Q1 2024 Vertex Pharmaceuticals Inc Earnings Call

May 6, 2024

Operator: Good day, and welcome to the Vertex Pharmaceuticals' Q1 2024 earnings conference 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. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

Good day and welcome to the vertex Pharmaceuticals first quarter 2024 earnings conference call.

Operator: Good day and welcome to the Vertex Pharmaceuticals' 1st Quarter 2024 Earnings Conference 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. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

Susie Lisa: All participants will be in a listen only mode should you need assistance. Please signal conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions I would now like to turn the conference over to MS. Susie Lisa. Please go ahead. Good evening. All my name is Susie Lisa and as the senior Vice President of Investor Relations. It is my.

Operator: 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. I would now like to turn the conference over to Ms. Susie Lisa. Please do so.

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 Q1 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 make 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.

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 1st 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.

Susie Lisa: To welcome you to our first quarter 2024 financial results Conference call.

Susie Lisa: On tonight's call, making prepared remarks, we have Dr. Reis makiwara money, very Texas, 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 make forward looking state.

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.

Susie Lisa: We will make 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 limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease and beta thalassemia, our pipeline, Vertex's anticipated acquisition of Alpine Immune Sciences 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 select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program.

We will make 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 limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease and beta thalassemia, our pipeline, Vertex's anticipated acquisition of Alpine Immune Sciences 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 select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program.

Susie Lisa: 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 limitation. Those regarding vertex is marketed medicines for cystic fibrosis sickle cell disease and beta thalassemia, our pipeline vertex is.

Susie Lisa: These statements, including without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, and beta thalassemia, our pipeline, Vertex's anticipated acquisition of Alpine Immune Sciences, 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 select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program. I will now turn the call over to Reshma.

These statements, including without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, and beta thalassemia, our pipeline, Vertex's anticipated acquisition of Alpine Immune Sciences, 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 select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program. I will now turn the call over to Reshma.

Susie Lisa: <unk> the acquisition of Alpine immune Sciences, and very Texas future financial performance are based on management's current assumptions actual outcomes and events could differ materially.

Actual outcomes and events could differ materially. I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program.

Susie Lisa: I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program. I will now turn the call over to Reshma. Thanks, Susie.

I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program.

Susie Lisa: I would also note that select financial results and guidance that we will review on the call. This evening are presented on a non-GAAP basis. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program I will now turn the call over to Ray Smith.

I will now turn the call over to Reshma. Thanks, Susie.

I will now turn the call over to Reshma.

Reshma Kewalramani: Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Continuing our strong momentum from 2023, we've kicked off 2024 with another quarter of excellent performance across the board. Vertex continued to reach more CF patients, delivering $2.7 billion in revenue in Q1, representing 13% growth versus the prior year period. We also began our journey of revenue diversification with the launch of CASGEVY in both sickle cell disease and beta thalassemia in multiple regions. In our late-stage pipeline, we continue to drive programs into phase three and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification, including, one, completing our regulatory submissions for the vanzacaftor triple in patients with cystic fibrosis six years and older in both the US.

Thanks, Susie. Good evening, all and thank you for joining us on the call today. Continuing our strong momentum from 2023, we kicked off 24 with another quarter of excellent performance across the board. Vertex continued to reach more CF patients, delivering 2.7 billion in revenue in Q1, representing 13% growth versus the prior year period. We also began our journey of revenue diversification with the launch of CASGEVY for both sickle cell disease and beta thalassemia in multiple regions.

Reshma Kewalramani: Thanks, Susie. Good evening, all and thank you for joining us on the call today.

Reshma Kewalramani: Good evening, all. And thank you for joining us on the call today. Continuing our strong momentum from 2023, we kicked off 24 with another quarter of excellent performance across the board. Vertex continued to reach more CF patients, delivering 2.7 billion in revenue in Q1, representing 13% growth versus the prior year period. We also began our journey of revenue diversification with the launch of CASGEVY for both sickle cell disease and beta thalassemia in multiple regions.

Thanks, Susie good evening, all and thank you for joining us on the call today, continuing our strong momentum from 'twenty 'twenty suite, we've kicked off 24 with another quarter of excellent performance across the board vertex continued to reach more CF patients delivering $2 7 billion in revenue in Q1.

Continuing our strong momentum from 2023, we kicked off '24 with another quarter of excellent performance across the board. Vertex continued to reach more CF patients, delivering $2.7 billion in revenue in Q1, representing 13% growth versus the prior year period. We also began our journey of revenue diversification with the launch of CASGEVY in both sickle cell disease and beta thalassemia, in multiple regions. In our late-stage pipeline, we continue to drive programs into Phase III and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification including, one, completing our regulatory submissions for the VANZACAFTOR triple in patients with cystic fibrosis, six years and older, in both the U.S. and the EU; initiating the rolling NDA submission for VX5-48, or SUZETRIGINE, in moderate to severe acute pain; three, advancing INAXAPLIN in to the Phase III portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age ten; and four, following the successful completion of the end of Phase II regulatory meeting with the FDA, we are on track to initiate the Phase III trials of SUZETRIGINE in painful diabetic peripheral neuropathy in the second half of this year. And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX-880 trial in type one diabetes, initiated clinical development of VX-407 in polycystic kidney disease and three, achieved regulatory clearances in multiple regions, including the U.S., and initiated the Phase i/II clinical trial of VX-670 in patients with myotonic dystrophy type one.

Susie Lisa: Resenting, 13% growth versus the prior year period.

Susie Lisa: We also began our journey of revenue diversification with the launch of cash JV in both sickle cell disease and beta thalassemia in multiple regions.

Reshma Kewalramani: In our late stage pipeline, we continue to drive programs into phase three and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification, including one, completing our regulatory submissions for the Vanzikaptor triple in patients with cystic fibrosis six years and older in both the US and the EU, initiating the rolling NDA submission for VX548 or Ciceptrogene in moderate to severe acute pain. Three, advancing an axoplanin to the phase three portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age ten.

Susie Lisa: Our late stage pipeline, we continue to drive programs into phase III and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification, including one completing our regulatory submissions for the vans the captor triple in patients with cystic fibrosis six years and older.

In our late-stage pipeline, we continue to drive programs into Phase III and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification including, one, completing our regulatory submissions for the VANZACAFTOR triple in patients with cystic fibrosis, six years and older, in both the U.S. and the EU; initiating the rolling NDA submission for VX5-48, or SUZETRIGINE, in moderate to severe acute pain; three, advancing INAXAPLIN in to the Phase III portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age ten; and four, following the successful completion of the end of Phase II regulatory meeting with the FDA, we are on track to initiate the Phase III trials of SUZETRIGINE in painful diabetic peripheral neuropathy in the second half of this year. And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX-880 trial in type one diabetes, initiated clinical development of VX-407 in polycystic kidney disease and three, achieved regulatory clearances in multiple regions, including the U.S., and initiated the Phase i/II clinical trial of VX-670 in patients with myotonic dystrophy type one.

Reshma Kewalramani: and the EU, initiating the rolling NDA submission for VX-548 or suzetrigine in moderate to severe acute pain; three, advancing inaxaplin into the phase 3 portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age 10; and four, following the successful completion of the end of phase 2 regulatory meeting with the FDA, we are on track to initiate the phase 3 trials of suzetrigine in painful diabetic peripheral neuropathy in the second half of this year. And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX-880 trial in type 1 diabetes, initiated clinical development of VX-407 in polycystic kidney disease, and three, achieved regulatory clearances in multiple regions, including the US, and initiated the phase 1/2 clinical trial of VX-670 in patients with myotonic dystrophy type 1.

and the EU, initiating the rolling NDA submission for VX-548 or suzetrigine in moderate to severe acute pain; three, advancing inaxaplin into the phase 3 portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age 10; and four, following the successful completion of the end of phase 2 regulatory meeting with the FDA, we are on track to initiate the phase 3 trials of suzetrigine in painful diabetic peripheral neuropathy in the second half of this year. And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX-880 trial in type 1 diabetes, initiated clinical development of VX-407 in polycystic kidney disease, and three, achieved regulatory clearances in multiple regions, including the US, and initiated the phase 1/2 clinical trial of VX-670 in patients with myotonic dystrophy type 1.

Susie Lisa: In both the U S and the EU initiating the rolling NDA submission for VX 548, or Susceptor gene in moderate to severe acute pain three advancing <unk> into the phase III portion of its pivotal trial in April one mediated kidney disease and expanding the eligible patient population.

Down to age 10 and for following the successful completion of the end of Phase II regulatory meeting with the F. D. A we are on track to initiate the phase III trials of <unk> in painful diabetic peripheral neuropathy in the second half of this year and milestones in our early.

Reshma Kewalramani: And four, following the successful completion of the end of phase two regulatory meeting with the FDA, we are on track to initiate phase three trials of Ciceptrogene in painful diabetic peripheral neuropathy in the second half of this year. Milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX880 trial in type one diabetes, initiated clinical development of VX407 in polycystic kidney disease, and three, achieved regulatory clearances in multiple regions, including the US, and initiated the phase one, two clinical trial of VX670 in patients with myotonic dystrophy type one.

And mid stage pipeline matched this pace of progress as we resumed the VX 880 trial in type one diabetes initiated clinical development of VX 407 in polycystic kidney disease, and three achieved regulatory clearances in multiple regions, including the U S and.

And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX-880 trial in type one diabetes, initiated clinical development of VX-407 in polycystic kidney disease and three, achieved regulatory clearances in multiple regions, including the U.S., and initiated the Phase i/II clinical trial of VX-670 in patients with myotonic dystrophy type one.

Susie Lisa: The phase one two clinical trial of VX 670 in patients with my Atonic dystrophy type one.

Reshma Kewalramani: Of course, we are very excited to expand the Vertex portfolio and team with our definitive agreement to acquire Alpine Immune Sciences, announced on 10 April 2024. Alpine's lead asset, povetacicept, or POVI, is a potential best-in-class phase three ready molecule for IgA nephropathy, or IgAN, a disease with high unmet need. POVI is also a molecule that holds pipeline-in-a-product potential in a number of other serious autoimmune renal diseases and cytopenias in phase two development. We see the acquisition as just the right fit with just the right assets at just the right phase of development, where Vertex's capabilities can accelerate POVI's development in IgAN and other indications. Lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities, with particular relevance for our development programs in gentler conditioning for CASGEVY and immune evasion for our type 1 diabetes cell therapies.

Of course, we are very excited to expand the Vertex portfolio and team with our definitive agreement to acquire Alpine Immune Sciences, announced on 10 April 2024. Alpine's lead asset, povetacicept, or POVI, is a potential best-in-class phase three ready molecule for IgA nephropathy, or IgAN, a disease with high unmet need. POVI is also a molecule that holds pipeline-in-a-product potential in a number of other serious autoimmune renal diseases and cytopenias in phase two development. We see the acquisition as just the right fit with just the right assets at just the right phase of development, where Vertex's capabilities can accelerate POVI's development in IgAN and other indications. Lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities, with particular relevance for our development programs in gentler conditioning for CASGEVY and immune evasion for our type 1 diabetes cell therapies.

Reshma Kewalramani: And, of course, we are very excited to expand the Vertex portfolio and team with our definitive agreement to acquire Alpine Immune Sciences, announced on April 10th. Alpine's lead asset, POVETACICEPT or POVE, is a potential best-in-class, Phase III-ready molecule for IgA nephropathy, or IgAN, a disease with high unmet need. POVE is also a molecule that holds a pipeline in a product potential in a number of other serious autoimmune renal diseases and cytopenias in Phase II development. We see the acquisition as just the right fit, with just the right assets at just the right phase of development, where Vertex's capabilities can accelerate POVE's development in IgAN and other indications. And lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities, with particular relevance for our development programs in gentler conditioning for CASGEVY and immune evasion for our type 1 diabetes cell therapies. We are excited to begin working with the Alpine team and, together, advance POVE into Phase III in IgAN later this year.

And, of course, we are very excited to expand the Vertex portfolio and team with our definitive agreement to acquire Alpine Immune Sciences, announced on April 10th. Alpine's lead asset, POVETACICEPT or POVE, is a potential best-in-class, Phase III-ready molecule for IgA nephropathy, or IgAN, a disease with high unmet need. POVE is also a molecule that holds a pipeline in a product potential in a number of other serious autoimmune renal diseases and cytopenias in Phase II development. We see the acquisition as just the right fit, with just the right assets at just the right phase of development, where Vertex's capabilities can accelerate POVE's development in IgAN and other indications.

Susie Lisa: And of course, we are very excited to expand the vertex portfolio and team with our definitive agreement to acquire Alpine immune Sciences announced on April 10th.

Susie Lisa: Alpine lead asset Covid passes theft, or Kobe is a potential best in class phase three ready molecule for Iga nephropathy are I again, a disease with high unmet need.

Susie Lisa: He is also a molecule that holds a pipeline in a product potential in a number of other serious autoimmune renal diseases and Cytopenia is in phase two development, we see the acquisition as just the right fit with just the right assets at just the right phase of development where virtu.

Reshma Kewalramani: We see the acquisition as just the right fit with just the right assets at just the right phase of development, where Vertex's capabilities can accelerate POVI's development in IgAN and other indications. And lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities, with particular relevance for our development programs in gentler conditioning for CASGEV and immune evasion for our type 1 diabetes cell therapies. We are excited to begin working with the Alpine team and, together, advance POVI into phase 3 in IgAN later this year.

Susie Lisa: Texas capabilities can accelerate toby's development in ICANN and other indications and lastly, alpine will add protein engineering and immunotherapy expertise to bear, Texas capabilities with particular relevance for our development programs and gentler conditioning for cash gebbie and immune evasion.

And lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities, with particular relevance for our development programs in gentler conditioning for CASGEVY and immune evasion for our type 1 diabetes cell therapies. We are excited to begin working with the Alpine team and, together, advance POVE into Phase III in IgAN later this year.

Susie Lisa: Type one diabetes cell therapies, we are excited to begin working with the alpine team and together advanced Kobe into phase III in I again later this year with that overview, let me now turn to a more detailed pipeline review this quarter I'll limit my comments to the programs with the most significant.

Reshma Kewalramani: We are excited to begin working with the Alpine team and together advance POVI into Phase 3 in IgAN later this year. With that overview, let me now turn to a more detailed pipeline review. This quarter, I'll limit my comments to the programs with the most significant recent updates: cystic fibrosis, pain, type 1 diabetes, and the pending Alpine acquisition. Starting with CF, we are very pleased with the Phase 3 results of the vanzacaftor triple we announced in early February as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride. Results from the vanzacaftor pivotal program met our high expectations and were an important milestone in our progress towards this aspiration.

We are excited to begin working with the Alpine team and together advance POVI into Phase 3 in IgAN later this year. With that overview, let me now turn to a more detailed pipeline review. This quarter, I'll limit my comments to the programs with the most significant recent updates: cystic fibrosis, pain, type 1 diabetes, and the pending Alpine acquisition. Starting with CF, we are very pleased with the Phase 3 results of the vanzacaftor triple we announced in early February as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride. Results from the vanzacaftor pivotal program met our high expectations and were an important milestone in our progress towards this aspiration.

Reshma Kewalramani: With that overview, let me now turn to a more detailed pipeline review. This quarter, I'll limit my comments to the programs with the most significant recent updates: cystic fibrosis, pain, type 1 diabetes and the pending Alpine acquisition. Starting with CF, we are very pleased with the Phase III results of the VANZA Triple we announced in early February, as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride. Results from the VANZA pivotal program met our high expectations and were an important milestone in our progress towards this aspiration. Results from the two randomized studies in patients 12 and above, demonstrated VANZA was non-inferior to TRIKAFTA on lung function and superior to TRIKAFTA on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 mmol/L and below the carrier level or normal levels of sweat chloride of less than 30 mmol/L.

With that overview, let me now turn to a more detailed pipeline review. This quarter, I'll limit my comments to the programs with the most significant recent updates: cystic fibrosis, pain, type 1 diabetes and the pending Alpine acquisition. Starting with CF, we are very pleased with the Phase III results of the VANZA Triple we announced in early February, as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride. Results from the VANZA pivotal program met our high expectations and were an important milestone in our progress towards this aspiration.

Susie Lisa: Recent updates cystic fibrosis pain type, one diabetes and the pending alpine acquisition.

Susie Lisa: Starting with CF, we are very pleased with the phase III results of the vans are triple we announced in early February as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride.

Reshma Kewalramani: Results from the VANSA Pivotal Program met our high expectations and were an important milestone in our progress towards this aspiration. Results from the two randomized studies in patients twelve and above demonstrated VANSA was non-inferior to Trikafta on lung function and superior to Trikafta on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of sixty millimoles per liter and below the carrier level or normal levels of sweat chloride of less than thirty millimoles per liter.

Susie Lisa: Results from the vans, a pivotal program met our high expectations.

Susie Lisa: And we're an important milestone in our progress towards this aspiration results from the two randomized studies in patients 12, and above demonstrated vanda was non inferior to try CAFTA on lung function and superior to try character on sweat chloride, including asthma.

Reshma Kewalramani: Results from the two randomized studies in patients 12 and above demonstrated vanzacaftor was non-inferior to TRIKAFTA on lung function and superior to TRIKAFTA on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 millimoles per liter and below the carrier level or normal levels of sweat chloride of less than 30 millimoles per liter. Included in the pivotal program was the Ridgeline study in patients 6 to 11 years of age. To underscore the potential impact of vanzacaftor, consider 95% of patients age 6 to 11 in this study achieved sweat chloride levels below the level of diagnosis for cystic fibrosis, and more than half reached sweat chloride levels considered to be in the normal or carrier level range of sweat chloride.

Results from the two randomized studies in patients 12 and above demonstrated vanzacaftor was non-inferior to TRIKAFTA on lung function and superior to TRIKAFTA on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 millimoles per liter and below the carrier level or normal levels of sweat chloride of less than 30 millimoles per liter. Included in the pivotal program was the Ridgeline study in patients 6 to 11 years of age. To underscore the potential impact of vanzacaftor, consider 95% of patients age 6 to 11 in this study achieved sweat chloride levels below the level of diagnosis for cystic fibrosis, and more than half reached sweat chloride levels considered to be in the normal or carrier level range of sweat chloride.

Results from the two randomized studies in patients 12 and above, demonstrated VANZA was non-inferior to TRIKAFTA on lung function and superior to TRIKAFTA on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 mmol/L and below the carrier level or normal levels of sweat chloride of less than 30 mmol/L. Included in the pivotal program was the RIDGELINE study in patients 6 to 11 years of age. To underscore the potential impact of VANZACAFTOR, consider, 95% of patients age 6 to 11 in this study achieved sweat chloride levels below the level of diagnosis for cystic fibrosis and more than half reached sweat chloride levels considered to be in the normal or carrier level range of sweat chloride.

Susie Lisa: Measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 millimole per liter and below the carrier level or normal levels of sweat chloride of less than 30 millimole per liter.

Reshma Kewalramani: Included in the Pivotal program was the Ridgeline study in patients 6 to 11 years of age. To underscore the potential impact of vancicaptor, consider 95% of patients age 6 to 11 in this study achieved sweat chloride levels below the level of diagnosis for cystic fibrosis, and more than half reached sweat chloride levels considered to be in the normal or carrier level range of sweat chloride.

Susie Lisa: Included in the pivotal program was the Ridge line study in patients six to 11 years of age to underscore the potential impact of vans. The capture consider 95% of patients age six to 11 in this study achieved sweat chloride levels Bill.

Susie Lisa: Although the level of diagnosis for cystic fibrosis.

Susie Lisa: And more than half reach sweat chloride levels considered to be in the normal or carrier level range of sweat chloride.

Reshma Kewalramani: We believe these results indicate that vanzacaftor could set a new standard in the treatment of CF. To round out the profile of the vanzacaftor triple, it's important to note that the therapy also offers the convenience of once-daily dosing and a substantially lower royalty burden. With these results in hand, we've been working rapidly to compile the regulatory marketing applications, and I am pleased to share that we have completed submissions in the US and EU for patients ages six years and older, ahead of our mid-year goal. In the US, we use one of our priority review vouchers, which, if the filing is accepted, provides an expedited six-month review versus the standard 10-month review timeline. We're also on track to complete submissions in the UK, Canada, Australia, New Zealand, and Switzerland by mid-year.

We believe these results indicate that vanzacaftor could set a new standard in the treatment of CF. To round out the profile of the vanzacaftor triple, it's important to note that the therapy also offers the convenience of once-daily dosing and a substantially lower royalty burden. With these results in hand, we've been working rapidly to compile the regulatory marketing applications, and I am pleased to share that we have completed submissions in the US and EU for patients ages six years and older, ahead of our mid-year goal. In the US, we use one of our priority review vouchers, which, if the filing is accepted, provides an expedited six-month review versus the standard 10-month review timeline. We're also on track to complete submissions in the UK, Canada, Australia, New Zealand, and Switzerland by mid-year.

Reshma Kewalramani: We believe these results indicate that VANZA could set a new standard in the treatment of CF. To round out the profile of the VANZACAFTOR Triple, it's important to note that the therapy also offers the convenience of once-daily dosing and a substantially lower royalty burden. With these results in hand, we've been working rapidly to compile the regulatory marketing applications and I'm pleased to share that we have completed submissions in the U.S. and EU for patients ages 6 years and older ahead of our mid-year goal. In the U.S., we used one of our priority review vouchers, which, if the filing is accepted, provides an expedited 6-month review versus the standard 10-month review timeline.

Susie Lisa: We believe these results indicate that vans that could set a new standard in the treatment of CF.

Susie Lisa: To round out the profile of the vans the captor triple its important to note that the therapy also offers the convenience of once daily dosing and a substantially lower royalty burden with these results in hand, we've been working rapidly to compile the regulatory marketing applications and I am pleased to share that we have completed submissions in the U S.

S and EU for patients ages six years and older are ahead of our mid year goal in the U S. We use one of our priority review vouchers, which if the filing is accepted provides an expedited six month review versus the standard 10 month review timeline. We're also on.

Reshma Kewalramani: We're also on track to complete submissions in the UK, Canada, Australia, New Zealand and Switzerland by mid-year. I'll close on CF with VX-522, our CFTR mRNA therapy, in development with our partners at Moderna for the treatment of the more than 5,000 people with CF who do not make any CFTR protein and therefore, cannot benefit from CFTR modulators. We continue to enroll in the multiple ascending dose portion of the study and expect data late in 2024 or early 2025.

Susie Lisa: Track to complete submissions in the U K, Canada, Australia, New Zealand and Switzerland by mid year I'll close on CF with VX five two to our C. F. T. R mrna therapy in development with our partners that Madonna the treatment of the more than 5000 people with CF.

Reshma Kewalramani: I'll close on CF with VX-522, our CFTR mRNA therapy in development with our partners at Moderna for the treatment of the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. We continue to enroll in the multiple ascending dose portion of the study and expect data late in 2024 or early 2025. Moving to the pain program and suzetrigine, our novel, highly selective NaV1.8 pain signal inhibitor. Suzetrigine offers the compelling combination of both strong safety and strong efficacy, with the potential to treat moderate to severe pain across multiple settings of care. In acute pain, suzetrigine has secured fast-track and breakthrough therapy designations, and we were very pleased that the FDA granted us a rolling NDA submission.

I'll close on CF with VX-522, our CFTR mRNA therapy in development with our partners at Moderna for the treatment of the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. We continue to enroll in the multiple ascending dose portion of the study and expect data late in 2024 or early 2025. Moving to the pain program and suzetrigine, our novel, highly selective NaV1.8 pain signal inhibitor. Suzetrigine offers the compelling combination of both strong safety and strong efficacy, with the potential to treat moderate to severe pain across multiple settings of care. In acute pain, suzetrigine has secured fast-track and breakthrough therapy designations, and we were very pleased that the FDA granted us a rolling NDA submission.

Susie Lisa: Who do not make any see FTR protein and therefore cannot benefit from CF TR modulators, we continue to enroll in the multiple ascending dose portion of this study and expect data late in 'twenty 'twenty four or early 2025.

Reshma Kewalramani: Moving to the pain program and SUZETRIGINE, our novel, highly selective NAV1.8 pain signal inhibitor. SUZETRIGINE offers a compelling combination of both strong safety and strong efficacy, with the potential to treat moderate to severe pain across multiple settings of care. In acute pain, SUZETRIGINE has secured fast-track and breakthrough therapy designations and we were very pleased that the FDA granted us a rolling NDA submission. I'm also pleased to share that multiple modules have already been submitted and we are on track to complete the submission this quarter. Consistent with our serial innovation strategy, the next asset in our acute pain pipeline is VX-993. We recently received IND clearance for the intravenous formulation of VX-993 and have already started the Phase 1 trial.

Moving to the pain program and SUZETRIGINE, our novel, highly selective NaV1.8 pain signal inhibitor. SUZETRIGINE offers a compelling combination of both strong safety and strong efficacy, with the potential to treat moderate to severe pain across multiple settings of care. In acute pain, SUZETRIGINE has secured fast-track and breakthrough therapy designations and we were very pleased that the FDA granted us a rolling NDA submission. I'm also pleased to share that multiple modules have already been submitted and we are on track to complete the submission this quarter.

Susie Lisa: Moving to the pain program and says cetera gene are novel highly selective NAV 1.8 pain signal inhibitor.

Susie Lisa: Does that <unk> offers a compelling combination of both strong safety and strong efficacy with the potential to treat moderate to severe pain across multiple settings of care.

Reshma Kewalramani: In acute pain, Ciceptrogene has secured fast-track and breakthrough therapy designations, and we were very pleased that the FDA granted us a rolling NDA submission. I'm also pleased to share that multiple modules have already been submitted, and we are on track to complete the submission this quarter. Consistent with our serial innovation strategy, the next asset in our QPANE pipeline is VX993. We recently received IND clearance for the intravenous formulation of VX993 and have already started the Phase 1 trial.

In acute pain Susceptor gene has secured fast track and breakthrough therapy designations and we were very pleased that the FDA granted us a rolling NDA submission.

Reshma Kewalramani: I'm also pleased to share that multiple modules have already been submitted, and we are on track to complete the submission this quarter. Consistent with our serial innovation strategy, the next asset in our acute pain pipeline is VX-993. We recently received IND clearance for the intravenous formulation of VX-993 and have already started the phase 1 trial. We're also planning a VX-993 oral formulation phase 2 study in acute pain, which we expect to initiate later this year. Beyond suzetrigine and VX-993, we continue to innovate in the NaV1.8 space and are also making strong progress preclinically with our NaV1.7 pain signal inhibition program that may be used alone or in combination with suzetrigine or other NaV1.8 inhibitors.

I'm also pleased to share that multiple modules have already been submitted, and we are on track to complete the submission this quarter. Consistent with our serial innovation strategy, the next asset in our acute pain pipeline is VX-993. We recently received IND clearance for the intravenous formulation of VX-993 and have already started the phase 1 trial. We're also planning a VX-993 oral formulation phase 2 study in acute pain, which we expect to initiate later this year. Beyond suzetrigine and VX-993, we continue to innovate in the NaV1.8 space and are also making strong progress preclinically with our NaV1.7 pain signal inhibition program that may be used alone or in combination with suzetrigine or other NaV1.8 inhibitors.

Susie Lisa: I'm also pleased to share that multiple modules have already been submitted and we are on track to complete the submission this quarter.

Consistent with our serial innovation strategy, the next asset in our acute pain pipeline is VX-993. We recently received IND clearance for the intravenous formulation of VX-993 and have already started the Phase 1 trial. We're also planning a VX-993 oral formulation Phase 2 study in acute pain, which we expect to initiate later this year. Beyond SUZETRIGINE and VX-993, we continue to innovate in the NAV1.8 space and are also making strong progress pre-clinically with our NAV1.7 pain signal inhibition program, that may be used alone or in combination with SUZETRIGINE or other NAV1.8 inhibitors. In peripheral neuropathic pain, or PNP, we are very pleased with the outcomes from the recently completed End of Phase II meeting with the FDA and are excited to begin the pivotal program for SUZETRIGINE in painful diabetic peripheral neuropathy, or DPN, in the second half of this year. The program will consist of two randomized sister studies of approximately 1000 patients each, with three arms in each study: a SUZETRIGINE 70mg arm once daily, a placebo arm and a PREGABALIN or LYRICA arm. The efficacy endpoints are based on the change from baseline to week 12.

Susie Lisa: Insistent with our serial innovation strategy. The next asset in our acute pain pipeline is VX 993, we recently received IND clearance for the intravenous formulation of VX 993, and have already started the phase one trial. We're also planning a VX 993 oral.

Reshma Kewalramani: We're also planning a VX993 oral formulation Phase 2 study in a QPANE, which we expect to initiate later this year. Beyond Cicetrogene and VX993, we continue to innovate in the NAV1.8 space and are also making strong progress preclinically with our NAV1.7 pain signal inhibition program that may be used alone or in combination with Cicetrogene or other NAV1.8 inhibitors. In Peripheral Neuropathic Pain, or PNP, we are very pleased with the outcomes from the recently completed End of Phase II meeting with the FDA and are excited to begin the pivotal program for Ciceptrogene in painful diabetic peripheral neuropathy, or DPN, in the second half of this year.

Susie Lisa: Asian Phase two study in acute pain, which we expect to initiate later this year.

Susie Lisa: Beyond etc, Gene and VX 993, we continue to innovate and then NAV 1.8 space and are also making strong progress pre clinically with our NAV. One seven pain signal inhibition program that may be used alone or in combination with cetera gene or other NAV 1.8 inhibitors.

Reshma Kewalramani: In peripheral neuropathic pain, or PNP, we are very pleased with the outcomes from the recently completed end of Phase 2 meeting with the FDA and are excited to begin the pivotal program for suzetrigine in painful diabetic peripheral neuropathy, or DPN, in the second half of this year. The program will consist of two randomized sister studies of approximately 1,000 patients each, with three arms in each study: a suzetrigine 70mg arm once daily, a placebo arm, and a pregabalin or Lyrica arm. The efficacy endpoints are based on the change from baseline to week 12. The primary endpoint is the comparison of suzetrigine versus placebo in the weekly average of the daily pain intensity score, or NPRS.

In peripheral neuropathic pain, or PNP, we are very pleased with the outcomes from the recently completed end of Phase 2 meeting with the FDA and are excited to begin the pivotal program for suzetrigine in painful diabetic peripheral neuropathy, or DPN, in the second half of this year. The program will consist of two randomized sister studies of approximately 1,000 patients each, with three arms in each study: a suzetrigine 70mg arm once daily, a placebo arm, and a pregabalin or Lyrica arm. The efficacy endpoints are based on the change from baseline to week 12. The primary endpoint is the comparison of suzetrigine versus placebo in the weekly average of the daily pain intensity score, or NPRS.

In peripheral neuropathic pain, or PNP, we are very pleased with the outcomes from the recently completed End of Phase II meeting with the FDA and are excited to begin the pivotal program for SUZETRIGINE in painful diabetic peripheral neuropathy, or DPN, in the second half of this year. The program will consist of two randomized sister studies of approximately 1000 patients each, with three arms in each study: a SUZETRIGINE 70mg arm once daily, a placebo arm and a PREGABALIN or LYRICA arm. The efficacy endpoints are based on the change from baseline to week 12.

Susie Lisa: And peripheral neuropathic pain or P. M. P. We are very pleased with the outcomes from the recently completed end of phase two meeting with the FDA and are excited to begin the pivotal program for Susceptor gene in painful diabetic peripheral neuropathy or D. P. M in the second half.

Susie Lisa: Of this year the.

Reshma Kewalramani: The program will consist of two randomized sister studies of approximately 1000 patients each with three arms in each study, a cecetrogene 70 milligram arm once daily, a placebo arm, and a pregabalin or Lyrica arm. The efficacy endpoints are based on the change from baseline to week 12.

Susie Lisa: The program will consist of two randomized sister studies of approximately 1000 patients each with three arms in each study.

Susie Lisa: Ah cetera, Jean 70 milligram arm once daily a placebo arm and a pregabalin or lyrica arm. The efficacy end points are based on the change from baseline to week 12.

Reshma Kewalramani: The primary endpoint is the comparison of SUZETRIGINE versus placebo in the weekly average of the daily pain intensity score or NPRS. The first key secondary endpoint will test for non-inferiority of SUZETRIGINE to PREGABALIN on the same NPRS pain score and if successful, we will test for superiority. And finally, the second key secondary is quality of life measures versus placebo. In order to evaluate the long-term safety and effectiveness of SUZETRIGINE, a subset of patients completing the 12-week study will have the opportunity to roll into a 52-week open-label extension study.

Susie Lisa: Primary endpoint is the comparison of cetera gene versus placebo in the weekly average of the daily pain intensity score or N. P. R. S.

Reshma Kewalramani: The first key secondary endpoint will test for non-inferiority of suzetrigine to pregabalin on the same NPRS pain score, and if successful, we will test for superiority. Finally, the second key secondary is quality of life measures versus placebo. In order to evaluate the long-term safety and effectiveness of suzetrigine, a subset of patients completing the 12-week study will have the opportunity to roll into a 52-week open-label extension study. Our goal continues to be a broad peripheral neuropathic pain label, and in support of this goal, we're also studying suzetrigine in lumbosacral radiculopathy, or LSR, a PNP condition for which there are no specifically indicated or approved treatments. LSR accounts for approximately 40% of all PNP patients and, together with DPN, make up more than 60% of the PNP segment.

The first key secondary endpoint will test for non-inferiority of suzetrigine to pregabalin on the same NPRS pain score, and if successful, we will test for superiority. Finally, the second key secondary is quality of life measures versus placebo. In order to evaluate the long-term safety and effectiveness of suzetrigine, a subset of patients completing the 12-week study will have the opportunity to roll into a 52-week open-label extension study. Our goal continues to be a broad peripheral neuropathic pain label, and in support of this goal, we're also studying suzetrigine in lumbosacral radiculopathy, or LSR, a PNP condition for which there are no specifically indicated or approved treatments. LSR accounts for approximately 40% of all PNP patients and, together with DPN, make up more than 60% of the PNP segment.

Susie Lisa: The first key secondary endpoint will test for non inferiority of CIS cetera gene two pregabalin on the same N. P. R. S pain score and if successful we will test for superiority.

Susie Lisa: And finally, the second key secondary is quality of life measures versus placebo.

Susie Lisa: In order to evaluate the long term safety and effectiveness of cetera gene a subset of patients completing the 12 week study will have the opportunity to roll into a 52 week open label extension study.

Reshma Kewalramani: Our goal continues to be a broad peripheral neuropathic pain label and in support of this goal, we're also studying SUZETRIGINE in lumbosacral radiculopathy or LSR, a PNP condition for which there are no specifically indicated or approved treatments. LSR accounts for approximately 40% of all PNP patients and together with DPN, makes up more than 60% of the PNP segment. We are continuing to enroll and dose our Phase 2 study of SUZETRIGINE in LSR and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions. Turning now, to type 1 diabetes. VX-880 is a stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events.

Our goal continues to be a broad peripheral neuropathic pain label and in support of this goal, we're also studying SUZETRIGINE in lumbosacral radiculopathy or LSR, a PNP condition for which there are no specifically indicated or approved treatments. LSR accounts for approximately 40% of all PNP patients and together with DPN, makes up more than 60% of the PNP segment. We are continuing to enroll and dose our Phase 2 study of SUZETRIGINE in LSR and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions.

Susie Lisa: Our goal continues to be a broad peripheral neuropathic pain label and in support of the skull. We're also studying <unk> in lumbosacral radiculopathy or L. S. R. A T N P condition for which there are no specifically indicated or approved treatments Alice our accounts were approximately.

Reshma Kewalramani: LSR accounts for approximately 40% of all PNP patients and, together with DPN, makes up more than 60% of the PNP segment. We are continuing to enroll and dose our Phase 2 study of cicetrogene in LSR, and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic, and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions. Now, turning to type 1 diabetes. VX880 is a stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events.

Susie Lisa: <unk>, 40% of all P. M P patients and together with D. P. N makeup more than 60% of the P. M. P segment, we are continuing to enroll and dose our phase II study of <unk> in LSI and I am pleased to share that the study is on track to complete enrollment by the end of.

We are continuing to enroll and dose our Phase 2 study of SUZETRIGINE in LSR and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions.

We are continuing to enroll and dose our Phase II study of SUZETRIGINE in LSR and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions.

Reshma Kewalramani: We are continuing to enroll and dose our phase 2 study of suzetrigine in LSR, and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transform the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic, and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions. Turning now to type 1 diabetes, VX-880 is our stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events. I'm pleased to share that after data review by the independent data monitoring committee, the VX-880 study has resumed. Parts A, B, and C of the global 17-patient study are fully enrolled, and we expect to complete dosing soon.

We are continuing to enroll and dose our phase 2 study of suzetrigine in LSR, and I'm pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transform the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic, and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions. Turning now to type 1 diabetes, VX-880 is our stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events. I'm pleased to share that after data review by the independent data monitoring committee, the VX-880 study has resumed. Parts A, B, and C of the global 17-patient study are fully enrolled, and we expect to complete dosing soon.

Susie Lisa: This year.

Susie Lisa: Just as we transform the treatment of CF. We believe we have the potential to transform the treatment of pain, both acute and neuropathic and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions.

Susie Lisa: Turning now to type one diabetes VX 880 is a stem cell derived fully differentiated islet cell therapy for patients with T. One D and impaired hypoglycemic awareness, who suffer from severe hypoglycemic events.

Turning now, to type 1 diabetes. VX-880 is a stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events. I'm pleased to share that after data review by the Independent Data Monitoring Committee, the VX-880 study has resumed. Parts A, B and C of the global 17-patient study are fully enrolled and we expect to complete dosing soon. We look forward to sharing updated data this June at the American Diabetes Association annual meeting. VX-264, the next asset in our T1D program, is our cells plus device program. Using the same VX-880 cells, which have already demonstrated efficacy, VX-264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device.

Reshma Kewalramani: I'm pleased to share that after data review by the Independent Data Monitoring Committee, the VX-880 study has resumed. Parts A, B, and C of the global 17-patient study are fully enrolled, and we expect to complete dosing soon. We look forward to sharing updated data this June at the American Diabetes Association annual meeting. VX264, the next asset in our T1D program, is our Salve Plus device program. Using the same VX880 cells, which have already demonstrated efficacy, VX264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device.

Susie Lisa: I am pleased to share that after data review by the independent data monitoring Committee. The VX 880 study has resumed part a b and C of the global 17 patient study are fully enrolled and we expect to complete dosing soon.

Reshma Kewalramani: We look forward to sharing updated data this June at the American Diabetes Association annual meeting. VX-264, the next asset in our T1D program, is our cell plus device program. Using the same VX-880 cells, which have already demonstrated efficacy, VX-264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device. This phase 1/2 study has completed part A, and part B is underway. Lastly, our hypoimmune program, which aims to evade the immune system by introducing certain edits into the same VX-880 cells, is yet another approach to avoiding the use of immunosuppressives. This program continues to advance in preclinical development. I'll conclude with a few comments on povetacicept, the lead asset from our pending acquisition of Alpine Immune Sciences.

We look forward to sharing updated data this June at the American Diabetes Association annual meeting. VX-264, the next asset in our T1D program, is our cell plus device program. Using the same VX-880 cells, which have already demonstrated efficacy, VX-264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device. This phase 1/2 study has completed part A, and part B is underway. Lastly, our hypoimmune program, which aims to evade the immune system by introducing certain edits into the same VX-880 cells, is yet another approach to avoiding the use of immunosuppressives. This program continues to advance in preclinical development. I'll conclude with a few comments on povetacicept, the lead asset from our pending acquisition of Alpine Immune Sciences.

We look forward to sharing updated data. This June at the American Diabetes Association annual meeting.

VX-264, the next asset in our T1D program, is our cells plus device program. Using the same VX-880 cells, which have already demonstrated efficacy, VX-264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device. This Phase 1/2 study has completed Part A and Part B is underway. Lastly, our Hypoimmune program, which aims to evade the immune system by introducing certain edits into the same VX-880 cells, is yet another approach to avoiding the use of immunosuppressives. This program continues to advance in pre-clinical development. I'll conclude with a few comments on POVETACICEPT, the lead asset from our pending acquisition of Alpine Immune Sciences. We are excited about the potential of POVETACICEPT across multiple dimensions, including pre-clinically with its high affinity and potency against both APRIL and BAFF pathways in pre-clinical assays, as well as high efficacy in cell and animal models of B cell-driven diseases

Susie Lisa: VX two six for the next asset in our T. One D program is our south plus device program.

Susie Lisa: Using the same we exited 80 cells, which have already demonstrated efficacy. The X 264 is designed to eliminate the need for immuno suppression by shielding the cells from the immune system in the proprietary device. This phase one two study has completed part a and part B is under.

Reshma Kewalramani: This Phase 1-2 study has completed Part A, and Part B is underway. Lastly, our hypoimmune program, which aims to evade the immune system by introducing certain edits into the same VX880 cells, is yet another approach to avoiding the use of immunosuppressives. This program continues to advance in preclinical development. I'll conclude with a few comments on Povitacicept, the lead asset from our pending acquisition of Alpine Immune Sciences. We are excited about the potential of Povitacicept across multiple dimensions, including preclinical with its high affinity and potency against both APRIL and BAS pathways in preclinical assays, as well as high efficacy in cell and animal models of B cell driven diseases

Susie Lisa: Way lastly, our hyper immune program, which aims to evade the immune system by introducing certain edits into the same VX 880 cells is yet another approach to avoiding the use of immunosuppressive. This program continues to advance in preclinical development.

Reshma Kewalramani: This program continues to advance in preclinical development. I'll conclude with a few comments on Povitacicept, the lead asset from our pending acquisition of Alpine Immune Sciences. We are excited about the potential of Povitacicept across multiple dimensions, including preclinical with its high affinity and potency against both APRIL and BAS pathways in preclinical assays, as well as high efficacy in cell and animal models of B cell driven diseases

I'll conclude with a few comments on POVETACICEPT, the lead asset from our pending acquisition of Alpine Immune Sciences. We are excited about the potential of POVETACICEPT across multiple dimensions, including pre-clinically with its high affinity and potency against both APRIL and BAFF pathways in pre-clinical assays, as well as high efficacy in cell and animal models of B cell-driven diseases; clinically, with patient data in IgAN through Phase II that look potentially best-in-class in proteinuria, in hematuria, GFR and clinical remission; better drug-like properties with direct patient benefit, including once every four-week dosing subcutaneously with low injection volume; a good safety and tolerability profile; the broadest development plan in the field and a robust IP portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the Phase III study in IgAN and readouts from the ongoing RUBY-3 and RUBY-4 basket studies in autoimmune renal diseases and cytopenias, respectively. With that, I'll turn it over to Stuart for a commercial overview. Thanks, Reshma.

Susie Lisa: I'll conclude with a few comments on Covid task receptor the lead asset from our pending acquisition of Alpine immune Sciences. We are excited about the potential of povitica set across multiple dimensions, including pre clinically with its high affinity and potency against both April and.

Reshma Kewalramani: We are excited about the potential of povetacicept across multiple dimensions, including preclinically with its high affinity and potency against both APRIL and BAFF pathways in preclinical assays, as well as high efficacy in cell and animal models of B cell-driven diseases. Clinically, with patient data in IgAN through phase 2 that look potentially best in class in proteinuria, in hematuria, GFR, and clinical remission, better drug-like properties with direct patient benefit, including once-every-four-week dosing subcutaneously with low injection volume, a good safety and tolerability profile, the broadest development plan in the field, and a robust IP portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the phase 3 study in IgAN and readouts from the ongoing RUBI3 and RUBI4 basket studies in autoimmune renal diseases and cytopenias, respectively. With that, I'll turn it over to Stuart for a commercial overview. Thanks, Reshma.

We are excited about the potential of povetacicept across multiple dimensions, including preclinically with its high affinity and potency against both APRIL and BAFF pathways in preclinical assays, as well as high efficacy in cell and animal models of B cell-driven diseases. Clinically, with patient data in IgAN through phase 2 that look potentially best in class in proteinuria, in hematuria, GFR, and clinical remission, better drug-like properties with direct patient benefit, including once-every-four-week dosing subcutaneously with low injection volume, a good safety and tolerability profile, the broadest development plan in the field, and a robust IP portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the phase 3 study in IgAN and readouts from the ongoing RUBI3 and RUBI4 basket studies in autoimmune renal diseases and cytopenias, respectively. With that, I'll turn it over to Stuart for a commercial overview.

Susie Lisa: Bass pathways in preclinical assays as well as high efficacy in cell and animal models of B cell driven diseases Clint.

Reshma Kewalramani: Clinically, with patient data in IGAN through Phase II that look potentially best in class in peritoneuria, in hematuria, GFR, and clinical remission. Better drug-like properties with direct patient benefit, including once every four-week dosing subcutaneously with low injection volume. A good safety and tolerability profile, the broadest development plan in the field, and a robust IP portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the Phase 3 study in IgAN and readouts from the ongoing Ruby 3 and Ruby 4 basket studies in autoimmune renal diseases and cytopenias, respectively. With that, I'll turn it over to Stuart for a commercial overview. Thanks, Reshma.

Susie Lisa: Clinically with patient data in I again through phase two that look potentially best in class in proteinuria, and hematuria GFR and clinical remission.

Susie Lisa: Better drug like properties with direct patient benefit, including once every four week dosing subcutaneously with low injection volume a good safety and Tolerability profile.

The broadest development plan in the field and a robust IP portfolio.

portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the Phase III study in IgAN and readouts from the ongoing RUBY-3 and RUBY-4 basket studies in autoimmune renal diseases and cytopenias, respectively.

portfolio.

Important upcoming POVI milestones in the second half of this year include initiation of the Phase III study in IgAN and readouts from the ongoing RUBY-3 and RUBY-4 basket studies in autoimmune renal diseases and cytopenias, respectively.

Important upcoming Povey milestones in the second half of this year include initiation of the phase III study in IGN and Readouts from the ongoing Ruby three and Ruby for basket studies in autoimmune renal diseases, and Cytopenia is respectively with that.

With that, I'll turn it over to Stuart for a commercial overview.

Susie Lisa: I'll turn it over to Stuart for a commercial overview.

Stuart Arbuckle: Thanks, Reshma. I'll first discuss CF, and then, as we're entering a new era of commercial diversification, 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 continue to grow the number of eligible patients receiving our CFTR modulators. Q1 year-over-year US growth was driven by continued strong performance of TRIKAFTA, including in patients ages two to five years old, following the approval in this patient population in April of last year. Outside the US, we also saw growth this quarter driven by the rollout of KAFTRIO in the EU in patients ages two to five, following approval in this age group in November 2023, and we will continue to drive access and uptake in more EU countries over the course of the year.

Stuart A. Arbuckle: Thanks, Reshma. I'll first discuss CF and then, as we're entering a new era of commercial diversification, 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 continue to grow the number of eligible patients receiving our CFTR modulators. First quarter year-over-year U.S. growth was driven by continued strong performance of TRIKAFTA, including in patients ages 2 to 5 years old, following the approval in this patient population in April of last year.

Stuart A. Arbuckle: Thanks, Russia, I'll first discuss C. F and then as we're entering a new era of commercial diversification provides some highlights of the ongoing cash Chevy launch and the outlook for that gene in acute pain.

Reshma Kewalramani: I'll first discuss CF, and then, as we're entering a new era of commercial diversification, 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 continue to grow the number of eligible patients receiving our CFTR modulators. Q1 year-over-year US growth was driven by continued strong performance of TRIKAFTA, including in patients ages two to five years old, following the approval in this patient population in April of last year. Outside the US, we also saw growth this quarter driven by the rollout of KAFTRIO in the EU in patients ages two to five, following approval in this age group in November 2023, and we will continue to drive access and uptake in more EU countries over the course of the year.

Stuart A. Arbuckle: I'll first discuss CF and then, as we're entering a new era of commercial diversification, provide some highlights of the ongoing Castievi launch and the outlook for cizetrogene in acute pain. As Reshma noted, we once again delivered strong results in CF as we continue to grow the number of eligible patients receiving our CFTR modulator. First quarter year-over-year U.S. growth was driven by continued strong performance of Trikafta in patients ages two to five years old, following its approval in this patient population in April of last year.

Stuart A. Arbuckle: As Rushmore noted we once again delivered strong results in CF as we continue to grow the number of eligible patients receiving Aussie FTR modulators.

Stuart A. Arbuckle: First quarter year over year U S growth was driven by continued strong performance of Tri CAFTA, including in patients ages two to five years old following the approval in this patient population in April of last year.

Stuart A. Arbuckle: Outside the U.S., we also saw growth this quarter driven by the rollout of KAFTRIO in the EU in patients ages 2 to 5, following approval in this age group in November 2023. And we will continue to drive access and uptake in more EU countries over the course of the year. Our outlook in CF is bright, in the short, medium and long-term. We will drive growth in the near-term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval for KALYDECO in patients between the ages of 1 month up to 4 months old. We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the U.S. and Canada later this year. And Brazil is a good example of a new geography.

Outside the U.S., we also saw growth this quarter driven by the rollout of KAFTRIO in the EU in patients ages 2 to 5, following approval in this age group in November 2023. And we will continue to drive access and uptake in more EU countries over the course of the year. Our outlook in CF is bright, in the short, medium and long-term. We will drive growth in the near-term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval for KALYDECO in patients between the ages of 1 month up to 4 months old. We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the U.S. and Canada later this year. And Brazil is a good example of a new geography.

Stuart A. Arbuckle: Outside the U S. We also saw growth this quarter driven by the rollout of Caf trio in the EU in patients ages two to five following approval in this age group in November 2023, and we will continue to drive access and uptake in more EU countries over the course of the year.

Reshma Kewalramani: Our outlook in CF is bright in the short, medium, and long term. We will drive growth in the near term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval of KALYDECO in patients between the ages of one month up to four months old. We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the US and Canada later this year. And Brazil is a good example of a new geography. Up to now, some patients in Brazil have been able to benefit from our CFTR modulators through named patient sales. We recently secured government reimbursement for TRIKAFTA in ages six plus and are in the process of launching TRIKAFTA for all eligible patients there.

Our outlook in CF is bright in the short, medium, and long term. We will drive growth in the near term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval of KALYDECO in patients between the ages of one month up to four months old. We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the US and Canada later this year. And Brazil is a good example of a new geography. Up to now, some patients in Brazil have been able to benefit from our CFTR modulators through named patient sales. We recently secured government reimbursement for TRIKAFTA in ages six plus and are in the process of launching TRIKAFTA for all eligible patients there.

Stuart A. Arbuckle: Our outlook in CF is bright in the short medium and long term, we will drive growth in the near term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval of Kalydeco in patients between the ages of one month up to four months old we also expect regulatory.

Stuart A. Arbuckle: We will drive growth in the near term by reaching more eligible patients, including younger age groups and additional geographies. For example, we recently received EU approval for Kalydeco in patients between the ages of one month and four months old. We also expect regulatory approvals for additional rare genotypes for Caftreo in the EU and Trikafta in the U.S. and Canada later this year. And Brazil is a good example of a new geography.

We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the U.S. and Canada later this year. And Brazil is a good example of a new geography. Up to now, some patients in Brazil have been able to benefit from our CFTR modulators through named patient sales. We recently secured government reimbursement for TRIKAFTA in ages 6-plus and are in the process of launching TRIKAFTA for all eligible patients there. We will then look to drive further CF growth over the medium-term with the VANZACAFTOR Triple combination launch as many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing. And there are also more than 6,000 patients who have discontinued one of our current CFTR modulators, who may be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the VANZACAFTOR Triple. Our launch preparations are well underway, including pre-approval information exchange with payers and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF. In the longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators.

We also expect regulatory approvals for additional rare genotypes for KAFTRIO in the EU and TRIKAFTA in the U.S. and Canada later this year. And Brazil is a good example of a new geography.

Stuart A. Arbuckle: Approvals for additional Regina types for Caf trio in the EU and try catheter in the U S and Canada later this year and Brazil is a good example of a new geography up to now some patients from Brazil have been able to benefit from Aussie FTR modulators through named patient sales. We recently secured government reimbursement for Tri CAFTA in Asia.

Stuart A. Arbuckle: Up to now, some patients in Brazil have been able to benefit from our CFTR modulators through named patient sales. We recently secured government reimbursement for Trikafta in ages six plus and are in the process of launching Trikafta for all eligible patients there. We will then look to drive further CF growth over the medium term with the vanzikaftor triple combination launch.

Up to now, some patients in Brazil have been able to benefit from our CFTR modulators through named patient sales. We recently secured government reimbursement for TRIKAFTA in ages 6-plus and are in the process of launching TRIKAFTA for all eligible patients there. We will then look to drive further CF growth over the medium-term with the VANZACAFTOR Triple combination launch as many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing. And there are also more than 6,000 patients who have discontinued one of our current CFTR modulators, who may be interested in a new treatment option.

Stuart A. Arbuckle: Six plus and are in the process of launching truck after for all eligible patients there.

Reshma Kewalramani: We will then look to drive further CF growth over the medium term with the Vanzacaftor triple combination launch, as many existing TRICAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing. There are also more than 6,000 patients who have discontinued one of our current CFTR modulators who may be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the Vanzacaftor triple. Our launch preparations are well underway, including pre-approval information exchange with payers, and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF.

We will then look to drive further CF growth over the medium term with the Vanzacaftor triple combination launch, as many existing TRICAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing. There are also more than 6,000 patients who have discontinued one of our current CFTR modulators who may be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the Vanzacaftor triple. Our launch preparations are well underway, including pre-approval information exchange with payers, and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF.

Stuart A. Arbuckle: We will then look to drive further CF growth over the medium term with the vans a catheter triple combination launch as many existing Troy catheter patients may seek to achieve even greater levels of CFT our function with 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.

Stuart A. Arbuckle: As many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing and there are also more than 6,000 patients who have discontinued one of our current CFTR modulators, who may be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the VANZACAFTOR Triple. Our launch preparations are well underway, including pre-approval information exchange with payers and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF. In the longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators. Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia.

As many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function with the added convenience of once-daily dosing and there are also more than 6,000 patients who have discontinued one of our current CFTR modulators, who may be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the VANZACAFTOR Triple. Our launch preparations are well underway, including pre-approval information exchange with payers and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF. In the longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators.

Stuart A. Arbuckle: May be interested in a new treatment option. Furthermore, there are 31 additional rare mutations not previously responsive to our other CFT. Our modulators that are responsive to the Venza CAFTA triple our launch preparations are well underway, including preapproval information exchange with payers and we are both encouraged by our interactions to date.

Furthermore, there are 31 additional rare mutations not previously responsive to our other CFTR modulators that are responsive to the VANZACAFTOR Triple. Our launch preparations are well underway, including pre-approval information exchange with payers and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF. Longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators.

Stuart A. Arbuckle: Our launch preparations are well underway, including pre-approval information exchange with payers, and we are both encouraged by our interactions to date and excited by the opportunity to launch our fifth medicine in CF. In the longer term, we expect continued growth in CF from our mRNA program, VX522, for the more than 5,000 people with CF who do not respond to CFTR modulators. Now turning to Casjevi and our launches in sickle cell disease and beta thalassemia.

Stuart A. Arbuckle: And excited by the opportunity to launch our fifth medicine in CF.

Reshma Kewalramani: Longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators. Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia, we are making strong progress with ATC activation, physician and patient engagement, and payer conversations. Enthusiasm from stakeholders is high in all regions, and our teams are working to translate this historic scientific achievement into meaningful patient benefit in the real world. Let me provide some insights on the launch with two key metrics we are sharing externally as important markers of our early launch progress: the number of activated authorized treatment centers, or ATCs, and patient cell collections. Recall that Vertex will recognize revenue for CASGEVY near the end of the patient journey at infusion.

Longer term, we expect continued growth in CF from our mRNA program, VX-522, for the more than 5,000 people with CF who do not respond to CFTR modulators. Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia, we are making strong progress with ATC activation, physician and patient engagement, and payer conversations. Enthusiasm from stakeholders is high in all regions, and our teams are working to translate this historic scientific achievement into meaningful patient benefit in the real world. Let me provide some insights on the launch with two key metrics we are sharing externally as important markers of our early launch progress: the number of activated authorized treatment centers, or ATCs, and patient cell collections. Recall that Vertex will recognize revenue for CASGEVY near the end of the patient journey at infusion.

Stuart A. Arbuckle: Longer term, we expect continued growth in CF from our mrna program VX 522 for the more than 5000 people with CF, who do not respond to see FTR modulators.

Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia. We are making strong progress with ATC activation, physician and patient engagement and payer conversations. Enthusiasm from stakeholders is high in all regions and our teams are working to translate this historic scientific achievement into meaningful patient benefit in the real world. Let me provide some insights on the launch with two key metrics we are sharing externally as important markers of our early launch progress: the number of activated authorized treatment centers or ATCs and patient cell collections. Recall that Vertex will recognize revenue for CASGEVY near the end of the patient journey, at infusion. Starting with ATC activation,

Stuart A. Arbuckle: Now turning to cash JV, and our launches in sickle cell disease and beta thalassemia.

Stuart A. Arbuckle: We are making strong progress with ATC activation, physician and patient engagement, and payer conversations. Enthusiasm from stakeholders is high in all regions, and our teams are working to translate this historic scientific achievement into meaningful patient benefit in the real world. Let me provide some insights on the launch with two key metrics we are sharing externally as important markers of our early launch progress, the number of activated authorized treatment centers or ATCs and patient cell collections. Recall that Vertex will recognize revenue for Castievi near the end of the patient journey at infusion. Starting with ATC activation,

Stuart A. Arbuckle: We are making strong progress with ATC activation physician and patient engagement and payer conversations enthused.

Stuart A. Arbuckle: Enthusiasm from stakeholders is high in all regions and our teams are working to translate this historic scientific achievement into meaningful patient benefit in the real world let.

Speaker Change: Let me provide some insights on the launch with two key metrics, we are sharing externally as important markers of our early launch progress the number of activated authorized treatment centers or a T CS and patient cell collections.

Speaker Change: Recall that vertex will recognize revenue for cash do you have any near the end of the patient journey as infusion.

Reshma Kewalramani: Starting with ATC activation, you may recall we are prioritizing approximately 75 ATCs globally and already had nine ATCs activated at launch, even ahead of knowing the final label or pricing for CASGEVY. We are pleased with our progress as we now have more than 25 activated centers, including centers in all regions where CASGEVY is approved. Even more important than the number of ATCs activated is patient initiations and cell collections. Many patients have begun the treatment journey, and as of mid-April, five patients already had cells collected. This is excellent progress given the short timeframe since approval and the complexity and length of the patient journey. These cell collections have occurred across all regions where CASGEVY is approved: the US, Europe, and the Middle East.

Starting with ATC activation, you may recall we are prioritizing approximately 75 ATCs globally and already had nine ATCs activated at launch, even ahead of knowing the final label or pricing for CASGEVY. We are pleased with our progress as we now have more than 25 activated centers, including centers in all regions where CASGEVY is approved. Even more important than the number of ATCs activated is patient initiations and cell collections. Many patients have begun the treatment journey, and as of mid-April, five patients already had cells collected. This is excellent progress given the short timeframe since approval and the complexity and length of the patient journey. These cell collections have occurred across all regions where CASGEVY is approved: the US, Europe, and the Middle East.

Speaker Change: Starting with ATC activation.

Starting with ATC activation. You may recall we are prioritizing approximately 75 ATCs globally and already had 9 ATCs activated at launch, even ahead of knowing the final label or pricing for CASGEVY. We are pleased with our progress as we now have more than 25 activated centers, including centers in all regions where CASGEVY is approved. Even more important than the number of ATCs activated, is patient initiations and cell collections. Many patients have begun the treatment journey and as of mid-April, five patients had already had cells collected.

Stuart A. Arbuckle: You may recall we are prioritizing approximately 75 ATCs globally and already had 9 ATCs activated at launch, even ahead of knowing the final label or pricing for Castievi. We are pleased with our progress as we now have more than 25 activated centers, including centers in all regions where Castievi is approved. Even more important than the number of ATCs activated is patient initiations and cell collections. Many patients have begun the treatment journey, and as of mid-April, five patients had already had cells collected.

Speaker Change: You may recall, we are prioritizing approximately 70 586 globally and already had nine atc's activated at launch even ahead of knowing the final label or pricing for cash JV. We are pleased with our progress as we now have more than 25 activated centers, including centers in all regions were cast JV is approved.

Speaker Change: Even more important than the number of Atc's activated is patient initiations and sell collections.

Speaker Change: Many patients have begun the treatment journey and as of mid April five patients already had cells collected.

Stuart A. Arbuckle: This is excellent progress given the short time frame since approval and the complexity and length of the patient journey. These sales collections have occurred across all regions where CASGEVY is approved -- the U.S., Europe and the Middle East. We also continue to make great progress with payers, who recognize the transformative clinical benefits of CASGEVY and are moving quickly to provide rapid and equitable access. In the U.S. commercial market, we have contracts and/or published policies in place for over 200 million lives or nearly 65% of total lives. In the government Medicaid sector, we have policies in place or active contract negotiations ongoing with 18 states. And, in the meantime, all states have confirmed their intent to provide case-by-case coverage.

This is excellent progress given the short timeframe since approval and the complexity and length of the patient journey the.

Speaker Change: These cells collections have occurred across all regions were cashed JV has approved the U S Europe and the middle East.

Reshma Kewalramani: We also continue to make great progress with payers who recognize the transformative clinical benefits of CASGEVY and are moving quickly to provide rapid and equitable access. In the US commercial market, we have contracts and/or published policies in place for over 200 million lives, or nearly 65% of total lives. In the government Medicaid sector, we have policies in place or active contract negotiations ongoing with 18 states, and in the meantime, all states have confirmed their intent to provide case-by-case coverage. Outside the US, we are also making progress with reimbursement and access, either through formal reimbursement agreements or early access programs. In Europe, we see strong traction in France with a reimbursed early access program in TDT.

We also continue to make great progress with payers who recognize the transformative clinical benefits of CASGEVY and are moving quickly to provide rapid and equitable access. In the US commercial market, we have contracts and/or published policies in place for over 200 million lives, or nearly 65% of total lives. In the government Medicaid sector, we have policies in place or active contract negotiations ongoing with 18 states, and in the meantime, all states have confirmed their intent to provide case-by-case coverage. Outside the US, we are also making progress with reimbursement and access, either through formal reimbursement agreements or early access programs. In Europe, we see strong traction in France with a reimbursed early access program in TDT.

Stuart A. Arbuckle: We also continue to make great progress with payers, who recognize the transformative clinical benefits of Castievi and are moving quickly to provide rapid and equitable access. In the U.S. commercial market, we have contracts and or published policies in place for over 200 million lives, or nearly 65% of total lives. In the government Medicaid sector, we have policies in place or active contract negotiations ongoing with 18 states. And, in the meantime, all states have confirmed their intent to provide case-by-case coverage.

Speaker Change: We also continued to make great progress with payers, who recognize the transformative clinical benefits of cash JV and are moving quickly to provide rapid and equitable access in the U S. Commercial market, we have contracts and or published policies in place for over 200 million lives or nearly 65% of total lives in the government med.

Speaker Change: The Cade sector, we have policies in place or active contract negotiations ongoing with 18 states and in the meantime, all states have confirmed their intent to provide case by case coverage.

Stuart A. Arbuckle: Outside the U.S., we are also making progress with reimbursement and access, either through formal reimbursement agreements or early access programs. In Europe, we see strong traction in France with a reimbursed Early Access Program in TDT. We're particularly pleased with our progress in the Middle East, which is a new region for Vertex and especially important for CASGEVY, given the high prevalence of sickle cell disease in particular and the government's clear focus on elevating the health of their citizens.

Speaker Change: Outside the U S. We are also making progress with reimbursement and access either through formal reimbursement agreements or early access programs in Europe, we see strong traction in France with a reimbursed early access program in T. D. T. We're particularly pleased with our progress in the Middle East, which is a new region for vertex and especially important for cash Jerry.

Reshma Kewalramani: We're particularly pleased with our progress in the Middle East, which is a new region for Vertex and especially important for CASGEVY, given the high prevalence of sickle cell disease in particular and the government's clear focus on elevating the health of their citizens. Since receiving regulatory approvals from KSA and Bahrain, we have worked with local healthcare authorities and refined our epidemiology estimates for the region. Our work indicates that the eligible 12-plus sickle cell disease and beta thalassemia population in KSA and Bahrain that we could serve is in excess of 23,000 patients, a potentially larger opportunity than even the US. These regions have the infrastructure to administer medicines like CASGEVY, given the prevalence of the diseases and relatively high volume of allogeneic stem cell transplants performed annually.

We're particularly pleased with our progress in the Middle East, which is a new region for Vertex and especially important for CASGEVY, given the high prevalence of sickle cell disease in particular and the government's clear focus on elevating the health of their citizens. Since receiving regulatory approvals from KSA and Bahrain, we have worked with local healthcare authorities and refined our epidemiology estimates for the region. Our work indicates that the eligible 12-plus sickle cell disease and beta thalassemia population in KSA and Bahrain that we could serve is in excess of 23,000 patients, a potentially larger opportunity than even the US. These regions have the infrastructure to administer medicines like CASGEVY, given the prevalence of the diseases and relatively high volume of allogeneic stem cell transplants performed annually.

Speaker Change: Given the high prevalence of sickle cell disease in particular, and the government's clear focus on elevating the health of their citizens since receiving regulatory approvals from KSA and Bahrain, we've worked with local health care authorities and refined our epidemiology estimates for the region.

Stuart A. Arbuckle: Since receiving regulatory approvals from KSA and Bahrain, we have worked with local healthcare authorities and refined our epidemiology estimates for the region. Our work indicates that the eligible 12-plus sickle cell disease and beta thalassemia population in KSA and Bahrain that we could serve, is in excess of 23,000 patients, a potentially larger opportunity than even the U.S. These regions have the infrastructure to administer medicines like CASGEVY, given the prevalence of the diseases and relatively high volume of allogeneic stem cell transplants performed annually. And importantly, we have already secured reimbursement agreements in KSA and Bahrain allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region. Shifting now to SUZETRIGINE.

Since receiving regulatory approvals from KSA and Bahrain, we have worked with local healthcare authorities and refined our epidemiology estimates for the region. Our work indicates that the eligible 12-plus sickle cell disease and beta thalassemia population in KSA and Bahrain that we could serve, is in excess of 23,000 patients, a potentially larger opportunity than even the U.S. These regions have the infrastructure to administer medicines like CASGEVY, given the prevalence of the diseases and relatively high volume of allogeneic stem cell transplants performed annually. And importantly, we have already secured reimbursement agreements in KSA and Bahrain allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region.

Work indicates that the eligible 12, plus sickle cell disease, and beta thalassemia population in KSA and Bahrain, but we could serve is in excess of 23000 patients are potentially larger opportunity than even the U S. These regions have the infrastructure to administer medicines like cash JV given the prevalence of the diseases.

Stuart A. Arbuckle: These regions have the infrastructure to administer medicines like CASGEVY given the prevalence of the diseases and the relatively high volume of allogeneic stem cell transplants performed annually. And importantly, we have already secured reimbursement agreements in KSA and Bahrain allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region, although now switching to susetragine.

Speaker Change: And relatively high volume of allogeneic stem cell transplants performed annually and importantly, we have already secured reimbursement agreements in KSA and Bahrain, allowing certain eligible patients to access cash Debbie for both sickle cell disease and transfusion dependent thalassemia. In addition to having activated a tea season collected sells for.

And importantly, we have already secured reimbursement agreements in KSA and Bahrain allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region.

Reshma Kewalramani: Importantly, we have already secured reimbursement agreements in KSA and Bahrain, allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region. Shifting now to suzetrigine, we believe this highly selective NaV1.8 pain-signaling inhibitor has the potential to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathic pain. This quarter, I'm going to limit my commercial comments to the opportunity in acute pain.

Importantly, we have already secured reimbursement agreements in KSA and Bahrain, allowing certain eligible patients to access CASGEVY for both sickle cell disease and transfusion-dependent thalassemia. In addition to having activated ATCs and collected cells from our first patients in the Middle East, we continue to work with local healthcare professionals to increase the number of ATCs and expand patient access in the region. Shifting now to suzetrigine, we believe this highly selective NaV1.8 pain-signaling inhibitor has the potential to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathic pain. This quarter, I'm going to limit my commercial comments to the opportunity in acute pain.

Speaker Change: Our first patients in the Middle East, we continue to work with local health care professionals to increase the number of Atc's and expand patient access in the region shifting.

Shifting now to SUZETRIGINE. We believe this highly selective NAV1.8 pain signal inhibitor has the potential to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathic pain. This quarter, I'm going to limit my commercial comments to the opportunity in acute pain. Throughout its clinical trials to date, SUZETRIGINE has shown a compelling combination of efficacy and safety, with strong potential to be used across a range of moderate to severe acute pain conditions, both surgical and non-surgical and across a range of settings.

Stuart A. Arbuckle: We believe this highly selective NAV1.8 pain signal inhibitor has the potential to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathic pain. This quarter, I'm going to limit my commercial comments to the opportunity in acute pain. Throughout its clinical trials to date, susetragine has shown a compelling combination of efficacy and safety, with strong potential to be used across a range of moderate to severe acute pain conditions, both surgical and non-surgical, and across a range of settings.

Speaker Change: Shifting now to seize at Eugene We believe this highly selective NAV one eight pain signal inhibitor has the potential to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathy pain. This quarter I'm going to limit my commercial comments to the opportunity in acute pain throughout its clinical trials to.

Reshma Kewalramani: Throughout its clinical trials to date, suzetrigine has shown a compelling combination of efficacy and safety, with strong potential to be used across a range of moderate to severe acute pain conditions, both surgical and non-surgical, and across a range of settings. This profile will ideally address the clear unmet need among both patients and physicians: effective pain relief with a favorable safety and tolerability profile. On prior Investor Webcasts, we provided details on this opportunity, including the magnitude: approximately 80 million patients are prescribed a medicine for moderate to severe acute pain each year in the US, and the high concentration, with approximately 2/3 of patients being treated in the institutional setting. There is further concentration within that setting in approximately 2,000 institutions that roll up to around 150 IDNs. Accordingly, they can be served with a specialty commercial infrastructure.

Throughout its clinical trials to date, suzetrigine has shown a compelling combination of efficacy and safety, with strong potential to be used across a range of moderate to severe acute pain conditions, both surgical and non-surgical, and across a range of settings. This profile will ideally address the clear unmet need among both patients and physicians: effective pain relief with a favorable safety and tolerability profile. On prior Investor Webcasts, we provided details on this opportunity, including the magnitude: approximately 80 million patients are prescribed a medicine for moderate to severe acute pain each year in the US, and the high concentration, with approximately 2/3 of patients being treated in the institutional setting. There is further concentration within that setting in approximately 2,000 institutions that roll up to around 150 IDNs. Accordingly, they can be served with a specialty commercial infrastructure.

Speaker Change: Date sees that gene has shown a compelling combination of efficacy and safety with strong potential to be used across a range of moderate to severe acute pain conditions, both surgical and nonsurgical and across a range of settings. This profile will ideally address the clear unmet need among both patients and physicians.

Stuart A. Arbuckle: This profile will ideally address the clear, unmet need among both patients and physicians -- effective pain relief with a favorable safety and tolerability profile. On prior investor webcasts, we provided details on this opportunity, including the magnitude -- approximately 80 million patients are prescribed a medicine for moderate to severe acute pain each year in the U.S. and for high concentration, with approximately two-thirds of patients being treated in the institutional setting. There is further concentration within that setting in approximately 2,000 institutions that roll up to around 150 IDNs. Accordingly, they can be served with a specialty commercial infrastructure.

Speaker Change: Effective pain relief with a favorable safety and Tolerability profile on prior Investor webcast. We provided details on this opportunity, including the magnitude approximately 18 million patients are prescribed the medicine for moderate to severe acute pain each year in the U S and the high concentration with approximately two thirds.

Speaker Change: <unk> of patients being treated in the institutional setting there is further concentration within that setting in approximately 2000 institutions that roll up to around 150 idms. Accordingly, they can be served with a specialty commercial infrastructure. We are also detailed the mix of settings for their over 1 billion calendar days of acute pain treatment.

Reshma Kewalramani: We have also detailed the mix of settings for the over 1 billion calendar days of acute pain treatment. 15% are prescribed and dispensed in an institutional setting, 35% are prescribed at discharge, and 50% are prescribed in physicians' offices. This quarter, I'll provide you with some insights on our go-to-market strategy and an update on the legislative and payer landscape. We are focused on the institutional setting, given these approximately 2,000 institutions account for 50% of acute pain prescriptions. Extensive market research has also helped us identify an initial set of specific acute pain conditions and procedure types with high clinical fit, such as high-volume surgical procedures, pain conditions that typically require prescription pain medicines at discharge, or where we can seek to replace or significantly reduce opioid utilization, and the related physician specialties that are likely to adopt and champion suzetrigine.

We have also detailed the mix of settings for the over 1 billion calendar days of acute pain treatment. 15% are prescribed and dispensed in an institutional setting, 35% are prescribed at discharge, and 50% are prescribed in physicians' offices. This quarter, I'll provide you with some insights on our go-to-market strategy and an update on the legislative and payer landscape. We are focused on the institutional setting, given these approximately 2,000 institutions account for 50% of acute pain prescriptions. Extensive market research has also helped us identify an initial set of specific acute pain conditions and procedure types with high clinical fit, such as high-volume surgical procedures, pain conditions that typically require prescription pain medicines at discharge, or where we can seek to replace or significantly reduce opioid utilization, and the related physician specialties that are likely to adopt and champion suzetrigine.

Stuart A. Arbuckle: We have also detailed the mix of settings for the over one billion calendar days of acute pain treatment. 15% are prescribed and dispensed in an institutional setting, 35% are prescribed at discharge and 50% are prescribed in physician's offices. This quarter, I'll provide you with some insights on our go-to-market strategy and an update on the legislative and payer landscape. We are focused on the institutional setting, given these approximately 2,000 institutions account for 50% of acute pain prescriptions. Extensive market research has also helped us identify an initial set of specific acute pain conditions and procedure types with high clinical fit, such as high volume surgical procedures, pain conditions that typically require prescription pain medicines at discharge or where we can seek to replace or significantly reduce opioid utilization and the related physician specialties that are likely to adopt and champion SUZETRIGINE.

We have also detailed the mix of settings for the over one billion calendar days of acute pain treatment. 15% are prescribed and dispensed in an institutional setting, 35% are prescribed at discharge and 50% are prescribed in physician's offices. This quarter, I'll provide you with some insights on our go-to-market strategy and an update on the legislative and payer landscape. We are focused on the institutional setting, given these approximately 2,000 institutions account for 50% of acute pain prescriptions.

Speaker Change: 15% are prescribed and dispensed in an institutional setting.

Speaker Change: 35% have prescribed at discharge and 50% are prescribed in physicians offices. This.

Stuart A. Arbuckle: This quarter, I'll provide you with some insights on our go-to-market strategy and an update on the legislative and payer landscape. We are focused on the institutional setting, given these approximately 2,000 institutions account for 50% of acute pain prescriptions. Extensive market research has also helped us identify an initial set of specific acute pain conditions and procedure types with high clinical fit, such as high volume surgical procedures, pain conditions that typically require prescription pain medicines at discharge, or where we can seek to replace or significantly reduce opioid utilization, and related physician specialties that are likely to adopt and champion susetragine.

Speaker Change: This quarter I'll provide you with some insights on our go to market strategy and an update on the legislative and payer landscape.

Speaker Change: We are focused on the institutional setting given these approximately 2000 institutions account for 50% of acute pain prescriptions extensive market research has also helped US identify an initial set of specific acute pain conditions and procedure types with high clinical fit such as high volume surgical procedures pain.

Extensive market research has also helped us identify an initial set of specific acute pain conditions and procedure types with high clinical fit, such as high volume surgical procedures, pain conditions that typically require prescription pain medicines at discharge or where we can seek to replace or significantly reduce opioid utilization and the related physician specialties that are likely to adopt and champion SUZETRIGINE. The key healthcare professionals we will be targeting include orthopedic, general and plastic surgeons, emergency department physicians, anesthesiologists and pain medicine specialists. Given the dynamics for new medicines to be approved for use in institutions, we expect the earliest uptake of SUZETRIGINE will occur at discharge. Recall, this discharge segment represents roughly 35% of the approximately 1.1 billion calendar days of acute pain treatment in the U.S. each year. The average prescription length in this setting is approximately two weeks.

Speaker Change: <unk> that typically require a prescription pain medicines at discharge or where we can seek to replace or significantly reduce opioid utilization and the related physician specialties that are likely to adopt and champions who's at Eugene The key health care professionals will be targeting include orthopedic general and plastic surgeons.

Stuart A. Arbuckle: The key healthcare professionals we will be targeting include orthopedic, general, and plastic surgeons, emergency department physicians, anesthesiologists, and pain medicine specialists. Given the dynamics for new medicines to be approved for use in institutions, we expect the earliest uptake of susetragine will occur at discharge. Recall, this discharge segment represents roughly 35% of the approximately 1.1 billion calendar days of acute pain treatment in the U.S. each year. The average prescription length in this setting is approximately two weeks.

Reshma Kewalramani: The key healthcare professionals we will be targeting include orthopedic, general, and plastic surgeons, emergency department physicians, anesthesiologists, and pain medicine specialists. Given the dynamics for new medicines to be approved for use in institutions, we expect the earliest uptake of suzetrigine will occur at discharge. Recall, this discharge segment represents roughly 35% of the approximately 1.1 billion calendar days of acute pain treatment in the US each year. The average prescription length in this setting is approximately two weeks. Treatment in this setting commonly includes opioids, where prescription length is shorter, four to five days, due to side effect profile, addiction concerns, and prescribing limits at the state, IDN, and hospital level. We are already engaging with key decision-makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs, and GPOs.

The key healthcare professionals we will be targeting include orthopedic, general, and plastic surgeons, emergency department physicians, anesthesiologists, and pain medicine specialists. Given the dynamics for new medicines to be approved for use in institutions, we expect the earliest uptake of suzetrigine will occur at discharge. Recall, this discharge segment represents roughly 35% of the approximately 1.1 billion calendar days of acute pain treatment in the US each year. The average prescription length in this setting is approximately two weeks. Treatment in this setting commonly includes opioids, where prescription length is shorter, four to five days, due to side effect profile, addiction concerns, and prescribing limits at the state, IDN, and hospital level. We are already engaging with key decision-makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs, and GPOs.

Speaker Change: Emergency Department physicians, anesthesiologists, and pain medicine specialists, given the dynamics for new medicines to be approved for use in institutions. We expect the earliest uptake of CS at Eugene will occur at discharge recall. This discharge segment represents roughly 35% of the approximately $1 1 billion callen.

Given the dynamics for new medicines to be approved for use in institutions, we expect the earliest uptake of SUZETRIGINE will occur at discharge. Recall, this discharge segment represents roughly 35% of the approximately 1.1 billion calendar days of acute pain treatment in the U.S. each year. The average prescription length in this setting is approximately two weeks. Treatment in this setting commonly includes opioids where prescription length is shorter -- four to five days -- due to side effect profile, addiction concerns and prescribing limits at the state and IDN and hospital level. We are already engaging with key decision-makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs and GPOs. We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus, plan to engage in contracting discussions in the second half of this year ahead of launch, to support the potential for accelerated formulary adoption.

Speaker Change: The days of acute pain treatment in the U S. Each year.

Speaker Change: The average prescription length in this setting is approximately two weeks treatment in this setting commonly includes opioids, where prescription lenses shorter four to five days due to side effect profile addiction concerns and prescribing limits at the state and IDM and hospital level.

Stuart A. Arbuckle: Treatment in this setting commonly includes opioids where the prescription length is shorter, four to five days, due to side effect profile, addiction concerns, and prescribing limits at the state, IDN, and hospital level. We are already engaging with key decision makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs, and GPOs. We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus plan to engage in contracting discussions in the second half of this year, ahead of launch, to support the potential for accelerated formulary adoption.

We are already engaging with key decision-makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs and GPOs. We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus, plan to engage in contracting discussions in the second half of this year ahead of launch, to support the potential for accelerated formulary adoption. We've also made great progress in the build-out of our commercial team. Our field leadership team are now on board and fully trained and having gated the hiring of the field force until after the Phase III data, we are now finalizing the hiring of 150 new customer-facing colleagues.

Speaker Change: We are already engaging with key decision makers across the formulary and access landscape, including pharmacist Pbms payers, IV Ns and Gpus.

Reshma Kewalramani: We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus plan to engage in contracting discussions in the second half of this year, ahead of launch, to support the potential for accelerated formulary adoption. We've also made great progress in the build-out of our commercial team. Our field leadership team are now on board and fully trained and have engaged in the hiring of the field force until after the phase 3 data. We are now finalizing the hiring of 150 new customer-facing colleagues. Finally, we know the significance of policy in the world of pain treatment, with important legislation like the NO PAIN Act already on track for implementation in 2025 and bills like the Alternatives to PAIN Act recently introduced.

We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus plan to engage in contracting discussions in the second half of this year, ahead of launch, to support the potential for accelerated formulary adoption. We've also made great progress in the build-out of our commercial team. Our field leadership team are now on board and fully trained and have engaged in the hiring of the field force until after the phase 3 data. We are now finalizing the hiring of 150 new customer-facing colleagues. Finally, we know the significance of policy in the world of pain treatment, with important legislation like the NO PAIN Act already on track for implementation in 2025 and bills like the Alternatives to PAIN Act recently introduced.

Speaker Change: We expect these stakeholders to make formulary and coverage decisions throughout the first year of the launch and thus plan to engage in contracting discussions in the second half of this year ahead of launch to support the potential for accelerated formulary adoption.

Stuart A. Arbuckle: We've also made great progress in the build-out of our commercial team. Our field leadership team is now on board and fully trained, and having gated the hiring of the field force until after the Phase 3 data, we are now finalizing the hiring of 150 new customer-facing colleagues.

Speaker Change: We've also made great progress in the build out of our commercial team our field leadership team on our board and fully trained and have engaged in the hiring of the field force until after the phase III data. We are now finalizing the hiring of 150, new customer facing colleagues.

Stuart A. Arbuckle: Finally, we know the significance of policy in the world of pain treatment, with important legislation like the NOPAIN Act -- already on track for implementation in 2025 -- and bills like the Alternatives to PAIN Act recently introduced. Our long-standing efforts continue to help shape state and federal policy initiatives to one, encourage consideration and use of non-opioid alternatives and two, remove financial barriers to choosing a branded non-opioid. Overall, we plan for a high-science, digitally-enabled commercialization approach with a strong focus on population health decision-makers. In addition, both patient advocacy and public policy efforts complement and supplement our commercial activities.

Speaker Change: Finally, we know the significance of policy in the world of pain treatment with important legislation like the no pain Act already on track for implementation in 2025 and bills like the alternatives to paint Act recently introduced a longstanding efforts continue to help shape state and federal policy initiatives to one encourage consideration.

Reshma Kewalramani: Our long-standing efforts continue to help shape state and federal policy initiatives to, one, encourage consideration and use of non-opioid alternatives, and two, remove financial barriers to choosing a branded non-opioid. Overall, we plan for a high-science, digitally-enabled commercialization approach with a strong focus on population health decision-makers. In addition, both patient advocacy and public policy efforts complement and supplement our commercial activities. 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 fundamentally redefine the treatment of pain and drive further diversified revenue growth.

Our long-standing efforts continue to help shape state and federal policy initiatives to, one, encourage consideration and use of non-opioid alternatives, and two, remove financial barriers to choosing a branded non-opioid. Overall, we plan for a high-science, digitally-enabled commercialization approach with a strong focus on population health decision-makers. In addition, both patient advocacy and public policy efforts complement and supplement our commercial activities. 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 fundamentally redefine the treatment of pain and drive further diversified revenue growth.

Speaker Change: The use of non opioid alternatives and to remove financial barriers to choosing a branded non opioid.

Speaker Change: Overall, we plan for a high science digitally enabled commercialization approach with a strong focus on population health decision makers.

Speaker Change: In addition, both patient advocacy and public policy efforts complement and supplement our commercial activities 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.

Stuart A. Arbuckle: 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 Vanzikafta triple combination. We are entering a new era of commercial diversification with the launch of Casjevi in the US, Europe, and the Middle East. And our launch preparations for susetrogine in acute pain are well underway as we seek to fundamentally redefine the treatment of pain and drive further diversified revenue growth. I'll now turn the call over to Charlie to review the financials. Thanks, Stuart. Vertex's excellent start to the year demonstrates once again our consistent, strong performance and attractive growth profile. First quarter 2024 revenue increased 13% year-over-year to $2.7 billion, with solid growth of 8% in the U.S. and 21% outside the U.S.

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 U.S., Europe and the Middle East. And our launch preparations for SUZETRIGINE in acute pain are well underway, as we seek to fundamentally redefine the treatment of pain and drive further diversified revenue growth.

Speaker Change: Diversification with the launch of cash JV in the U S Europe, and the middle East and our launch preparations for <unk> in acute pain are well underway as we seek to fundamentally redefine the treatment of pain and drive further diversified revenue growth.

Stuart A. Arbuckle: And our launch preparations for susetrogine in acute pain are well underway as we seek to fundamentally redefine the treatment of pain and drive further diversified revenue growth. I'll now turn the call over to Charlie to review the financials. Thanks, Stuart. Vertex's excellent start to the year demonstrates once again our consistent, strong performance and attractive growth profile. First quarter 2024 revenue increased 13% year-over-year to $2.7 billion, with solid growth of 8% in the U.S. and 21% outside the U.S.

I'll now turn the call over to Charlie to review the financials.

Reshma Kewalramani: I'll now turn the call over to Charlie to review the financials. Thanks, Stuart. Vertex's excellent start to the year demonstrates once again our consistent, strong performance and attractive growth profile. Q1 2024 revenue increased 13% year over year to $2.7 billion, with solid growth of 8% in the US and 21% outside the US. The drivers of this strong start were in line with our expectations, with some outperformance due to channel inventory phasing in select international markets. Q1 US growth was driven by continued strong performance of TRIKAFTA, including in patients ages two to five, following the approval in this patient population in April of last year, partially offset by the typical pattern of seasonally higher gross to net in the first quarter.

Speaker Change: I'll now turn the call over to Charlie to review the financials.

Charles Wagner: Thanks, Stuart. Vertex's excellent start to the year demonstrates once again our consistent, strong performance and attractive growth profile. Q1 2024 revenue increased 13% year over year to $2.7 billion, with solid growth of 8% in the US and 21% outside the US. The drivers of this strong start were in line with our expectations, with some outperformance due to channel inventory phasing in select international markets. Q1 US growth was driven by continued strong performance of TRIKAFTA, including in patients ages two to five, following the approval in this patient population in April of last year, partially offset by the typical pattern of seasonally higher gross to net in the first quarter.

I'll now turn the call over to Charlie to review the financials. Thanks, Stuart. Vertex's excellent start to the year demonstrates once again our consistent, strong performance and attractive growth profile. First quarter 2024 revenue increased 13% year-over-year to $2.7 billion, with solid growth of 8% in the U.S. and 21% outside the U.S.

I'll now turn the call over to Charlie to review the financials.

Charles F. Wagner: Thanks Stuart.

Charles F. Wagner: Vertex is excellent start to the year demonstrates once again, our consistent strong performance and attractive growth profile first quarter 'twenty 'twenty four revenue increased 13% year over year to 2.7 billion with solid growth of 8% in the U S and 21% outside the U S.

Thanks, Stuart. Vertex's excellent start to the year demonstrates, once again, our consistent, strong performance and attractive growth profile. 1st quarter 2024 revenue increased 13% year-over-year to $2.7 billion, with solid growth of 8% in the U.S. and 21% outside the U.S. The drivers of this strong start were in line with our expectations, with some outperformance due to channel inventory phasing in select international markets. 1st quarter U.S. growth was driven by continued strong performance of TRIKAFTA, including in patients ages 2 to 5, following the approval in this patient population in April of last year, partially offset by the typical pattern of seasonally higher gross-to-net in the 1st quarter. Outside the U.S., growth was also driven by the KAFTRIO 2-5 launch and a benefit from channel inventory phasing is expected to reverse in subsequent quarters, similar to the dynamics we saw in the first half of 2023. 1st quarter 2024 combined non-GAAP R&D, acquired IP R&D and SG&A expenses were $1 billion compared to $1.2 billion in the 1st quarter of 2023.

Charles Wagner: Thanks, Stuart. Vertex's excellent start to the year demonstrates, once again, our consistent, strong performance and attractive growth profile. 1st quarter 2024 revenue increased 13% year-over-year to $2.7 billion, with solid growth of 8% in the U.S. and 21% outside the U.S. The drivers of this strong start were in line with our expectations, with some outperformance due to channel inventory phasing in select international markets. 1st quarter U.S. growth was driven by continued strong performance of TRIKAFTA, including in patients ages 2 to 5, following the approval in this patient population in April of last year, partially offset by the typical pattern of seasonally higher gross-to-net in the 1st quarter.

Charles F. Wagner: The drivers of this strong start were in line with our expectations, but performance due to channel inventory phasing in select international markets. First quarter U.S. growth was driven by continued strong performance of Trikafta in patients ages two to five, following the approval in this patient population in April of last year, partially offset by the typical pattern of seasonally higher gross to net in the first quarter. Outside the U.S., growth was also driven by the caf trio two to five launch and a benefit from channel inventory phasing is expected to reverse in subsequent quarters, similar to the dynamics we saw in the first half of 2023. First quarter 2024 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $1 billion compared to $1.2 billion in the first quarter of 2023.

Charles F. Wagner: The drivers of this strong start we're in line with our expectations with some outperformance due to channel inventory phasing in select international markets first quarter U S growth was driven by continued strong performance of Trek HAFTA, including in patients ages two to five following the approval in this patient population in April of last year part.

Charles F. Wagner: Really offset by the typical pattern of seasonally higher gross to net in the first quarter.

Reshma Kewalramani: Outside the US, growth was also driven by KAFTRIO two to five launch, and a benefit from channel inventory phasing that is expected to reverse in subsequent quarters, similar to the dynamics we saw in the first half of 2023. First quarter 2024 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $1 billion, compared to $1.2 billion in the first quarter of 2023. Included in Q1 2024 results are $77 million of acquired IP R&D charges, compared to $347 million of such charges in the first quarter of 2023.

Outside the US, growth was also driven by KAFTRIO two to five launch, and a benefit from channel inventory phasing that is expected to reverse in subsequent quarters, similar to the dynamics we saw in the first half of 2023. First quarter 2024 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $1 billion, compared to $1.2 billion in the first quarter of 2023. Included in Q1 2024 results are $77 million of acquired IP R&D charges, compared to $347 million of such charges in the first quarter of 2023.

Outside the U S growth was also driven by Caf trio two to five launch and a benefit from channel inventory phasing is expected to reverse in subsequent quarters similar to the dynamics. We saw in the first half of 2023.

Outside the U.S., growth was also driven by the KAFTRIO 2-5 launch and a benefit from channel inventory phasing is expected to reverse in subsequent quarters, similar to the dynamics we saw in the first half of 2023. 1st quarter 2024 combined non-GAAP R&D, acquired IP R&D and SG&A expenses were $1 billion, compared to $1.2 billion in the 1st quarter of 2023. Included in Q1 '24 results are 77 million of acquired IP R&D charges compared to 347 million of such charges in the 1st quarter of 2023. Non-GAAP R&D expenses in Q1 '24 were relatively flat year-over-year and reflect growing investment in the advancement of our broad, earlier stage R&D portfolio offset by reduced costs from the recent successful completion of multiple late stage clinical trials for CASGEVY, VANZACAFTOR and SUZETRIGINE, as well as the associated transition of certain costs from R&D to COGS and inventory.

Charles F. Wagner: First quarter 2024, combined non-GAAP R&D acquired IP, R&D and SG&A expenses were 1 billion compared to $1 2 billion in the first quarter of 2023.

Charles F. Wagner: Included in Q1'24 results are 77 million of acquired IP R&D charges compared to 347 million of such charges in the first quarter of 2023. Non-GAAP R&D expenses in Q1'24 were relatively flat year over year and reflect growing investment in the advancement of our broad earlier stage R&D portfolio offset by reduced costs from the recent successful completion of multiple late stage clinical trials for CasGeV, VanZaCaptor, and SuzetraGene, as well as the associated transition of certain costs from R&D to COGS and inventory.

Charles F. Wagner: Included in Q1, 'twenty four results are $77 million of acquired IP R&D charges compared to $347 million of such charges in the first quarter of 2023, non-GAAP R&D expenses in Q1, 'twenty four were relatively flat year over year and reflect growing investment in the advancement of our broad earlier stage earned.

Reshma Kewalramani: Non-GAAP R&D expenses in Q1 2024 were relatively flat year over year and reflect growing investment in the advancement of our broad earlier-stage R&D portfolio, offset by reduced costs from the recent successful completion of multiple late-stage clinical trials for CASGEVY, vanzacaftor, and suzetrigine, as well as the associated transition of certain costs from R&D to COGS and inventory. The increase in non-GAAP SG&A costs versus Q1 2023 includes investment in the commercial organization and launch activities for CASGEVY and acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 as we advance inaxaplin into phase 3 development in ADPKD, initiate the suzetrigine phase 3 program in painful diabetic peripheral neuropathy, and continue to invest in preparation for upcoming potential new commercial launches, including the further build-out of our suzetrigine team.

Non-GAAP R&D expenses in Q1 2024 were relatively flat year over year and reflect growing investment in the advancement of our broad earlier-stage R&D portfolio, offset by reduced costs from the recent successful completion of multiple late-stage clinical trials for CASGEVY, vanzacaftor, and suzetrigine, as well as the associated transition of certain costs from R&D to COGS and inventory. The increase in non-GAAP SG&A costs versus Q1 2023 includes investment in the commercial organization and launch activities for CASGEVY and acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 as we advance inaxaplin into phase 3 development in ADPKD, initiate the suzetrigine phase 3 program in painful diabetic peripheral neuropathy, and continue to invest in preparation for upcoming potential new commercial launches, including the further build-out of our suzetrigine team.

Non-GAAP R&D expenses in Q1 '24 were relatively flat year-over-year and reflect growing investment in the advancement of our broad, earlier stage R&D portfolio offset by reduced costs from the recent successful completion of multiple late stage clinical trials for CASGEVY, VANZACAFTOR and SUZETRIGINE, as well as the associated transition of certain costs from R&D to COGS and inventory. The increase in non-GAAP SG&A costs versus Q1 '23 includes investment in the commercial organization and launch activities for CASGEVY and acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 as we advance INAXAPLIN into Phase III development in AMKD, initiate the SUZETRIGINE Phase III program in painful diabetic peripheral neuropathy and continue to invest in preparation for upcoming potential new commercial launches, including the further build out of our SUZETRIGINE team.

The portfolio offset by reduced costs from the recent successful completion of multiple late stage clinical trials for cast gebbie vans, a character and suzette regime as well as the associated transition of certain costs from R&D to Cogs in inventory the increase in non-GAAP SG&A costs versus Q1 'twenty three.

Charles F. Wagner: The increase in non-GAAP SG&A costs versus Q1-23 includes investment in the commercial organization and launch activities for CAS-GEVI and acute pain. We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 as we advance Axipline into phase 3 development in AMKD, initiate the susetrogene phase 3 program in painful diabetic peripheral neuropathy, and continue to invest in preparation for upcoming potential new commercial launches, including the further build out of our susetrogene team.

Charles F. Wagner: Includes investment in the commercial organization and launch activities for cast gebbie in acute pain, we anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 'twenty 'twenty four as we advance <unk> into phase III development in a M. K D. Initiate this is after gene phase III program in painful diabetic peripheral.

We anticipate the quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 as we advance INAXAPLIN into Phase III development in AMKD, initiate the SUZETRIGINE Phase III program in painful diabetic peripheral neuropathy and continue to invest in preparation for upcoming potential new commercial launches, including the further build out of our SUZETRIGINE team. 1st quarter 2024 non-GAAP operating income was $1.3 billion, a 48% increase compared to $902 million in non-GAAP operating income in the 1st quarter of 2023. 1st quarter 2024 non-GAAP effective tax rate of 17.4% compares to 21.3% in Q1 '23 and includes a benefit from a discrete adjustment to Vertex's income tax reserves. 1st quarter 2024 non-GAAP earnings per share were $4.76, including benefits from revenue and expense phasing as well as a lower tax rate, compared to $3.05 in the 1st quarter of 2023. We ended the quarter with $14.6 billion in cash and investments.

Charles F. Wagner: Referral neuropathy and continued to invest in preparation for upcoming potential new commercial launches, including the further build out of our seuss at Trojan team first quarter 2024, non-GAAP operating income was 1.3, billion% to 48% increase compared to $902 million and non-GAAP operating income in the first quarter.

Reshma Kewalramani: First quarter 2024 non-GAAP operating income was $1.3 billion, a 48% increase compared to $902 million in non-GAAP operating income in the first quarter of 2023. First quarter 2024 non-GAAP effective tax rate of 17.4% compares to 21.3% in Q1 2023 and includes a benefit from a discrete adjustment to Vertex's income tax reserves. First quarter 2024 non-GAAP earnings per share were $4.76, including benefits from revenue and expense phasing, as well as a lower tax rate compared to $3.05 in the first quarter of 2023. We ended the quarter with $14.6 billion in cash and investments. We will use a portion of this cash on hand to fund the $4.9 billion acquisition of Alpine Immune Sciences, which is expected to close this quarter, subject to certain customary conditions. Alpine is a prime example of our priority for capital deployment to invest in innovation, including external innovation via business development.

First quarter 2024 non-GAAP operating income was $1.3 billion, a 48% increase compared to $902 million in non-GAAP operating income in the first quarter of 2023. First quarter 2024 non-GAAP effective tax rate of 17.4% compares to 21.3% in Q1 2023 and includes a benefit from a discrete adjustment to Vertex's income tax reserves. First quarter 2024 non-GAAP earnings per share were $4.76, including benefits from revenue and expense phasing, as well as a lower tax rate compared to $3.05 in the first quarter of 2023. We ended the quarter with $14.6 billion in cash and investments. We will use a portion of this cash on hand to fund the $4.9 billion acquisition of Alpine Immune Sciences, which is expected to close this quarter, subject to certain customary conditions. Alpine is a prime example of our priority for capital deployment to invest in innovation, including external innovation via business development.

Charles F. Wagner: First quarter 2024 non-GAAP operating income was $1.3 billion, a 48% increase compared to $902 million in non-GAAP operating income in the first quarter of 2023. First quarter 2024 non-GAAP effective tax rate of 17.4% compares to 21.3% in Q1-23 and includes a benefit from a discrete adjustment to Vertex's income tax reserve. First quarter 2024 non-GAAP earnings per share were $4.76, including benefits from revenue and expense phasing, as well as a lower tax rate compared to $3.05 in the first quarter of 2023. We ended the quarter with $14.6 billion in cash and investments.

Charles F. Wagner: Of 2023 first quarter 2024, non-GAAP effective tax rate of 17.4% compares to 21, 3% in Q1 'twenty three and includes a benefit from a discrete adjustment to vertex as income tax reserves.

1st quarter 2024 non-GAAP effective tax rate of 17.4% compares to 21.3% in Q1 '23 and includes a benefit from a discrete adjustment to Vertex's income tax reserves. 1st quarter 2024 non-GAAP earnings per share were $4.76, including benefits from revenue and expense phasing as well as a lower tax rate, compared to $3.05 in the 1st quarter of 2023. We ended the quarter with $14.6 billion in cash and investments. We will use a portion of this cash on hand to fund the $4.9 billion acquisition of Alpine Immune Sciences, which is expected to close this quarter, subject to certain customary conditions. Alpine is a prime example of our priority for capital deployment, to invest in innovation, including external innovation via business development. We see multi-billion-dollar potential for Phase III-ready POVETACICEPT, given its transformative and best-in-class potential in IgAN, a disease area with high unmet need. We also look forward to exploring POVE's full potential in other serious diseases. Additionally, we deployed over $140 million of cash in the first quarter to repurchase 336,000 shares.

Charles F. Wagner: First quarter, 2024, non-GAAP earnings per share or $4.76, including benefits from revenue and expense phasing as well as a lower tax rate compared to $3.05 in the first quarter of 2023.

Charles F. Wagner: We ended the quarter with $14 6 billion in cash and investments we will use a portion of this cash on hand to fund the $4.9 billion acquisition of Alpine immune sciences, which is expected to close this quarter subject to certain customary conditions Alpine is a prime example of our priority for capital deployment to invest in innovation.

Charles F. Wagner: We will use a portion of this cash on hand to fund the $4.9 billion acquisition of Alpine Immune Sciences, which is expected to close this quarter subject to certain customary conditions. Alpine is a prime example of our priority for capital deployment to invest in innovation, including external innovation via business development. We see multi-billion-dollar potential for Phase III-ready povitacicept, given its transformative and best-in-class potential in IgAN, a disease area with high unmet need. We also look forward to exploring POVI's full potential in other serious diseases. Additionally, we deployed over $140 million of cash in the first quarter to repurchase 336,000 shares.

Alpine is a prime example of our priority for capital deployment, to invest in innovation, including external innovation via business development. We see multi-billion-dollar potential for Phase III-ready POVETACICEPT, given its transformative and best-in-class potential in IgAN, a disease area with high unmet need. We also look forward to exploring POVE's full potential in other serious diseases. Additionally, we deployed over $140 million of cash in the first quarter to repurchase 336,000 shares.

Including external innovation via business development, we see multibillion dollar potential for phase III ready poet tests accept given is transformative and best in class potential and I again, a disease area with high unmet need. We also look forward to exploring povich full potential and other serious diseases.

Reshma Kewalramani: We see multi-billion dollar potential for phase 3-ready povetacicept, given its transformative and best-in-class potential in IgAN, a disease area with high unmet need. We also look forward to exploring POVI's full potential in other serious diseases. Additionally, we deployed over $140 million of cash in Q1 to repurchase 336,000 shares. Now switching to guidance, there's no change to our 2024 total product revenue guidance range of $10.55 to 10.75 billion, representing revenue growth of 8% at the midpoint at current exchange rates. We have high visibility into this revenue outlook. We expect continued growth in CF as we continue to reach more patients, including younger ones, in core markets and select other countries, as well as contribution in H2 2024 from the commercial launch of CASGEVY in approved indications and geographies.

We see multi-billion dollar potential for phase 3-ready povetacicept, given its transformative and best-in-class potential in IgAN, a disease area with high unmet need. We also look forward to exploring POVI's full potential in other serious diseases. Additionally, we deployed over $140 million of cash in Q1 to repurchase 336,000 shares. Now switching to guidance, there's no change to our 2024 total product revenue guidance range of $10.55 to 10.75 billion, representing revenue growth of 8% at the midpoint at current exchange rates. We have high visibility into this revenue outlook. We expect continued growth in CF as we continue to reach more patients, including younger ones, in core markets and select other countries, as well as contribution in H2 2024 from the commercial launch of CASGEVY in approved indications and geographies.

Charles F. Wagner: Additionally, we deployed over $140 million of cash in the first quarter to repurchase 336000 shares.

Charles F. Wagner: Now, switching to guidance. There's no change to our 2024 total product revenue guidance range of $10.55 to $10.75 billion, representing revenue growth of 8% at the mid-point at current exchange rates. We have high visibility into this revenue outlook. We expect continued growth in CF as we continue to reach more patients, including younger ones, in core markets and select other countries, as well as contribution in the second half of the year from the commercial launch of CASGEVY in approved indications and geographies.

Charles F. Wagner: Now switching to guidance, there's no change to our 2024 total product revenue guidance range of $10.55 billion to $10.75 billion, representing revenue growth of 8% at the midpoint at current exchange rates, we have high visibility into this revenue outlook. We expect continued growth in CF as we continue to reach more patients including <unk>.

Charles F. Wagner: The ones in core markets and select other countries as well as contribution in the second half of the year from the commercial launch of cast JV in approved indications and geographies.

Reshma Kewalramani: For total Vertex operating expenses, we continue to project $4.3 to 4.4 billion in full year 2024 combined non-GAAP, SG&A, R&D, and acquired IP R&D. This operating expense range continues to include approximately $125 million in currently anticipated IP R&D charges. Upon the close of the Alpine acquisition, we expect Alpine's projected non-GAAP operating expenses for the remainder of 2024 to be absorbed within this guidance range, but note the potential impacts of transaction accounting, including any potential acquired IP R&D charges, will be determined at the time of closing. There's also no change to our full year 2024 non-GAAP effective tax rate guidance range of 20% to 21%. In closing, Vertex posted excellent results yet again to start off the year as we delivered strong revenue growth, regulatory approvals, and commercial launches.

For total Vertex operating expenses, we continue to project $4.3 to 4.4 billion in full year 2024 combined non-GAAP, SG&A, R&D, and acquired IP R&D. This operating expense range continues to include approximately $125 million in currently anticipated IP R&D charges. Upon the close of the Alpine acquisition, we expect Alpine's projected non-GAAP operating expenses for the remainder of 2024 to be absorbed within this guidance range, but note the potential impacts of transaction accounting, including any potential acquired IP R&D charges, will be determined at the time of closing. There's also no change to our full year 2024 non-GAAP effective tax rate guidance range of 20% to 21%. In closing, Vertex posted excellent results yet again to start off the year as we delivered strong revenue growth, regulatory approvals, and commercial launches.

Charles F. Wagner: For total Vertex operating expenses, we continue to project $4.3 to $4.4 billion in full year 2024 combined non-GAAP SG&A, R&D and acquired IP R&D. This operating expense range continues to include approximately $125 million in currently anticipated IP R&D charges. Upon the close of the Alpine acquisition, we expect Alpine's projected non-GAAP operating expenses for the remainder of 2024 to be absorbed within this guidance range but note, the potential impacts of transaction accounting, including any potential acquired IPR&D charges, will be determined at the time of closing. There is also no change to our full year 2024 non-GAAP effective tax rate guidance range of 20% to 21%.

Charles F. Wagner: For total vertex operating expenses, we continue to project $4.3 billion to $4.4 billion in full year 'twenty 'twenty four combined non-GAAP SG&A R&D and acquired IP R&D.

Charles F. Wagner: This operating expense range continues to include approximately $125 million and currently anticipated IP R&D charges. Upon the close of the Alpine acquisition. We expect alpine is projected non-GAAP operating expenses for the remainder of 2024 to be absorbed within this guidance range, but note the potential impacts of transact.

Charles F. Wagner: <unk> accounting, including any potential acquired IP R&D charges will be determined at the time of closing.

Charles F. Wagner: There's also no change to our full year 2024, non-GAAP effective tax rate guidance range of 20% to 21%.

Charles F. Wagner: In closing, Vertex posted excellent results yet again to start off the year as we delivered strong revenue growth, regulatory approvals and commercial launches. We also strengthened our capabilities in preparation for additional near-term launches, progressed our mid and earlier stage pipeline and entered the clinic in our 10th disease area of ADPKD. Importantly, we also announced the anticipated acquisition of Alpine Immune Sciences, a compelling fit with Vertex's strategy. Post-close, we aim to leverage Vertex's clinical, regulatory and commercial capabilities to accelerate development and commercialization of POVE.

Charles F. Wagner: In closing vertex posted excellent results, yet again to start off the year as we delivered strong revenue growth regulatory approvals and commercial launches.

Reshma Kewalramani: We also strengthened our capabilities in preparation for additional near-term launches, progressed our mid- and earlier-stage pipeline, and entered the clinic in our 10th disease area of ADPKD. Importantly, we also announced the anticipated acquisition of Alpine Immune Sciences, a compelling fit with Vertex's strategy. Post-close, we aim to leverage Vertex's clinical, regulatory, and commercial capabilities to accelerate development and commercialization of POVI. We are targeting approval in IgAN in 2027 and contribution to Vertex's revenue growth and diversification beginning in 2028, leveraging a specialty market approach with attractive margins. As we move through 2024, we anticipate further important milestones, as detailed on slide 18, to mark our continued progress in multiple disease areas. Please note that this pipeline slide will not reflect programs from Alpine Immune Sciences until post-transaction close.

We also strengthened our capabilities in preparation for additional near-term launches, progressed our mid- and earlier-stage pipeline, and entered the clinic in our 10th disease area of ADPKD. Importantly, we also announced the anticipated acquisition of Alpine Immune Sciences, a compelling fit with Vertex's strategy. Post-close, we aim to leverage Vertex's clinical, regulatory, and commercial capabilities to accelerate development and commercialization of POVI. We are targeting approval in IgAN in 2027 and contribution to Vertex's revenue growth and diversification beginning in 2028, leveraging a specialty market approach with attractive margins. As we move through 2024, we anticipate further important milestones, as detailed on slide 18, to mark our continued progress in multiple disease areas. Please note that this pipeline slide will not reflect programs from Alpine Immune Sciences until post-transaction close.

Charles F. Wagner: We also strengthened our capabilities in preparation for additional near term launches progressed, our mid and earlier stage pipeline and entered the clinic and our 10th disease area of 80 PK D. Importantly.

Charles F. Wagner: Importantly, we also announced the anticipated acquisition of Alpine immune sciences, a compelling fit with vertex is strategy.

Charles F. Wagner: Clothes, we aim to leverage vertex as clinical regulatory and commercial capabilities to accelerate development and commercialization of Povey, we're targeting approval and again in 2027% and contribution to vertex as revenue growth and diversification beginning in 2028, leveraging our specialty market approach with attractive margins.

Charles F. Wagner: We are targeting approval in IgAN in 2027 and contribution to Vertex's revenue growth and diversification beginning in 2028, leveraging a specialty market approach with attractive margins. As we move through 2024, we anticipate further important milestones -- as detailed on slide 18 -- to mark our continued progress in multiple disease areas. Please note that this pipeline slide will not reflect programs from Alpine Immune Sciences until post-transaction close. We look forward to updating you on our progress on future calls and I'll now ask Susie to begin the Q&A period. We will now begin the question and answer session. Go ahead, Ms. Susie.

We are targeting approval in IgAN in 2027 and contribution to Vertex's revenue growth and diversification beginning in 2028, leveraging a specialty market approach with attractive margins. As we move through 2024, we anticipate further important milestones -- as detailed on slide 18 -- to mark our continued progress in multiple disease areas. Please note that this pipeline slide will not reflect programs from Alpine Immune Sciences until post-transaction close. We look forward to updating you on our progress on future calls and I'll now ask Susie to begin the Q&A period.

Charles F. Wagner: As we move through 'twenty 'twenty four we anticipate further important milestones as detailed on slide 18 to Mark our continued progress in multiple disease areas. Please note that this pipeline slide will not reflect programs from alpine immune sciences until post transaction close we look forward to updating you on our progress on future.

Reshma Kewalramani: We look forward to updating you on our progress on future calls, and I'll now ask Susie to begin the Q&A period. We will now begin the question-and-answer session. Go ahead, Ms. Susie. No, that's great. Thanks, Chuck. All right. To ask a question, please press star then one on your touch-tone 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, we'll pause momentarily to assemble our roster. And the first question will come from Jeff Meacham with Bank of America. Please go ahead. Great. Good afternoon, guys. Thanks for the question. I had a few on the filings. So the first question is for vanzacaftor. Do you think you guys will get a claim for the sweat chloride benefit?

We look forward to updating you on our progress on future calls, and I'll now ask Susie to begin the Q&A period.

Charles F. Wagner: Calls and I'll now ask Susie to begin the Q&A period.

Operator: We will now begin the question-and-answer session. Go ahead, Ms. Susie.

Operator: We will now begin the question and answer session. Go ahead, Ms. Susie.

Susie Lisa: We will now begin the question and answer session.

Susie Lisa: No, that's great. Thanks, Chuck.

Susie Lisa: Go ahead Ms Susie.

Susie Lisa: No that's great. Thanks Chuck.

Susie Lisa: Nope, that's great. Thanks, Chuck. Alright. To ask a question, please press star then 1 on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys.

Susie Lisa: Nope, that's great. Thanks, Chuck.

Operator: All right. To ask a question, please press star then one on your touch-tone 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, we'll pause momentarily to assemble our roster. And the first question will come from Jeff Meacham with Bank of America. Please go ahead.

Alright. To ask a question, please 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. And the first question will come from Geoff Meacham with Bank of America. Please go ahead. Great afternoon, guys. Thanks for the questions. I had a few on the filings.

Operator: Alright. To ask a question, please 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.

Susie Lisa: Alright to ask a question. Please 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, we'll pause momentarily to assemble our roster.

Operator: And to withdraw your question, please press star then 2. And at this time, we'll pause momentarily to assemble our roster. And the first question will come from Geoff Meacham with Bank of America. Please go ahead. Great afternoon, guys. Thanks for the questions. I had a few on the filings.

And the first question will come from Geoff Meacham with Bank of America. Please go ahead. Great afternoon, guys. Thanks for the questions. I had a few on the filings.

And the first question will come from Geoff Meacham with Bank of America. Please go ahead.

Susie Lisa: And the first question will come from Geoff Meacham with Bank of America. Please go ahead.

Geoff Meacham: Great. Afternoon, guys. Thanks for the question. I had a few on the filings. So, the first question is for VANZA -- do you think you guys will get a claim for the sweat chloride benefit? It seems like, obviously, you'll have the Phase III data on the label. I'm just curious what you can do from a regulatory perspective to kind of elevate the sweat chloride benefit. So, that's the first question. The second one, kind of the same question for 548 and acute pain. Do you think that -- are you guys going to push to make a claim as an option to opioids or to LYRICA? I wondered if the regulatory climate can drive that. Thank you.

Geoff Meacham: Great. Good afternoon, guys. Thanks for the question. I had a few on the filings. So the first question is for vanzacaftor. Do you think you guys will get a claim for the sweat chloride benefit?

Geoff Meacham: Great. Good afternoon, guys. Thanks for the question.

Geoff Meacham: So, the first question is for Vanza. Do you think you guys will get a claim for the sweat chloride benefit? It seems like obviously you'll have the phase 3 data on the label. I'm just curious what you can do from a regulatory perspective to kind of elevate the sweat chloride benefit.

Geoff Meacham: I had a few on the filings. So the first question is for vans.

Geoff Meacham: Do you think you guys will get a claim for the sweat chloride benefit it seems like obviously youll have the phase III data on the label I'm. Just curious what you can do from a regulatory perspective to kind of elevate the sweat chloride benefit.

Reshma Kewalramani: It seems like, obviously, you'll have the phase 3 data on the label. I'm just curious what you can do from a regulatory perspective to kind of elevate the sweat chloride benefit. So that's the first question. The second one, kind of the same question for 548 and acute pain. Do you think that are you guys going to push to make a claim as an option to opioids or to Lyrica? I wondered if the regulatory climate can drive that. Thank you. Yeah. Hey, Jeff, this is Reshma. Let me take those questions. On the vanzacaftor triple, if you go back and look at all of the CFTR modulated labels, you'll see that we always have sweat chloride in the labels, and they are reflected because it is indeed a pharmacodynamic or PD marker.

It seems like, obviously, you'll have the phase 3 data on the label. I'm just curious what you can do from a regulatory perspective to kind of elevate the sweat chloride benefit. So that's the first question. The second one, kind of the same question for 548 and acute pain. Do you think that are you guys going to push to make a claim as an option to opioids or to Lyrica? I wondered if the regulatory climate can drive that. Thank you.

Geoff Meacham: So, that's the first question. The second one, kind of the same question for 548 and acute pain. Do you think that you guys are going to push to make a claim as an option for opioids or for Lyrica? I wondered if the regulatory climate could drive that.

So, that's the first question.

Vans: So that's the first question the second one kind of the same question for 540 <unk> acute pain do you think that you guys are going to push.

The second one, kind of the same question for 548 and acute pain. Do you think that you guys are going to push to make a claim as an option for opioids or for Lyrica? I wondered if the regulatory climate could drive that. Thank you.

Vans: Make a claim for as an option.

Vans: <unk> or xolair.

Vans: Oh, Lyrica I wondered if the regulatory climate and can drive that thank you.

Reshma Kewalramani: Yeah. Hey, Jeff, this is Reshma. Let me take those questions. On the vanzacaftor triple, if you go back and look at all of the CFTR modulated labels, you'll see that we always have sweat chloride in the labels, and they are reflected because it is indeed a pharmacodynamic or PD marker.

Vans: Yeah, Hey, Jeff This is Ray Schmitt, let me take those questions.

Reshma Kewalramani: Thank you. Yeah. Hey, Geoff, this is Reshma.

Thank you.

On the vans a catheter triple if you go back and look at all of the C. F. T. R. Modulate labeled you'll see that we always have a sweat chloride in the labels and they are reflected because it is indeed, a pharmacodynamic or PD marker. So I fully expect that the.

Reshma Kewalramani: Yeah. Hey, Geoff, this is Reshma. Let me take those questions. On the VANZACAFTOR Triple, if you go back and look at all of the CFTR-modulated labels, you'll see that we always have sweat chloride in the labels and they are reflected because it is, indeed, a pharmacodynamic or PD marker. So, I fully expect that the sweat chloride data from the VANZA Triple studies will be reflected in the label. Obviously, we are just at the point of having submitted the filing so, we're not at the point of label negotiations yet but if history serves as a guide, I expect that sweat chloride will absolutely be in the label.

Reshma Kewalramani: So I fully expect that the sweat chloride data from the vanzacaftor triple studies will be reflected in the label. Obviously, we are just at the point of having submitted the filing, so we're not at the point of label negotiations yet. But if history serves as a guide, I expect that sweat chloride will absolutely be in the label. On VX-548, Jeff, I think your question was about the DPN and diabetic peripheral neuropathy study, but let me broaden the question about VX-548 and acute pain because that's the filing that we have already initiated the rolling submission. We've already submitted a few of the modules, and we expect, as I said in my prepared remarks, to complete the filing this quarter.

So I fully expect that the sweat chloride data from the vanzacaftor triple studies will be reflected in the label. Obviously, we are just at the point of having submitted the filing, so we're not at the point of label negotiations yet. But if history serves as a guide, I expect that sweat chloride will absolutely be in the label. On VX-548, Jeff, I think your question was about the DPN and diabetic peripheral neuropathy study, but let me broaden the question about VX-548 and acute pain because that's the filing that we have already initiated the rolling submission. We've already submitted a few of the modules, and we expect, as I said in my prepared remarks, to complete the filing this quarter.

Reshma Kewalramani: Let me take those questions. On the VANSA-CAFTR triple, if you go back and look at all of the CFTR modulated labels, you'll see that we always have sweat chloride in the labels, and it is reflected because it is indeed a pharmacodynamic or PD marker. So I fully expect that the sweat chloride data from the VANSA triple studies will be reflected in the label. Obviously, we are just at the point of having submitted the filing, so we're not at the point of label negotiations yet, but if history serves as a guide, I expect that sweat chloride will absolutely be in the label.

Vans: Sweat chloride data from the vans are triple studies will be reflected in the label. Obviously, we're just at the point of having submitted the filing so we're not at the point of label negotiations yet, but if history serves as a guide I expect the sweat chloride will absolutely be in the label on VX 548, Jeff I think your quest.

Vans: <unk> was about the.

Vans: D P in diabetic peripheral neuropathy study, but let me broaden the question about five four at an acute tank is that's the filing that we have already initiated the rolling submission. We've already submitted a few of the modules and we expect as I said in my prepared remarks to complete the filing this quarter.

Reshma Kewalramani: We are submitting all of the data that we generated in acute pain, and the same will be true when it comes to the diabetic peripheral neuropathy data. And insofar as the acute pain phase 3 results are versus placebo as a primary endpoint, but there are data that have the opioid arm in there, I expect that it will be a discussion with the regulators about how exactly they want to display it. We are not at the point for the acute pain studies to have label negotiations and quite a bit far away from it for the DPN studies, which are just starting phase 3. But I will say that the reason we have a pregabalin arm in the phase 3 DPN study is exactly for that reason, for us to be able to share the data with prescribers.

We are submitting all of the data that we generated in acute pain, and the same will be true when it comes to the diabetic peripheral neuropathy data. And insofar as the acute pain phase 3 results are versus placebo as a primary endpoint, but there are data that have the opioid arm in there, I expect that it will be a discussion with the regulators about how exactly they want to display it. We are not at the point for the acute pain studies to have label negotiations and quite a bit far away from it for the DPN studies, which are just starting phase 3. But I will say that the reason we have a pregabalin arm in the phase 3 DPN study is exactly for that reason, for us to be able to share the data with prescribers.

Vans: We are submitting all of the data that we generated in acute pain and the same will be true when it comes to the diabetic peripheral neuropathy data and in so far as the acute pain phase three results are versus placebo.

Reshma Kewalramani: On VX-548, Geoff, I think your question was about the DPM - diabetic peripheral neuropathy -- study but let me broaden the question about 548 in acute pain because that's the filing that we have already initiated the rolling submission. We've already submitted few of the module then, we expect, as I said in my prepared remarks, to complete the filing this quarter. We are submitting all of the data that we generated in acute pain and the same will be true when it comes to the diabetic peripheral neuropathy data and insofar as the acute pain Phase III results are versus placebo as the primary endpoint. But there are data that have the opioid arm in there, I expect that it will be a discussion with the regulators about how exactly they want to display it. We are not at the point for the acute pain studies to have label negotiations and quite a bit far away from it for the DPN studies, which are just starting Phase III. But I will say that the reason we have a PREGABALIN arm in the Phase III DPN study is exactly for that reason, for us to be able to share the data with prescribers.

On VX-548, Geoff, I think your question was about the DPM - diabetic peripheral neuropathy -- study but let me broaden the question about 548 in acute pain because that's the filing that we have already initiated the rolling submission. We've already submitted few of the module then, we expect, as I said in my prepared remarks, to complete the filing this quarter. We are submitting all of the data that we generated in acute pain and the same will be true when it comes to the diabetic peripheral neuropathy data and insofar as the acute pain Phase III results are versus placebo as the primary endpoint.

Vans: As the primary endpoint, but there are data that have the opioid.

Vans: Arm in there I expect that it will be a discussion with the regulators about how exactly they want to display. It we are not at the point for the acute pain studies to have label negotiations and quite a bit far away from it for that DPM studies, which are just starting phase III, but I will.

But there are data that have the opioid arm in there, I expect that it will be a discussion with the regulators about how exactly they want to display it. We are not at the point for the acute pain studies to have label negotiations and quite a bit far away from it for the DPN studies, which are just starting Phase III. But I will say that the reason we have a PREGABALIN arm in the Phase III DPN study is exactly for that reason, for us to be able to share the data with prescribers.

Vans: I'll say that the reason we have a pregabalin arm in the phase III DPM study is exactly for that reason for us to be able to share the data with prescribers.

Reshma Kewalramani: Rachel, just a quick follow-up to that, just on the alternative to opioids. I mean, obviously, you don't know yet when it comes to the label, but do you think you'll need that to help with Medicare kind of reimbursement? Yeah. So on the acute pain side, Jeff, I think that the most important data are going to be the primary endpoint data, and I'll ask Stuart to comment on that in a minute. And with regard to securing reimbursement and ensuring that there are no barriers to prescribing a non-opioid, we see that as a very important place for policy. Stuart? Yeah. Thanks, Rachel. So first thing I would say, Jeff, is remember we are seeking a broad, moderate, severe acute pain label so that the product could be used if the physician decides and the patient wants to for any type of acute pain.

Geoff Meacham: Rachel, just a quick follow-up to that, just on the alternative to opioids. I mean, obviously, you don't know yet when it comes to the label, but do you think you'll need that to help with Medicare kind of reimbursement?

Reshma Kewalramani: Reshma, just a quick follow-up to that, just on the alternative to opioids. I mean, obviously, you don't know yet when it comes to the label but do you think you'll need that to help with Medicare kind of reimbursement? Yeah, so on the acute pain side, Jeff, I think that the most important data are going to be the primary endpoint data. And I'll ask Stuart to comment on that in a minute. And with regard to securing reimbursement and ensuring that there are no barriers to prescribing non-opioid medicines, we see that as a very important place for policy. Stuart?

Geoff Meacham: Reshma, just a quick follow-up to that, just on the alternative to opioids. I mean, obviously, you don't know yet when it comes to the label but do you think you'll need that to help with Medicare kind of reimbursement?

Vans: Just a quick follow up to that just on.

Vans: The alternative to opioids.

Vans: Obviously, you don't know yet when it comes to the label, but do you think you'll need that to help with Medicare reimbursement.

Reshma Kewalramani: Yeah. So on the acute pain side, Jeff, I think that the most important data are going to be the primary endpoint data, and I'll ask Stuart to comment on that in a minute. And with regard to securing reimbursement and ensuring that there are no barriers to prescribing a non-opioid, we see that as a very important place for policy. Stuart?

Speaker Change: Yeah. So on the on the acute pain side, Jeff I think that the.

Reshma Kewalramani: Yeah. So, on the acute pain side, Geoff, I think that the most important data are going to be the primary endpoint data. And I'll ask Stuart to comment on that in a minute. And with regard to securing reimbursement and ensuring that there are no barriers to prescribing non-opioid medicines, we see that as a very important place for policy. Stuart?

Speaker Change: The most important data are going to be the primary endpoint data and I'll ask Stuart to comment on that in a minute and with regard to securing reimbursement and ensuring that there are no barriers to prescribing non opioid we see that as a very important place for policy Stuart.

Stuart Arbuckle: Yeah. Thanks, Rachel. So first thing I would say, Jeff, is remember we are seeking a broad, moderate, severe acute pain label so that the product could be used if the physician decides and the patient wants to for any type of acute pain.

Stuart A. Arbuckle: Yeah. Thanks <unk> so.

Stuart A. Arbuckle: Yeah. Thanks, Reshma. So, first thing I would say, Geoff, is to remember, we are seeking a broad, moderate-severe acute pain label so that the product could be used if the physician decides and the patient wants to for any type of acute pain. And so, we're not really looking for a label that's looking to niche us or pre-position us relative to other agents that are out there. We want physicians to have the broadest possible ability to use the product in the patients they see fit. As Reshma says, the primary endpoint, which talks to the really strong efficacy we see in moderate-severe acute pain, is clearly very important -- as is all the additional safety and tolerability data that we have to support VX-548. In combination with the fact that, given its mechanism, it doesn't have addictive potential. So, we're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for. Thank you very much.

Yeah. Thanks, Reshma. So, first thing I would say, Geoff, is to remember, we are seeking a broad, moderate-severe acute pain label so that the product could be used if the physician decides and the patient wants to for any type of acute pain. And so, we're not really looking for a label that's looking to niche us or pre-position us relative to other agents that are out there. We want physicians to have the broadest possible ability to use the product in the patients they see fit. As Reshma says, the primary endpoint, which talks to the really strong efficacy we see in moderate-severe acute pain, is clearly very important -- as is all the additional safety and tolerability data that we have to support VX-548. In combination with the fact that, given its mechanism, it doesn't have addictive potential. So, we're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for.

Stuart A. Arbuckle: First thing I would say Jeff is remember we are seeking a broad moderate to severe acute pain label the product could be used if the physician decides and the patient wants to you for any type of acute pain.

Reshma Kewalramani: We're not really looking for a label that's looking too niche or pre-positionist relative to other agents that are out there. We want physicians to have the broadest possible ability to use the product in the patients they see fit. As Rachel says, the primary endpoint, which talks to the really strong efficacy we see in moderate to severe acute pain, is clearly very important, as is all the additional safety and tolerability data that we have to support VX-548 in combination with the fact that, given its mechanism, it doesn't have addictive potential. We're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for. Great. Thank you very much. You bet.

We're not really looking for a label that's looking too niche or pre-positionist relative to other agents that are out there. We want physicians to have the broadest possible ability to use the product in the patients they see fit. As Rachel says, the primary endpoint, which talks to the really strong efficacy we see in moderate to severe acute pain, is clearly very important, as is all the additional safety and tolerability data that we have to support VX-548 in combination with the fact that, given its mechanism, it doesn't have addictive potential. We're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for.

Stuart A. Arbuckle: And so we're not really looking for a label is looking to nisha or pre position us relative to other agents that are out there we want physicians to have the broadest possible ability.

Stuart A. Arbuckle: We want physicians to have the broadest possible ability to use the product in the patients they see fit. As Reshma says, you know, the primary endpoint, which talks to the really strong efficacy we see in moderate, severe acute pain, is clearly very important, as is all the additional safety and tolerability data that we have to support VX548 in combination with the fact that, given its mechanism, it doesn't have addictive potential. So we're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for. Thank you very much.

Stuart A. Arbuckle: To use the product and the patients they see fit as restaurant says you know the primary endpoint, which talks to the really strong efficacy we see in moderate to severe acute pain is clearly very important as it is all the additional safety and Tolerability data that we have to support VX 548.

As Reshma says, the primary endpoint, which talks to the really strong efficacy we see in moderate-severe acute pain, is clearly very important -- as is all the additional safety and tolerability data that we have to support VX-548. In combination with the fact that, given its mechanism, it doesn't have addictive potential. So, we're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for.

Stuart A. Arbuckle: In combination with the fact that given its mechanism it doesn't have it.

Stuart A. Arbuckle: Victor potential so we're really looking at the full range of efficacy and safety, which I think is going to be the most important thing that's going to allow physicians to decide who they want to prescribe the product for.

Geoff Meacham: Great. Thank you very much.

Speaker Change: Great. Thank you very much.

Reshma Kewalramani: You bet.

Speaker Change: You bet.

Geoff Meacham: Thank you very much.

Reshma Kewalramani: The next question will come from Jessica Fye with J.P. Morgan. Please go ahead. Hey, guys. Thanks for taking my question. I'm curious, for your various NaV1.8 and NaV1.7 programs, would you consider advancing maybe another molecule for musculoskeletal pain, perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Just curious if you kind of have any thoughts about that so as to not leave potential value on the table. Thank you. Yeah. Hey, thanks for that question, Jeff. So just to set the stage, we see three distinct areas in pain: acute pain, neuropathic pain, and then everything else. And in everything else, I would add musculoskeletal pain. It's the kind of osteoarthritis kind of pain.

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

Stuart A. Arbuckle: You bet. The next question will come from Jessica Fye, with J.P. Morgan. Please go ahead. Thanks for taking my question. I'm curious about your various Nav 1.8 and 1.7 programs. Would you consider advancing maybe another molecule for musculoskeletal... perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Curious if you kind of have any thoughts about that so as to not leave potential value on the table. Yeah, hey, thanks for that question, Jess.

Reshma Kewalramani: You bet.

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

The next question will come from Jessica Fye, with J.P. Morgan. Please go ahead. Thanks for taking my question. I'm curious about your various Nav 1.8 and 1.7 programs. Would you consider advancing maybe another molecule for musculoskeletal... perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Curious if you kind of have any thoughts about that so as to not leave potential value on the table. Yeah, hey, thanks for that question, Jess.

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

Jessica Fye: Hey, guys. Thanks for taking my question. I'm curious, for your various NaV1.8 and NaV1.7 programs, would you consider advancing maybe another molecule for musculoskeletal pain, perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Just curious if you kind of have any thoughts about that so as to not leave potential value on the table. Thank you.

Yeah.

Jessica Fye: Hey, guys. Thanks for taking my question I'm curious for your various.

Thanks for taking my question. I'm curious about your various Nav 1.8 and 1.7 programs. Would you consider advancing maybe another molecule for musculoskeletal... perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Curious if you kind of have any thoughts about that so as to not leave potential value on the table. Yeah, hey, thanks for that question, Jess.

Jessica Fye: Hey, guys. Thanks for taking my question. I'm curious, for your various NaV1.8 and 1.7 programs, would you consider advancing maybe another molecule for musculoskeletal pain, perhaps engaging a commercial partner to the extent it's not a Vertexian sales detail? Just curious if you kind of have any thoughts about that so as to not leave potential value on the table. Thank you.

Jessica Fye: Yes, one eight and $1 seven programs.

Jessica Fye: Would you consider advancing maybe another molecule for musculoskeletal pain, perhaps engaging a commercial partner to the extent, it's not a vertex in sales detail.

Jessica Fye: Curious if you kind of have any thoughts about that so as to not leave potential value on the table. Thank you.

Reshma Kewalramani: Yeah. Hey, thanks for that question, Jeff. So just to set the stage, we see three distinct areas in pain: acute pain, neuropathic pain, and then everything else. And in everything else, I would add musculoskeletal pain. It's the kind of osteoarthritis kind of pain.

Yeah. Hey, thanks for that question, Jess. So, just to set the stage, we see three distinct areas in pain, acute pain, neuropathic pain and then, everything else. And in everything else, I would add musculoskeletal pain. It's the kind of osteoarthritis kind of pain. We fully intend to serve all patients and I fully do expect that our NAV1.8 -- and when the time is right, the NaV1.7 or the NaV1.7-1.8 combinations -- our pain assets will serve patients with musculoskeletal pain. And I say that because, as you know, the predecessor molecule to VX-548, VX-150, already demonstrated that potential. But we wanna go one step at a time here. So, first, we're gonna do acute and neuropathic pain and we see the research, development and commercialization as completely Vertexian.

Reshma Kewalramani: Yeah. Hey, thanks for that question, Jess. So, just to set the stage, we see three distinct areas in pain, acute pain, neuropathic pain and then, everything else. And in everything else, I would add musculoskeletal pain. It's the kind of osteoarthritis kind of pain. We fully intend to serve all patients and I fully do expect that our NAV1.8 -- and when the time is right, the NaV1.7 or the NaV1.7-1.8 combinations -- our pain assets will serve patients with musculoskeletal pain. And I say that because, as you know, the predecessor molecule to VX-548, VX-150, already demonstrated that potential.

Speaker Change: Yeah, Hey, thanks for that question Jeff.

Stuart A. Arbuckle: So just to set the stage, we see three distinct areas in pain, acute pain, neuropathic pain, and then everything else. And to everything else, I would add musculoskeletal pain. It's the kind of osteoarthritis kind of pain.

Speaker Change: To set the stage, we see three distinct areas in pain acute pain.

Speaker Change: Europe, Pathic pain, and then everything else and in everything else I would add muscular skeletal pain, it's the kind of osteoarthritis kind of pain.

Reshma Kewalramani: We fully intend to serve all patients, and I fully do expect that our NaV1.8 and, when the time is right, the NaV1.7 or the NaV1.7, 1.8 combinations, our pain assets will serve patients with musculoskeletal pain. And I say that because, as you know, the predecessor molecule to VX-548, VX-150, already demonstrated that potential. But we want to go one step at a time here. So first, we're going to do acute and neuropathic pain, and we see the research, development, and commercialization as completely Vertexian. And then for the musculoskeletal pain, whether that's with VX-548, the next-in-class medicine, VX-993, or the ones that come after that, again, either NaV1.8 or NaV1.7 alone or in combination, any of those for musculoskeletal pain, we will get them to patients, but we will not be commercializing that ourselves because it is a primary care cell.

We fully intend to serve all patients, and I fully do expect that our NaV1.8 and, when the time is right, the NaV1.7 or the NaV1.7, 1.8 combinations, our pain assets will serve patients with musculoskeletal pain. And I say that because, as you know, the predecessor molecule to VX-548, VX-150, already demonstrated that potential. But we want to go one step at a time here. So first, we're going to do acute and neuropathic pain, and we see the research, development, and commercialization as completely Vertexian. And then for the musculoskeletal pain, whether that's with VX-548, the next-in-class medicine, VX-993, or the ones that come after that, again, either NaV1.8 or NaV1.7 alone or in combination, any of those for musculoskeletal pain, we will get them to patients, but we will not be commercializing that ourselves because it is a primary care cell.

Reshma Kewalramani: We fully intend to serve all patients, and I fully expect that our NAV1-8, and when the time is right, the NAV1-7 or the NAV1-7, 1-8 combinations, our pain assets will serve patients with musculoskeletal pain. And I say that because, as you know, the predecessor molecule to VX548, VX150, has already demonstrated that potential. But we wanna go one step at a time here. So first, we're gonna do acute and neuropathic pain, and we see the research, development, and commercialization as completely vertexian.

Speaker Change: We fully intend to serve all patients and I fully expect that our NAV, one eight and when the time is right. The NAV, one seven or the NAV 1718 combinations are pain assets will serve patients with muscular skeletal pain and I say that because as you know the predecessor molecule to VX five four at the X.

But we wanna go one step at a time here. So, first, we're gonna do acute and neuropathic pain and we see the research, development and commercialization as completely Vertexian. And then, for the musculoskeletal pain, whether that's with VX-548, the next-in-class medicine, VX-993 or the ones that come after that -- again, either NaV1.8 or NaV1.7 alone or in combination, any of those for musculoskeletal pain, we will get them to patients but we will not be commercializing that ourselves because it is a primary care cell. But we do absolutely see value there and we see a need to help those patients. But one step at a time. First, neuropathic and acute pain -- and that, we will do ourselves. The next question will come from Salveen Richter, with Goldman Sachs. Please go ahead.

Speaker Change: One <unk> already demonstrated that potential, but we want to go one step at a time here. So first we're gonna do acute in neuropathic pain, and we see the research development and commercialization is completely vertex Ian and then for the muscular skeletal pain, whether that's with VX 548.

Reshma Kewalramani: And then for musculoskeletal pain, whether that's with VX548, the next in class medicine, VX993, or the ones that come after that, again, either NAV1-8 or NAV1-7 alone or in combination, any of those for musculoskeletal pain, we will get them to patients, but we will not be commercializing that ourselves because it is a primary care clinic. But we do absolutely see value in that, and But one step at a time, first neuropathic and acute pain, and that we will do ourselves. The next question will come from Salveen Richter, with Goldman Sachs. Please go ahead.

Speaker Change: The next in class Medicine, VX 993, or the ones that come after that again, either NAV, one eight or NAV, one seven alone or in combination those are any of those for muscular skeletal pain, we will get them to patients, but we will not be commercializing that ourselves because it is.

Speaker Change: As a primary care sell but we do absolutely see value there and we see a need to help those patients, but one step at a time first neuropathic and acute pain and that we will do ourselves.

Reshma Kewalramani: But we do absolutely see value there, and we see a need to help those patients. But one step at a time, first neuropathic and acute pain, and that we will do ourselves. Thanks. The next question will come from Salveen Richter with Goldman Sachs. Please go ahead. Good afternoon. Thanks for taking my question. Two-part here on the acute pain program. With regard to engaging with key decision-makers, can you help us to understand the importance of the hospital administrators who are taking into account the legislative tailwinds versus the physician treaters here in the specific articles that you cited, and how they might make or work together here to make a decision?

But we do absolutely see value there, and we see a need to help those patients. But one step at a time, first neuropathic and acute pain, and that we will do ourselves.

Jessica Fye: Thanks.

Operator: The next question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Thanks.

Thanks. The next question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Jessica Fye: Thanks.

Operator: The next question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Speaker Change: The next question will come from Salvia richer with Goldman Sachs. Please go ahead.

Salveen Richter: Good afternoon. Thanks for taking my question. Two-part here on the acute pain program. With regard to engaging with key decision-makers, can you help us to understand the importance of the hospital administrators who are taking into account the legislative tailwinds versus the physician treaters here in the specific articles that you cited, and how they might make or work together here to make a decision? And my second question is, what hospitals really need to make an argument for using it in low opioids and whether outcomes data is required, be it reduction in recovery room time, or lower usage of opioids, or rates of addictions being reported? Thank you.

Salveen Richter: Good afternoon. Thanks for taking my question two part here on the acute pain program with regard to engaging with key decision makers can you help us to understand the importance of the hospital administrators, who are taking into account the legislative tailwind.

Salveen Richter: Good afternoon, thanks for taking my question. Two-part here on the acute pain program. With regard to engaging with key decision-makers, can you help us to understand the importance of the hospital administrators who are taking into account the legislative tailwinds versus the physician treaters here in the specific verticals that you cited and how they might make or work together here to make a decision? And my second question is, what hospitals really need to make an argument for using it in low opioids and whether outcomes data is required, be it reduction in recovery room time or lower usage of opioids or rates of addictions being reported. Thank you.

Salveen Richter: Versus the physician treaters here in the in the specific verticals that you've cited and how they might make.

Salveen Richter: Our work together here to make a decision and my second question is what hospitals really need to make an argument for using it and in love opioids.

Reshma Kewalramani: And my second question is, what hospitals really need to make an argument for using it in low opioids and whether outcomes data is required, be it reduction in recovery room time, or lower usage of opioids, or rates of addictions being reported? Thank you. Sure. Salveen, let me ask Stuart to comment. Yeah. So Salveen, all of the stakeholders that you described are going to be important in making decisions on the use of a new medicine in the institutional setting. So administrators are certainly going to be important, but as are our physician advocates who are going to advocate based on the efficacy and safety of the medicine. And the process is a relatively standardized process. It's not going to be created newly for suzetrigine.

Salveen Richter: Weather outcomes data that's required the production recovery room time, or lower usage of opioids or rates of addiction being reported thank you.

Reshma Kewalramani: Sure. Salveen, let me ask Stuart to comment.

Speaker Change: Sure. So I mean, let me ask Stuart to comment, yes, so shelving.

Stuart A. Arbuckle: Sure, Salveen. Let me ask Stuart to comment. Yes. So, Salveen, all of the stakeholders that you described are going to be important in making decisions about the use of a new medicine in the institutional setting. So administrators are certainly going to be important, but so are our physician advocates who are going to advocate based on the efficacy and safety of the medicine, and the process is a relatively standardized process. It's not going to be created new for cizetrogene.

Reshma Kewalramani: Sure, Salveen. Let me ask Stuart to comment.

Stuart Arbuckle: Yeah. So Salveen, all of the stakeholders that you described are going to be important in making decisions on the use of a new medicine in the institutional setting. So administrators are certainly going to be important, but as are our physician advocates who are going to advocate based on the efficacy and safety of the medicine. And the process is a relatively standardized process. It's not going to be created newly for suzetrigine.

Yes. So, Salveen, all of the stakeholders that you described are going to be important in making decisions on the use of a new medicine in the institutional setting. So, administrators are certainly going to be important but as are physician advocates who are going to advocate based on the efficacy and safety of the medicine. And the process is a relatively standardized process, it's not going to be created merely for SUZETRIGINE. This is a standard process that hospitals go through to decide whether they're going to put it on their formulary and typically go through some sort of P&T committee process where all of the various stakeholders, be it physicians, be it the pharmacy team, be it the administrators, are all going to be making that decision collectively. They're particularly interested in the use, obviously, within the institutional setting. Use in the discharge setting is typically something which is a little bit more straightforward and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of a medicine like SUZETRIGINE.

Stuart A. Arbuckle: Yes. So, Salveen, all of the stakeholders that you described are going to be important in making decisions on the use of a new medicine in the institutional setting. So, administrators are certainly going to be important but as are physician advocates who are going to advocate based on the efficacy and safety of the medicine. And the process is a relatively standardized process, it's not going to be created merely for SUZETRIGINE.

Stuart A. Arbuckle: All of the stakeholders that you described they're going to be important in making decisions.

Stuart A. Arbuckle: The use of a new medicine in the institutional setting so administrators are certainly going to be.

Stuart A. Arbuckle: But as a physician advocates who are going to advocate, but advocate based on the efficacy and safety of the medicine and the process is a relatively standardized process its not going to be created newly forces at Eugene. This is a standard process that hospitals go through to decide whether they're going to put it.

This is a standard process that hospitals go through to decide whether they're going to put it on their formulary and typically go through some sort of P&T committee process where all of the various stakeholders, be it physicians, be it the pharmacy team, be it the administrators, are all going to be making that decision collectively. They're particularly interested in the use, obviously, within the institutional setting. Use in the discharge setting is typically something which is a little bit more straightforward and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of a medicine like SUZETRIGINE.

Reshma Kewalramani: This is a standard process that hospitals go through to decide whether they're going to put it on their formulary, and it'll typically go through some sort of P&T committee process where all of the various stakeholders, be it physicians, be it the pharmacy team, be it the administrators, are all going to be making that decision collectively. They're particularly interested in the use, obviously, within the institutional setting. Use in the discharge setting is typically something which is a little bit more straightforward, and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of a medicine like suzetrigine.

This is a standard process that hospitals go through to decide whether they're going to put it on their formulary, and it'll typically go through some sort of P&T committee process where all of the various stakeholders, be it physicians, be it the pharmacy team, be it the administrators, are all going to be making that decision collectively. They're particularly interested in the use, obviously, within the institutional setting. Use in the discharge setting is typically something which is a little bit more straightforward, and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of a medicine like suzetrigine.

Stuart A. Arbuckle: This is a standard process that hospitals go through to decide whether they're going to put it on their formulary and typically go through some sort of P&T committee process where all of the various stakeholders, be it physicians, be it the pharmacy team, be it the administrators, are all going to be making that decision collectively. They're particularly interested in its use, obviously, within the institutional setting. Use in the discharge setting is typically something which is a little bit more straightforward, and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of a medicine like cizetrogene.

Stuart A. Arbuckle: On their formulary and it's typically go through some sort of PMT committee process, where all of the various stakeholders be it physicians be it the pharmacy team. The administrators are all going to be making that decision.

Decision collectively of they're particularly interested in the use obviously within the institutional setting using the discharge setting is typically something which is a little bit more straightforward and that's why I suggested in my prepared remarks that we see that as the likely setting where there is going to be the earliest uptake of <unk>.

Stuart A. Arbuckle: A medicine like likes is that gene in terms of some of the outcomes data that you are referring to.

Reshma Kewalramani: In terms of some of the outcomes data that you were referring to, I think the clearest way of describing is every patient that is treated with suzetrigine when the other choice would have been an opioid is essentially providing opioid sparing for that patient. So that data, in many ways, is kind of already sort of readily available just from the data that we've already shared. And I think that data, in addition to all the other efficacy and safety data we've got, is going to be pretty impactful and compelling to the various stakeholders we've described. Thank you. The next question will come from Evan Sigerman with BMO Capital. Please go ahead. Hi, guys. Thank you so much for taking my question.

In terms of some of the outcomes data that you were referring to, I think the clearest way of describing is every patient that is treated with suzetrigine when the other choice would have been an opioid is essentially providing opioid sparing for that patient. So that data, in many ways, is kind of already sort of readily available just from the data that we've already shared. And I think that data, in addition to all the other efficacy and safety data we've got, is going to be pretty impactful and compelling to the various stakeholders we've described.

Stuart A. Arbuckle: In terms of some of the outcomes data that you were referring to, I think that the clearest way of describing is every patient that is treated with SUZETRIGINE when the other choice would have been an opioid, is essentially providing opioid-sparing for that patient. So that data, in many ways, is kind of already sort of readily available just from the data that we've already shared. And I think that data, in addition to all the other efficacy and safety data we've got, is going to be pretty impactful and compelling to the various stakeholders we've described. Thank you. The next question will come from Evan Seigerman with BMO Capital. Please go ahead. Hi guys.

In terms of some of the outcomes data that you were referring to, I think that the clearest way of describing is every patient that is treated with SUZETRIGINE when the other choice would have been an opioid, is essentially providing opioid-sparing for that patient. So that data, in many ways, is kind of already sort of readily available just from the data that we've already shared. And I think that data, in addition to all the other efficacy and safety data we've got, is going to be pretty impactful and compelling to the various stakeholders we've described.

Stuart A. Arbuckle: I think that the clearest way of describing is every patient that is treated with suzette Eugene when the other choice would have been an opioid is essentially providing opioid sparing for that patient. So that data in many ways is kind of already sort of readily available just from the data that we've already that we've already shared and I think that data.

Stuart A. Arbuckle: In addition to all the other efficacy and safety data, we've got is going to be pretty pretty impactful and compelling to the various stakeholders. We've described.

Salveen Richter: Thank you.

Speaker Change: Thank you.

Thank you. The next question will come from Evan Seigerman with BMO Capital. Please go ahead. Hi guys.

Salveen Richter: Thank you.

Operator: The next question will come from Evan Sigerman with BMO Capital. Please go ahead.

The next question will come from Evan Seigerman with BMO Capital. Please go ahead. Hi guys.

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

Speaker Change: The next question will come from Evan <unk> with BMO capital. Please go ahead.

Evan Seigerman: Hi, guys. Thank you so much for taking my question. I'd love to know if you could provide any additional color on how many patients in the United States have gotten their cells collected and maybe how we should think about the growth of cell collections in the US going forward? I'm just trying to understand what your trajectory of this could be like this year and next year. Thank you so much.

Evan Seigerman: Hi, guys. Thank you so much for taking my question. I'd love to know if you can provide any additional color on how many patients in the United States have gotten their cells collected and maybe how we should think about the growth of cell collections in the U.S. going forward? I'm just trying to understand what your trajectory of this could be like this year and next year. Thank you so much.

Evan Seigerman: Thank you so much for taking my questions. I'd love to know if you can provide any additional color on how many patients in the United States have gotten their cells collected and maybe how we should think about the growth of cell collections in the U.S. going forward. I'm just trying to understand what your trajectory for this could be like this year and next year. Thank you so much.

Evan: Hi, guys. Thank you so much for taking my questions Love to know if you can provide any additional color on how many patients in the United States have gotten their cells collected and maybe how we should think about the growth of cell collections in the U S going forward I'm just trying to understand what's your trajectory of this could be like this year and next year. Thank you so much.

Reshma Kewalramani: I'd love to know if you could provide any additional color on how many patients in the United States have gotten their cells collected and maybe how we should think about the growth of cell collections in the US going forward? I'm just trying to understand what your trajectory of this could be like this year and next year. Thank you so much. Yeah. Hey, Evan, just to set expectations, we're not going to comment very specifically on patients and exactly where they are in the cell collection process and in each region, but I will ask Stuart to give you a little bit of color commentary on what we're seeing.

Reshma Kewalramani: Yeah. Hey, Evan, just to set expectations, we're not going to comment very specifically on patients and exactly where they are in the cell collection process and in each region, but I will ask Stuart to give you a little bit of color commentary on what we're seeing. If I was stealing Stuart's thunder, if you really think about when CASGEVY was approved, which is December and January, I am so very pleased at the number of ATCs that are activated around the globe and the number of patients who have already started cell collection. Stuart, is there anything you want to add?

Speaker Change: Yeah, Hey, Evan just to set expectations, we're not going to comment.

Reshma Kewalramani: Yeah. Hey, Evan, just to set expectations, we're not going to comment very specifically on patients and exactly where they are in the cell collection process and in each region but I will ask Stuart to give you a little bit of color commentary on what we're seeing. And if I was stealing Stuart's thunder -- if you really think about when CASGEVY was approved, which is December and January, I am so very pleased with the number of ATCs that are activated around the globe and the number of patients who have already started cell collection. Stuart, is there anything you want to add?

Speaker Change: Very specifically on patients and exactly where they are in the south collection process and in each region, but I will ask Stuart to give you a little bit of color commentary on what we're seeing in.

Reshma Kewalramani: If I was stealing Stuart's thunder, if you really think about when CASGEVY was approved, which is December and January, I am so very pleased at the number of ATCs that are activated around the globe and the number of patients who have already started cell collection. Stuart, is there anything you want to add? Only that we are expecting the momentum to build based on all of the feedback that we've got and the trends that we're seeing in activations and cell collections. As Rachel said, we're delighted to have had five cell collections already. As she also mentioned, that represents patients in every region in which we are operating, including, obviously, the United States, and we expect those trends to continue to ramp up during the course of 2024, which we've always said was going to be a foundational year for CASGEVY. Great. Thank you.

Speaker Change: If I was stealing Stuart's Thunder.

Stuart A. Arbuckle: Now if you really think about when.

Stuart A. Arbuckle: Cash JV was approved which is December and January I am so very pleased that the number of atc's better activated around the globe and the number of patients who have already started cell collection. So it is there anything you want to add.

Stuart Arbuckle: Only that we are expecting the momentum to build based on all of the feedback that we've got and the trends that we're seeing in activations and cell collections. As Rachel said, we're delighted to have had five cell collections already. As she also mentioned, that represents patients in every region in which we are operating, including, obviously, the United States, and we expect those trends to continue to ramp up during the course of 2024, which we've always said was going to be a foundational year for CASGEVY.

Stuart A. Arbuckle: Only that we are expecting the momentum to build, based on all of the feedback that we've got and the trends that we're seeing in activations and cell collections. As Reshma said, we're delighted to have had five cell collections already. As she also mentioned, that represents patients in every region in which we are operating, including, obviously, the United States. We expect those trends to continue to ramp up during the course of 2024, which we've always said was going to be a foundational year for CASGEVY.

Speaker Change: Only that we are expecting the momentum to build based on all of the feedback that we've gotten the trends that we're seeing in activations and sell collections as restaurants said, we're delighted to have had five silk silk collections already.

She also mentioned that represents.

Speaker Change: Patients in every region in which we are operating including obviously, the United States and we expect those trends to continue to ramp up during the course of 2024, which we've always said was going to be a foundational year for cash Jerry.

Evan Seigerman: Great. Thank you.

Speaker Change: Great. Thank you.

Reshma Kewalramani: The next question will come from Colin Bristow with UBS. Please go ahead. Hey, good afternoon and congrats for the quarter. Maybe first, on the pain pipeline, I see you're advancing 993 to phase two. Could you just give us any sort of color or detail on how you expect this to be differentiated? And does this advancement mean you won't be taking 973 forward, which I think also recently completed phase one? And then, if I may, a quick housekeeping one. Any inventory moves in the quarter that we should be aware of? Thanks. Yep. Hey, Colin, let me break that up into two questions. One on inventory, which I will ask Charlie to comment on first, and then I'll come back on 993 and 973. Yeah.

Operator: The next question will come from Colin Bristow with UBS. Please go ahead.

Speaker Change: The next question will come from Colin Bristow with UBS. Please go ahead.

Stuart A. Arbuckle: Great, thank you. The next question will come from Colin Bristow with UBS. Please go ahead. Hey, good afternoon and congratulations on the quarter. Maybe first on the pain pipeline, I see you're advancing 993 to phase two. Could you just give us any sort of color or detail on how you expect this to be differentiated?

Evan Seigerman: Great, thank you.

The next question will come from Colin Bristow with UBS. Please go ahead. Hey, good afternoon and congratulations on the quarter. Maybe first on the pain pipeline, I see you're advancing 993 to phase two. Could you just give us any sort of color or detail on how you expect this to be differentiated?

Operator: The next question will come from Colin Bristow with UBS. Please go ahead.

Colin Bristow: Hey, good afternoon and congrats for the quarter. Maybe first, on the pain pipeline, I see you're advancing 993 to phase two. Could you just give us any sort of color or detail on how you expect this to be differentiated? And does this advancement mean you won't be taking 973 forward, which I think also recently completed phase one? And then, if I may, a quick housekeeping one. Any inventory moves in the quarter that we should be aware of? Thanks.

Colin Bristow: Hey, good afternoon and congrats on the quarter. Maybe first on the pain pipeline, I see you're advancing 993 to Phase II. Could you just give us any sort of color or detail on how you expect this to be differentiated? And does this advancement mean you won't be taking 973 forward -- which I think also recently completed Phase I? And then, if I may, a quick housekeeping one: any inventory moves in the quarter that we should be aware of? Thanks.

Colin Nigel Bristow: Hey, good afternoon, and congrats on the quarter maybe.

Colin Nigel Bristow: Maybe first in the paint pipeline I see you are advancing 993 to phase two.

Could you just give us any sort of color or detail on how you expect this to be differentiated and does this advancement mean, you won't be taking 973 board, which I think also.

Colin Nigel Bristow: And does this advancement mean you won't be taking 973 forward, which I think also recently completed phase one? And then, if I may, a quick housekeeping question: any inventory moves in the quarter that we should be aware of? Thanks.

Colin Nigel Bristow: <unk> phase one.

Speaker Change: If I may a quick housekeeping, one any inventory moves in the quarter that we should be aware of thanks.

Reshma Kewalramani: Yep. Hey, Colin, let me break that up into two questions. One on inventory, which I will ask Charlie to comment on first, and then I'll come back on 993 and 973.

Speaker Change: Yeah, Hey, Collin, let me break that up into two questions.

Charles F. Wagner: Yep. Hey, Colin, let me break that up into two questions. One on inventory, which I will ask Charlie to comment on first, and then I'll come back on 993 and 973. Colin, in my prepared remarks, I had mentioned that we saw some benefit in the first quarter from the phasing of international channel inventory, so I assume that's what you're talking about. That benefit was on the order of $75 to $100 million in the quarter, and I expect that to begin to reverse in the second quarter.

Reshma Kewalramani: Yep. Hey, Colin, let me break that up into two questions. One on inventory -- which I will ask Charlie to comment on first -- and then, I'll come back on 993 and 973.

Speaker Change: One on inventory, which I will ask Charlie to comment on first and then I'll come back on 99, three and 97 three it.

Charles Wagner: Yeah. Colin, in my prepared remarks, I had mentioned that we saw some benefit in Q1 from phasing of international channel inventory, so I assume that's what you're talking about. That benefit was on the order of $75 to $100 million in the quarter, and I expect that to begin to reverse in Q2.

Charles Wagner: Colin, in my prepared remarks, I had mentioned that we saw some benefit in the 1st quarter from the phasing of international channel inventory so, I assume that's what you're talking about. That benefit was on the order of $75 to $100 million in the quarter and I expect that to begin to reverse in the 2nd quarter.

Reshma Kewalramani: Colin, in my prepared remarks, I had mentioned that we saw some benefit in Q1 from phasing of international channel inventory, so I assume that's what you're talking about. That benefit was on the order of $75 to $100 million in the quarter, and I expect that to begin to reverse in Q2. On VX-993, VX-973, Colin, this is all part of serial innovation. VX-993 is a little bit further ahead than VX-973 in terms of the preclinical package, the manufacturing, and all of the things we need to do to get our medicines ready to go into phase 2. That's why that one is ready to go. VX-973 is just a little bit further behind. What are we looking for in terms of differentiation? There's really two major elements other than our overarching serial innovation strategy.

Charles F. Wagner: They're calling in my prepared remarks, I mentioned that we saw some benefit in the first quarter from phasing of international channel inventories. So I assume that's what you're talking about.

Charles F. Wagner: That benefit was on the order of $75 million to $100 million in the quarter and I expect that to begin to reverse in the second quarter.

Reshma Kewalramani: On VX-993, VX-973, Colin, this is all part of serial innovation. VX-993 is a little bit further ahead than VX-973 in terms of the preclinical package, the manufacturing, and all of the things we need to do to get our medicines ready to go into phase 2. That's why that one is ready to go. VX-973 is just a little bit further behind. What are we looking for in terms of differentiation? There's really two major elements other than our overarching serial innovation strategy.

Charles F. Wagner: On line nine 397 three collyn.

Reshma Kewalramani: On 993, 973, Colin -- this is all part of serial innovation. 993 is a little bit further ahead than 973 in terms of the pre-clinical package, the manufacturing and all of the things we need to do to get our medicines ready to go into Phase II. That's why that one is ready to go. 973 is just a little bit further behind. What are we looking for in terms of differentiation? There's really two major elements other than our overarching serial innovation strategy. But very specifically, one, we are looking for molecules that can be both oral and IV. VX-548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons, not able to take by mouth.

Charles F. Wagner: This is all part of our cereal innovation 99, three is a little bit further ahead than 97th we in terms of the pre clinical package the manufacturing and all of the things we need to do to get our medicines ready to go into phase two that's why that one is ready to go.

Charles F. Wagner: 970, <unk>, just a little bit further behind what are we looking for in terms of differentiation.

Reshma Kewalramani: There are really two major elements other than our overarching serial innovation strategy. But very specifically, one, we are looking for molecules that can be both oral and IV. VX548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons not able to take it by mouth.

Charles F. Wagner: There's really two major elements.

Charles F. Wagner: Other than our overarching serial innovation strategy, but very specifically one we are looking for molecules that can be both oral and IV VX five four right is oral only because our goal here is to own the waterfront and pain management include.

But very specifically, one, we are looking for molecules that can be both oral and IV. VX-548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons, not able to take by mouth. The second big goal here is to ensure that we have medicines with the right drug-like properties that can be, therefore, combined with the NaV1.7 -- which is also making good progress in pre-clinical development. So, that's what we're really looking for. And why 993 next? It's because it's a little bit further ahead. And 973, we're going to be working on just as soon as all of the data are ready there.

But very specifically, one, we are looking for molecules that can be both oral and IV.

Reshma Kewalramani: But very specifically, one, we're looking for molecules that can be both oral and IV. VX-548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons not able to take by mouth. The second big goal here is to ensure that we have medicines with the right drug-like properties that can be therefore combined with the NaV1.7, which is also making good progress in preclinical development. So that's what we're really looking for. And why VX-993 next? It's because it's a little bit further ahead. And VX-973, we're going to be working on just as soon as all of the data are ready there. Great. Thank you. The next question will come from Terrence Flynn with Morgan Stanley. Please go ahead. Great. Thanks for taking the question.

But very specifically, one, we're looking for molecules that can be both oral and IV. VX-548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons not able to take by mouth. The second big goal here is to ensure that we have medicines with the right drug-like properties that can be therefore combined with the NaV1.7, which is also making good progress in preclinical development. So that's what we're really looking for. And why VX-993 next? It's because it's a little bit further ahead. And VX-973, we're going to be working on just as soon as all of the data are ready there.

VX-548 is oral only because our goal here is to own the waterfront on pain management, including for those patients who may be just coming out of surgery or for other reasons, not able to take by mouth. The second big goal here is to ensure that we have medicines with the right drug-like properties that can be, therefore, combined with the NaV1.7 -- which is also making good progress in pre-clinical development. So, that's what we're really looking for. And why 993 next? It's because it's a little bit further ahead. And 973, we're going to be working on just as soon as all of the data are ready there.

Charles F. Wagner: <unk> for those patients who may be just coming out of surgery or for other reasons not able to take by mouth. The second big goal here is to ensure that we have medicines with the right drug like properties that can be.

Reshma Kewalramani: The second big goal here is to ensure that we have medicines with the right drug-like properties that can be combined with NAV1.7, which is also making good progress in preclinical development. So that's what we're really looking for. And why 993 next? It's because it's a little bit further ahead.

Charles F. Wagner: Therefore, combined with the NAV, one seven which is also making good progress in preclinical development. So that's what we're really looking for and why 99 three next it's because it's a little bit further ahead and 97, three we're going to be working on it just as soon as all of the data already there.

Reshma Kewalramani: And 973 we're going to be working on just as soon as all of the data are ready there. Great, thank you. The next question will come from Terence Flynn with Morgan Stanley. Please go ahead. Great. Thanks for taking the question. Maybe a two-part question for me as well.

And 973 we're going to be working on just as soon as all of the data are ready there.

Colin Bristow: Great. Thank you.

Operator: The next question will come from Terrence Flynn with Morgan Stanley. Please go ahead.

Speaker Change: Alright, thank you.

Great, thank you. The next question will come from Terence Flynn with Morgan Stanley. Please go ahead. Great. Thanks for taking the question. Maybe a two-part question for me as well.

Colin Bristow: Great, thank you.

The next question will come from Terence Flynn with Morgan Stanley. Please go ahead. Great. Thanks for taking the question. Maybe a two-part question for me as well.

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

Speaker Change: The next question will come from Terence Flynn with Morgan Stanley. Please go ahead.

Terence Flynn: Great. Thanks for taking the question. Maybe a two-part for me as well. I was just wondering if you can give us any insight on a potential presentation venue for the VX-548 Phase 3 data. And then the second question relates to CASGEVY. I was just wondering any directional insight on pricing and reimbursement in the Middle East. Thank you.

Great. Thanks for taking the question. Maybe a two-part question for me as well. I was just wondering if you can give us any insight on a potential presentation venue for the 548 Phase 3 data. And then, the second question relates to Cass Gevey. I was just wondering any directional insight on pricing and reimbursement in the Middle East. Thank you. Yeah, I'm VX548.

Terence Flynn: Great. Thanks for taking the question. Maybe a two-part for me as well. I was just wondering if you can give us any insight on a potential presentation venue for the 548 Phase III data. And then, the second question relates to CASGEVY. I was just wondering, any directional insight on pricing and reimbursement in the Middle East? Thank you.

Terence Flynn: Great. Thanks for taking the question maybe a two part for me as well. It was just wondering if you can give us any insight on a potential presentation venue for the 548 phase III data and then the second question relates to cast Debbie I was just wondering any directional insight on pricing and reimbursement in the middle East. Thank you.

Reshma Kewalramani: Maybe a two-part for me as well. I was just wondering if you can give us any insight on a potential presentation venue for the VX-548 Phase 3 data. And then the second question relates to CASGEVY. I was just wondering any directional insight on pricing and reimbursement in the Middle East. Thank you. Yeah. On VX-548, fall meetings, shall we say, you should expect more data on 548 with those Phase 3 results, certainly not only in congress forum but in publication. So I'd say fall meetings. And let me ask Stuart to comment on CASGEVY in the Middle East. It is a really exciting opportunity for us. Yeah. Super exciting opportunity for us, Terrence, which is why we provided a little bit more color on it.

Terence Flynn: I was just wondering if you can give us any insight on a potential presentation venue for the 548 Phase 3 data. And then, the second question relates to Cass Gevey. I was just wondering any directional insight on pricing and reimbursement in the Middle East. Thank you. Yeah, I'm VX548.

Reshma Kewalramani: Yeah. On VX-548, fall meetings, shall we say, you should expect more data on 548 with those Phase 3 results, certainly not only in congress forum but in publication. So I'd say fall meetings. And let me ask Stuart to comment on CASGEVY in the Middle East. It is a really exciting opportunity for us.

Yeah.

Terence Flynn: On VX five four rate.

Reshma Kewalramani: Yeah. On VX-548 -- fall meetings, shall we say. You should expect more data on 548 with those Phase III results. Certainly, not only in Congress form but in publication-side, say, fall meetings? And let me ask Stuart to comment on CASGEVY in the Middle East. It is a really exciting opportunity for us.

Reshma Kewalramani: Fall meetings, shall we say. You should expect more data on 548 with those phase 3 results, certainly not only in Congress form but in publication. So I'd say Fall Meetings. And let me ask Stuart to comment on Kashevi in the Middle East.

Terence Flynn: Fall meetings shall we say you should expect more data on a FIFO rate with those phase III results.

Speaker Change: Certainly not only in Congress form, but in publications, let's say fall meetings and let me ask.

Stuart A. Arbuckle: It is a really exciting opportunity for us. Yeah, a really exciting opportunity for us, Terence, which is why we provided a little bit more color on it specifically to answer your question. We don't provide pricing data at an individual country level, but suffice to say the price we are receiving in the existing reimbursement agreements that we've signed there reflect the transformative value of the product and the lifetime benefits that patients can accrue from it. And that's going to be the same kind of philosophy we're going to have everywhere around the world where we're commercializing cash jewelry. The next question will come from Phil Nadeau with T.D. Cowan. Please go ahead.

It is a really exciting opportunity for us.

Speaker Change: Stewart to comment on cash JV in the Middle East It is a really exciting opportunity for us.

Yeah. Super exciting opportunity for us, Terence, which is why we provided a little bit more color on it. Specifically, to answer your question, we don't provide pricing data at the individual country level but suffice to say the price we are receiving in the existing reimbursement agreements that we've signed there, reflect the transformative value of the product and the lifetime benefits that patients can accrue from it. And that's going to be the same kind of philosophy we're going to have everywhere around the world where we're commercializing CASGEVY. The next question will come from Phil Nadeau with T.D. Cowan. Please go ahead.

Stuart A. Arbuckle: Yeah. Super exciting opportunity for us, Terence, which is why we provided a little bit more color on it. Specifically, to answer your question, we don't provide pricing data at the individual country level but suffice to say the price we are receiving in the existing reimbursement agreements that we've signed there, reflect the transformative value of the product and the lifetime benefits that patients can accrue from it. And that's going to be the same kind of philosophy we're going to have everywhere around the world where we're commercializing CASGEVY.

Stuart Arbuckle: Yeah. Super exciting opportunity for us, Terrence, which is why we provided a little bit more color on it. Specifically to answer your question, we don't provide pricing data at an individual country level, but suffice to say, the price we are receiving in the existing reimbursement agreements that we've signed there reflect the transformative value of the product and the lifetime benefits that patients can accrue from it. And that's going to be the same kind of philosophy we're going to have everywhere around the world where we're commercializing CASGEVY.

Stewart: Super exciting opportunity.

Stewart: Forest tenants, which is why we provided a little bit more color on it specifically to answer your question we.

Reshma Kewalramani: Specifically to answer your question, we don't provide pricing data at an individual country level, but suffice to say, the price we are receiving in the existing reimbursement agreements that we've signed there reflect the transformative value of the product and the lifetime benefits that patients can accrue from it. And that's going to be the same kind of philosophy we're going to have everywhere around the world where we're commercializing CASGEVY. The next question will come from Phil Nadeau with TD Cowen. Please go ahead. Good afternoon. Thanks for taking our questions. Two from us. First, on the suzetrigine formulary and access discussions. Stuart, I think you made an interesting comment that you thought enabling reimbursement ahead of opioids in the acute pain setting will be something that government programs could help incentivize or something to that effect. Could you speak a bit more about that?

Stewart: We don't provide pricing data or at a individual country level, but suffice to say the price we are.

Stewart: Receiving in the existing reimbursement agreements that we've signed there.

Stewart: Reflect the transformative value of the product and the the lifetime benefits that patients can accrue from it and.

Stewart: That's going to be the same kind of philosophy, we're gonna have everywhere around the world, where we're commercializing cast Jerry.

Operator: The next question will come from Phil Nadeau with TD Cowen. Please go ahead.

Geoffrey Christopher Meacham: The next question will come from film to do with TD Cowen. Please go ahead.

Phil Nadeau: Good afternoon. Thanks for taking our questions. Two from us. First, on the suzetrigine formulary and access discussions. Stuart, I think you made an interesting comment that you thought enabling reimbursement ahead of opioids in the acute pain setting will be something that government programs could help incentivize or something to that effect. Could you speak a bit more about that? In particular, are your formulary and access discussions suggesting that in the absence of legislative initiatives, it's likely that 548 will be reimbursed after opioids in the acute pain setting? And then second, small commercial question. Can you give us some sense of how big Brazil could be for the CF franchise? Thanks.

Phil Nadeau: Good afternoon. Thanks for taking our questions, two from us. First, on the SUZETRIGINE formulary and access discussions. Stuart, I think you made an interesting comment that you thought enabling reimbursement ahead of opioids in the acute pain setting will be something that government programs could help incentivize or something to that effect. Could you speak a bit more about that and, in particular, are your formulary and access discussions suggesting that in the absence of legislative initiatives, it's likely that 548 will be reimbursed after opioids in the acute pain setting? And then, second, small commercial question. Can you give us some sense of how big Brazil could be for the CF franchise? Thanks.

Geoffrey Christopher Meacham: Afternoon. Thanks for taking my questions two from US first on this is trudging formulary access discussions.

Geoffrey Christopher Meacham: He made an interesting comment that you thought.

Geoffrey Christopher Meacham: Enabling reimbursement head of opioids in the acute pain setting will be something that.

Phil Nadeau: First on the CISS-TRI gene formulary and access discussions, Stuart, I think you made an interesting comment that you thought Enabling Reimbursement Ahead of Opioids in the Acute Pain Setting will be something that government programs could help incentivize, or something to that effect. Could you speak a bit more about that, and in particular, are your formulary and access discussions suggesting that? In the absence of legislative initiatives.

Geoffrey Christopher Meacham: Government.

Geoffrey Christopher Meacham: Government programs could help incentivize us or something to that effect could you speak a bit more about that in particular are your formulary access discussing discussions suggesting that.

Reshma Kewalramani: In particular, are your formulary and access discussions suggesting that in the absence of legislative initiatives, it's likely that 548 will be reimbursed after opioids in the acute pain setting? And then second, small commercial question. Can you give us some sense of how big Brazil could be for the CF franchise? Thanks. Yep. Phil, I will ask Stuart to comment on both CF in Brazil. You know that we have regulatory approval and reimbursement there as well as formulary discussions on suzetrigine. But just to make sure we are on the same page, the formulary discussions are separate from our discussions with policymakers. The common theme is that both of those stakeholders, and frankly, all of the stakeholders, are very aware of the opioid crisis. They have high awareness of suzetrigine, and there is enthusiasm to using non-opioids. But those discussions are separate. Over to you, Stuart. Yeah.

Geoffrey Christopher Meacham: In the absence of legislative initiatives.

Stuart A. Arbuckle: It's likely that 548 will be reimbursed after opioids in the acute pain setting. And a second small commercial question. Can you give us some sense of how big Brazil could be for the French CF?

Geoffrey Christopher Meacham: It's likely that it will be reimbursed after opioids in the acute pain setting.

The second.

Geoffrey Christopher Meacham: Commercial question can you give us some sense of how big Brazil could be for the CF franchise. Thanks.

Reshma Kewalramani: Yep. Phil, I will ask Stuart to comment on both CF in Brazil. You know that we have regulatory approval and reimbursement there as well as formulary discussions on suzetrigine. But just to make sure we are on the same page, the formulary discussions are separate from our discussions with policymakers. The common theme is that both of those stakeholders, and frankly, all of the stakeholders, are very aware of the opioid crisis. They have high awareness of suzetrigine, and there is enthusiasm to using non-opioids. But those discussions are separate. Over to you, Stuart.

Geoffrey Christopher Meacham: Yep.

Reshma Kewalramani: Yeah. Phil, I will ask Stuart to comment on both CF in Brazil -- you know that we have regulatory approval and reimbursement there -- as well as formulary discussions on SUZETRIGINE. But just to make sure we are on the same page, the formulary discussions are separate from our discussions with policymakers. The common theme is that both of those stakeholders and frankly, all of the stakeholders, are very aware of the opioid crisis. They have high awareness of SUZETRIGINE and there is enthusiasm to using non-opioids. But those discussions are separate. Over to you, Stuart.

Speaker Change: Phil I will ask Stuart.

Stuart A. Arbuckle: Stewart to comment on both CF in Brazil.

Stewart: You know that we have regulatory approval and reimbursement there as well as formulary discussions as this sector gene, but just to make sure. We are on the same page.

Stewart: The formulary discussions are are separate from our discussions with <unk>.

Stewart: Policymakers. The common theme is that both of those stakeholders and frankly all of the stakeholders are very aware of the opioid crisis they have high awareness.

Reshma Kewalramani: The common theme is that both of those stakeholders, and, frankly, all of the stakeholders, are very aware of the opioid crisis. They have high awareness of sucetrogene, and there is enthusiasm for using non-opioids. But those discussions are separate. Over to you, Stuart.

Stewart: This of Susceptor gene and there is enthusiasm to using non opioids, but those discussions are separate.

Stuart Arbuckle: Yeah. So just to add to that, Rachel, what I would say, Phil, is that the policy initiatives that we've seen so far are really looking at trying to reduce financial disincentives for patients and indeed for institutions to selecting a branded non-opioid in a market which is obviously currently dominated by generic opioids. And so that's why things like NO PAIN Act, which is providing an additional payment above the DRG in the outpatient and ambulatory surgical center setting, is important there. And then on the patient side, the Alternatives to PAIN Act is looking at in Medicare Part D, ensuring that there are no copay disadvantages to a patient for using a branded non-opioid in a market where there are already generic opioids. So I'd say that's the kind of the policy landscape.

Reshma Kewalramani: So just to add to that, Rachel, what I would say, Phil, is that the policy initiatives that we've seen so far are really looking at trying to reduce financial disincentives for patients and indeed for institutions to selecting a branded non-opioid in a market which is obviously currently dominated by generic opioids. And so that's why things like NO PAIN Act, which is providing an additional payment above the DRG in the outpatient and ambulatory surgical center setting, is important there. And then on the patient side, the Alternatives to PAIN Act is looking at in Medicare Part D, ensuring that there are no copay disadvantages to a patient for using a branded non-opioid in a market where there are already generic opioids. So I'd say that's the kind of the policy landscape.

Stewart: Over to you Stuart Yeah, So just to add to that restaurant, what I would say Phil is that the policy.

Stuart A. Arbuckle: Yes. So, just to add to that, Reshma, what I would say, Phil, is that the policy initiatives that we've seen so far are really looking at trying to reduce financial dis-incentives for patients and, indeed, for institutions to selecting a branded non-opioid in a market which is, obviously, currently dominated by generic opioids. And so, that's why things like NOPAIN, which is providing an additional payment above the DRG in the outpatient and ambulatory surgical center setting, is important there. And then, on the patient side, the Alternatives to PAIN Act is looking at in Medicare Part D, ensuring that there are no co-pay disadvantages to a patient for using a branded non-opioid in a market where there are already generic opioids.

Stewart:

Stuart A. Arbuckle: Initiatives that we've seen so far are really looking at trying to reduce financial disincentives.

Stuart A. Arbuckle: For patients and indeed for institutions to selecting a branded non opioid in a market, which is obviously currently dominated by generic opioids and so that's why.

Stuart A. Arbuckle: Things like no pain, which is providing an additional payment above the DRG and the outpatient and ambulatory surgical center setting is important there.

And then, on the patient side, the Alternatives to PAIN Act is looking at in Medicare Part D, ensuring that there are no co-pay disadvantages to a patient for using a branded non-opioid in a market where there are already generic opioids. So, I'd say that's the policy landscape. Those are kind of slightly different discussions than we're having with the institutions and the stakeholders there, which are much more clinically-based on whether this is the right medicine to be using in the patients who are being prescribed and dispensed medicines in the institutional setting. So, that's how I would describe the difference between the conversations. They're obviously linked in some ways but they have a different focus from the policy side to the institutional side. Maybe just to follow up, the basis for our question is that we recently did a survey, and 75% of physicians thought that patients would have to step through a generic opioid. Is that Vertex's expectation as well?

Stuart A. Arbuckle: And on the patient side the alternatives to paint Act is looking at in Medicare part D. Ensuring that there are no copay disadvantages to a patient for using a branded non opioid in a market where there are already generic opioids. So I'd say, that's the kind of the policy.

Stuart A. Arbuckle: So I'd say that's the policy landscape. Those are kind of slightly different discussions than we're having with the institutions and the stakeholders there, which are much more clinically based on whether this is the right medicine to be using in the patients who are being prescribed and dispensed medicines in the institutional setting. So that's how I would describe the difference between the conversations. They're obviously linked in some ways, but they have a different focus from the policy side to the institutional side. Maybe just to follow up, the basis for our question is that we recently did a survey, and 75% of physicians thought that patients would have to step through a generic opioid. Is that Vertex's expectation as well?

Reshma Kewalramani: Those are kind of slightly different discussions than we're having with the institutions and the stakeholders there, which were much more clinically based on whether this is the right medicine to be using in the patients who are being prescribed and dispensed medicines in the institutional setting. So that's how I would describe the difference between the conversations. They're obviously linked in some ways, but they have a different focus from the policy side to the institutional side. Maybe just to follow up, the basis for our question is we recently did a survey, and 75% of physicians thought that patients would have to step through a generic opioid. Is that Vertex's expectation as well? I can't really speculate on exactly what's going to happen with, for instance, 2,000 institutions, but my hope would be that that's not what's happening.

Those are kind of slightly different discussions than we're having with the institutions and the stakeholders there, which were much more clinically based on whether this is the right medicine to be using in the patients who are being prescribed and dispensed medicines in the institutional setting. So that's how I would describe the difference between the conversations. They're obviously linked in some ways, but they have a different focus from the policy side to the institutional side.

Stuart A. Arbuckle: Land scape those are kind of slightly different discussions that we're having with the the institutions and the stakeholders, there which were much more clinically based.

Stuart A. Arbuckle: On whether this is the right medicine to be using in the patients who are being prescribed and dispensed.

Stuart A. Arbuckle: Medicines in the institutional setting so that's how I would describe the difference between the conversations they are obviously linked.

Stuart A. Arbuckle: Some ways, but they are they have a different focus from the policy side to the institutional side.

Phil Nadeau: Maybe just to follow up, the basis for our question is we recently did a survey, and 75% of physicians thought that patients would have to step through a generic opioid. Is that Vertex's expectation as well?

Phil Nadeau: Maybe just to follow up. The basis for our question is that we recently did a survey and 75% of physicians thought that patients would have to step through a generic opioid. Is that Vertex's expectation as well?

Speaker Change: Maybe just to follow up the basis for the question as we recently did a survey and 75% of physicians thought.

Speaker Change: Patients would have to step through a generic opioids is that is that for Texas expectation as well.

Stuart Arbuckle: I can't really speculate on exactly what's going to happen with, for instance, 2,000 institutions, but my hope would be that that's not what's happening. I don't think it's very reasonable to expect a patient to have to step through a therapy which has significant side effect liability, including addictive potential, when there is a product available which has very good efficacy from a pain control perspective and has an excellent safety and tolerability profile, including lack of addictive potential. So I don't think that would be something that we certainly wouldn't be advocating, and I don't think would be particularly medically reasonable. I didn't answer the second part of your question, which was around Brazil. We estimate there's around 1,500 patients who are eligible for TRIKAFTA. That's six and over in Brazil.

Stuart A. Arbuckle: You know, I can't really speculate on exactly what's going to happen with, for instance, 2,000 institutions but my hope would be that that's not what's happening. I don't think it's very reasonable to expect a patient to have to step through a therapy which has significant side effect liability -- including addictive potential -- when there is a product available which has very good efficacy from a pain control perspective and has an excellent safety and tolerability profile, including lack of addictive potential. So, I don't think that would be something that we would, certainly, wouldn't be advocating and I don't think it would be particularly medically reasonable.

Speaker Change: I can't really speculate on exactly what's going to happen with the for instance, 2000 institutions, but my hope would be that that's not what's happening I don't think it's very reasonable to expect a patient to have to step through a <unk>.

Reshma Kewalramani: I don't think it's very reasonable to expect a patient to have to step through a therapy which has significant side effect liability, including addictive potential, when there is a product available which has very good efficacy from a pain control perspective and has an excellent safety and tolerability profile, including lack of addictive potential. So I don't think that would be something that we certainly wouldn't be advocating, and I don't think would be particularly medically reasonable. I didn't answer the second part of your question, which was around Brazil. We estimate there's around 1,500 patients who are eligible for TRIKAFTA. That's six and over in Brazil.

Speaker Change: Therapy, which has significant side effect liability, including addictive potential when there is a product available which has very good efficacy from a pain control perspective, and has an excellent safety and tolerability profile, including a lack of addictive potential. So I don't think that would be something that we.

Stuart A. Arbuckle: So I don't think that would be something that we would certainly wouldn't be advocating and I don't think it would be particularly medically reasonable. And then I didn't answer the second part of your question, which was about Brazil.

So I don't think that would be something that we would certainly wouldn't be advocating and I don't think it would be particularly medically reasonable.

Speaker Change: Would certainly wouldn't be advocating and I don't think it would be particularly medically reasonable.

And then I didn't answer the second part of your question, which was about Brazil. We estimate there are around 1,500 patients who are eligible for Trikafta, that is, six and over, in Brazil. As I mentioned in my prepared remarks, a number of those patients did already have access to Trikafta through named patient sales, but we now have a reimbursement agreement with the national government there, which is going to allow us to launch the medicine and make it available for all of those patients now. That's very helpful.

And then, I didn't answer the second part of your question, which was around Brazil. We estimate there's around 1,500 patients who are eligible for TRIKAFTA that's 6 and over, in Brazil. As I mentioned in my prepared remarks, a number of those patients did already have access to TRIKAFTA through named patient sales but we now have a reimbursement agreement with the national government there, which is going to allow us to launch the medicine and make it available for all of those patients now.

Speaker Change: Got it and I didn't answer the second part of your question, which was around Brazil. We estimate was around 1500 patients who are eligible for Tri class track after that six and over in Brazil as I mentioned in my prepared remarks, a number of those patients did already have access to try CAFTA through named patient sales, but we.

Stuart A. Arbuckle: We estimate there are around 1,500 patients who are eligible for Trikafta, that is, six and over, in Brazil. As I mentioned in my prepared remarks, a number of those patients did already have access to Trikafta through named patient sales, but we now have a reimbursement agreement with the national government there, which is going to allow us to launch the medicine and make it available for all of those patients now. That's very helpful.

Reshma Kewalramani: As I mentioned in my prepared remarks, a number of those patients did already have access to TRIKAFTA through named patient sales, but we now have a reimbursement agreement with the national government there, which is going to allow us to launch the medicine and make it available for all of those patients now. That's very helpful. Thanks again for taking our questions. The next question will come from Olivia Brayer with Cantor Fitzgerald. Please go ahead. Hey, good afternoon. Thank you for the question. What's your level of confidence that you'll get priority review in acute pain? And Stuart, I know you've talked about the commercial build-out, but what's your base case for when you'll start to actually see revenue recognition from that program? And just quick clarification on CASGEVY.

As I mentioned in my prepared remarks, a number of those patients did already have access to TRIKAFTA through named patient sales, but we now have a reimbursement agreement with the national government there, which is going to allow us to launch the medicine and make it available for all of those patients now.

Speaker Change: Now have a reimbursement agreement with the National government, there, which is going to allow us to launch the medicine and make it available for all of those patients now.

Phil Nadeau: That's very helpful. Thanks again for taking our questions.

Speaker Change: That's very helpful. Thanks, again for taking my questions.

Operator: The next question will come from Olivia Brayer with Cantor Fitzgerald. Please go ahead.

Phil Nadeau: That's very helpful. Thanks again for taking our questions.

Speaker Change: The next question will come from Olivia Brayer with Cantor Fitzgerald. Please go ahead.

Phil Nadeau: Thanks again for taking our question. The next question will come from Olivia Brayer with Cancer Fitzgerald. Please go ahead. Hey, good afternoon.

Thanks again for taking our question.

The next question will come from Olivia Brayer with Cancer Fitzgerald. Please go ahead. Hey, good afternoon.

Operator: The next question will come from Olivia Brayer with Cantor Fitzgerald. Please go ahead.

Olivia Brayer: Hey, good afternoon. Thank you for the question. What's your level of confidence that you'll get priority review in acute pain? And Stuart, I know you've talked about the commercial build-out, but what's your base case for when you'll start to actually see revenue recognition from that program? And just quick clarification on CASGEVY. Just wanted to clarify that I heard five patients have already finished collection versus just having initiated the cell collection process. Thank you.

Olivia Brayer: Hey, good afternoon. Thank you for the question. What's your level of confidence that you'll get priority review in acute pain? And Stuart, I know you've talked about the commercial build-out but what's your base case for when you'll start to actually see revenue recognition from that program? And just a quick clarification on CASGEVY -- just wanted to clarify that I heard five patients have already finished collection versus just having initiated the cell collection process. Thank you.

Olivia Brayer: Thank you for the question. What's your level of confidence that you'll get priority review in acute pain? And Stuart, I know you've talked about the commercial build-out, but what's your base case for when you'll start to actually see revenue recognition from that program? And just a quick clarification on Catch Jevy.

Olivia Brayer: Hey, good afternoon, and thank you for the question, what's your level of confidence that Youll get priority review in acute pain and Stuart I know you've talked about the commercial build out but what's your base case for when you'll start to actually see revenue recognition from that program and just quick clarification on cash Chevy.

Reshma Kewalramani: Just wanted to clarify that I heard five patients have already finished collection versus just having initiated the cell collection process. Thank you. Perfect. Hey, Olivia, this is Rachel. Let me take one and three, and then I'll ask Stuart to take the question on where are we exactly with pain commercialization. On number three again, just to set expectations on CASGEVY, we're thrilled with the number of ATCs, 25, since approval, which has been in just the last few months. And we commented on the cell collection, but we're not going to comment any further on exactly where each one patient is in their journey. Sorry. On VX-548 and acute pain, three things to say.

Olivia Brayer: I just wanted to clarify that I heard five patients have already finished collection versus just having initiated the cell collection process. Thank you.

Stuart A. Arbuckle: Just wanted to clarify that I heard five patients have already finished their collections versus just having initiated the cell collection process. Thank you. Hey Olivia, this is Reshma.

Just wanted to clarify that I heard five patients have already finished their collections versus just having initiated the cell collection process. Thank you.

Hey Olivia, this is Reshma. Let me take one and three and then I'll ask Stuart to take the question on where we are exactly with pain commercialization. On number three, again, just to set expectations on CASGEVY, we're thrilled with the number of ATCs -- 25 since approval -- which has been in just the last few months. And we commented on the cell collection but we're not going to comment any further on exactly where each one patient is in their journey. On VX-548 and acute pain, three things to say. Maybe the most important thing is, we'll know whether or not we've received priority review in about a -- after we complete the submission and then, it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable. We have fast-track status, we have breakthrough designation and our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential. I'll turn it over to Stuart for the question about where we are with the acute pain launch and when we're going to be out there. Yeah. So, the recruitment of our teams is going very well.

Reshma Kewalramani: Hey Olivia, this is Reshma. Let me take one and three and then I'll ask Stuart to take the question on where we are exactly with pain commercialization. On number three, again, just to set expectations on CASGEVY, we're thrilled with the number of ATCs -- 25 since approval -- which has been in just the last few months. And we commented on the cell collection but we're not going to comment any further on exactly where each one patient is in their journey. On VX-548 and acute pain, three things to say.

Reshma Kewalramani: Perfect. Hey, Olivia, this is Rachel. Let me take one and three, and then I'll ask Stuart to take the question on where are we exactly with pain commercialization. On number three again, just to set expectations on CASGEVY, we're thrilled with the number of ATCs, 25, since approval, which has been in just the last few months. And we commented on the cell collection, but we're not going to comment any further on exactly where each one patient is in their journey. Sorry. On VX-548 and acute pain, three things to say.

<unk>: Sure thing Hey, Olivia this is <unk>, let me take one and three and then I'll ask Stewart to take.

Reshma Kewalramani: Let me take one and three and then I'll ask Stuart to take the question on where we are exactly with pain commercialization. On number three again, just to set expectations for cast chevy, we're thrilled with the number of ATCs, 25 since approval, which has been in just the last few months. And we commented on the cell collection, but we're not going to comment any further on exactly where each patient is in their journey.

unknown: The question on where are we exactly with paying commercialization and number three again just to set expectations I guess JV with thrilled with the number of Atc's 25 cents.

unknown: Approval was which has been in just the last few months and we commented on the cell collection, but we're not going to comment any further on exactly where each one patient is in their journey.

Reshma Kewalramani: On VX548 and acute pain, three things to say. Maybe the most important thing is we'll know whether or not we've received Priority Review in about a month after we complete the submission, and then it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable.

unknown: Sorry on VX 548.

unknown: And acute pain are three things to say maybe the most important thing is we'll know whether or not we received.

On VX-548 and acute pain, three things to say. Maybe the most important thing is, we'll know whether or not we've received priority review in about a -- after we complete the submission and then, it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable. We have fast-track status, we have breakthrough designation and our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential.

Reshma Kewalramani: Maybe the most important thing is we'll know whether or not we've received priority review in about 60 days after we complete the submission, and then it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable. We have fast-track status. We have breakthrough designation. And our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential. I'll turn it over to Stuart for the question about where are we with the acute pain launch and when we're going to be out there. Yeah. So the recruitment of our teams is going very well. Obviously, we are in the middle of our rolling submission here.

Maybe the most important thing is we'll know whether or not we've received priority review in about 60 days after we complete the submission, and then it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable. We have fast-track status. We have breakthrough designation. And our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential. I'll turn it over to Stuart for the question about where are we with the acute pain launch and when we're going to be out there.

Maybe the most important thing is, we'll know whether or not we've received priority review in about a -- after we complete the submission and then, it takes some 60 days or so for the FDA to tell us what the final review timelines will be. However, the leading indicators of whether or not we will get priority review are all quite favorable. We have fast-track status, we have breakthrough designation and our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential. I'll turn it over to Stuart for the question about where we are with the acute pain launch and when we're going to be out there.

unknown: Priority review in.

unknown: In about.

unknown: After we complete the submission and then it takes.

unknown: I'm 60 days or so for the FDA to tell us what the.

unknown: What the final review timelines will be.

unknown: However, the leading indicators of whether or not we will get priority review are all quite favorable we have fast track status, we have breakthrough designation and our conversations with the FDA.

Stuart A. Arbuckle: We have fast-track status, we have breakthrough designation, and our conversations with the FDA have shown me that they have high enthusiasm for a medicine that has high efficacy and does not have addictive potential. I'll turn it over to Stuart for the question about where we are with the acute pain launch and when we're going to be out there. Yeah, so the recruitment of our teams is going very well.

unknown: Has have.

unknown: Show me that they have high enthusiasm for a medicine that has high.

I'll turn it over to Stuart for the question about where we are with the acute pain launch and when we're going to be out there.

Efficacy and does not have addictive potential I'll turn it over to Stuart for the question about where are we with the acute pain launching when we're going to be out there.

Stuart A. Arbuckle: Yeah. So, the recruitment of our teams is going very well. Obviously, we are in the middle of our rolling submission here. Obviously, once we've completed that, we'll get an indication from the regulators on when we could expect our PDUFA date to be and we are going to be launch-ready. In terms of the question around revenue recognition -- this is unlike CASGEVY, I would say, which has an extended treatment process, where revenue recognition is at infusion. This is a small molecule and, therefore, we're going to be selling and distributing it in the normal way. And so, there really isn't going to be that kind of lag, I would suggest, around revenue recognition, that people are aware of with CASGEVY.

Stuart Arbuckle: Yeah. So the recruitment of our teams is going very well. Obviously, we are in the middle of our rolling submission here. Obviously, once we've completed that, we'll get an indication from the regulators on when we could expect our PDUFA date to be, and we are going to be launch ready. In terms of the question around revenue recognition, this is unlike CASGEVY, I would say, which has an extended treatment process where revenue recognition is at infusion. This is a small molecule, and therefore, we're going to be kind of selling and distributing it in the normal way. And so there really isn't going to be that kind of lag, I would suggest, around revenue recognition that people are aware of with CASGEVY.

Stuart A. Arbuckle: Obviously, we are in the middle of our rolling submission here, and obviously, once we've completed that, we'll get an indication from the regulators on when we can expect our PDUFA date to be. And we are going to be launch-ready in terms of the question around revenue recognition. This is unlike CASJEVI, I would say, which has an extended treatment process where revenue recognition is at infusion. This is a small molecule, and therefore, we're going to be selling and distributing it in the normal way.

Stuart A. Arbuckle: Yeah. So the recruitment of our teams is going very well obviously, we are in the middle of our rolling submission here. Obviously once we've completed that we'll get an indication from the from the regulators on when we.

Reshma Kewalramani: Obviously, once we've completed that, we'll get an indication from the regulators on when we could expect our PDUFA date to be, and we are going to be launch ready. In terms of the question around revenue recognition, this is unlike CASGEVY, I would say, which has an extended treatment process where revenue recognition is at infusion. This is a small molecule, and therefore, we're going to be kind of selling and distributing it in the normal way. And so there really isn't going to be that kind of lag, I would suggest, around revenue recognition that people are aware of with CASGEVY. Great. Thank you both. The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead. Hey, good afternoon. I got a couple. First on IgAN. When Vertex is ready to launch an IgAN, it's likely Otsuka will have GFR data.

Stuart A. Arbuckle: Could expect our <unk> date to be and we are going to be launch ready and because of the question around revenue recognition.

Stuart A. Arbuckle: This is unlike cash Jerry I would say, which has an extended treatment process, where revenue recognition is that infusion. This is a small molecule and therefore, we're going to be kind of selling and distributing it in the in the normal way and so that really isn't going to be that kind of lag I would suggest around revenue recognition that people are aware.

Olivia Brayer: Great. Thank you both.

Stuart A. Arbuckle: With cash JV.

Speaker Change: Great. Thank you both.

Operator: The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead.

Stuart A. Arbuckle: Okay.

Stuart A. Arbuckle: And so there really isn't going to be that kind of lag, I would suggest, around revenue recognition, that people are aware of with CASGEVY. Great, thank you both. The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead. Hey, good afternoon. I've got a couple. First, on IGAN; when Vertex is ready to launch an IGAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially?

And so there really isn't going to be that kind of lag, I would suggest, around revenue recognition, that people are aware of with CASGEVY.

Speaker Change: The next question will come from <unk>.

Geoffrey Christopher Meacham: <unk> <unk> with Guggenheim Securities. Please go ahead.

Debjit Chattopadhyay: Hey, good afternoon. I got a couple. First on IgAN. When Vertex is ready to launch an IgAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially? And then on DM1 with the IND cleared and the phase 1/2 underway, do you think myotonia is an approvable endpoint, or is the agency going to ask for splicing correction with strength or force measurements? Thanks so much.

Great, thank you both. The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead. Hey, good afternoon. I've got a couple. First, on IGAN; when Vertex is ready to launch an IGAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially?

Olivia Brayer: Great, thank you both.

Geoffrey Christopher Meacham: Hey, good afternoon.

The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead. Hey, good afternoon. I've got a couple. First, on IGAN; when Vertex is ready to launch an IGAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially?

Operator: The next question will come from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead.

Geoffrey Christopher Meacham: A couple of first one again when verdict is.

Hey, good afternoon. I've got a couple. First, on IGAN; when Vertex is ready to launch an IGAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially? And then on DM-1, with the IND cleared and the Phase 1-2 underway, do you think Myotonia is an approvable endpoint, or is the agency gonna ask for slicing correction with strength or force measurements? Thanks so much. Yeah. Hey, Debjit, let me take both of those.

Debjit Chattopadhyay: Hey, good afternoon. I've got a couple. First, on IgAN -- when Vertex is ready to launch an IgAN, it's likely Otsuka will have GFR data. How are you thinking about navigating this commercially? And then, on DM1 with the IND cleared and the Phase I/II underway, do you think myotonia is an approvable endpoint or is the agency gonna ask for slicing correction with strength or force measurements? Thanks so much.

We're ready to launch and I again, it's likely at Newco will have GFR data.

Reshma Kewalramani: How are you thinking about navigating this commercially? And then on DM1 with the IND cleared and the phase 1/2 underway, do you think myotonia is an approvable endpoint, or is the agency going to ask for splicing correction with strength or force measurements? Thanks so much. Yeah. Hey, Debjit, let me take both of those. On DM1 or myotonic dystrophy type 1, we actually haven't had a chance to talk about it extensively, but this is a program that is in phase 1/2 inpatient. So we are going to have the opportunity in this study to not only assess safety but to assess efficacy as well. With regard to what the agency might want to see for the endpoint for approval, the real answer is I don't know yet because we haven't gotten to that phase in the clinical trial.

Geoffrey Christopher Meacham: How are you thinking about navigating this commercially and.

Debjit D. Chattopadhyay: And then on DM-1, with the IND cleared and the Phase 1-2 underway, do you think Myotonia is an approvable endpoint, or is the agency gonna ask for slicing correction with strength or force measurements? Thanks so much. Yeah. Hey, Debjit, let me take both of those.

Geoffrey Christopher Meacham: And then on the M. One, but the I N D cleared and the phase one two underway do you think myotonia.

Geoffrey Christopher Meacham: As an approvable endpoint or is the agency going to ask for life and correction, but.

Speaker Change: Trent or force measurements. Thanks, so much.

Yeah. Hey, Debjit, let me take both of those. On DM1 or myotonic dystrophy type one, we actually haven't had a chance to talk about it extensively but this is a program that is in Phase I/II inpatient. So, we are gonna have the opportunity in this study to not only assess safety but to assess efficacy as well. With regard to what the agency might wanna see for the endpoint for approval, the real answer is, I don't know yet because we haven't gotten to that phase in the clinical trial. But your point around is myotonia is possible, insofar as this is a disease that is a rare disease, a serious disease and one that doesn't have any therapies that target the underlying cause of the disease or that very specifically works on the genetic defect, I think that opportunity is there and we've seen a lot of openness for accelerated endpoints in these kinds of rare, serious diseases.

Reshma Kewalramani: Yeah. Hey, Debjit, let me take both of those. On DM1 or myotonic dystrophy type one, we actually haven't had a chance to talk about it extensively but this is a program that is in Phase I/II inpatient. So, we are gonna have the opportunity in this study to not only assess safety but to assess efficacy as well. With regard to what the agency might wanna see for the endpoint for approval, the real answer is, I don't know yet because we haven't gotten to that phase in the clinical trial.

Reshma Kewalramani: Yeah. Hey, Debjit, let me take both of those. On DM1 or myotonic dystrophy type 1, we actually haven't had a chance to talk about it extensively, but this is a program that is in phase 1/2 inpatient. So we are going to have the opportunity in this study to not only assess safety but to assess efficacy as well. With regard to what the agency might want to see for the endpoint for approval, the real answer is I don't know yet because we haven't gotten to that phase in the clinical trial.

Speaker Change: Yeah, Hey, Doug Let me, let me take both of those.

Reshma Kewalramani: On DM1, or myotonic dystrophy type one, we actually haven't had a chance to talk about it extensively, but this is a program that is in phase one, two, inpatient. So we are gonna have the opportunity in this study to not only assess safety but to assess efficacy as well. With regard to what the agency might wanna see for the endpoint for approval, the real answer is I don't know yet because we haven't gotten to that phase in the clinical trial.

Speaker Change: One or my Atonic dystrophy type one we actually haven't had a chance to talk about it extensively but.

Doug: This is a program that is in phase <unk> in patients. So we are going to have the opportunity in this study to not only assess safety, but to assess efficacy as well with regard to what the agency might want to see for the endpoint for approval.

Doug: The real answer is I don't know yet because we haven't gotten to that phase in the clinical trial.

Reshma Kewalramani: But your point around is myotonia possible insofar as this is a disease that is a rare disease, a serious disease, and one that doesn't have any therapies that target the underlying cause of the disease or that very specifically works on the genetic defect? I think that opportunity is there, and I've seen and we've seen a lot of openness for accelerated endpoints in these kinds of rare serious diseases. On IgA nephropathy, so the most important things to know about IgA nephropathy is that it's a serious chronic disease. This is a disease that over time leads to decline in GFR and end-stage renal disease, death, or transplantation. The most important thing that I would be looking at as a nephrologist is efficacy because proteinuria is known to translate to GFR and therefore the decline in renal function.

But your point around is myotonia possible insofar as this is a disease that is a rare disease, a serious disease, and one that doesn't have any therapies that target the underlying cause of the disease or that very specifically works on the genetic defect? I think that opportunity is there, and I've seen and we've seen a lot of openness for accelerated endpoints in these kinds of rare serious diseases. On IgA nephropathy, so the most important things to know about IgA nephropathy is that it's a serious chronic disease. This is a disease that over time leads to decline in GFR and end-stage renal disease, death, or transplantation. The most important thing that I would be looking at as a nephrologist is efficacy because proteinuria is known to translate to GFR and therefore the decline in renal function.

Reshma Kewalramani: But your point about whether myotonia is possible is right on, insofar as this is a rare disease, a serious disease, and one that doesn't have any therapies that target the underlying cause of the disease or that very specifically work on the genetic defect. I think that opportunity is there, and we've seen a lot of openness for accelerated endpoints in these kinds of rare, serious diseases.

Doug: Your point around is myotonia possible and so far as this is a disease that is.

But your point around is myotonia is possible, insofar as this is a disease that is a rare disease, a serious disease and one that doesn't have any therapies that target the underlying cause of the disease or that very specifically works on the genetic defect, I think that opportunity is there and we've seen a lot of openness for accelerated endpoints in these kinds of rare, serious diseases.

Doug: A rare disease, a serious disease and one that doesn't have any therapies that target the underlying cause of the disease or the very specifically.

Doug: Works on the the genetic defect I think that opportunity is there and I've seen.

Doug: And we've seen a lot of openness for accelerated endpoints in these kinds of rare serious diseases.

Reshma Kewalramani: On IgA nephropathy. So, the most important things to know about IgA nephropathy is that it's a serious chronic disease. And this is a disease that, over time, leads to decline in GFR and end-stage renal disease, death or transplantation. The most important thing that I would be looking at as a nephrologist, is efficacy. Because proteinuria is known to translate to GFR and, therefore, the decline in renal function. So, if we have a medicine that has high reductions in proteinuria and, as I said in my prepared remarks, everything that we've seen from POVE -- pre-clinically and clinically through Phase II -- is best-in-class across many dimensions but certainly, including efficacy. I think that's the drug that physicians will choose.

Doug: <unk> nephropathy.

Doug: So the most important things to know about Iga nephropathy is that it's a serious chronic disease and this is a disease that over time leads to decline in GFR and end stage renal disease depth or transplantation. The most important thing that.

Doug: I would be looking at as a nephrologist is efficacy.

Because proteinuria is known to translate to GFR and therefore, the decline in renal function. So if we have a medicine that has by reductions in proteinuria and as I said in my prepared remarks every.

Reshma Kewalramani: So if we have a medicine that has high reductions in proteinuria, and as I said in my prepared remarks, everything that we've seen from POVI preclinically and clinically through phase 2 is best in class across many dimensions, but certainly including efficacy, I think that's the drug that physicians will choose. One last quick question, please, Chuck. Yes, ma'am. That will come from Ms. Lisa Bayko with Evercore ISI. Hi. Thanks for squeezing me in. So just two from me. Just to follow up on IgA nephropathy, have you thought any more about how you might highlight having BLyS? Because in addition to APRIL, I think that's one kind of key differentiator of this program. And just wondering how you're thinking about how you could differentiate on that point.

So if we have a medicine that has high reductions in proteinuria, and as I said in my prepared remarks, everything that we've seen from POVI preclinically and clinically through phase 2 is best in class across many dimensions, but certainly including efficacy, I think that's the drug that physicians will choose.

Doug: That we've seen from Povey pre clinically and clinically through phase II is best in class across many dimensions, but certainly including efficacy I think that's the drug that physicians will choose.

Susie Lisa: One last quick question, please, Chuck.

Speaker Change: One last quick question. Please Joe.

Liisa Bayko: One last quick question, please, Chuck. Yes, ma'am, that will come from Ms. Liisa Bayko with Evercore ISI. Hi, thanks for squeezing me in. So just two from me.

Susie Lisa: One last quick question, please, Chuck.

Operator: Yes, ma'am. That will come from Ms. Lisa Bayco from Evercore ISI

Yes, ma'am. That will come from Ms. Liisa Bayko with Evercore ISI. Hi, thanks for squeezing me in. So just two from me.

Operator: Yes, ma'am. That will come from Ms. Liisa Bayko with Evercore ISI.

Yes, ma'am that will come from Ms. Lisa <unk> with Evercore ISI.

Liisa Bayko: Hi, thanks for squeezing me in. So, just two from me. Just to follow up on IgN nephropathy, have you thought any more about how you might highlight having BLISS? Because in addition to APRIL, I think that's one kind of key differentiator of this program and just wondering how you're thinking about how you could differentiate on that point. I don't know if there are biopsies or some kind of different point that you could really highlight the potential benefits of BLISS. And then, just for CF and TRIKAFTA for the quarter. I noticed you had your price increase yet sales looked slightly down, quarter-over-quarter. Can you kind of just describe, in the U.S., what's going on? Was there some higher gross net inventory changes, whatnot? It'd be great for some color there. Thank you so much.

Liisa Bayco: Hi. Thanks for squeezing me in. So just two from me. Just to follow up on IgA nephropathy, have you thought any more about how you might highlight having BLyS? Because in addition to APRIL, I think that's one kind of key differentiator of this program. And just wondering how you're thinking about how you could differentiate on that point. I don't know if there's biopsies or some kind of different point that you could really highlight the potential benefits of povetacicept. And then just for CF and TRIKAFTA for the quarter, I noticed you had your price increase, yet sales looked slightly down quarter over quarter. Can you kind of just describe in the US what's going on? Was there some higher gross to net inventory changes, whatnot? That'd be great. First, color there. Thank you so much.

Speaker Change: Yes.

Reshma Kewalramani: Just to follow up on IGN nephropathy. Have you thought any more about how you might highlight having bliss? Because, in addition to April, I think that's one kind of key differentiator of this program. And just wondering how you're thinking about how you could differentiate on that point.

Lisa: Hi, Thanks for squeezing me in so just two from me.

Lisa: Just a follow up on Iga nephropathy have you thought anymore about how you might highlight.

Lisa: Bliss because in addition to April.

Lisa: That's one kind of key differentiator of this program and I'm just wondering how youre thinking about how you could differentiate on that point I don't know, if theres biopsies or something some.

Reshma Kewalramani: I don't know if there's biopsies or some kind of different point that you could really highlight the potential benefits of povetacicept. And then just for CF and TRIKAFTA for the quarter, I noticed you had your price increase, yet sales looked slightly down quarter over quarter. Can you kind of just describe in the US what's going on? Was there some higher gross to net inventory changes, whatnot? That'd be great. First, color there. Thank you so much. Hey, Lisa. Let me take the IgAN question first, and then I'll ask Charlie to comment on CF. On IgAN, you are correct in pointing out that it's a dual inhibitor. It's an inhibitor of BAFF as well as APRIL. And this is one of the most attractive features of povetacicept, is this dual inhibition.

Lisa: Some kind of different point that you could really highlight the potential benefits of uplift and then just for the.

Reshma Kewalramani: I don't know if there are biopsies or some, some kind of different point that you could really highlight the potential benefits of bliss. And then just for CF and Trikafta for the quarter. I noticed, you know, you had your price increase, yet sales looked slightly down quarter over quarter. Can you kind of just describe what's going on in the US?

Lisa: For for CF and <unk> for the quarter.

Lisa: I noticed you had your price increase yet sales look slightly down quarter over quarter can you kind of prescribed in the U S. What's going on with her some higher.

Reshma Kewalramani: Was there some higher gross net inventory changes, etc.? It'd be great for some color there. Thank you so much. Lisa, I'll take the IGANG question first and then I'll ask Charlie to comment on CF. On IgAN, you are correct in pointing out that it's a dual inhibitor. It's an inhibitor of BAS as well as APRIL. And this is one of the most attractive features of povitacicept is this dual inhibition. Yes, preclinically, we can certainly share, and we have information, and you'll certainly see all of this in the fullness of time. The inhibition of BAS and the measurement of that, and how we can show that preclinically. We can also do that with APRIL.

Was there some higher gross net inventory changes, etc.? It'd be great for some color there.

Lisa: Higher gross to net inventory changes and whatnot that'd be great personal color there. Thank you so much.

Reshma Kewalramani: Hey, Lisa. Let me take the IgAN question first, and then I'll ask Charlie to comment on CF. On IgAN, you are correct in pointing out that it's a dual inhibitor. It's an inhibitor of BAFF as well as APRIL. And this is one of the most attractive features of povetacicept, is this dual inhibition.

Thank you so much. Lisa, I'll take the IGANG question first and then I'll ask Charlie to comment on CF. On IgAN, you are correct in pointing out that it's a dual inhibitor. It's an inhibitor of BAS as well as APRIL. And this is one of the most attractive features of povitacicept is this dual inhibition. Yes, preclinically, we can certainly share, and we have information, and you'll certainly see all of this in the fullness of time. The inhibition of BAS and the measurement of that, and how we can show that preclinically. We can also do that with APRIL.

Thank you so much.

Reshma Kewalramani: Thanks, Liisa. Let me take the IgAN question first and then, I'll ask Charlie to comment on CF. On IgAN, you are correct in pointing out that it's a dual inhibitor. It's an inhibitor of BAFF as well as APRIL. And this is one of the most attractive features of POVETACICEPT -- is this dual inhibition. Yes, pre-clinically, we can certainly share and we have information and you'll certainly see all of this in the fullness of time. The inhibition of BAFF and the measurement of that and how we can show that pre-clinically. We can also do that with APRIL.

Speaker Change: Let me take the <unk> question first and then I'll ask Charlie to comment on CF.

Speaker Change: On eigen.

Speaker Change: You are correct in pointing out that it's a dual inhibitor, it's an inhibitor of bass as well as April and this is one of the most attractive features of pull of attacks of Sept. As this dual inhibition.

Reshma Kewalramani: Yes, preclinically, we can certainly share, and we have information, and you'll certainly see all of this with the fullness of time, the inhibition of BAFF and the measurement of that and how we can show that preclinically. We can also do that with APRIL. However, I think the data that's more interesting is the clinical data which is already available, and that is with this dual APRIL BAFF inhibitor on proteinuria. But I'd encourage you to look at the poster from the WCN meeting that Alpine showed. It has proteinuria results. It has hematuria results. It has GFR results, and it has a composite of remission. And I find those data very, very interesting, particularly the hematuria results clinically because, as you know, hematuria is a hallmark of this disease along with proteinuria. Let me turn it over to Charlie on the question about CF and US. Yeah, Lisa.

Yes, preclinically, we can certainly share, and we have information, and you'll certainly see all of this with the fullness of time, the inhibition of BAFF and the measurement of that and how we can show that preclinically. We can also do that with APRIL. However, I think the data that's more interesting is the clinical data which is already available, and that is with this dual APRIL BAFF inhibitor on proteinuria. But I'd encourage you to look at the poster from the WCN meeting that Alpine showed. It has proteinuria results. It has hematuria results. It has GFR results, and it has a composite of remission. And I find those data very, very interesting, particularly the hematuria results clinically because, as you know, hematuria is a hallmark of this disease along with proteinuria. Let me turn it over to Charlie on the question about CF and US.

Charles F. Wagner: Yes, pre clinically we can certainly share and we have information and Youll certainly see all of this with the fullness of time.

Charles F. Wagner: The inhibition of Bath, and the measurement of that and how we can show that pre clinically. We can also do that with April. However, I think the data. That's more interesting is the clinical data, which is already available and that is with this dual April.

Reshma Kewalramani: However, I think the data that's more interesting is the clinical data -- which is already available. And that is, with this dual APRIL-BAFF inhibitor for proteinuria. But I'd encourage you to look at the poster from the WCN meeting that Alpine showed. It has proteinuria results, it has hematuria results, it has GFR results and it has a composite of remission. And I find those data very, very interesting particularly, the hematuria results, clinically. Because, as you know, hematuria is a hallmark of this disease, along with proteinuria.

Charles F. Wagner: Back inhibitor on proteinuria, but I'd encourage you to look at the poster from the WCS meeting that alpine showed it has hurt noria results.

Charles F. Wagner: It has hematuria results.

Charles F. Wagner: It has GFR results and it has a composite of a remission and I find those data very very interesting, particularly the haematuria results clinically because as you know he maturities a hallmark of this disease along with partner Yeah, Let me turn it over to Charlie on the question about <unk>.

Charles F. Wagner: Let me turn it over to Charlie on the question about CF and US. Yeah, Liisa, on the quarter. I wouldn't read too much into sequential quarter fluctuations. We saw strong volume growth in the US year over year. As we normally do, we see some seasonal growth to net in the first quarter, and the benefit of the price increase really isn't fully reflected in the quarter that comes throughout the balance of the year. So all of those factors affect the comparison.

Let me turn it over to Charlie on the question about CF and U.S.

Charles Wagner: Yeah, Lisa. On the quarter, I wouldn't read too much into sequential quarter fluctuations. We saw strong volume growth in the US year-over-year. As we normally do, we see some seasonal gross-to-net in the first quarter, and the benefit of the price increase really isn't fully reflected in the quarter that comes throughout the balance of the year. So all of those factors affect the comparison. But overall, very, very strong year-over-year growth in the US and outside the US.

Charles F. Wagner: And U S.

Charles Wagner: Yeah. Liisa, on the quarter, I wouldn't read too much into sequential quarter fluctuations. We saw strong volume growth in the U.S., year-over-year. As we normally do, we see some seasonal gross-to-net in the 1st quarter and the benefit of the price increase really isn't fully reflected in the quarter that comes throughout the balance of the year. So, all of those factors affect the comparison. But overall, very, very strong year-over-year growth in the U.S. and outside the U.S..

Reshma Kewalramani: On the quarter, I wouldn't read too much into sequential quarter fluctuations. We saw strong volume growth in the US year-over-year. As we normally do, we see some seasonal gross-to-net in the first quarter, and the benefit of the price increase really isn't fully reflected in the quarter that comes throughout the balance of the year. So all of those factors affect the comparison. But overall, very, very strong year-over-year growth in the US and outside the US. Thanks. Thanks, Chuck. 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 using replay access code 10186968. Again, that is 10186968. Thank you for your time today. You may now disconnect.

Charles F. Wagner: Yes, Lisa on the quarter I wouldn't read too much into sequential quarter fluctuations, we saw strong volume growth in the U S year over year.

Charles F. Wagner: As we normally do we see some seasonal gross to net in the first quarter and the benefit of the price increase really isn't fully reflected in the quarter that comes throughout the balance of the year. So all of those factors affect the comparison, but overall very very strong year over year growth in the U S and outside the U S.

Charles F. Wagner: But overall, very, very strong year over year growth in the US and outside. Thanks, Chuck. 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 using replay access code 101-869-68. Again, that is 101-869-68. Thank you for your time today. You may now disconnect.

But overall, very, very strong year over year growth in the US and outside.

Liisa Bayco: Thanks.

Susie Lisa: Thanks, Chuck.

Speaker Change: Thanks Chuck.

Operator: 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 using replay access code 10186968. Again, that is 10186968. Thank you for your time today. You may now disconnect.

Speaker Change: This concludes our question and answer session.

Speaker Change: As well as our conference call for today.

Thanks, Chuck. 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 using replay access code 101-869-68. Again, that is 101-869-68. Thank you for your time today. You may now disconnect.

Susie Lisa: Thanks, Chuck.

Speaker Change: You for attending today's presentation, a replay of today's event will be available. Shortly after the call concludes by dialing one 870, 734 475 to nine or one four <unk> to 31 70088 using replay access code 1018.

Operator: 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 using replay access code 101-869-68. Again, that is 101-869-68. Thank you for your time today. You may now disconnect.

Speaker Change: 6968 again that is 10186968. Thank you for your time today you may now disconnect.

Speaker Change: Okay.

[music].

Speaker Change: Okay.

Speaker Change: [music].

Operator: ... The Bulletproof Executive, 2013

Q1 2024 Vertex Pharmaceuticals Inc Earnings Call

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