Agios Pharmaceuticals, Inc. ($AGIO)

Good morning, and welcome to Agios Pharmaceuticals Business Update 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 Morgan Stanford, Head of Investor Relations at Agios.

Thank you, Michelle. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals global license for Cevidoplenib, a next-generation SYK inhibitor for the treatment of immune thrombocytopenia, or ITP. You can access the slides for today's call by going to the Investors section of our website, agios.com. Please note, we'll be making certain forward-looking statements today. Actual events and results could differ materially from those expressed or implied by any forward-looking statements due to 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. On the call with me today from Agios are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; and Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development. Joining us for the Q&A session are also Feta Milanova, Chief Commercial Officer; and Krishnan Diswanadan, Chief Strategy and Operations Officer. Following prepared remarks, we will open the call for questions. With that, I am pleased to turn the call over to Brian.

Thanks, Morgan. Good morning, everyone, and thank you for joining us. Please move to the next slide. We are pleased to announce that we have entered into a global license agreement with Ocotech, a clinical stage drug discovery and development company headquartered in South Korea for Cevidoplenib, an oral next-generation SYK inhibitor for the treatment of immune thrombocytopenia, or ITP. This agreement represents a natural extension of our long-term strategy, which is centered on building sustainable leadership in rare hematology, starting with our established foundation in hemolytic anemias with mitapivat and tevapivat. From there, we're executing a disciplined expansion into adjacent diseases where we can leverage our proven capabilities, focusing on indications with well-understood biology, chronic management and shared specialist physicians. Next slide, please. Importantly, we're not starting from scratch. We've built and scaled a differentiated rare hematology capability with mitapivat, demonstrating clinical proof of activity in PK deficiency, executing a strong early ACVeSMi U.S. commercial launch in thalassemia and advancing toward potential U.S. accelerated approval in sickle cell disease with additional Phase III data to come at the European Hematology Association Congress later this month. Together, these capabilities spanning development, regulatory execution and commercialization position us to efficiently develop and deliver sevadoplinib, a next-generation SYK inhibitor in ITP. Next slide, please. Sarah will provide more details shortly, but at a high level, this transaction represents a disciplined move into a clinically validated mechanism where we believe Cevidoplenib can meaningfully improve on first-generation SYK inhibitors. And importantly, where Phase II has already demonstrated activity on endpoints aligned with ITP registrational trials. In the U.S. alone, approximately 90,000 adult patients are diagnosed with ITP and roughly 24,000 adults have failed a prior therapy, creating a significant unmet need. SYK inhibition is a clinically and commercially validated mechanism. However, there are meaningful tolerability limitations with first-generation SYK inhibitors that limit durability of treatment effects. Here, we see potential for Cevidoplenib as a next-generation SYK inhibitor to transform the treatment landscape. ITP is a clear adjacency to our existing portfolio, one that capitalizes on our existing expertise in rare hematology. Similar to thalassemia, ITP patients are mostly treated by community hematologist oncologists and also similar to thalassemia, this is a chronic rare disease management model requiring effective, impactful patient support and community engagement. We view this as derisked across several dimensions. First, the SYK mechanism is clinically validated. Second, the ITP treatment paradigm is well established. And third, Cevidoplenib has already demonstrated activity on endpoints aligned with ITP registrational trials. Above all else, this in-licensing opportunity is disciplined capital allocation with a $25 million upfront payment and milestones gated to key value inflection points and up to $1 billion in nonrisk-adjusted peak year sales potential in the U.S. With that, I'll hand the call to Sarah to discuss the ITP landscape at a high level as well as the unique attributes of Cevidoplenib. Sarah?

Thank you, Brian. Next slide, please. ITP is an autoimmune disorder characterized by antibody-driven platelet destruction, leading to increased bleeding risk. Diagnosis is often made by exclusion, typically at platelet counts below 100,000 with patients experiencing chronic symptoms such as bruising, bleeding and fatigue. Despite the availability of multiple treatment classes, ITP remains a disease where durable disease control is difficult to achieve. Of the approximately 200,000 diagnosed patients globally, including 90,000 adults in the U.S., many continue to cycle through therapies without sustained platelet responses. In practice, the limitation is not lack of options, but the inability of current therapies to consistently deliver durable, well-tolerated responses. On the next slide, you can see the current ITP treatment landscape. First-line therapy remains corticosteroids, which provide rapid platelet increases through broad immunosuppression, but are often not durable and carry meaningful toxicity. In the second-line setting, thrombopoietin receptor agonists are widely used. While effective at increasing platelet production, these therapies do not address the underlying disease biology, contributing to high rates of relapse. More recently, targeted therapies, including BTK inhibitors and first-generation SYK inhibitors have demonstrated activity. However, durability and tolerability have remained inconsistent. As a result, despite multiple lines of therapy, patients often continue to cycle through treatments without achieving sustained control. SYK inhibition directly targets a central driver of disease biology in ITP. Autoantibody-coated platelets are recognized by Fc receptors on macrophages, activating a SYK-mediated signaling cascade that drives platelet destruction. By inhibiting SYK, this pathway is interrupted upstream, preventing immune-mediated clearance of platelets. Importantly, because SYK sits at the convergence of these immune pathways, targeting it offers a mechanistically focused approach to address the underlying disease rather than simply increasing platelet production. Next slide, please. While SYK inhibition has established proof of mechanism, first-generation agents have been limited by tolerability and inconsistent coverage restricting sustained responses. Levidoplinib is a next-generation SYK inhibitor designed with improved selectivity and a PK profile that enables consistent exposure and sustained target inhibition, key drivers of durable response in a chronic disease setting. Clinically, we see clear dose-dependent activity supporting target engagement alongside a favorable safety profile in Phase II without evident dose-limiting toxicities. Taken together, Cevidoplenib is a differentiated SYK inhibitor with the potential to deliver more consistent durable responses in ITP. Please move to the next slide. Cevidoplenib was evaluated in a global randomized controlled Phase II trial. The primary endpoint was a composite that assessed platelet response greater than or equal to 30,000 per microliter and a doubling of platelet count relative to baseline, an average of 2 previous counts based on the last 2 platelet counts at the time of evaluation. Importantly, this was a novel endpoint that is not aligned with primary endpoints typically used in ITP registrational trials. In a disease characterized by significant day-to-day platelet variability, an endpoint based on a response at any single visit can introduce variability and may not fully capture the durability of platelet response over time. When evaluated using endpoints aligned with clinical practice and regulatory precedents, specifically platelet counts equal or more than 30,000 per microliter, we observed a clear separation versus placebo, consistent with biologic activity for this mechanism. And importantly, when durability is considered, defined by repeated responses across visits, the data demonstrates sustained platelet control, particularly at the 400-milligram dose. Taken together, these results establish a clear signal of clinical activity and support advancement into Phase III with a program designed around durability-based endpoints aligned with regulatory precedents. We plan to initiate Phase III in the first half of 2028 following completion of additional CMC work. With that, I'll hand the call to Cecilia to review the financials.

Thank you, Sarah. Next slide, please. The Cevidoplenib licensing deal is structured to be capital efficient with a modest upfront and the majority of consideration tied to key development and regulatory inflection points. Specifically, the deal includes a $25 million upfront payment and up to $140 million in development and regulatory milestones. While our initial focus is ITP, the structure also provides optionality to expand into additional indications. On the back end, Ospotech is eligible for tiered royalties and milestones upon successful commercialization. There are 2 points to highlight. First, capital is deployed over time with balance of payments aligned to value-creating milestones. Second, excluding the $25 million upfront payment, we still expect full year 2026 operating expenses to be approximately flat versus 2025. With that, I will hand the call back to Brian for closing remarks.

Thanks, Cecilia. Next slide, please. This transaction brings together 3 key elements: a clinically validated mechanism, a differentiated next-generation asset and Phase II data demonstrating activity on registrational relevant endpoints. Just as importantly, we've structured the deal with clear capital discipline, enabling us to expand into ITP while remaining fully focused on delivering our 2026 priorities. Next slide, please. With the addition of Cevidoplenib, we are further strengthening our position in rare hematology, broadening our mechanistic portfolio, adding a next-generation SYK inhibitor and expanding into a high-value adjacent indication where our capabilities directly translate. Looking ahead, we are focused on advancing Cevidoplenib toward potential Phase III initiation in the first half of 2028, following completion of additional CMC work. We see this as a compelling combination of validated biology, differentiated molecular design and efficacy aligned with registrational expectations, supporting a credible path forward. With that, we appreciate your continued interest in Agios, and I'd now like to open the call for questions. Michelle, please open the line.

[Operator Instructions] Our first question comes from Mark Frahm with TD Cowen.

On the transaction. Maybe one for Sarah. Just I think in the ITP space, we've seen historically a handful of kind of earlier stage smaller data sets look quite attractive and then in different cases, sometimes meaningfully decline but still be positive in Phase III and others get so bad that they ultimately don't get replicated at all in Phase III. Just what gives you kind of confidence that this data is more reliable than some of those prior cases in ITP? And then maybe just on a process thing on getting to the Phase III in the first half of '28. Can you maybe walk through what exactly needs to happen? Is that just tech transfer work? Or is there also kind of some longer-term tox studies and things like that, that also need to be completed before you can move into Phase III?

Yes. Thanks, Mark. I'm going to start just by again reiterating we're really excited to have this opportunity. It's a really nice fit strategically with our rare hematology leadership, has diversifying elements, larger market potential, et cetera. I have the benefit this morning of having Krishnan with us, who has worked really hard on identifying this asset and with the diligence that comes with it. So I think this is a 2-parter. One is differentiation points versus incumbents, which we talked about a little bit in the prepared comments. And the second is the CMC further development.

Yes. So if you look at the ITP market today, what we see is really there is no dominant oral therapy that exists that provides a well-tolerated profile and a durable response. And that's what Cevidoplenib is intended to deliver on. With respect to your question around what additional activities need to occur, it's really the rate-limiting step is CMC scale up from a process development perspective. It's typical of any oral molecule that's advancing into Phase III registrational trials. That's what we see. And then as part of diligence, we've done a deep dive in terms of the total data sets that enable us to give confidence around the potential for advancing into Phase III. And I'll turn it over to Sarah around the Phase III components.

Yes. Thanks, Mark. And so I think the question around the confidence of -- based on other SYK inhibitors going into Phase III. So to Krishnan's point, like I think here, the data across several secondary endpoints have been very consistent, including all of the endpoints that are aligned to primary endpoints and registrational endpoints into Phase III. So that gives us confidence, the consistency across the data there. And then in addition, the safety profile generated in a global Phase II trial was very favorable, meaning that many patients were being able to be assessed, which also gives us confidence into Phase III.

Our next question comes from Gregory Renza with Truist Securities.

It's Anish on for Greg. Congrats on the deal. Just a couple of quick ones from us. First, just on asset differentiation. How does Sevi's improved kinase selectivity translate to the consistent exposure mentioned today, that mean for patient tolerability and chronic use? And second, on commercial synergies, you mentioned a strong overlap with your existing prescriber base. Can you quantify how much of the mitapivat hematologist base currently treats ITT? How does this asset leverage your current commercial footprint?

Yes. Thanks for the question. So on the first part, the potency of this SYK inhibitor, it's a very potent SYK inhibitor. And at the same time, it is actually very targeted selective inhibition. So some of the kinases that are implicated in some of the side effect profiles are really not being touched by our inhibitors. So that gives us confidence and that paired with the Phase II data observed gives us confidence on that favorable safety profile. And in regards to the overlap in the commercial space, I'll hand it over to Sarah.

Absolutely. We do see this asset with 2 potential commercial synergies as we mentioned in the remarks. The first one is it is exactly the same community hematology oncology [ treater ] base. We haven't provided direct numbers on the actual [indiscernible] overlap, but it is significant when you look at the community setting and the thalassemia and sickle cell disease. Very importantly, it is the same commercialization model and capabilities, which we have built for Thalasamia and we'll continue to expand through sickle cell disease on 2 dimensions. The first one is kind of the data-driven targeted deployment, utilizing a lot of claims data and analytics for us to be very efficient in the way we approach our customers. And the second one is the community engagement and the comprehensive patient services capabilities, which are critical for successful execution of a launch like that but when it comes to patient starts but also patients continuing on therapy. In the short term, there will be a very minimal commercial investment, given we are starting the study in the first half of 2028. And as we progress the thalassemia and the potential sickle cell disease launch in the future, we will look for further synergies when it comes to the ITP indication launch for [indiscernible].

Our next question comes from Samantha Semico with Citi.

Congrats on the in-licensing. Just wanted to ask a bit about the durability response that you've been talking about. What degree of durability are you looking to see? And how -- what gives you confidence that you can achieve that from the Phase II data specifically? And I guess, will you test this as well in Phase III so we can actually see that effect.

Yes. Thanks for the question. So the Phase II data generated in this global trial, there were several endpoints that were specifically looking at platelet improvement in at least 4 out of 6 visits, which is speaking to durability in the response, and that percentage was higher than what has been generated so far on other -- with other inhibitors and BTK inhibitors. So that gives us confidence to take this forward. And that is, of course, also one of the endpoints that we know is important to continue to study in Phase III. And then the phase III, again, like the fact that people have really tolerated this drug very well is important as well as we take this forward into Phase III.

Okay. That's very helpful. And then I had a follow-up. Just one slide where you talked about chronic use with a combinable profile. I'm wondering if you could elaborate a bit on what you mean there. Do you see potential for combination regimens here? And if so, what mechanisms would you see as potential combination partners.

Yes. Maybe I'll have Krishnan weigh on that one as well because we spent a lot of time studying the ITP market.

Yes. As you think about the evolution of the ITP market, one of the advances we're seeing is combination therapy. So an agent that's very well tolerated is important to have as a combination partner as agents are moving earlier lines. And so we think sevidoplinb has the potential to really maximize value, both in the context of the second-line population plus as monotherapy with the potential of combination.

Our next question comes from Salveen Richter with Goldman Sachs.

This is Sonya on for Salveen. Could you just speak to any FDA feedback that you've gotten on the Phase II data package, particularly around the lack of stats on the primary endpoint?

This is Sarah. So in regards to the FDA engagements, we are now going to work on to our Phase III and take the CNC work into account as well. So those will happen in the context of normal development.

Our next question comes from Eric Schmidt with Cantor Fitzgerald.

This is [indiscernible] on for Eric. A few more on the CMG aspect here. Could you share a little bit more on the cost of that CMC go up? And what you're expecting the probability of staying on schedule with for 2 years and how that impacts the cash runway?

Yes. Thanks, [indiscernible]. I think it was a little hard to hear, but I think you were asking about CMC and the cost of CMC. Yes, go ahead.

I'll take the first part. So for -- as we mentioned, for 2026, we are not changing our guidance. Our OpEx does remain approximately flat to 2025. We are looking to absorb the expenses for the next couple of years into our operating expense base as well. So this doesn't change our continued press to profitability.

And I'll comment on the work that's necessary for the CMC efforts. Really, if you think about where the asset is today, the asset has completed Phase II. So the manufacturing has been completed for Phase II. What we're really doing now is scaling up the manufacturing process and optimizing that process to get ready for Phase III to meet an ideal commercial profile. So really, that's the work that's necessary now. And that's what we intend to do between now to initiate a Phase III trial in the first half of 2028.

Our next question comes from Tessa Romero with JPMorgan.

Double clicking here, how much will this development program in ITP cost Agios and what is the right way to think about time lines for completing pivotal and a potential approval here?

Maybe, Cecilia, can start. It's probably a little bit too early, Test, to comment on the time lines, but we can at least reiterate some of the comments around the OpEx?

Yes. So the structure and the time line for this allows us to continue to focus on our 2026 priorities, which we've established earlier this year. The initial spend, as we mentioned, is going to be focused on CMC -- and then, obviously, starting in 2028, we see the safety expenses there as well. So we continue to evaluate our cost structure as we mentioned, if you take out -- if you take out the onetime upfront payment milestone of $25 million, we are keeping the guidance for this year and we continue to evaluate our cost structure as we go through the different catalysts that we have for the rest of the pipeline as well.

And Tess, taking a step back to what's really exciting about this it does set us up without doing time lines today. This sets us up for the next wave of launches to start. And certainly, nearer term, we're quite excited about the opportunity that we have with ESI in thalassemia. That launch, as you know, is well underway, has started very nicely. We're also, of course, looking forward to or opportunity in sickle cell disease with mitapivat. So it's -- the cadence of launches is something that we're very mindful of as well.

Our next question comes from Emily Badner with H.C. Wainwright & Company.

This is Joey on for Emily. Congratulations on the deal. Just 2 from us. On safety, just wanted to touch on the -- there's transient liver enzyme elevations and GI events seem the most common for -- in terms of how frequent were those elevations in Phase II and any patients discontinued due to toxicity trying to compare with fostamatinib and then on modeling, just wondering the $25 million payment to [indiscernible], is that second quarter anticipating?

Right. So we start with -- Sarah, do you want to start on the safety questions, and then we can bridge to OpEx.

Yes. So the drug was very low well tolerated in the Phase II with very limited GI events which are the most commonly observed or one of the most we observed on the BTK inhibitors and on the SYK inhibitors. And so Nova and Dario is very limited in the patient population as it relates to ALT increase in ASP increase observed in the Phase II, also much less actually compared to others. And then very importantly, as it relates to safety. There have been cases of hypertension described other drum [indiscernible] as I highlighted before, the selectivity on different kinases is not specific inhibitor BTK inhibitors versus semidoxlanib is actually very specific. So we do like the hypertension in the neutropenia that has been observed in these other compounds was also much, much less on this one. So the safety profile overall has been very good. And therefore, we're like excited about that aspect. We are excited about the efficacy. Of course, we're also excited about the safety profile and tolerability profile we serve today.

In terms of the upfront payment, similar to how we booked the [indiscernible] deal back, it's going to be recognized as an R&D expense, and you can model it in Q2.

And our final question comes from Luca Issi with RBC.

Congrats on the deal. It seems like a kind of a great strategic fit here for Agios. Also, I know this is maybe a little bit of kind of beyond the scope of this call, but given this is the first public call since the discontinuation of the back of that for MDS. Wonder if you could comment on what happened there and whether there's any kind of read-through to sickle cell disease? And maybe related to it, if you can kind of remind us the doses that you have tested. The MDS versus doses that you're planning to test in sickle-cell disease. Again, any context there?

Yes. Luca, I'll let Sarah speak in just a second. I'll just -- just a first emphatic comment, no read-through to sickle cell disease. These are 2 very different diseases. And -- and we disclosed last week that we -- you've made the decision to not proceed with development of Teapivat for MDS for low-risk MDS, but we are very much looking forward to the readout of sickle cell disease -- the doses.

Yes. No. And indeed, as Brian mentioned, so we discontinued the program because the efficacy that we observed in this broad patient population, the signal was not strong enough to warrant it to move forward and as you know, we've had made changes from Phase II to IV, and we went into a more challenging patient population with IB and indeed also tested higher doses. These higher doses, they did lead to good ATP increases across the range of the different doses tested there. So we know we really have the full target engagement as it relates to ATP. And very importantly, the safety profile was very good. So from an efficacy perspective, we do not see a -- so 2 sickle cell disease just because this was not -- on hemolytic anemia, a different concept than the other hemolytic anemias that we've is with PK activation, and that's why we have highlighted that as a high-risk program. And the safety profile was very good. And so that is important.

Thank you. I'm showing no further questions. I'd like to turn the call back over to Brian Goff for closing remarks.

All right. Thanks, Michelle. Thanks, everyone, for joining. In closing, this transaction reflects a clear and disciplined step. While we're building on our established foundation to expand into a high value adjacent indication where our capabilities directly translate. We remain focused on execution with a strong path ahead across our core programs and important data readouts in the near term. I would like to thank the entire Agios team for their continued dedication and execution, which has enabled us to reach this point and continue to advance our leadership in rare [indiscernible]. log. We look forward to updating you on our progress in the months ahead, including sharing new mitapivat data in thalassemia and sickle cell disease at the 2026 EHA Congress later this month in Stockholm highlighted by an oral plenary presentation featuring our Phase III RiseUP trial in sickle cell disease. So thank you very much for your continued support, and we will speak soon.

Thank you for your participation. You may now disconnect. Everyone, have a great day.