Agios Pharmaceuticals, Inc. (AGIO) Earnings Call Transcript & Summary

Good morning, and welcome to Agios' First Quarter 2025 Conference Call. [Operator Instructions] 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.

Thank you, operator. Good morning, everyone, and welcome to Agios' conference call and webcast to discuss our first quarter 2025 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; Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development; Tsveta Milanova, Chief Commercial Officer; and Cecilia Jones, Chief Financial Officer. 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.

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. And with approximately $1.4 billion 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, PYRUKYND 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 2 additional commercial launches to support our potential multibillion-dollar opportunity for PYRUKYND. We are planning for a potential approval and launch in thalassemia in the U.S. in September of this year, followed by sickle cell disease in 2026. Beyond PYRUKYND, 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 3 key priorities: first, maximizing the potential of the PYRUKYND franchise, including the pursuit of new indications. 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 toward important milestones. Earlier this year, we announced positive top-line results from the ACTIVATE-Kids T 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. For tebapivat, our novel PK activator, we expect to complete enrollment in the ongoing Phase IIb study in lower-risk MDS by year-end and to initiate enrollment in a Phase II study in sickle cell disease by mid-2025. Additionally, we expect to file an investigational new drug application for AG-236, our siRNA targeting TMPRSS6 inhibition intended for the treatment of polycythemia vera in mid-2025. And the most significant expected events for 2025 include the September 7 PDUFA goal date for our sNDA filing of PYRUKYND in thalassemia, now only 4 months away, and the Phase III 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 hold significant value for shareholders and have transformative potential for patients. Before I turn it over to Sarah, I'd like to formally welcome Krishnan Viswanadhan, who joined us in March as Chief Corporate Development and Strategy Officer, having previously served as the President and Chief Operating Officer of Be Biopharma and in various senior roles at both Bristol-Myers Squibb and Celgene. 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.

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. Today, patients have limited or no effective treatment options, with 67% of diagnosed patients in the U.S. having no approved therapies. In 2024, we announced positive results from the ENERGIZE and ENERGIZE-T Phase III 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 III 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 PYRUKYND for this indication in the U.S., European Union, Kingdom of Saudi Arabia, and the United Arab Emirates. As Brian mentioned, in the U.S., we are now just 4 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 120,000 to 135,000 individuals across the U.S. and EU5, with a global prevalence exceeding 3 million. 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 III RISE UP study completed 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 2 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. 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 III study in late 2025 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 crisis and making patients feel better. 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. Patients will be randomized to either 2.5 5 or 7.5 milligrams of tebapivat QD or placebo. The primary endpoint will be a hemoglobin response as defined by an increase of at least 1 gram per deciliter from week 10 to 12 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 lower-risk MDS, where we aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in the disease. MDS affects approximately 75,000 to 80,000 patients in the U.S. and EU5 with lower-risk MDS accounting for approximately 70% 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, 2 items to note in our early-stage pipeline programs. For AG-181 targeting phenylketonuria, we are progressing to studying multiple ascending doses in our ongoing healthy volunteer study midyear. We are also on track to file an IND mid-2025 for AG-236, our siRNA targeting TEMPR-6 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 Tsveta.

Thanks, Sarah. Our commercial organization is driven by the potential to expand PYRUKYND indications to include both thalassemia and sickle cell disease by 2026. 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 PYRUKYND represents a multibillion-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 PYRUKYND. Thalassemia patients are diagnosed and known to the health care system. The burden of disease is well-characterized. And there are well-established KOLs and patient advocacy groups. All these elements will help drive adoption. We are now just 4 months away from a potential U.S. 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 health care 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'm proud to report that our team has organized several highly attended patient programs in Cantonese, Mandarin and Arabic. 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. 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 PYRUKYND in thalassemia 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 6,000 adults diagnosed with thalassemia in the U.S., with most patients diagnosed before adulthood. With the availability of claims data, we can identify where these patients are managed within the health care system, offering valuable clarity for our launch preparations. Within that population, we estimate that PYRUKYND's initial launch focus will address approximately 65% of the adult thalassemia patient population. We expect patients with more frequent contact with the health care 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 are non-transfusion-dependent, but already are experiencing complications or debilitating fatigue. We conducted market research to identify top clinical characteristics health care providers will consider when prescribing PYRUKYND. 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, PYRUKYND's profile is well-positioned for each of these important criteria. Central to our messaging is the transformative profile of PYRUKYND in thalassemia, characterized by a number of forests. 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 36-week durability of effect in reducing transfusion burden. This is what motivates us to deliver PYRUKYND 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 2025, we generated $8.7 million in net PYRUKYND revenue compared to $8.2 million in the first quarter of last year. In the U.S., a total of 234 patients have completed a prescription enrollment form, including 11 in the first quarter of 2025, a 5% increase versus the prior quarter. This has translated into 136 net patients on therapy, also an increase of 5% 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. 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 this underserved patient populations around the world. With that, I'll turn the call over to Cecilia.

Thanks, Tsveta. Our first quarter 2025 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 2025 net PYRUKYND revenue was $8.7 million, an increase of 6% compared to $8.2 million in the first quarter of 2024. Compared to the fourth quarter of 2024, 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. Importantly, as Tsveta 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. Gross 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 our 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 the 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. 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 Tsveta described earlier into a significant revenue trajectory for thalassemia. Returning to the first quarter results. Cost of sales for the quarter was $1.1 million. R&D expenses were $72.7 million for the first quarter, an increase of $4.1 million compared to the first quarter of 2024. This was primarily attributed to an increase in workforce-related expenses and costs associated with the clinical trials of tebapivat 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&A expenses were $41.5 million for the first quarter, an increase of $10.5 million compared to the prior year quarter. This was primarily driven by an increase in commercial-related activities, including head count as we prepare for the potential approval of PYRUKYND 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 $1.4 billion. As Brian mentioned, we expect this balance, together with anticipated product revenue and interest income, will provide the financial independence for potential PYRUKYND 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 PYRUKYND. 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.

Thanks, Cecilia. We believe the remainder of 2025 will be incredibly exciting for Agios based on the potential approval and launch of PYRUKYND in 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. Operator, please open the line.

[Operator Instructions] Our first question will come from the line of Gregory Renza from RBC Capital Markets.

Congrats on the progress. Brian, it's really helpful to hear your confirmation about no advisory committee for the September PDUFA. I'm just curious if you can comment on, 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.

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

No, it's 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.

And I will just take the opportunity, Greg, to reinforce the fact that I think you heard the excitement in Tsveta's voice. We're now 4 months away from the PDUFA. And I must say the commercial team is very prepared, and 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.

And maybe a quick follow-up. Just broadly with the sickle cell community and as you think about especially tebapivat and the enrollment there, how has the Oxbryta wean off the current market conditions? How is that, in your view, impacted the recruitment of trials, the sickle cell community as they sort of transition and await for new options in the marketplace?

Sure. You bet. Sarah can start and then Tsveta might want to add a little color too on sickle cell in general and the opportunity in front of us.

Yes. And so, from our perspective, of course, we were disappointed when Oxbryta 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.

Yes. And just to add to Sarah, of course, from us commercially, sickle cell disease is a large market. There are over 100,000 patients in the U.S. The withdrawal of Oxbryta was devastating for the community, and that just strengthens the unmet medical need. We are excited about the potential opportunity to have 2 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 our launch preparations and the engagement with the community. They deserve the trust and respect and we'll continue to do so.

Our next question will come from the line of Alec Stranahan from Bank of America.

Congrats on the progress in the quarter. Maybe first, since you alluded to it a couple of times, maybe you could just remind us about your plans for launching mitapivat ex-U.S. When could these approvals come through for that? 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.

Yes. Thanks, Alec. I'm going to let Tsveta take over on that question. I will just start by reinforcing by far, the 2 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.

Yes, absolutely. So, when it comes to ex-U.S., as Sarah noted, we have submitted to 4 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. 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 uptake. 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.

And on economics, maybe Cecilia, you can touch on that.

Yes, Alec, on the economics, as we announced last year, we have the partnership with NewBridge. This is, I'll call it, a revenue split, which allows us to leverage a little bit the best of both worlds, as Sarah said, NewBridge knowledge of the region with our team support knowledge of the 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.

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?

Yes. 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 our real focus for corporate strategy, capital allocation specifically. And in order of priority, first, it's getting these launches right. We're really excited, as we've noted, about thalassemia now with the PDUFA just 4 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 2026. 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. 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.

Our next question will come from the line of Divya Rao from TD Cowen.

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

So, thanks, Divya, for the question. So no, our communication with the agency on our programs has been the same as before. So I think it is a normal back and forth in the context of -- especially for the filing, it's a normal back and forth communication with questions and answers. So as you know, the PDUFA date is September 7, and it's -- 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.

And 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 2 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.

Our next question comes from the line of Hiro Nagayumi from Cantor.

This is Hiro on behalf of Eric Schmidt here at Cantor. I wanted to ask a bit about the rationale and conviction for starting the Phase II tebapivat study in sickle cell in mid-2025 prior to the Phase III readout of PYRUKYND in late 2025.

Yes. I think -- again, Hiro, that's going to be a 2-part. Sarah should start with tebapivat itself and why we're excited about it. And then Tsveta 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.

So Hiro, like we were very pleased with the Phase I data that we have generated in 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 II, which we're very excited about starting mid-year. And then, of course, within drug development, this is where Tsveta's organization and the R&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 Tsveta.

Absolutely. So the way I think about it is really in 3 steps. The first one is it's a 100,000 patient population with a very large unmet medical need. And when you think about like this market, it can easily absorb and it's of the 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 2 products, we are actually looking to grow the patient population with our portfolio of products. We'll actually, more specifically, as Sarah said, position tebapivat after we have the mitapivat data, the RISE UP data. So starting now will allow us to actually have the 2 data sets and make the best informed decisions for us how to move forward with Phase III.

And I think folks listening in may know Tsveta's background, too, but in prior life, Tsveta 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.

Next question will come from the line of Emily Bodnar from H.C. Wainwright.

I guess for thalassemia, maybe if you can 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 treatments?

Yes. Perfect. Tsveta.

So first of all, I'll start with how excited we are about the potential launch in thalassemia, which is just 4 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 health care system. There is a good understanding and characterization of the unmet need across both transfusion-dependent and non-transfusion-dependent patients. Our disease state education actually primarily focuses on the non-transfusion-dependent patients, which actually relates to your question. And of course, there are 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 PYRUKYND has a strong 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 communications with their health care providers. They are likely to hear about the therapy first, and we see them as a good starting point for our commercial uptake.

Our next question comes from the line of Andrew Berens from Leerink Partners.

This is Amanda on for Andy. It seems that you're starting to discuss more tebapivat more frequently in sickle cell disease and are slated to start the Phase II. 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 the tebapivat study versus RISE UP or any endpoints, differences there that might be a focus? Any learnings that you're taking into this new trial? And also, have tebapivat shown any signs of impacting the liver in these early studies? Or how are you thinking about that?

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 II and then thoughts ahead.

So the Phase II for tebapivat is sort of a classic dose-finding study, 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 Tsveta and I discussed earlier, I think this is really about -- we're in a phase that the drug has shown promise in a Phase I. So now we're bringing it forward to a Phase II so it can continue to establish its benefit risk profile. And so far, we have not observed a liver signal on tebapivat. But we will continue to accrue safety data in that program. And then as Tsveta 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, obviously, Phase III comes after Phase II.

And again, this is -- 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.

Our next question will come from the line of Tess Romero from JPMorgan.

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 REMS is needed? Or can you rule this out at this point?

Thanks, Tess, for the question. So, the 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, et cetera. It's a less defined process than, for instance, the EMA at which certain point you can submit your filing and then you receive questions that's very specific date, et cetera. What we have mentioned before is that we have a collaborative engagement with the FDA. We're receiving questions back and forth. This is part of the standard process that we feel it's a very normal engagement at this point in time with the agency. Again, like I think the only thing that I would really anchor towards to 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. In regards to rents 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.

[Operator Instructions] Our next question will come from the line of Salveen Richter from Goldman Sachs.

This is Lydia on for Salveen. Congrats on all the progress. Maybe just another one on the potential thalassemia launch. Could you just comment on any anticipated evolution of PYRUKYND pricing in the context of payer feedback, the existing price in PKD, and the patient population here?

Thank you for the question. I can't wait for the September 7 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 product, 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 very positive feedback on the product profile. We have a very strong market access team, and I'm very confident we can navigate the pricing opportunity with thalassemia very well.

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

All right. Thanks a lot, Victor, and thank you very much, everybody, for participating in today's call. We are, as we've noted, 4 months into another busy year, and we're 4 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.

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