of our partner here. So the way I would think about it is underlying cause of disease and b cell mediated diseases. We have two phase III studies going on is a very clever design by alpine scientists Theres, a Ruby suite, which is a basket of b cell mediated. In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Yes, so no pain. Mike is looking at the add-on payment to patients who are treated in the outpatient ambulatory surgical center setting.

Stuart Arbuckle: We have two Phase III studies going on, is a very clever design by Alpine scientists, theres, a Ruby-3, which is a basket of B-Cell mediated renal diseases, Iga Nephropathy, which is now going to Phase III this month. It has lupus nephritis in there, anchor associated nephritis, as well as membranous, all of these diseases are B-Cell mediated diseases, in many of these diseases proteinuria is important. But I'll tell you for example in membranous PLA2R is a very important biomarker, and in some of the nephritities, as you may know, hematuria is very very important. So I think protein is, proteinuria is clearly very important in Iga Nephropathy, and it's prominence is elevated because of the FDA's acceptance of proteinuria in Iga Nephropathy, as an accelerated approval endpoint, but hematuria is important and some looking at biomarkers like PLA2R is important in others. And in the Ruby-4 basket, these are B-Cell mediated heme diseases, it's really not about proteinuria, it's about other markers of interest like, it could be something like hemoglobin, or in the case of ITP it would be platelets. But the way, the way I would look at it, and my enthusiasm for POVETACICEPT is because it is such a good B-Cell, it's such a good medicine to tamped down the B-Cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Reshma Kewalramani: We have two Phase III studies going on, is a very clever design by Alpine scientists, theres, a Ruby-3, which is a basket of B-Cell mediated renal diseases, Iga Nephropathy, which is now going to Phase III this month. It has lupus nephritis in there, anchor associated nephritis, as well as membranous, all of these diseases are B-Cell mediated diseases, in many of these diseases proteinuria is important.

As you said, we were not listed as one of the products, but that is because we're not approved. And so, yes, we do anticipate being added to that list once...

Speaker Change #104: In renal diseases, Iga nephropathy, which is now going to phase III. This month, it has lupus nephritis and their anchor associated nephritis as well as membranous all of these diseases are b cell mediated diseases in many of these diseases proteinuria is important but I'll tell you for example. <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Susette Jejean is approved.

In terms of in the Medicare area, maybe you're also thinking of the Alternatives to Pain Act, which is looking to level the playing field in terms of

things like step therapy and not allowing things like that and utilization management in Part D and also making sure that there is parity in terms of the co-pay.

Speaker Change #106: <unk> and membrane S. P. L E to R is a very important biomarker and in some of the fruit of these as you may know hematuria is very very important. So I think protein is a partner is clearly very important in iga nephropathy and its prominence as elevated because of the fda's. Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Stuart Arbuckle: But I'll tell you for example in membranous PLA2R is a very important biomarker, and in some of the nephritities, as you may know, hematuria is very very important. So I think protein is, proteinuria is clearly very important in Iga Nephropathy, and it's prominence is elevated because of the FDA's acceptance of proteinuria in Iga Nephropathy, as an accelerated approval endpoint, but hematuria is important and some looking at biomarkers like PLA2R is important in others. And in the Ruby-4 basket, these are B-Cell mediated heme diseases, it's really not about proteinuria, it's about other markers of interest like, it could be something like hemoglobin, or in the case of ITP it would be platelets. But the way, the way I would look at it, and my enthusiasm for POVETACICEPT is because it is such a good B-Cell, it's such a good medicine to tamped down the B-Cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Reshma Kewalramani: But I'll tell you for example in membranous PLA2R is a very important biomarker, and in some of the nephritities, as you may know, hematuria is very very important. So I think protein is, proteinuria is clearly very important in Iga Nephropathy, and it's prominence is elevated because of the FDA's acceptance of proteinuria in Iga Nephropathy, as an accelerated approval endpoint, but hematuria is important and some looking at biomarkers like PLA2R is important in others.

For patients between opioids and non-opioids. In terms of commercial, as you said, these are less relevant to that. This is really sort of, as you said, blocking and tackling is what we'll be doing in talking to commercial plans.

Unknown Executive: And Mike, on the question about POVI, I think the question was, how should we think about POVI in IgA nephropathy? And then how should we think about it in the other studies? Is it all about proteinuria? So the way I would think about it is as an underlying cause of disease and B cell mediated diseases. We have two phase two studies going on. It was a very clever design by Alpine scientists.

Speaker Change #104: Acceptance of proteinuria in Iga nephropathy, as an accelerated approval endpoint, but he maturity is important and some looking at biomarkers like <unk> is important and others and in the Ruby for basket. These are b cell mediated heme diseases, it's really not about proteinuria it. It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

And Mike, on the question on POVI, I think the question was, how should we think about POVI in IgA nephropathy? And then how should we think about it in the other studies? Is it all about proteinuria?

So, the way I would think about it is underlying cause of disease and B-cell mediated diseases. We have two phase two studies going on, it was a very clever design by Alpine scientists.

Reshma Kewalramani: And in the Ruby-4 basket, these are B-Cell mediated heme diseases, it's really not about proteinuria, it's about other markers of interest like, it could be something like hemoglobin, or in the case of ITP it would be platelets. But the way, the way I would look at it, and my enthusiasm for POVETACICEPT is because it is such a good B-Cell, it's such a good medicine to tamped down the B-Cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Speaker Change #104: It's about our other markers of interest like it could be something like hemoglobin or in the case of <unk> it would be platelets, but the way the the way I would look at it in and my enthusiasm for <unk> is because it is such a good b cell. It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

Unknown Executive: There's a ruby three, which is a basket of B cell mediated renal diseases, IgA nephropathy, which is now going to phase three this month. It has lupus nephritis in it, ANCA associated nephritis, as well as membranous. All of these diseases are B cell mediated diseases. In many of these diseases, proteinuria is important. But I'll tell you, for example, in membranous, PLA2R is a very important biomarker. And in some of the nephritides, as you may know, hematuria is very, very important.

There's a Ruby 3, which is a basket of B-cell mediated renal diseases, IgA nephropathy, which is now going to phase 3 this month.

It has lupus nephritis in there, anka-associated nephritis, as well as membranous. All of these diseases are B-cell mediated diseases. In many of these diseases, proteinuria is important.

Speaker Change #104: It's such a good medicine to two tamped down the b cells, because its dual inhibition and impacts maturation proliferation and differentiation of B cells, and that's where my optimism for B cell mediated diseases comes from.

But I'll tell you, for example, in membranous, PLA2R is a very important biomarker, and in some of the nephritides, as you may know,

Michael Yee: Thank you.

Unknown Executive: So I think proteinuria is clearly very important in IgA nephropathy, and its prominence is elevated because of the FDA's acceptance of proteinuria in IgA nephropathy as an accelerated approval endpoint. But hematuria is important in some, and looking at biomarkers like PLA2R is important in others. And in the ruby four basket, these are B cell-mediated heme diseases. It's really not about proteinuria. It's about other markers of interest. It could be something like hemoglobin or, in the case of ITP, it would be platelets.

Reshma Kewalramani: Yep.

Susie Lisa: Thanks Mike, Chuck we'll wrap it there please.

hematuria is very, very important. So I think

Operator: Thank you, this concludes our question and answer session as well as our conference call for today, thank you for attending today's presentation. A replay of today's event will be available shortly after the call concludes by dialing 18773447529 or 14123170088, using replay access code 10186971. Thank you for your participation and you may now disconnect.

Protein is, proteinuria is clearly very important in IgA nephropathy and its prominence is elevated because of the FDA's acceptance of proteinuria in IgA nephropathy as an accelerated approval end point, but hematuria is important in some, looking at biomarkers like PLA2R is important in others.

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And in the Ruby 4 basket, these are B-cell mediated heme diseases. It's really not about proteinuria. It's about other markers of interest, like it could be something like hemoglobin or in the case of ITP, it would be platelets. But the way I would look at it and my enthusiasm for Povitacicept...

Unknown Executive: But the way I would look at it and my enthusiasm for povitocicep is because it is such a good B cell, it's such a good medicine to tamp down the B cells because it's dual inhibition and impacts maturation, proliferation, and differentiation of B cells. And that's where my optimism about B cell-mediated diseases comes from. Thank you. Yep. Thank you. This concludes our question and answer session as well as our conference call for today. Thank you for attending today's presentation. A replay of today's event will be available shortly after the call concludes by dialing 1-877-344-7529 or 1-412-317-0088.

is because it is...

Such a good

Thank you.

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