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

All right. Great. Good morning, everyone, and welcome to day 1 of the 2026 Bank of America Healthcare Conference. My name is Alec Stranahan. I cover SMID Biotech here at BofA. And I'm the analyst covering Agios, and I'm pleased to be joined today by Brian Goff, Chief Executive Officer; Sarah Gheuens, Chief Medical Officer and Head of R&D; and Tsveta Milanova, Chief Commercial Officer. Thanks for being here, guys.

Thank you very much.

Yes. We're looking forward to a great 30-minute fireside. But maybe just to start off, Brian, if you want to tee up the conversation with recent updates. You've had a couple of press releases out this morning.

We did, which we're quite proud of. Yes, happy to. And thanks again, Alec, for hosting us yet again. And everybody, thanks for tuning in to learn more about the exciting year and future that we have underway at Agios. 2026 has been a lot of action already in a very good way. We started this year with our launch of AQVESME, mitapivat, for thalassemia. And we just reported our first quarter results, really the first quarter of that launch, which we're quite proud of, great momentum, really good healthy start. Launches, of course, are a long journey. But as a starting point, we're very pleased with how that's begun. And Tsveta is here to share more about that launch as well. Secondly, as you just mentioned, Alec, we had a press release this morning where we disclosed that we have now filed our sNDA for mitapivat for sickle cell disease. We're pursuing the accelerated pathway, and we disclosed this morning, high level, the construct of the confirmatory study that is affiliated with that accelerated pathway. And I'll just say that for this morning's discussion, we're happy to talk about both of those 2 aspects. We won't go into more detail than what we put in the press release because we have coming in next month at the European Hematology Association meeting, actually a plenary session for RISE UP data for sickle cell disease. And there, we plan to give the totality of the data as well as more details on the confirmatory study. We also have, as we're building out our pyruvate kinase activation franchise, we have another meaningfully more potent next-generation PK activator known as tebapivat. And tebapivat, we're pursuing in Phase II studies in 2 other areas. One is low-risk MDS. And actually, this quarter, we're looking forward to the readout for -- top line readout for low-risk MDS. We always describe that as a higher risk, very high reward potential program. And then secondly, also in sickle cell disease in the second half of this year, we have a Phase II study with tebapivat. We're looking forward to that data readout. We have a couple of other earlier-stage Phase I programs. One is AG-236 for polycythemia vera, right in our sweet spot of rare hematology. And we have AG-181, which is a very novel mechanism for phenylketonuria, also Phase I study in PKU patients, and we're looking forward in the second half of this year to proof of mechanism data. So the last thing I'll say is we are very focused on capital allocation discipline, OpEx discipline. We've guided to keeping our OpEx approximately flat to 2025. And I must say, given this range of high-quality value-creating opportunities, it is a challenge, but we're very committed to that. So exciting year, a lot to talk about, and I'll turn it back to you for questions.

Great. Yes. Obviously, a lot going on at Agios right now. And you mentioned a couple of key updates. You've got your newly launched product in thalassemia, AQVESME; an sNDA filing expected, I guess, now in 2Q or in 3Q for sickle cell; and tebapivat Phase II readout is coming this year, I guess. If you had to sort of direct the conversation, where do you see the biggest re-rating catalysts across these 3 milestones?

Interesting question. So you're indirectly asking me to pick a favorite catalyst, which I will not do because I think it's really exciting right now at Agios. And fundamentally, our mission is to deliver on all fronts. One way you could think about it is investors often look at 2 different things simultaneously. One is -- one lens would be short-term value creation, of course. And there, we have a lot to talk about with AQVESME as well as the pathway for mitapivat in sickle cell disease. And the other is investors are looking at how can you continue to advance and grow your PK activation franchise. And there, again, with the benefit of tebapivat and some really exciting near-term Phase II readouts, that's a really nice setup for the potential ahead. I think from our perspective, as I said, all 3 are important, whether it's commercial execution, which Tsveta and the team are doing a really terrific job or regulatory progress. And there, Sarah and her team, as we just disclosed this morning, are really advancing things nicely. And then, of course, just continuing to move the pipeline along and diversify.

Great. You had a pretty meaningful update this morning, the alignment on the confirmatory endpoint of transfusion dependence in sickle cell. It sounds like the sNDA is over the finish line. So that's the ticking clock, 60 days, puts you in 3Q for an acceptance and a PDUFA date with an accelerated time line would put you maybe beginning of 2Q. Is that kind of the right way to be thinking about the path forward?

So we have -- I think you're right on all fronts about now we can check the box of sNDA filed confirmatory study clearly aligned. We feel very strongly that this represents clinical benefit as aligned with the FDA and certainly the community. But maybe I'll have Sarah talk a little bit about where we go from here and next steps.

Well, yes. So we are very excited about the update that we were able to give this morning. So the submission of the sNDA, which means that we indeed have alignment on the confirmatory trial in which we are further looking to demonstrate clinical benefit. As you know, we've observed very strong clinical benefit in the hemoglobin responders, which allows us to go on this path. And we've announced the details of the trial as well this morning in which we -- as you may have noticed, is 159 patients. So it's a relatively small sample size. We try to optimize trial execution and feasibility as well as taking trial costs into account and are very pleased that we were able to get to alignment with the FDA, which allowed us to make that announcement this morning. Further data, we will be presenting at EHA that underpins the clinical trial. So more to come at EHA. Plenary there is, of course, a very big thing for us. So we're very excited about that. And as it relates to the milestones, you've mentioned, indeed, it's now 60 days that the FDA -- that clock is basically ticking, which brings us to Q3 in which we'll get more insight in the PDUFA date at that point as well.

Great. I guess maybe double-clicking on the transfusion dependence. I think this was the question that folks had. And also the study population, you're now going from 12 years old and up, whereas RISE UP, I think, was 18, right?

16.

16. So I guess when you think about the powering assumptions within the study, how did you come to 159? It's a very specific number. And what would you expect on that transfusion burden dependence endpoint, especially as you move to earlier patients?

Yes. So it's indeed transfusion independence that we're looking for between week 4 and week 52. We are enriching the trial population to an episodically transfused patient population to be able to demonstrate that benefit, and it is completely informed by the RISE UP data that we have. So that data, as I mentioned, will be presented at EHA. Again, it's really about the sample size we need to be able to demonstrate clinical benefit driven by the data and then, of course, the feasibility on execution.

Okay. And I guess on that transfusion burden dependence, is there any signals that you've provided, either the top line of RISE UP or earlier data that you point investors to, to sort of understanding the potential benefit there? Or is it more of an additional burden of proof at EHA that will be supporting that data?

No. So it's -- the data was prospectively and systematically collected in RISE UP. So it's that data. We had episodically transfused patients in RISE UP. So that's the data that we base this on. This is completely informed by RISE UP data set. So all of that detail, though, we will highlight at the plenary. So come to the plenary.

Okay. And I guess on the perceived benefit from physicians that you've spoken to, obviously, you've got the hemoglobin benefit. I think that's pretty concrete from the data that you've shared. When you talk to physicians, what's important for their patients in terms of a meaningful benefit to disease? I know sickle cell pain crises has been sort of held in the industry, but it hasn't really proved out to be a great clinical endpoint. So how does transfusion burden dependence kind of reflect the patient need?

Yes. So it's like hemolytic anemia. So people do need on occasion transfusions for a variety of different reasons as we've seen in our clinical trial, just like other hemolytic anemias in which case people may not need regular transfusions, but they still need transfusions. So we have demonstrated a benefit in these other indications on transfusion burden. And in the RISE UP trial, again, we have clinically meaningful data there as well. For sickle cell disease specifically, it is a problem. They really are trying to avoid transfusions because each transfusion can lead to alloimmunization and it's becoming then harder to transfuse people as well. So something that can lead to avoidance of transfusions altogether is always welcomed in sickle cell disease and hemolytic anemia.

And maybe, Tsveta can just add here, too, because, again, just to reinforce the confirmatory study, of course, and the transfusion endpoint is what is aligned as clinically beneficial, but really for the accelerated pathway, right? The bigger picture, I think, Tsveta could talk about for the hemolytic anemia profile.

Absolutely. The potential label based on the accelerated approval will be really based on the RISE UP data we've presented. And we had an opportunity to interact with the clinical community at ASH and follow-up ASH after we presented kind of the data as a press release about their feedback on the profile. So what we are hearing is like basically 3 things. The first one, they are very excited about the hemoglobin responder data because it very much aligns with how they treat and manage their patients. They will look for hemoglobin response, hemolytic parameters response and seeing that if they see an improvement from that aspect, the patients could potentially have a longer-term benefit in terms of quality of life, fatigue as well as VOCs is very beneficial. The second thing that gives them confidence is the consistency of the data they see in sickle cell disease across the 3 hemolytic anemias that we have studied the product in PK deficiency, thalassemia and now sickle cell disease. And that also translates to the third point, which is the in-market experience with the product, both through the launches that we've had in PK deficiency and thalassemia and the years of patient exposure in the market and across the clinical development of mitapivat. And all of these 3 elements are very important for that community from a clinical perspective, but also from a patient perspective who will be looking for that experience as well.

And I'll just -- I'll add to that, that one, we get a lot of questions from investors about our profile, etavopivat and so on. And safety should not be underestimated. And the fact that as Tsveta notes, we now have years of safety establishment with mitapivat, very robust data set in sickle cell disease specifically. And the fact that we've got synchronization of the thalassemia AQVESME launch underway at the same time, where there is overlap of clinicians who treat thalassemia patients as well as sickle cell disease, that's a pretty important attribute that we have as well.

Right. And obviously, in RISE UP, if you go one level deeper on the hemoglobin responders, you actually do start to see a benefit on the pain as well.

Across the cohorts. Yes.

You mentioned etavopivat from Novo. We saw their Phase III data recently. I guess did these -- there was kind of a temporal overlap with the conversations you were having with the FDA. I wonder if that readout fed into any of the discussions you were having around your...

Well, the short answer is no. So that data did not influence our regulatory path. As we highlighted, we are on that accelerated approval path. In regards to the data that was announced, it's very limited, right? The data that was announced. So we really need to wait and see and get more data to be able to put interpretation around the numbers that were given. In short, I think for us, it's -- what was put out there confirms that PK activation is a good thing for sickle cell disease. And so that, of course, is where we are excited because with PK activation, we have mitapivat that is now really far ahead. And I think the safety exposure on that product is really very important. And then we also, of course, have tebapivat, which is the next-generation PK activator that we're studying. And for which we are having a data readout for sickle cell disease second half of this year.

Yes. I guess just a follow-up to that, Sarah. In a world where there's multiple oral PK activators, whether it's mitapivat and tebapivat or mitapivat, etavopivat, I guess, what do you ultimately think drives prescribing here? Is it on the efficacy differentiation? If so, what is the efficacy endpoint that you differentiate on? Is it safety, like Brian mentioned? Is it on kind of timing to market? How do you think about that?

It's a little bit of everything, I would say. I think it's really a little bit of everything. The efficacy part, of course, it's hard to comment on that because we don't know everything yet on the other PK activators, right? So -- but experience in market is really important and then the safety exposure that is something that mitapivat is uniquely positioned with right now because we have so much across a different range of diseases, very important in the context of this disease as well.

Yes. This is -- I mean this one for sure is multifaceted. You have the product, as we talked about, clinical efficacy data, safety, experience in the marketplace. Then, of course, you have access dynamics that we have a lot of experience of how to navigate through that in rare diseases. And then, of course, I think sickle cell disease needs to be held to a kind of different standard because of the long legacy of setbacks this community has had. Trust and connection with the community really makes a big difference. And we've invested and I think invested in that and have established great credibility with the community broadly.

Okay. That's great. I guess last question on sickle, and then I want to talk about the AQVESME launch. Just around the sNDA, which label that will fall under? Is it PYRUKYND or AQVESME? Obviously, the REMS doesn't seem to be a huge hurdle for thal. It sounds like it's not a big burden either in sickle. But how do you sort of think about which bucket to drop sickle in?

Yes. So as you know, we have optionality, right? We have PYRUKYND without REMS and AQVESME with the REMS. I think one thing, if I may say, like I think Tsveta's team now has shown that they can really flawlessly execute on a launch in a rare disease with the REMS. So that's one. And then the second piece, of course, is, as we've stated before, that in RISE UP, the data is really favorable on the safety front. So this may not warrant the REMS. So more to come.

Okay. Okay. Is there a consideration around pricing within that, too? Because I think each drug has a different price point.

As Sarah mentioned, commercially, we'll be ready to execute irrespective of the scenario. And really, once we have the label, we will assess the pricing opportunities there. And of course, we'll monitor the competitive environment. But irrespective of the brand name, I think we'll be very well positioned to maximize the opportunity.

Okay. Great. And maybe we can shift to thalassemia. So you went from 44 prescriptions in January to 242 by the end of 1Q, which is a pretty strong sequential build. I guess what are sort of the internal metrics you're watching most closely to judge whether the launch is on track?

Absolutely. As Brian mentioned, we are very pleased with the initial reception of the thalassemia community when it comes to AQVESME. When I look at the first quarter, we generated 242 prescriptions from REMS-certified physicians. I wouldn't consider kind of the buildup from 44 to 244 (sic) [ 242 ] as a sequential growth because the demand was actually generated consistently across the quarter. The unique dynamic that we had is that the REMS was not operational until end of January. So some of the demand that was generated in January got pulled through later, but we still had a very, very strong quarter, reflective of the 242 prescriptions. Looking ahead, the 2 elements that we were really focused on is increasing the breadth of prescribing because thalassemia is managed in the community. And as we think about sustainability of the launch over time, that's a very important element for us. We saw a very strong geographic representation from across the country in the first quarter, and we'll continue with these efforts. And the second element is the efficiency of moving patients through the REMS program because that is really important as we initiate therapy and patients continue on that dimension as well. And that will really allow us to further penetrate the NTDT patient segment, which is 2/3 of the opportunity for us.

Yes. Great.

And can I just add one thing, Alec, too, is that your very first question, if you had asked me maybe 3 months ago, which of the catalysts are the least appreciated by the investors? I think AQVESME fits right up there. And what's so exciting about where we are now is this team really knows what they're doing in rare diseases. And we knew that thalassemia would be a particularly hard launch to analog, so to speak. And we knew it was a show-me story. And here we are, as Tsveta said, great start. Of course, launches are a long journey. So we're already looking ahead several continued segments of penetration down the road, but the team is really executing well. And again, given all the things that we have in front of us, the timing is perfect because the next show-me story will be upon potential approval in sickle cell disease, okay, let's see how you can do, and this is a really nice backdrop.

Okay. And I guess, how should we think about scripts trending in 2Q and beyond? 44 to 242 is a big jump, but you expect that early in the launch. I guess, how should we be modeling scripts? And then you also have the 10- to 12-week lag as well. So how should people be thinking about the scripts ramp and also the conversion into sales?

Yes. As I said, for me, I think it's important to look at the first quarter as a totality of the 242 rather than the kind of acceleration from 44 to 242 because that's really a representation of demand across the full quarter. Moving forward, the things that I said are very important for us. We will continue with breadth of prescribing when it comes to the clinicians and the penetration into the NTDT segment, which is going to be driven by continuous education, but also the fact that AQVESME has been on the market and that experience in the market is going to increase as well. And the third element, we mentioned the 10 to 12 weeks from prescription to treatment initiation. In the initial quarter, that was actually a little bit shorter, and that's not completely unexpected because you get the most engaged and eager both patients and physicians to prescribe. Over time, we expect that to move closer to the 10 to 12 weeks. And that's primarily driven by the fact that we'll be penetrating the NTDT segment with patients who have less frequent physician visits, and they might take a little bit longer to kind of complete all the steps of the REMS. When you think about actually time from prescription to treatment initiation, another important aspect is the insurance dynamic. That's completely independent of REMS, that's standard for any specialty program. And as the team is advancing in terms of getting payer policies in place and going through the REMS process, we'll be looking to shorten the time as much as possible as well.

Okay. And maybe just one further point on the transfusion dependent and non-transfusion dependent. You mentioned that the NTD patients are roughly 2/3 of the addressable population here. I guess what are sort of the specific levers that drive that inflection towards the larger NTD segment? I know most of the patients in early prescribing were transfusion dependent.

Absolutely. And the team already has done a great job in starting to penetrate that segment. In the first quarter, we had both transfusion-dependent patients as well as very engaged non-transfusion-dependent patients. And we see prescriptions coming also from the alpha and beta segment of the population, which is fantastic. Looking ahead, we'll continue to do 2 things, which we have been already doing, and one of them is education, education on the burden of disease in the NTDT segment, which was a very strong focus for us ahead of the launch and continues to be. And the second one is really ensuring that there is a good understanding of the in-market experience with AQVESME, especially in the NTDT segment. The TD segment is very well connected through the patient associations, and there is a lot of patient-to-patient interaction, and we'll look for ways to ensure that the NTDT segment also start hearing about that in-market experience. And as the clinicians get more comfortable with the product, we see that as an important step to move to penetrate that space as well.

I would add one really fascinating dynamic about thalassemia is it's a little bit of a global launch within the U.S. in a way because you have the Mediterranean population as a key part in the United States, Arabic. And then in the case of alpha thalassemia, it's often the Asian population. And one key feature that Tsveta and the team have put in place is multilingual, multicultural patient support. We have people who speak Arabic, Mandarin. Tsveta shared a recent example of even a thalassemia patient who needed American sign language, and we were ready. And those kinds of little vignettes of patient experience have incredible word-of-mouth effect as well. And so that will be really important as we penetrate further into the non-transfusion-dependent population.

So white glove service.

Very much so in a way that really matters.

Yes, yes, yes. And I know you've got a positive CHMP opinion in hand and also EC approvals may be imminent or expected shortly, I guess. How should investors frame the ex-U.S. revenue contribution? Is that maybe a second half? Or is that more of a 2027 sort of across Europe and the Gulf?

So we have a very capital-efficient deployment strategy when we think about commercial geographic expansion ex-U.S. First and foremost, the U.S. continues to be our biggest commercial opportunity, and we just talked about the successful start of the AQVESME launch, and we plan to continue on that one. Ex-U.S., there are 2 regions of importance. First is the Gulf region, GCC, that's driven by the prevalence of that region and the first approval for thalassemia is within the Kingdom of Saudi Arabia. What's important for that region is that there is a high prevalence of thalassemia. A small proportion of patients are actually managed in the institutions, but what is going to drive the actual penetration in the market and ultimately revenue is the market access process that is in there. And initially, what happens in these regions is that you have named patient sales and prescriptions until the product gets the national procurement and kind of national adoption and penetration based on the tender dynamics in those countries. So for the first couple of years, we would expect kind of low penetration and slow ramp of the revenues. In Europe, after we have the approval formally, we've been working with our partner, Avanzanite to prioritize markets with high prevalence of thalassemia as well as pricing and reimbursement system, which will support the value proposition of AQVESME, and we'll be executing on these selective launches across the region. Again, the European health care systems actually have a lag between European approval and actual in-country reimbursement of about 12 to 18 months. So I see the ex-U.S. opportunities really ramping up, not in the first couple of years of launch, but further down the line. That's why we continue to be focused on the U.S. and executing there.

Okay. That makes sense. And maybe one last question. I want to circle back on the EHA presence that you guys have. I think 10 presentations accounted in your press release. I imagine most folks will be focused on the RISE UP plenary. But maybe thinking more broadly, I think there was also some data for thal, some data on kind of benefits of long-term treatment. So maybe you could just unpack sort of the abstracts that we saw.

Yes, exactly. So we're very proud of our presence at EHA, which again confirms that PK activation is a good thing for hemolytic anemias across the board. The plenary -- the RISE UP plenary, of course, is like the crown jewel. It's going to be exciting to be able to present the totality of the data there and show the clinical benefit that we have demonstrated. And then in regards to thalassemia, we continue to demonstrate long-term benefit. We were also able to include data on the placebo switchers who went into the open-label extension on drug and have shown even a better hemoglobin response rate in that group. So very excited about that data across the board.

And can I take the opportunity to drop in a plug? So we have, in addition to the very exciting RISE UP plenary in Stockholm, Sweden at EHA, we also will have on that Saturday, an investor event as well. And again, as we said upfront, we'll be really excited to unpack even more about RISE UP, talk more about the confirmatory study and of course, the rest of our exciting pipeline to come.

Okay. Great. Well, we'll stay tuned for that in June. And I think with that, we're out of time. So Sarah, Tsveta, Brian, thank you so much for the great conversation. Thanks, everyone, for attending.

Thanks a lot, Alec. Thank you, everyone.

Thank you.