Q2 2024 Agios Pharmaceuticals Inc Earnings Call
Speaker Change: Good morning and welcome to ASJA's second quarter 2024 conference call. At this time, our participants are in a listen-only mode. There will be a question and answer session at the end.
Operator: Please be advised that this call is being recorded at Agios' request. And with that, I'm pleased to turn the call over to Brian.
Chris Taylor: Please be advised that this call is being recorded at Agios request. I would now like to turn the call over to Chris Taylor, VP Investor Relations and Corporate Communications for Agios.
Chris Taylor: Thank you, Operator. Good morning, everyone, and welcome to Agios conference call and webcast to discuss second quarter 2024 financial results and recent business highlights.
Speaker Change: You can access slides for today's call by going to the Investors section of our website at www.agios.com.
Speaker Change: On today's call, I'm joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Tsveta Milanova, our Chief Commercial Officer, and Cecilia Jones, our Chief Financial Officer.
Speaker Change: Before we get started, I'd like to remind everyone that some of the statements we make on this call will include forward-looking statements.
Speaker Change: Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC.
Speaker Change: And with that, I'm pleased to turn the call over to Brian .
Brian Goff: Thanks Chris. Good morning everyone and thank you for joining us. Our mission at Agios is to develop and deliver transformative medicines that elevate and extend the lives of patients living with rare diseases.
Brian Goff: Our foundation leverages Mitopivet's novel mechanism of action which improves overall red blood cell health and has been a key driver of our positive clinical data readouts in recent years.
Brian: I'm delighted to report that we continued our positive momentum in Q2, with multiple key milestones announced this quarter. First, we announced that the Phase 3 Energized T Study of midipivet met both the primary endpoint and all key secondary endpoints in adults with transfusion-dependent alpha or beta thalassemia. Importantly, ENERGIZE-T is the first Phase III study to demonstrate the efficacy of an oral disease-modifying treatment for transfusion-dependent alpha and beta thalassemia. Second, data from the Positive Phase III Energized Study of Mitopibed in adults with alpha or beta thalassemia who are not regularly transfused were presented by leading KOLs in two presentations at the recent European Hematology Association Congress in Madrid, including a plenary session.
Brian Goff: I'm delighted to report that we continued our positive momentum in Q2 with multiple key milestones announced this quarter. Thank you. Thank you.
Brian: Taken together with the positive data from ENERGIZE-T, we plan to submit an SNDA for midipivet in thalassemia based on all available data from both ENERGIZE and ENERGIZE-T by the end of 2024, seeking a label that covers people living with all subtypes of thalassemia. Third, we announced that Agios has agreed to sell its rights to a 15% royalty Under the terms of the agreement, Agios will receive an upfront payment of $905 million upon approval of warasidinib by the FDA.
Brian Goff: We announced that the Phase III Energized T Study of Mitopivet met both the primary endpoint and all key secondary endpoints in adults with transfusion-dependent alpha or beta thalassemia.
Brian Goff: Importantly, ENERGIZE-T is the first Phase III study to demonstrate efficacy of an oral disease-modifying treatment for transfusion-dependent alpha and beta thalassemia.
Brian Goff: Second, data from the positive phase 3 energized study of midipibed in adults with alpha or beta thalassemia who are not regularly transfused.
Brian Goff: were presented by leading KOLs in two presentations at the recent European Hematology Association Congress in Madrid, including a plenary session.
Brian Goff: Taken together with the positive data from ENERGIZE-T, we plan to submit an SNDA for midipivet enthalasemia based on all available data from both ENERGIZE and ENERGIZE-T by the end of 2024
Brian Goff: Seeking a label that covers people living with all subtypes of thalassemia.
Brian Goff: Third, we announced that Agios has agreed to sell its rights to a 15% royalty on potential U.S. net sales of Serbia's borosidinib to Royalty Pharma.
Brian Goff: Under the terms of the agreement, Agios will receive an upfront payment of $905 million upon approval of warasidinib by the FDA.
Brian: Cecilia will revisit the details in a moment, and I would like to thank her for directing the process and structuring a tremendous agreement for Agios, our shareholders, and a win-win for both Agios and Royalty Pharma. This transaction will provide us with the financial independence to prepare for potential launches in thalassemia and sickle cell disease as we build a multi-billion dollar PK activation franchise, as well as the ability to opportunistically expand our pipeline.
Brian Goff: Cecilia will revisit the details in a moment and I would like to thank her for directing the process and structuring a tremendous agreement for Agios, our shareholders, and a win-win for both Agios and Royalty Pharma.
Speaker Change: This transaction will provide us with the financial independence to prepare for potential launches in thalassemia and sickle cell disease as we build a multi-billion dollar PK activation franchise.
Brian: And fourth, just this morning, we announced top-line data from the Phase 3 Activate Kids T Study of midipivet in children with PK deficiency who are regularly transfused. This is truly a pioneering study for Agios, the first pediatric study of Mitopibet, and representative of our commitment to pursue the potential of Mitopibet as a treatment for children with rare diseases.
Speaker Change: as well as the ability to opportunistically expand our pipeline. And fourth, just this morning, we announced top-line data from the Phase 3 Activate Kids T Study of Mitopivet in children with PK deficiency who are regularly transfused.
Speaker Change: This is truly a pioneering study for Agios, a first pediatric study of midipivet and representative of our commitment to pursue the potential of midipivet as a treatment for children with rare diseases.
Brian: We are also pleased to report that we have completed enrollment in the Activate Kids study, and we look forward to the top-line readout in 2025. Sarah will provide a detailed update on our progress and upcoming milestones across R&D in just a few minutes. Leveraging the positive data observed in the ENERGIZE and ENERGIZE-T studies of midipivet, which together encompass all thalassemia subtypes, our expanding commercial organization is actively preparing for a potential U.S. launch of midipivet in thalassemia in 2025.
Speaker Change: We are also pleased to report that we have completed enrollment in the Activate Kids study and we look forward to the top line readout in 2025.
Speaker Change: Building on this progress, we look forward to several additional upcoming milestones, including completing enrollment in the Phase III portion of the Rise Up Study of Mitopivet in Sickle Cell Disease by the end of this year, and reporting data next year.
Speaker Change: Sarah will provide a detailed update on our progress and upcoming milestones across R&D in just a few minutes.
Sarah Gheuens: Given the consistent and compelling data we've generated across the MidaPivet Development Program,
Speaker Change: and the high unmet need in each of our target disease areas.
Speaker Change: We believe Mitopivet has the potential to transform the course of multiple hemolytic anemias by improving red blood cell health and to become a multi-billion dollar franchise.
Speaker Change: Leveraging the positive data observed in the ENERGIZE and ENERGIZE-T studies of midipivet, which together encompass all thalassemia subtypes, our expanding commercial organization is actively preparing for a potential U.S. launch of midipivet in thalassemia in 2025.
Speaker Change: as well as the potential launch in sickle cell disease in 2026.
Speaker Change: Tsveta will provide greater detail on the market opportunity in thalassemia and the team's robust preparation for launch as well as an update on our current launch in PK deficiency in just a bit.
Speaker Change: As part of our news release this morning, we were delighted to announce two updates related to the commercialization of pyrokine outside the U.S.
Brian: First, we've entered into a distribution agreement with Newbridge Pharmaceuticals, a leading player in the Gulf region, and second, Medipivet has received breakthrough medicine designation from the Saudi FDA. Finally, as you'll hear from Cecilia, we ended the second quarter with a strong cash position with approximately $645 million in cash and investments on the balance sheet, and we have the potential to further bolster our cash position by an additional $1.1 billion upon the potential FDA approval of Oracide. With that, I'll turn the call over to Sarah. Thanks, Brian.
Speaker Change: First, we've entered into a distribution agreement with Newbridge Pharmaceuticals, a leading player in the Gulf region. And second, Medipivet has received Breakthrough Medicine designation from the Saudi FDA.
Speaker Change: Finally, as you'll hear from Cecilia, we ended the second quarter with a strong cash position with approximately $645 million in cash and investments on the balance sheet.
Speaker Change: And we have the potential to further bolster our cash position by an additional 1.1 billion dollars upon the potential FDA approval of loracidinib. With that, I'll turn the call over to Sarah.
Sarah: This morning, we were very pleased to announce top-line data from the Phase 3 Activate Kids T Study of metaphylase in children with CK deficiency who are regularly transmitted, and importantly, the first completed pediatric study of metaprevan for ARCH. Next year, we aim to report top-line data from this second study and will review all available data from both the Activate Kids T and Activate Kids Study. So, now to the data from Activate Kids C reported today.
Sarah Gheuens: Thanks Brian . This morning we were very pleased to announce top-line data from the Phase 3 Activate Kids T Study of metaphylase in children with CK deficiency who are regularly transused.
Sarah Gheuens: which is the first Phase III study to report data in this population, and importantly, the first completed pediatric study of metaphevatin for algeals.
Sarah Gheuens: We are also pleased to report that we have completed enrollment in a complementary activated kits study of metapivas in children with PK deficiency who are not regularly transfused.
Sarah Gheuens: Next year, we aim to report top-line data from this second study and we'll review all available data from both Deactivate Kids T and Deactivate Kids Studies.
Sarah Gheuens: So turning now to the data from Activate Kit C reported to date.
Sarah Gheuens: As this first slide depicts, our Pediatric PK Deficiency Program includes two Phase III studies evaluating regularly transused and not regularly transused pediatric patients with parotid kinase deficiency in activated kits C and activated kits respectively.
Sarah Gheuens: Children represent approximately 20% of the total patient population in PK deficiency and there are no therapies approved for pediatric PK deficiency.
Sarah Gheuens: Turning to the top-line results announced this morning for the ACTIVATE Kids T trial. A total of 49 patients were enrolled in the study, with patients randomized 2-to-1 to either metaphytoside daily or placebo.
Sarah: The study consists of a 32-week double-blind period followed by an open-label extension period. The results were clinically meaningful as transfusion-free response and normal hemoglobin response, two key secondary endpoints in this study, were only observed in patients in the metaphysat arm. Safety results for Mitapivat were consistent with the safety profile for Mitapivat previously observed in adults with PK deficiency who are regularly in
Sarah Gheuens: The study consists of a 32-week double-blind period followed by an open-label extension period.
Speaker Change: 30 of the 32 patients in the metaphevat arm and 16 of the 17 in the placebo arm completed the double blind period of the study.
Sarah Gheuens: As we noted in our news release this morning, using Bayesian methodology, the pre-specified statistical criterion for the primary endpoint in ACTIVATE Kids T was not met using low or moderate borrowing of data from the ACTIVATE Teeth study in adults.
Sarah Gheuens: The results were clinically meaningful as transfusion-free response and normal hemoglobin response, two key secondary endpoints in this study, were only observed in patients in the metaphevat arm.
Sarah Gheuens: Transfusion reduction response was defined as an equal or more than 33% reduction in the total red blood cell transfusion volume from week 9 through week 32 of the double-blind period, normalized by weight and actual study drug duration, compared with the historical transfusion volume standardized by weight into 24 weeks.
Sarah Gheuens: 28.1% of patients in the metabolite arm achieved a transfusion reduction response compared to 11.8% of patients in the placebo arm.
Sarah Gheuens: In addition, a higher proportion of patients in the metaphevat arm compared to the placebo arm achieved the secondary endpoints of transfusion-free response and normal hemoglobin response, which were measured from week 9 through week 32 of the double-blind period.
Sarah Gheuens: Six patients, nearly 20% in the metaprofile arm compared to zero in the placebo arm, had a transfusion-free response with no red blood cell transfusions. And four patients in the metaprofile arm compared to zero in the placebo arm achieved a normal hemoglobin response.
Sarah Gheuens: defined as hemoglobin concentrations within normal limits at least once 8 weeks or more after a transfusion.
Sarah Gheuens: Safety results for Mitapivat were consistent with the safety profile for Mitapivat previously observed in adults with PK deficiency who are regularly transfused.
Sarah: During the double-blind treatment period of the study, a similar proportion of patients had adverse events in the metaprofas and placebo arms, and there were no discontinuations of study treatment due to adverse events. Turning to our progress in thalassemia, greater detail was provided on efficacy, and Importantly, patients treated with Mitabevat experienced improvements on multiple health-related quality-of-life measures, including fatigue and walking capacity.
Sarah Gheuens: During the double-blind treatment period of the study, a similar proportion of patients had adverse events in the metaphevas and placebo arms, and there were no discontinuations of study treatment due to AEs. We plan to present a more detailed analysis of the Phase III Activate Kids T data at an upcoming medical meeting.
Sarah Gheuens: We hope that this study will be the first of several pediatric studies to make a positive impact in the lives of children facing rare hemolytic anemia, including thalassemia and sickle cell disease.
Sarah Gheuens: Turning to our progress in thalassemia.
Speaker Change: An overview of the data from the Phase III ENERGIZE study was presented in a plenary session at the IHA meeting in June by Dr. Ali Taher from the American University of Beirut Medical Center.
Sarah Gheuens: And in a poster detailing health-related quality of life and patient-reported outcome measures were presented by Dr. Kevin Kuo from the University of Toronto and in an investor webcast.
Speaker Change: Greater detail was provided on efficacy and safety. Importantly, patients treated with Mitabevat experienced improvements on multiple health-related quality-of-life measures, including fatigue and walking capacity.
Sarah: A total of 268 patients were enrolled, with patients randomized 2 to 1 to either 100 mg metaprofac twice daily or placebo. The study met its primary endpoint of transfusion reduction response, defined as an equal or more than 50% reduction in transfused red blood cell units with a reduction of equal or more than 2 units of transfused red blood cells in any consecutive 12-week period through week 48 compared with baseline. 30.4% of patients achieved the primary end point compared to 12.6% of patients in the placebo arm.
Speaker Change: Moreover, nine 9% of patients in the <unk> arm achieved the secondary endpoints of transfusion independence defined as remaining transfusion free for equal or more than eighth consecutive weeks through week 48, compared to one 1% in the placebo arm.
Sarah: Finally, during the 48-week double-blind period, the incidence of adverse events was similar between Mitaphevat and placebo, with 5.8% of the patients in the Mitaphevat arm experiencing an AE that led to discontinuation, compared to 1.2% of patients in the placebo arm.
Speaker Change: Finally during the 48 week double blind period incidents of adverse events were similar between <unk> and placebo arm with five 8% of the patients and let me talk about arm experiencing an AE that led to discontinuation compared to one 2% of patients in the placebo arm.
Sarah: We look forward to presenting a more detailed analysis of these data at an upcoming medical meeting. As Brian mentioned, we are quite pleased to note that Metaphevat has received a Breakthrough Medicine designation by the SFDA or the Saudi FDA. The Breakthrough Medicine program aims to facilitate and accelerate the development and review of new drugs that address unmet medical needs in the treatment of serious or life-threatening conditions. Turning to sickle cell... Given the positive data we generated in the Phase II portion of the RISE UP study, as well as the positive data we have generated in other hemolytic anemias, we are confident in the potential for metapifa to become a convenient, first-in-class, and best-in-class treatment option that improves red blood cell health for patients living with sickle cell. Thanks, Sarah.
Speaker Change: We look forward to presenting a more detailed analysis of these data at an upcoming medical meeting.
Speaker Change: Taken together the data from energized and energized strongly underscoring <unk> potential to become a foundational convenient oral treatment option for all subtypes of thalassemia Alpha and beta thalassemia and transfusion dependent and non transfusion dependent thalassemia. We are on track to file an NDA that incorporates <unk>.
Speaker Change: All data from both studies by the end of this year seeking a label that covers people living with all subtypes of thalassemia.
Speaker Change: As Brian mentioned, we are quite pleased to note that this topic that has received a breakthrough medicine designation by the FDA or the Saudi FDA.
Brian Goff: I think pipeline, including beginning enrollment of the phase II B study evaluating higher doses of our novel PK Activator AG nine for six now named <unk> in lower risk Mds.
Seth: Are eager to share more details at the trial gets underway soon with that I will now turn the call over to set up.
Tsveta Milanova: Today, a diagnosis of thalassemia can be daunting for patients and their families. Having just returned from the Cooley's Anemia Foundation Patient and Family Conference in Atlanta, we heard many powerful stories emphasizing the debilitating impact that leukemia may have on patients and their families. All forms of thalassemia bring high rates of serious morbidities, reduced quality of life, and a heightened risk of premature death.
Seth: Thanks Ara.
Speaker Change: A diagnosis of thalassemia can be daunting for patients and their families.
Speaker Change: Having just returned from the Cooley's anemia Foundation patient and family conference in Atlanta, We have heard many powerful stories emphasizing the debilitating impactful lithemia may have on patients and their families.
Seth: All forms of Philips EMEA brings higher rates of serious morbidities reduced quality of life and a heightened risk of premature death.
Tsveta Milanova: It is challenging for patients to navigate the disease because treatment options are limited and the burden of disease, as well as the associated cost of care, is significant. Based on the positive data we have generated in the ENERGYSE and ENERGYSE-T studies, we aim to transform the treatment of this disease and bring to market the first therapy approved for all thalassemia subtypes. In addition to the consistent and compelling data we have generated in the META-PIVOT development program, we believe there are three key factors that have the potential to support adoption of pyrotimes in thalassemia in the U.S. Second, both patients and providers are concentrated in a limited number of centers, with approximately 50% of all diagnosed patients treated at fewer than 150 affiliated practices, providing a clear focus for our initial launch. And third,
Seth: It is challenging for patients to navigate the disease because treatment options are limited and the burden of disease as well as the associated cost of care is significant.
Tsveta Milanova: Since some of the centers of excellence were included in our clinical trials, some treating physicians already have first-hand experience with MitoPiva. As we continue to progress toward a potential launch in the U.S., our team is focused on four key areas of launch preparation.
Speaker Change: Some of the centers of excellence what included in our clinical trials. It sounds reading physicians already have firsthand experience with me to be about.
Speaker Change: Taken together, we believe we are well positioned to provide a potential foundational treatment options for patients with the leukemia, regardless of subtype.
Tsveta Milanova: Third, we are executing a disciplined expansion of our commercial and medical teams to right-size the organization for a successful launch in this larger, but still rare, market. On slide 24, we have provided some of the messaging that our team is using in our new disease state education campaigns for both patients and healthcare providers, especially working to reset the perception that non-transfusion-dependent patients are at less risk. Next is a graphic from our campaign.
Speaker Change: And we continue to progress towards a potential launch in the U S.
Speaker Change: Our team is focused on four key areas of launch preparation.
Speaker Change: We continue to conduct extensive market research and claims data analyses to further refine our market insights and our physician targeting.
Speaker Change: Second.
Speaker Change: We commenced a new disease indications on Fannie Mae designed for both patients and clinicians highlighting the long term complications and burden of disease across all of the leukemia subtypes.
Speaker Change: I will share a little more about this campaign in a moment.
Tsveta Milanova: It highlights how we are communicating to physicians that the serious risk of morbidity can exist regardless of the leukemia patient's transfusion history. The response has been very positive, with the images and messaging resonating with both patients and healthcare providers. I mentioned that our team continues to deepen our market understanding. On this slide, you can see the insights from recent market research that helped elucidate the top clinical characteristics health care providers will consider when prescribing pyrokinesis. Outside of the U.S., the Gulf Cooperation Council, or GCC, region is home to approximately 70,000 patients.
Speaker Change: We've built a team here.
Speaker Change: And some of the leading treatment centers in the region, where part of our clinical trials.
Tsveta Milanova: Today, we are pleased to announce that we have entered into a distribution agreement with Newbridge Pharmaceuticals to prepare for a potential commercialization of pyrokines in the GCC region. We are excited to join Fortis with Newbridge as we drive towards potential commercialization in the region. As noted on slide 27, Saudi Arabia accounts for the largest patient population in the GCC. We are quite proud of the team's efforts to successfully secure a breakthrough medicine designation for mitotepia interleukemia, which was granted by the SFDA, the Saudi Arabian FDA. As noted in the last bullet, the access path in individual GCC countries usually begins with a price set at the regulatory level, followed by access to health authorities, local institutions, the private sector, and national standards.
Today, we're pleased to announce that we have entered into a distribution agreement with nobody from US you would think those two pretty bad for a potential commercialization of viral kinds in the GCC region.
Speaker Change: Newbridge, a leading specialty company headquartered in Dubai will commercialize violent crime in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. We are excited to join forces with Newbridge as we drive towards potential commercialization in the region.
Speaker Change: As noted on slide 27, Saudi Arabia accounts, where the largest patient population in the GCC. We are quite proud of the team's effort to successfully secure a breakthrough medicine busy nation for me to be about entellus, EMEA, which was granted by the S. N V. A Saudi M D. A.
Speaker Change: It.
Tsveta Milanova: These are key elements in the process which we look forward to navigating over time with our partner Newbridge. Let me now provide an update on the current launch of pyrokines in PK-deficient patients. In the U.S., a total of 201 patients have completed a prescription enrollment form, including 13 in the second quarter of 2024, a 7% increase versus the prior quarter.
Cecilia Jones: This has translated into 128 net patients on therapy, a 7% increase versus the prior quarter. Patients on Therapy continue to span from a growing and diverse prescriber base of 173 physicians and represents a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population in the U.S. We continue to be encouraged by the persistency of patients on treatment and remain focused on efficiently identifying providers likely to treat patients with PK deficiency.
Cecilia Jones: We believe that the capabilities we continue to strengthen through the current PKD launch, including efficient targeting analytics, patient and physician awareness and education, and patient access, will provide a firm foundation from which to maximize potential future U.S. launches of Mitapiva, including in thalassemia in 2025 and in sickle cell disease in 2026. Above all, we are inspired and energized by the potential to bring a new therapy to this underserved With that, I'll turn the call over to Cecilia. Thanks, Tsveta.
Cecilia Jones: Our second quarter 2024 financial results can be found in the press release we issued this morning, and more detail will be included in our 10Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few. Second quarter 2024 net IROCAN revenue was $8.6 million, an increase of $1.9 million compared to the second quarter of 2023. Consistent with other rare disease launches, Prostionette has been and is expected to be in the 10 to 20% range on an annual basis. Cost of sales for the quarter was $1.5 million.
Speaker Change: Found in the press release, we issued this morning and more detail will be included in our 10-Q, which will be filed later today.
Speaker Change: Let's take a moment to provide some context and highlight a few key points.
Second quarter 2024, net <unk> revenue was $8 6 million, an increase of $1 9 million compared to a second quarter of 2023.
Speaker Change: Insistent with other rare disease launches production that has been and is expected to be in the 10% to 20% range on an annual basis.
Speaker Change: As we pivot our organization's focus through this other female launch preparedness, we expect to see more muted growth going forward and quarter over quarter variability in PKU revenues.
Speaker Change: Cost of sales for the quarter was $1 $5 million.
Speaker Change: R&D expenses were $77 4 million for the second quarter, an increase of $8 $5 million compared to the second quarter of 2023.
Brian: The year-over-year increase was primarily attributable to an increase in costs associated with the TEMPER VI program in license from Anilam last year. SG&A expenses were $35.5 million for the second quarter, an increase of $5.1 million compared to the same quarter in 2023. As a reminder, this quarter, we announced that the company has agreed to sell the rights to its 15% royalty on potential U.S. net sales of Cervius or Acidinib to royalty farmers.
Speaker Change: Year over year increase was primarily attributable to an increase in costs associated with the $10 six programs in licensed from <unk> 91 last year.
Brian: In addition, we still retain the right to a potential $200 million milestone from Cervier upon FDA approval of boracidinib from the divestiture of our Oncology business. We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined cash allocation approach as we prepare to support potential future launches of Pyro. As we move toward additional potential value-creating models in the near term, I am confident that our strong balance sheet will continue to enable us to execute from a position of strength. I will now turn the call back over to Brian for his closing remarks.
Operator: Thanks, Cecilia. Driven by a novel and differentiated mechanism of action that improves red blood cell health, Midipivet has continued to deliver positive late-stage data readouts across three hemolytic anemias, and we're pleased to have now completed our first phase three trial in a pediatric patient population. Based on this consistent and compelling data package and the demonstrated strength of the Agios team, we continue to believe that Midipivet is poised to become a first-in-class and best-in-class treatment option for multiple indications and to become a multi-billion-dollar franchise.
Speaker Change: Where we aim to file an NDA by the end of this year and seeks a label that covers people living with all subtypes of the disease as.
Operator: As we continue to take steps towards realizing our vision of becoming a leading rare disease company, we'll continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation with all of our partners, including the patients, physicians, caregivers, and participants in our clinical development program. With that, we'll now open the call to questions. And our first question comes from Eric Schmidt from Cantor Fitzgerald. Your line is now open.
Speaker Change: As we continue to take steps towards realizing our vision of becoming a leading rare disease company. We will continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation.
Speaker Change: Finally, I'd like to thank all of our employees for their hard work and dedication to our mission of developing and delivering transformative medicines that elevate and extend the lives of patients living with rare diseases.
Speaker Change: And all of our partners, including the patients physicians caregivers and participants in our clinical development programs.
Speaker Change: With that we'll now open the call for questions.
Speaker Change: And thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: Withdraw your question. Please press star one again.
Speaker Change: Please standby, while we compile the Q&A roster and we ask that you limit yourself to one question and one follow up again Thats one question and one follow up one moment for our first question.
Speaker Change: And our first question comes from Eric Schmidt from Cantor Fitzgerald. Your line is now open.
Brian: Thanks, Arc. And Tsveta worked really hard with quite a large team on this new arrangement with Newbridge and GCC. You know that that's our, And I'll just close by saying that that breakthrough medicines designation in Saudi Arabia is pretty unusual. And so we've been pleased to have that as a recognition of, as Tsveta noted, just a profound unmet need in that region. So, you know, it's an important part of the puzzle for us as we get ready to expand our presence outside the U.S. and particularly focus on these high-end, mid-need regions. Great, thanks a lot.
Eric Thomas Schmidt: You bet, and thank you. Brian, I know you've talked about M&A, and I'd say, you know, your language has been, you know, relatively cautious, I guess, in the past. And then I have a follow-up question. Yeah, sure.
Brian: And thanks a lot. Obviously, I just want to reiterate, again, I'm very proud of the work that Cecilia did with the royalty monetization of voracidinib. That's an important step. And as a side note, voracidinib itself is a mark of excellence for agioscience.
Brian: It's very important for patients. And, of course, it adds to our potential balance sheet enhancement. The focus is the efficient use of capital no matter what.
Speaker Change: Well no matter, what but certainly puts us in a position of strength our top priority above all else is preparing for.
Brian: This certainly puts us in a position of strength. Our top priority above all else is preparing for and delivering upon these really important launches that we have in the near term. And we're quite excited about the fact that, with success, these could be back-to-back launches.
Speaker Change: And delivering upon these really important launches that we have near term.
Speaker Change: We're quite excited about the fact that with.
Speaker Change: With success this could be back to back launches Dallas EMEA.
Brian: Thalassemia, you know, Tsveta and the team are preparing for next year. And as we noted in our comments, with sickle cell disease, the RISE UP trial is on track for complete enrollment by year end. That points to data readout next year, and then, again, the possibility for a back-to-back launch. So that's the number one priority.
Speaker Change: Scott and the team are preparing for next year and as we noted in our comments with sickle cell disease. The rise up trial is on track for complete enrollment by year end that points towards data readout next year, and then again the possibility for a back to back launch. So that's the number one priority secondly.
Brian: Secondly, we continue to make great progress on advancing our own internal pipeline, and, of course, that will use some of the capital. A great example is MDS, and we're looking forward to commencing the Phase 2B study for low-risk MDS. That's a market that is growing beautifully, and we're very excited about that potential. Maybe you could just talk about your view around VOCs as an endpoint and the applicability for a broad population. Yeah, that's a great one for Sarah.
Speaker Change: <unk>.
Speaker Change: We continue to make great progress on advancing our own internal pipeline and of course that will.
Speaker Change: Use some of the capital a Great example is Mds and.
Speaker Change: We're looking forward to commencing on the phase <unk> study for low risk Mds that is a market that is growing beautifully and we're very excited about that potential.
Sarah: Thank you. You're right. Not all patients experience VOCs. And as you know, our intent is to deliver a product that can treat all aspects of sickle cell disease, so hemolytic anemia and sickle cell pain crises. But, I mean.
Sarah: Just to be able to measure that treatment effect, but our anticipation is that it can work for no matter how many sickle cell pain crises you have, including just one or zero. Unfortunately, that patient population can't enroll in the trial because we will not be able to measure a treatment effect in that patient population over the course of a year. Again, the drug is meant to address. As you know, that's supported by a bunch of secondary endpoints, of which one is indeed focused on fatigue because that's what we hear from patients and from physicians that fatigue is very, very, impactful and burdensome to the patient population. And, as typical for all of our designs, we really try to incorporate patient feedback and therefore have incorporated fatigue as a main secondary endpoint.
Sarah: As you know, we've just announced the thalassemia trial data ENERGIZE, in which we did meet our key secondary endpoint for the first time on a patient-reported outcome that measures fatigue, so we are very hopeful for the results of the study as well. Thank you. And one moment for our next question, and our next question comes from Gregory Renza from RBC Capital Markets. Your line is now open.
Gregory James Renza: Sure, thanks for the question. So, in Activate Kids T, we really tried to design a study that is appropriate for an ultra-rare disease population and, therefore, chose to really leverage the adult data we have generated to get to a sample size that would be appropriate for this phase of development and provide us with adequate data. So we have to use a pretty complex statistical methodology to look at, and study them, and that gives them specific ways.
Tsveta Milanova: We can't say that across the board we see a treatment effect, so that's why we were very specific in the press release around our low or moderate weight borrowing of the adult study data because the data, you know, while we see, There's, there's a lot in there, Greg. And so maybe we'll just focus on the crux of your question that I heard was focused on the unmet need. And I think Tsveta could certainly put some color on that because, she noted in her prepared comments, we just returned from the Cooley's Anemia Foundation meeting, which is the annual meeting for thalassemia patients in the U.S.
Speaker Change: Also obviously an impact to the family. So that's why we are very excited about the results actually because we do feel like there was a meaningful story it.
Speaker Change: To be to be towards out of this study.
Speaker Change: The main goal of course of the study, which we also can't.
Speaker Change: Which we're very happy about is the safety assessment right. This is our first pediatric clinical trial after completing an adult program in.
Speaker Change: And get to an indication statement. There. So this is our first endeavor to really expand the age range of that patient population and so from that perspective, we do feel the safety data is very important the efficacy data that we have generated.
Speaker Change: Very encouraging and we're very excited about the next steps in the development.
Tsveta Milanova: It's a pretty inspiring venue to be in and certainly brings home the range of unmet need that exists. But keep in mind, these are the engaged patients. These are the ones that are actually skewed towards transfusion dependency and attend meetings like that.
Tsveta Milanova: But Tsveta has a lot of insights that we're continuing to build upon. Of course, this is the most engaged and educated audience, and it was great to get their feedback. And, Greg, as you mentioned, we've heard it very clearly from the physician community and market research that they'll consider all of the relevant endpoints that we measure in our clinical trials as patients' characteristics when making a treatment decision, being hemoglobin level, transfusion burden, iron overload, and, of course, fatigue. And Sarah talked about the importance of fatigue both in thalassemia and sickle cell disease. Thanks, Tsveta.
Tsveta Milanova: So, I would like to come back to the hemoglobin cutoff in the clinical trials. As you know, we have the clinical trial endpoints of one gram per deciliter or more that we look at, but to your point, Greg, there are patients who may not reach that bar of, you know, becoming a responder in the clinical trial but still may experience some benefits. And we have seen that in our PKD patient population.
Within distribution in the patient population exposed to meet up enough person exposed to placebo looks like and you can see a very similar figure in the policy that patient population is what we have shown before in the iron age kinase deficiency patient population. So there is definitely people who are improving some of their hemoglobin followings, but may not reach that.
Speaker Change: Clinical trial endpoint, which is also one of the reasons why it could set up points of hemolysis components. It's important how patients feel is important. So this is why we allow.
Speaker Change: Patients and physicians to decide at the end of a clinical trial to still roll over in an open label extension, even if they don't meet the clinical trial bar.
Speaker Change: And thank you and one moment our next question.
Tsveta Milanova: We also see that in the thalassemia patient population. We highlighted, as Dr. Taher showed, a waterfall plot showing how the hemoglobin distribution in the patient population exposed to metaprofile versus exposed to placebo looks like, and you can see a very similar figure in the thalassemia patient population as what we have shown before in the spironate kinase deficiency patient population. So, there are definitely people who are improving some of their hemoglobin values, but they have not reached that clinical trial endpoint, which is also one of the reasons why, to Tsveta's point, the hemolysis component is important, and how patients feel is important. And our next question comes from Divya Rao from TD Cowen. Your line is now open. Okay, that's helpful.
And our next question comes from Diarrhea ROE from TD Cowen. Your line is now open.
Divya Rao: And then on AD946, I was curious when we would, when we could expect to see the Phase 2a data, and if it would be at a medical meeting or if that's okay. First, Divya, we have to practice saying Teva Pivat, because that's the L-V-I-N-A, and we're going to try to do the same, because 946 is burned into our heads. But Sarah, do you want to comment on the NPS? Teva Pivat
Sarah: I honestly, the numbers are still burned in my head as well, so apologies if I switch. But yes, as mentioned, our current milestone and focus is the Phase 2B, so the team is very, very focused on that. And we will announce that later when we present the 2A data. And if we're successful, this would be not only novel PK activation but in a pill form, which would be very significant for patients.
Speaker Change: And I just wanted to reemphasize real quick that again for Mds and we'll learn as we proceed through the clinical trial program here, but this is a very compelling market for US. We certainly took note of.
Speaker Change: The <unk> recently reported sales data that shows now a run rate in excess of $1 6 billion annualized there is very high unmet need in this population certainly as is the case in all the diseases. We pursue there is room for multiple mechanisms of action and if we're successful this would be not only.
Speaker Change: <unk> PK activation, but in a pill form which would be very significant for patients.
Speaker Change: And thank you and one moment our next question.
<unk> Richter: And our next question comes from <unk> Richter from Goldman Sachs. Your line is now open.
Sarah: We're very pleased with the results in the key secondary endpoints. The two trials have now completed and their data read out, so we are very eager to move forward in the development and the regulatory engagement and are looking forward to really having the review start. And our next question comes from Tess Romero from J.P. Morgan. Your line is now open.
Tessa Thomas Romero: Hi, good morning, Brian and team. Thanks for taking our question. On the regulatory side in the U.S. for thalassemia, how should we think about the gating factors at this point for your submission of the SNDA? And is the base case here a standard or priority review? And then our second question is just to follow up on the arrangement with Newbridge. So Tess, we're excited about that arrangement.
Speaker Change: At this point for your submission of the S. N D. A N is the base case here of standard or priority review.
Speaker Change: And then our second question is just a follow up on the arrangement with Newbridge, how should we think about the soonest, we could start to see revenue Miss here and how many patients have balancing here specifically in the Saudi region. Thanks.
Speaker Change: Sure you want to start with regulatory pathway. Yeah. So again, we're very eager to work together with the SBA and submit the package for their review and assessment. So we're doing a typical our typical process is really a result comments.
Brian: But just to come back to, by far, our number one priority is the U.S., and again, we're thrilled to have the opportunity. And Tsveta is working very assertively with the commercial team to build out our commercial prowess in rare diseases, building on the momentum we've had in PKD and moving into thalassemia and hopefully beyond sickle cell as well. You're welcome. And thank you, and one moment for our next question. Hey guys, thanks for taking our questions and just a couple from us.
Speaker Change: The opportunity instead of is working very assertively with the commercial team to build out our commercial prowess in rare diseases building on the momentum we've had in PK and moving into Fallas, EMEA and hopefully beyond sickle cell as well.
Speaker Change: Thanks, so much for taking our question Youre welcome.
Speaker Change: And thank you and one moment for our next question.
Speaker Change: And our next question comes from Alex Stranahan from Bank of America. Your line is now open.
Operator: First, one follow-up on the SNDA submission and just sort of framing the data that will be going into that. Is the full data we should expect by the end of this year, kind of the complete picture of what the FDA will be reviewing and anything incremental and efficacy from that update or more just sort of expanding on the safety and, and the secondaries. And then one question on the PK study in the non-transfusion setting next year. Any read-throughs to be made from the data today to that study? Obviously, different primary endpoints and different patient populations. Thanks.
Alex Stranahan: Hey, guys. Thanks for taking our questions just a couple from us.
Alex Stranahan: First one follow up on the <unk>.
Speaker Change: The NDA submission.
Sarah: So, the two randomized clinical trials have completed, and they've been locked, and we have the data. So, we're very, very excited to put that together. We are really doing the standard type of work that we would normally be doing for a submission that follows the standard cuts, timelines, and updates that we need to do and are very eager to work with the regulators and get that process started. There are always questions back and forth, so we're just going to go through the motions.
Sarah: Regarding the Activate Kids T endpoints, so we are, you know, very pleased with the data that was generated in this clinical trial. Yeah, and thoughts on the link or the read-through, as it would be called, to activate kids' non-transfusion-dependent patients. So, again, it's a similar methodology applied for activated kits. It's a non-regularly transfused patient population, and we're blinded, so we are very eager to get to the next point, and then we'll get that data back.
Speaker Change: To activate our kids non transfusion dependent patients.
Speaker Change: So again this is it's a similar methodology are applied for activation kits, it's not regularly transfused patient population that we're blind.
Speaker Change: So we are very eager to get to the next point and then we'll we'll we'll get that data package.
Sarah: We, in the ACTIVATE Kids T trial, are very pleased because the transfusion-free response truly highlights that the mechanism of action of metaphebate is applicable to kids as well, and so now we're hoping that that also translates into the other trial.
Speaker Change: We aim to activate T trial, we are very pleased because of the transfusion free response truly highlight the mechanism of action has been talking about is applicable to us too.
Speaker Change: Two kits as well and so now we're hoping that that also translates into the other trial.
Speaker Change: Thank you.
Speaker Change: And thank you.
Justin: Thank you. Thanks, Justin. And so, thanks a lot, everybody, for the great questions and for participating in today's call. This is clearly a very exciting time at Agios, and just thinking of, Thank you for watching!