Agios Pharmaceuticals Q1 2025 Earnings Report

Agios Pharmaceuticals EPS Results

• Actual EPS: -$1.55
• Consensus EPS: -$1.80
• Beat/Miss: Beat by +$0.25
• One Year Ago EPS: N/A

Agios Pharmaceuticals Revenue Results

• Actual Revenue: $8.73 million
• Expected Revenue: $9.86 million
• Beat/Miss: Missed by -$1.13 million
• YoY Revenue Growth: N/A

Agios Pharmaceuticals Announcement Details

• Quarter: Q1 2025
• Date: 5/1/2025
• Time: Before Market Opens
• Conference Call Date: Thursday, May 1, 2025
• Conference Call Time: 8:00AM ET

Agios Pharmaceuticals (NASDAQ:AGIO), a biopharmaceutical company, discovers and develops medicines in the field of cellular metabolism in the United States. Its lead product includes PYRUKYND (mitapivat), an activator of wild-type and mutant pyruvate kinase (PK), enzymes for the treatment of hemolytic anemias. The company develops AG-946, a PK activator for treating lower-risk myelodysplastic syndrome and hemolytic anemias; and AG-181, a phenylalanine hydroxylase stabilizer for the treatment of phenylketonuria. Its preclinical product is siRNA for the treatment of polycythemia vera, a rare blood disorder. Agios Pharmaceuticals, Inc. was incorporated in 2007 and is headquartered in Cambridge, Massachusetts.

Agios Pharmaceuticals Q1 2025 Earnings Call Transcript

Key Takeaways

• Agios is on track for a September 7, 2025 PDUFA goal date for its sNDA of mitapivat (PyroKine) in thalassemia, supported by positive Phase III ENERGIZE and ENERGIZE T data and consistent FDA engagement without a planned advisory committee.
• The Phase III Rise Up study in sickle cell disease is expected to read out in late 2025, with two independent primary endpoints in hemoglobin response and vaso-occlusive crisis rate, paving the way for a potential 2026 U.S. filing and launch.
• Agios continues to advance its mid-stage pipeline by completing Phase IIb enrollment of tebapivat in low-risk MDS by year-end 2025, initiating a Phase II dose-finding study of tebapivat in sickle cell disease by mid-2025, and filing an IND for AG-236 in polycythemia vera mid-2025.
• Preparation for the thalassemia launch includes doubling the U.S. sales force, multi-language disease-state education campaigns targeting patients and physicians, and proactive payer engagement to ensure formulary coverage and patient access.
• Backed by approximately $1.4 billion in cash and marketable securities and a disciplined capital allocation approach, Agios expects to be financially independent through new approvals and product launches, making 2025 a breakout year.

Presentation

[Operator]

Good morning, and welcome to Agil's First Quarter twenty twenty five Conference Call. At this time, all participants are in a listen only mode. There will be a question and answer session at the end. Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Chris Taylor, Vice President of Investor Relations and Corporate Communications for Agios.

[Christopher Taylor, VP - IR & Corporate Communications at Agios Pharmaceuticals]

Thank you, operator. Good morning, everyone, and welcome to Agios conference call and webcast to discuss our first quarter twenty twenty five financial results and recent business highlights. You can access the slides for today's call by going to the Investors section of our website, agios.com. On today's call, we'll hear from our Chief Executive Officer, Brian Goff Doctor. Sarah Hewins, Chief Medical and Head of Research and Development, Sveta Milanova, Chief Commercial Officer and Cecilia Jones, Chief Financial Officer.

[Christopher Taylor, VP - IR & Corporate Communications at Agios Pharmaceuticals]

Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward looking statements. 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. And with that, I'm pleased to turn the call over to Brian.

[Brian Goff, CEO at Agios Pharmaceuticals]

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. Today, we are fortunate to have multiple late stage programs nearing critical readouts or potential commercialization and have a very strong balance sheet. We are maintaining our focus on executing against the objectives we've laid out, including the ongoing regulatory reviews of our thalassemia program for which we have seen continued and consistent FDA engagement.

[Brian Goff, CEO at Agios Pharmaceuticals]

And with approximately $1,400,000,000 of cash on hand and a disciplined approach to capital allocation, we believe we will have financial independence to fund the company through new approvals and product launches, while advancing our pipeline, all of which is especially notable in today's market environment. Our lead product, PyroKind, or mitapivat, a pyruvate kinase activator, has a novel mechanism of action that improves red blood cell metabolism and increases the amount of energy, or ATP, available to support red blood cell health. We have the exciting prospect of two additional commercial launches to support our potential multibillion dollar opportunity for pyrokine. We are planning for a potential approval and launch in thalassemia in The U. S.

[Brian Goff, CEO at Agios Pharmaceuticals]

In September of this year, followed by sickle cell disease in 2026. Beyond pyruvate kinase, our early and mid stage pipeline is robust and poised for clinical advancement, offering a strong foundation for innovation and long term growth. And finally, supporting it all is our highly experienced team and the strong balance sheet I noted earlier. We look at 2025 as a breakout year for Agios as we focus on three key priorities. First, maximizing the potential of the pyrokind franchise, including the pursuit of new indications.

[Brian Goff, CEO at Agios Pharmaceuticals]

Second, advancing and diversifying our key pipeline programs. And third, strategically focusing our capital deployment to sustain and drive our growth. We have begun the year with a strong start executing towards important milestones. Earlier this year, we announced positive top line results from the ACTIVATE Kids Phase III trial of mitapivat in pediatric patients with PK deficiency who are not regularly transfused. We also anticipate some exciting developments for our mid and early stage pipeline programs.

[Brian Goff, CEO at Agios Pharmaceuticals]

For tebapivat, our novel PK activator, we expect to complete enrollment in the ongoing Phase IIb study in low risk MDS by year end, and to initiate enrollment in a Phase II study in sickle cell disease by mid-twenty twenty five. Additionally, we expect to file an investigational new drug application for AG-two thirty six, our siRNA targeting TMPRSS6 inhibition intended for the treatment of polycythemia vera in mid-twenty twenty five. And the most significant expected events for 2025 include the September 7 PDUFA goal date for our sNDA filing of pyrokinin thalassemia, now only four months away, and the phase three readout of the Rise Up study of mitapivat in sickle cell disease by year end. As you can see, this year promises to be exciting with multiple catalysts across our pipeline that holds significant value for shareholders and have transformative potential for patients. Before I turn it over to Sarah, I'd like to formally welcome Krishnan Viswanathan, who joined us in March as Chief Corporate Development and Strategy Officer, having previously served as the President and Chief Operating Officer of B BioPharma and in various senior roles at both Bristol Myers Squibb and Celgene.

[Brian Goff, CEO at Agios Pharmaceuticals]

His diverse experience and strategic vision will be instrumental in maximizing the potential of our current assets while also exploring potential expansion opportunities. With that, let me now turn it over to Sarah.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Thanks, Brian. Our pipeline includes a well rounded mix of late stage programs nearing market entry and promising mid and early stage opportunities. Thalassemia is a rare lifelong inherited blood disorder that causes chronic anemia, and patients with thalassemia often experience a range of debilitating complications such as organ damage, stroke, and other serious health issues. One of the most commonly cited patient concerns is chronic fatigue, which is unaddressed by the currently available therapies. Common management strategies for thalassemia such as blood transfusions and iron chelation therapy can also lead to significant secondary effects compounding the health challenges patients face.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Today, have limited or no effective treatment options with sixty seven percent of diagnosed patients in The US having no approved therapies. In 2024, we announced positive results from the ENERGIZE and ENERGIZE T Phase three trials evaluating mitapivat versus placebo in adults with non transfusion dependent and transfusion dependent alpha or beta thalassemia, respectively. Based on the compelling clinical profile observed in both the ENERGIZE and ENERGIZE T Phase three studies, we believe mitapivat has the potential to become a foundational and convenient oral medication for thalassemia patients regardless of their genotype or transfusion needs. In December, we announced the simultaneous filing for regulatory approval of pyrokine for this indication in The U. S, European Union, Kingdom Of Saudi Arabia, and The United Arab Emirates.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

As Brian mentioned, in The U. S, we are now just four months away from our PDUFA goal date of September 7, and our interactions with the FDA have continued as expected. The FDA has communicated that at this time, no advisory committee meeting is planned and the review is ongoing. Moving on to sickle cell disease. This inherited lifelong blood disorder is estimated to affect approximately one hundred and twenty thousand to one hundred and thirty five thousand individuals across The US and EU5 with a global prevalence exceeding three million.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Clinical features of sickle cell disease are chronic hemolytic anemia and vaso occlusion, which can lead to pain, poor quality of life, organ damage, and early mortality. There is an urgent need for novel therapeutic options, and our data to date indicate that mitapivat may be a transformational therapy for these patients with the ability to address multiple aspects of the disease. The Phase three Rise Up study completes enrollment in October 2024 with over 200 patients enrolled globally, achieving this milestone just over a year after recruitment began. In this study, we have two independent primary endpoints, hemoglobin response and analyzed rate of sickle cell pain crises. Attaining either primary endpoint allows us to apply alpha to the testing of the trial's key secondary endpoints.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

With our secondary endpoints, we are using a variety of measures to assess mitapivat's potential in improving how patients feel and function. We expect to report top line results from this Phase three study in late twenty twenty five with a potential regulatory filing and U. S. Approval in 2026. We believe mitapivat has the potential to emerge as a best in class therapy aimed at addressing the high unmet need in this disease by improving anemia, reducing sickle cell pain crises, and making patients feel better.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Beyond mitapivat, we aim to further address the broad range of disease manifestations in diverse areas of unmet need in sickle cell disease. Since not every patient will respond to a given therapy, we see an opportunity to expand the patient population with complementary approaches. To that end, tebapivat, which is a potent PK activator currently being explored as a potential treatment option for low risk MDS may also hold promise in sickle cell disease. We are planning to begin enrollment in a Phase II study of tebapivat in sickle cell disease in the coming months. This will be a randomized placebo controlled dose finding study, including a total of 56 patients.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Patients will be randomized to either two point five, five, or seven point five milligrams of tebapibat QD or placebo. The primary endpoint will be a hemoglobin response as defined by an increase of at least one gram per deciliter from week ten to twelve compared to baseline, and secondary endpoints will include the hemolysis and patient reported outcomes evaluating how patients feel and function. We expect data from this study will provide proof of concept for tebapivat and enable us to select the dose for phase III. As I mentioned, tebapivat is also being evaluated in a Phase IIb study in low risk MDS, where we aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in the disease. MDS affects approximately seventy five thousand to eighty thousand patients in The U.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

S. And EU5, with lower risk MDS accounting for approximately seventy percent of all MDS cases. We are on track to complete enrollment in this study later this year with a data readout planned for early next year. And finally, two items to note in our early stage pipeline programs. For AG-one hundred eighty one targeting sphenylketonuria, we are progressing to studying multiple ascending doses in our ongoing healthy volunteer study midyear.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

We are also on track to file an IND mid-twenty twenty five for AG-two thirty six, our siRNA targeting TMPRSS6 intended for the treatment of polycythemia vera. So we are quite excited about the progress planned across the entire portfolio this year. With that, I will now turn the call over to Sarah.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Thanks, Sarah. Our commercial organization is driven by the potential to expand viral kinds indications to include both thalassemia and sickle cell disease by 2026.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

In thalassemia, we are aiming to deliver the first therapy indicated to treat all subtypes of the disease. And with sickle cell disease, our goal is to deliver a novel oral therapy that improves anemia, reduces vaso occlusive crisis, or VOCs, and improves fatigue. Across these indications, we believe SpiroKind represents a multi billion dollar opportunity. Looking at the upcoming potential launch of thalassemia in The U. S, the underlying market dynamics in thalassemia support a significant opportunity for pyrokind.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Thalassemia patients are diagnosed and known to the healthcare system. The burden of disease is well characterized, and there are well established KOLs and patient advocacy groups. All of these elements will help drive adoption. We are now just four months away from a potential U. S.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Approval, and our team is working diligently to prepare for a potential launch. First, we are executing a robust disease state education campaign focused on both patients and healthcare providers. Our campaign highlights thalassemia disease pathophysiology, long term complications and burden, and the importance of frequent monitoring and management. Additionally, it embraces the cultural diversity of the thalassemia patient community. I am proud to report that our team has organized several highly attended patient programs in Cantonese, Mandarin, and Arabic.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Feedback from the community has been overwhelmingly positive, and we are planning additional programs as we prepare for launch. Second, we have rightsized our cross functional team to ensure a successful launch in this larger, yet still rare market. For example, for PK deficiency, we have had a sales team of 20 professionals, and for thalassemia, we have strategically grown the sales organization to approximately twice that size. This team is fully on board, focusing on disease state education and detailed account profiling to enable a focused and effective launch shortly after approval. And third, our market access team is actively engaging and educating payers on thalassemia through pre approval information exchange meetings to facilitate disease understanding and support patient access.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Feedback from payer research and these interactions has been positive, with recognition of the unmet need and the strength of the product profile. We expect the majority of patients to be on commercial plans. As a reminder, the initial coverage of pyrokinesia will be through medical exception process while policies are still being established. Given our experience and strong track record in PK deficiency, we are well positioned to navigate the medical exception process and replicate the success we have had with PK deficiency. There are approximately six thousand adults diagnosed with thalassemia in The U.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

S, with most patients diagnosed before adulthood. With the availability of claims data, we can identify where these patients are managed within the healthcare system, offering valuable clarity for our launch preparations. Within that population, we estimate that Spinal Kine's initial launch focus will address approximately sixty five percent of the adult thalassemia patient population. We expect patients with more frequent contact with the healthcare system due to their disease symptoms to be considered for therapy first. These patients include those who are transfusion dependent, as well as those who

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

are non

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

transfusion dependent but already are experiencing complications or debilitating fatigue. We conducted market research to identify top clinical characteristics healthcare providers will consider when prescribing PyroKind. Four key attributes were identified as most important: impact on hemoglobin levels, reduction in transfusion burden, improvement of fatigue, and iron overload. Taking into account these elements, Final Cut's profile is well positioned for each of these important criteria. Central to our messaging is the transformative profile of quirky chain thalassemia characterized by a number of firsts.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

This is potentially the first therapy for alpha and beta thalassemia patients, the first oral therapy for the disease, the first treatment to demonstrate quality of life improvement for non transfusion dependent patients, and the first treatment to demonstrate thirty six weeks durability of effect in reducing transfusion burden. This is what motivates us to deliver PyroKine as quickly as possible to people suffering from thalassemia. Finally, let me provide a brief update on revenue for the first quarter. In the first quarter of twenty twenty five, we generated $8,700,000 in net Spirofan revenue compared to $8,200,000 in the first quarter of last year. In The U.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

S, a total of two thirty four patients have completed a prescription enrollment form, including eleven in the first quarter of twenty twenty five, a 5% increase versus the prior quarter. This has translated into one hundred and thirty six net patients on therapy, also an increase of five percent versus the prior quarter. And we continue to see strong persistence. We believe the capabilities we continue to strengthen through the current launch will provide a foundation helping us to maximize potential U. S.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Launches in thalassemia in 2025 and in sickle cell disease in 2026. In closing, we are inspired and energized by the potential to bring a new therapy to these underserved patient populations around the world. With that, I'll turn the call over to Cecilia.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Thanks, Zara. Our first quarter twenty twenty five financial results can be 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. Let me now take a moment to provide some context and highlight a few key points. First quarter twenty twenty five net PyroKine revenue was 8,700,000 an increase of 6% compared to $8,200,000 in the first quarter of twenty twenty four. Compared to the fourth quarter of twenty twenty four, revenues decreased by 19%, primarily due to the benefit of year end stocking and adjustments to certain revenue reserves that we previously noted for Q4.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Importantly, as Veda detailed, we saw an increase in both new prescriptions and new patient starts in the first quarter since the January label update, which we see as a strong testament to the product's profile. Growth to net has generally been and is expected to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches and will also experience quarter to quarter variability. As a reminder, with our focus on thalassemia disease state education as we prepare for a September 7 PDUFA date, we continue to expect 2025 revenues for PK deficiency to be relatively flat compared to 2024. Regarding thalassemia, it is worth noting that it can take several weeks, particularly at launch, between a prescription enrollment form and a patient initiating therapy. Combined with the expected time to set up payer access, we're looking at a more of a partial quarter in Q4, which should be factored into modeling revenue expectations for 2025.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Obviously, we are eager for the September 7 PDUFA date to arrive and the team is well prepared for it. And looking forward to 2026 and beyond, we are optimistic about the team's ability to translate the favorable market dynamics that Sveta described earlier into a significant revenue trajectory for thalassemia. Returning to the first quarter results, cost of sales for the quarter was $1,100,000 R and D expenses were $72,700,000 for the first quarter, an increase of $4,100,000 compared to the first quarter of twenty twenty four. This was primarily attributed to an increase in workforce related expenses and costs associated with the clinical trials of tevapivat in lower risk MDS and sickle cell disease, partially offset by lower costs associated with the clinical trials of mitapivat in thalassemia and pediatric PKD. SG and A expenses were $41,500,000 for the first quarter, an increase of $10,500,000 compared to the prior year quarter.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

This was primarily driven by an increase in commercial related activities, including headcount, as we prepare for the potential approval of Pyrocan in thalassemia later this year. We are closely monitoring the potential for new tariffs to increase our operating expenses, but at this time we do not anticipate a material impact. Please see our 10 Q filing later today for additional related disclosures. We ended the first quarter with cash, cash equivalents and marketable securities of approximately $1,400,000,000 As Brian mentioned, we expect this balance together with anticipated product revenue and interest income will provide the financial independence for potential Pyrocan launches in thalassemia and sickle cell disease, advancing existing programs and opportunistically expanding our pipeline through both internally and externally discovered assets. In closing, 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 PyroGuide.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

As we move toward additional potential value creating milestones this year, we are confident that our balance sheet will continue to enable us to execute from a position of strength. I will now turn the call back over to Brian.

[Brian Goff, CEO at Agios Pharmaceuticals]

Thanks, Cecilia. We believe the remainder of 2025 will be incredibly exciting for Agios based on the potential approval and launch of pyrokinin thalassemia, a critical Phase III readout in sickle cell disease, and important anticipated progress across our mid and early stage pipeline. In closing, I'd like to briefly reinforce our fortunate position of having a very strong balance sheet, which provides us with the ability to independently execute across our key priorities. We remain committed to disciplined cash allocation and long term shareholder value creation as we all navigate the current market environment. With that, I'd like to now open the call for questions.

[Brian Goff, CEO at Agios Pharmaceuticals]

Operator, please open the line.

[Operator]

Thank you. Our first question will come from the line of Gregory Renza from RBC Capital Markets. Your line is open.

[Gregory Renza, Director & Senior Analyst of Biotechnology Equity Research at RBC Capital Markets]

Great. Hey, Brian and team. Congrats on the progress. Thanks for taking my questions. Brian, it's really helpful to hear your confirmation about no advisory committee for the September PDUFA.

[Gregory Renza, Director & Senior Analyst of Biotechnology Equity Research at RBC Capital Markets]

I'm just curious if you can comment on that first, has that mid cycle review happened? I think it should have already occurred. Just wanted to get clarity on that. And secondly, what are the next steps? As you mentioned, the engagement with FDA has been strong as you think about labeling and the next steps of the late cycle.

[Gregory Renza, Director & Senior Analyst of Biotechnology Equity Research at RBC Capital Markets]

Thanks so much.

[Brian Goff, CEO at Agios Pharmaceuticals]

Yes, sure. And as you noted, we're really pleased with how we're progressing. It's been very consistent with the FDA in the fact that we were able to say at this time, it's been communicated no AdCom, but of course, it's an ongoing regulatory review. Sarah, do you want to add color from your perspective?

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

No, exactly what you just said. I think we are pleased with the process. We are engaged with the agencies, right? Because we've filed in multiple regions and everything is progressing. We're very much looking forward to our PDUFA date of September 7.

[Brian Goff, CEO at Agios Pharmaceuticals]

And I will just take the opportunity, Greg, to reinforce the fact that I think you heard the excitement in Sveta's voice. We're now four months away from the PDUFA, and I must say the commercial team is very prepared, we're very much looking forward to getting to that date and then hopefully having the opportunity to serve the patients who count on us.

[Gregory Renza, Director & Senior Analyst of Biotechnology Equity Research at RBC Capital Markets]

That's really helpful. And maybe a quick follow-up, broadly with the sickle cell community, and as you think about, especially tebipipin and the enrollment there, how has the Oxbreda weaned off the current market conditions? How has that, in your view, impacted the recruitment of trials that the sickle cell community as they sort of transition and await for new options in the marketplace?

[Brian Goff, CEO at Agios Pharmaceuticals]

Thank you, and Yes, Sarah can, sure, you bet. Sarah can start, and then Sveta might want to add a little color too on sickle cell in general and the opportunity in front of us.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Yes, and so from our perspective, of course, we were disappointed when VOXX was withdrawn, because we really are looking for all drugs that can potentially provide benefit for patients and hope that sickle cell disease patients ultimately will have many options to choose from. From our perspective on the clinical trial conduct, we have not observed any changes as it relates to our programs. Yeah, and just to add to Sarah, of course, from us commercially, sickle cell disease is a large market. There are over one hundred thousand patients in The U. S.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

The withdrawal of Brighton was devastating for the community, and that just strengthens the need. We are excited about the potential opportunity to have two products on the market to serve that community, and for us to continue to grow the number of patients who can benefit from an innovative therapy. When it comes to kind of the sentiment, of course, we're going to take that into account as far as our launch preparations and the engagement with the community. They deserve the trust and respect and will continue to do so.

[Operator]

Thank you. One moment for our next question. Our next question will come from the line of Alec Stranahan from Bank of America. Your line is open.

[Alec Stranahan, Analyst at Bank of America]

Okay. Great. Yeah. Thanks for the questions, and and congrats on the progress in in the quarter. Maybe first, since you alluded to it a couple of times, maybe maybe you could just remind us about your plans for launching mitapivat ex US.

[Alec Stranahan, Analyst at Bank of America]

When could these approvals come through for THAL? And do you think it would make sense to try and keep the economics in house by leaving the launches yourself given the strong balance sheet? And then I've got a follow-up.

[Brian Goff, CEO at Agios Pharmaceuticals]

Yeah, thanks, Alex. I'm going let Sveta take over on that question. I will just start by reinforcing our by far the two most important geographies for thalassemia is first the U. S. And secondly, the Gulf Region GCC, and we are very well prepared with regard to both of those.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Yeah, absolutely. So when it comes to ex US, as Sarah noted, we have submitted to core regulatory authorities, UAE, Saudi Arabia, and Europe, from a commercial launch preparation and priority. Saudi or the GCC region is the next priority for us. When we look at the ex U. S.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Opportunity, when you think about launch and timing and uptake, I would say that especially the Gulf countries, they are a lot more similar to the European market, so it takes some time from approval to actually get on formularies, get access to patients, and see the updates. We have a very strong partner in The Gulf, with Newbridge, which we believe that they will be very well positioned to combine our strong expertise and knowledge in thalassemia with their strong expertise and knowledge in the region to execute on our behalf successfully.

[Brian Goff, CEO at Agios Pharmaceuticals]

And on economics, maybe Cecilia can touch on that.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Yes. On the economics, as we announced last year, we have the partnership with Newbridge. This is, I call it, a revenue split, which allows us to leverage a little bit the best of both worlds, as Fela said, Newbridge knowledge of the region with our team support knowledge of product, and it's an efficient way for capital deployment for us. For Europe, we plan to do something very similar in terms of the structure, and we'll provide an update when we do so.

[Alec Stranahan, Analyst at Bank of America]

Okay, great. And then maybe one, great to see Krishnan joining the team. Curious if bringing him on board to lead corporate strategy represents any shifts in kind of the way you're thinking or allocating resources going forward, either through increased BD or areas of pipeline focus? Thank you.

[Brian Goff, CEO at Agios Pharmaceuticals]

Yeah, thanks. I'm really happy to have Krishnan on board. He's a very experienced leader across, as I noted in my earlier comments, multiple companies, senior roles, very well connected individual, and we're just delighted to have him on the team. To answer your question, it's not a shift, it's really building capabilities and a reinforcement of a real focus for corporate strategy, capital allocation specifically. And in order of priority first, it's getting these launches right.

[Brian Goff, CEO at Agios Pharmaceuticals]

We're really excited, as we've noted, about thalassemia now with the PDUFA just four months away. We are equally excited about the RISE UP data that will play out at the end of this year, and that could present a back to back launch scenario with sickle cell launch towards the end of twenty twenty six. We also are not a one product company. We're really proud to talk about the middle and earlier part of our pipeline today. And so that's a key priority.

[Brian Goff, CEO at Agios Pharmaceuticals]

And third is BD. Any healthy biopharma biotech company should always be looking at how to continue to build out the pipeline. And we have a very strong balance sheet. As I noted, we will be extremely disciplined because we have internal opportunities that sets a very high bar, but Krishnan really adds to that capability. And again, we're just delighted to have him on the team.

[Alec Stranahan, Analyst at Bank of America]

Excellent, thanks for the color.

[Brian Goff, CEO at Agios Pharmaceuticals]

You're very welcome.

[Operator]

Thank you. One moment for our next question. Our next question comes from the line of Divya Rao from TD Cowen. Your line is open.

[Divya Rao, Analyst at Cowen]

Hi, Brian and team. This is Divya on for Mark. I'll add my congrats on all the progress. Just one question from us. Have you seen any changes to your communication frequency with the FDA given the recent reshuffling that's been happening at the agency?

[Divya Rao, Analyst at Cowen]

And then is there a deadline for when the FDA needs to inform you of a potential outcome?

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So thanks, Nivia, for the questions. So no, our communication with the agency and our programs have been the same as before. So I think it is a normal back and forth, especially for the filing, it's a normal back and forth communication with questions and answers. As you know, the PDUFA date is September 7, and as the review is ongoing, an agency always has the opportunity to request for an advisory committee. To date, though, they have informed us that there is no advisory committee planned and that the review is still ongoing.

[Brian Goff, CEO at Agios Pharmaceuticals]

Thank you. Divya, I'll just take the opportunity to give credit to the FDA, because we know that there have been a lot of dynamics. But I think this also reinforces that this is a high unmet need area where we have two stellar studies that read out last year and the data that we've put into our file really aligns beautifully with what we hear consistently is the unmet need that we're trying to fulfill. So we're appreciative of that continued focus and really pleased with how we're progressing.

[Operator]

Thank you. One moment for our next question. Our next question comes from the line of Nagayomi from Cantor. Your line is open.

[Hiromichi Nagayumi, Associate - Biotech Equity Research at Cantor Fitzgerald]

Hi. This is Hiro on behalf of Eric Schmidt here at Cantor. Thanks so much for taking our question. I wanted to ask a bit about the rationale and conviction for starting the Phase II tebapivat study in sickle cell in mid-twenty twenty five prior to the Phase III readout of Pirogant in late twenty twenty five.

[Brian Goff, CEO at Agios Pharmaceuticals]

Yeah, I think, again, Hiro, that's going be a two parter. Sarah should start with tebapivat itself and why we're excited about it, and then Sveta can add more about what we're trying to achieve in sickle cell for the patient community in general, which clearly needs more, not fewer, options ahead.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So, Hirou, we were very pleased with the phase one data that we have generated for tebapivat in sickle cell disease. And when you look at drug development at that program specifically, that allows us to move forward to a phase two, which we're very excited about starting mid year. And then, of course, within drug development, this is where the SEDAS organization and the R and D organization, we work very closely together because we will always design our trials towards the product profile that we believe can make meaningful change. And with that, I'll hand it over to Sarah.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Absolutely.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

So, the way I think about it is really in three steps. The first one is it's a 100,000 patient population with a very large unmet medical need, and when you think about this market, it can easily absorb any sort of need of multiple therapies. The second one is the fact that we hear it loud and clear from KOLs and physicians and experts in the field. Not every patient will respond to every single therapy, so they would like to have many options so they can choose from and find the best options for their therapy. And when it comes to timing and the co positioning of the two products, we are actually looking to grow the patient population with our portfolio of products.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

We'll actually more specifically, as far as that, position TevaPivot after we have mitapivat data, the rise up data. So starting now will allow us to actually have the two data sets and make the best informed decisions for us how to move forward with Phase III.

[Brian Goff, CEO at Agios Pharmaceuticals]

And I think folks listening in may know Sveta's background too, but in prior life, Sveta has a lot of experience building lasting franchises that have a very similar dynamic of serving an even greater patient population. So we're looking to leverage her expertise in that regard.

[Operator]

Thank you so One

[Operator]

moment for our next question. Next question will come from the line of Emily Bodnar from H. C. Wainwright. Your line is open.

[Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.]

Hi, good morning. Thanks for taking the questions. I guess for thalassemia, maybe if you could touch a bit on your plans for marketing for non transfusion dependent patients compared to transfusion dependent patients, particularly on the non transfusion side since those patients currently don't have any treatment? Thanks.

[Brian Goff, CEO at Agios Pharmaceuticals]

Yeah, perfect. Shweta?

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

So, first of all, I'll start with how excited we are, about the potential launch in thalassemia, which is just four months away. We have deployed the team, and I can say that we are ready for launch. So, that's really, really exciting and energizing. When it comes to the market itself, I just want to mention very quickly, it's a really attractive rare disease market. Patients are diagnosed and known to the healthcare system.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

There is a good understanding and characterization of the unmet need across both transfusion dependent and non transfusion dependent patients. Our disease based education actually primarily focuses on the non transfusion dependent patients, which actually relates to your question, and of course, they're well established KOLs and patient advocacy groups that will help us drive adoption. When it comes in terms of prioritization and different approaches for both patient populations, we believe PyroKine has a value proposition across both transfusion dependent and non transfusion dependent patients. Our initial launch focus will actually be equally deployed against the transfusion dependent patients, but also on the non transfusion dependent patients which have hemoglobin levels less than 10, already have developed complications, or are experiencing debilitating fatigue. And the reason for that is that these patients are already in an active engagement and communication with their healthcare providers.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

They're likely to hear about the therapy first, and we see them as a good starting point for our commercial uptake.

[Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.]

Perfect. Thank you.

[Operator]

Thank you. One moment for our next question. Our next question comes from the line of Andrew Berens from Leerink Partners. Your line is open.

[Amanda Acosta-Ruiz, Equity Research Associate - Biotechnology at Leerink Partners]

Hi, everyone. This is Amanda on for Andy. Thanks for taking our question. It seems that you're starting to discuss more tebipivat more frequently in sickle cell disease and are slated to start the the phase two. Is there any color that you can provide on kind of differences on how you're thinking of like patients going into that study and then the type of that study versus rise up or any endpoints differences there that might be a focus, any learnings that you're taking into this new trial?

[Amanda Acosta-Ruiz, Equity Research Associate - Biotechnology at Leerink Partners]

And also, has sedaparibat shown any signs of impacting the liver in these early studies? Or how are you thinking about that? Thanks.

[Brian Goff, CEO at Agios Pharmaceuticals]

Sure, Amanda. I'll just start by making a comment that we will follow a very staged process to guide us on how we continue to differentiate, but perhaps Sarah can just add a little bit on the design itself for the phase two, and then thoughts ahead.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So the phase two for tebapivat is sort of a classic dose finding study in which we're looking for proof of concept of tebapivat by looking at a hemoglobin response, so it's a very standard development in sickle cell disease, I would say. As Sedai and I discussed earlier, I think this is really about we're in a phase that the drug has shown promise in a phase one, so now we're bringing it forward to a phase two so it can continue to establish its benefitrisk profile, and so far we have not observed a liver signal on debactivation, but we will continue to accrue safety data in that program. Then as Feta highlighted earlier, between each development phase, we work very closely with our commercial team to make sure that the trials we design can meet the product profile that commercial is requesting to be met at the end of the trial, And that will be driven by how the market evolves, and how the population is growing, and the unmet need within that patient population. And so that is a little bit too early now to discuss because, well, obviously phase three comes after phase

[Brian Goff, CEO at Agios Pharmaceuticals]

And again, this follows our disciplined approach with capital allocation. We don't want to get ahead of ourselves. Just as last year, we waited for the ENERGIZE data readout before we started building our commercial team, very similar approach here as we look to build a sickle cell franchise, we will learn more from the Phase II and then we'll make the right decisions at that time.

[Operator]

Thank you. One moment for our next question. Our next question will come from the line of Tess Romero from JPMorgan. Your line is open.

[Tessa Romero, Equity Analyst at J.P. Morgan]

Hey, guys. Thanks so much for taking our question.

[Brian Goff, CEO at Agios Pharmaceuticals]

Sure.

[Tessa Romero, Equity Analyst at J.P. Morgan]

In IUF, double clicking back to a prior question, can you confirm or not if you have completed the mid cycle meeting? And if so, can you comment on any high level discussion you have had around labeling? And is there a scenario where a REMS is needed, or can you rule this out at this point? Thanks so much.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Thanks, Tess, for the question. So, process with the FDA, they will announce to you the end date of the review, which is the PDUFA goal date of September 7, so we're really working towards that with them, and along the way you have different touch points, which may or may not be meetings or questions, etcetera. It's a less defined process than, for instance, the EMA, at which certain points you can submit your filing, and then you receive questions at very specific dates, etc. What we have mentioned before is that we have a collaborative engagement with the FDA. We're receiving questions back and forth.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

This is part of the standard process that we feel it's a very normal engagement at this point in time with the agency. And again, like I think the only thing that I would really anchor towards two is the September 7 date at this point in time. The labeling negotiations, as we've mentioned, the review is ongoing, right? To date, they have not informed us that there will be an advisory committee, but the review is ongoing, as we've mentioned. Labeling negotiations typically go later in the process of a review cycle, so it's too early for that.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

In regards to RINs or not, I think you can only really fully be certain when you have reached your PDUFA goal date on what the ultimate label shows and what will be required. But I think right now, we're very pleased with where we are. And it's, from our perspective, just a normal process.

[Tessa Romero, Equity Analyst at J.P. Morgan]

Thank you.

[Operator]

Thank you.

[Operator]

Our next question will come from the line of Salveen Richter from Goldman Sachs. Your line is open.

[Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs]

Hi, good morning. This is Lydia on for Salveen. Thanks so much for taking our question and congrats on all the progress. Maybe just another one on the potential thalassemia launch. Could you just comment on any anticipated evolution of pyrokines pricing in the context of payer feedback, the existing price in PKD and the patient population here?

[Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs]

Thanks so much.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

Thank you for the question. I can't wait for the SETENZA seven PDUFA date and for us to talk a little bit more specifics about pricing then. But, of course, any pricing decision will be anchored in the value proposition of the label that we get. Based on where we stated today, thalassemia is a rare disease, and from a payer perspective, we don't expect that category to be managed. All the interactions and the payer research that we've done indicate that there is a good understanding of the unmet medical need and a very positive feedback on the product profile.

[Tsveta Milanova, CCO at Agios Pharmaceuticals]

We have a very strong market access team, and I'm very confident we can navigate the pricing opportunity with thalassemia very well.

[Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs]

Thanks so much.

[Operator]

Thank you. I'm not showing any further questions at this time. I would now like to turn the call over back to Brian for any closing remarks.

[Brian Goff, CEO at Agios Pharmaceuticals]

All right. Thanks a lot, Victor, and thank you very much, everybody, for participating in today's call. We are, as we've noted, four months into another busy year and we're four months away from the PDUFA date for thalassemia, which is very exciting. So we really believe that at Agios we're poised to deliver transformative new therapies for patients and create significant long term value to our shareholders. So thanks again and we look forward to speaking with all of you again real soon.

[Operator]

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.

Participants

Executives

• Christopher Taylor, VP - IR & Corporate Communications
• Brian Goff, CEO
• Sarah Gheuens, Chief Medical Officer and Head of Research & Development
• Tsveta Milanova, CCO
• Cecilia Jones, CFO

Analysts

• Gregory Renza, Director & Senior Analyst of Biotechnology Equity Research at RBC Capital Markets
• Alec Stranahan, Analyst at Bank of America
• Divya Rao, Analyst at Cowen
• Hiromichi Nagayumi, Associate - Biotech Equity Research at Cantor Fitzgerald
• Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.
• Amanda Acosta-Ruiz, Equity Research Associate - Biotechnology at Leerink Partners
• Tessa Romero, Equity Analyst at J.P. Morgan
• Lydia Erdman, Biotech Equity Research Analyst at Goldman Sachs