Agios Pharmaceuticals at RBC Capital: Strategic Moves in Rare Diseases

On Wednesday, May 21, 2025, Agios Pharmaceuticals (NASDAQ:AGIO) presented at the RBC Capital Markets Global Healthcare Conference 2025, outlining its strategic advancements in treating rare blood diseases. The company highlighted its promising pipeline, financial strength, and commercial readiness, while addressing concerns over drug safety and market challenges.

Key Takeaways

• Agios is advancing mitapivat for thalassemia with a PDUFA date set for September 7.
• Strong financial position with $1.4 billion on the balance sheet, bolstered by royalty monetization.
• Positive Phase 3 data for thalassemia and ongoing studies for sickle cell disease.
• Commercial strategy emphasizes market readiness and clinician awareness.
• Liver safety concerns are being managed effectively with updated monitoring guidelines.

Financial Results

• Cash Position: Agios ended Q1 with approximately $1.4 billion, strengthened by royalty monetization.
• Pyrukyne (Mitapivat) Sales (PKD): 234 prescription enrollment forms received, with 136 patients currently on therapy.

Operational Updates

• Thalassemia Program: ENERGIZE and ENERGIZE T Phase 3 studies achieved statistical significance. Regulatory filings submitted in multiple regions, with the FDA PDUFA goal date set for September 7.
• Sickle Cell Disease Program: The Rise Up Phase 3 study is fully enrolled, with data expected by year-end.
• Commercial Readiness: The team is prepared for an early launch of mitapivat in thalassemia, following a mid-2024 scale-up.

Future Outlook

• Thalassemia Approval and Launch: Anticipating FDA decision by September 7, with expected label updates on liver monitoring.
• Sickle Cell Disease Data Readout: Rise Up Phase 3 data expected by year-end, targeting improvements in hemoglobin and reduction in pain crises.
• Tebipivat Development: Phase 2 study for sickle cell disease to commence mid-year, with ongoing Phase 2b study in low-risk MDS.

Q&A Highlights

• Regulatory Filing and Interactions: No advisory committee meeting planned for thalassemia sNDA; consistent FDA project management.
• Commercial Strategy for Thalassemia: Larger market opportunity compared to PKD due to well-defined patient populations and clinician awareness.
• Sickle Cell Disease Trial Endpoints: Primary endpoints include hemoglobin increase and reduction in pain crises, with secondary focus on fatigue.

For a deeper dive into Agios Pharmaceuticals’ strategic insights and plans, please refer to the full transcript below.

Full transcript - RBC Capital Markets Global Healthcare Conference 2025:

Greg Renzo, Biotech Analyst, RBC: Great. Good morning, everyone. We’re going to get started, and welcome back to day two of the twenty twenty five RBC Global Healthcare Conference. My name is Greg Renzo, of the biotech analysts, and we’re pleased to be joined today by Agios Pharmaceuticals. And and joining us from from the company is the chief executive officer, Brian Goff, as well as the chief financial officer, Cecilia Jones.

Guys, it’s great to great to have you. Thanks for joining us.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you very much for hosting us, Greg, and thanks a lot, everyone, for joining us.

Greg Renzo, Biotech Analyst, RBC: So, Brian, we’ll just have you get us started, with you providing an overview of Agios, where you are, your focus, with pyrokin or mitapivat, and, the variety of inherited rare blood cell diseases. Over to you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. Sure. Thanks a lot. It’s a really exciting period. And, for the folks who are new to the Agios story, I’ll just begin with our mission, which is to develop and deliver medicines that have transformative potential to elevate and extend the lives of patients who are living with rare diseases.

And our core focus is on diseases that involve the destruction and dysfunction of red blood cells. So specifically, we’re talking about pyruvate kinase deficiency or PKD, thalassemia, sickle cell disease, and low risk myelodysplastic syndrome or MDS. Our flagship product, as you just mentioned, is pyrukyne, chemically known as mitapivat. And pyrukyne involves a really unique mechanism of action that essentially improves the metabolism of the red blood cell. And the result of that is that the red blood cell is healthier, better hydrated, and, thrives better in the face of these very challenging diseases.

Now, pyrokine, really pleased with the fact that we’ve cleared our third year of commercialization already, which has given us great experience with pyrokine mitapivat in PKD, it’s currently commercialized in The U. S. And we’re actively seeking additional indications in both thalassemia and sickle cell disease. I mentioned it’s an exciting period. Last year, 2024, was in many ways a transformative year for Agios.

The highlight of last year was, that we read out two pivotal phase three studies for thalassemia known as ENERGIZE and ENERGIZE T, and the strength of that package is that across both studies, we achieved statistical significance on all key, primary and all primary and all key secondary endpoints, and that put us in a position to December of last year, we announced that we simultaneously filed for regulatory approval in thalassemia, in four different regions. And so that’s The US, Kingdom Of Saudi Arabia, United Arab Emirates, and in Europe. And then we started this year on a strong note, in January announcing that the FDA has accepted our regulatory file for thalassemia and granted a PDUFA goal date of September 7. And if you’re keeping track, that’s only about three and a half months away, which we’re really excited about. Meanwhile, our commercial team led by sputum melanoma melanoma melanoma we were just talking about this earlier.

It’s apologies. Led by Sveta is very well prepared for, our potential launch in thalassemia. And what’s important about this is that thalassemia patients in The U. S. Have very limited approved therapeutic options.

Two thirds of the patients have none, and that’s the non transfusion dependent patients, who have alpha thalassemia or beta thalassemia. So we’re excited about that. The other big event last year was in sickle cell disease. We were really pleased to announce in October that we fully enrolled our Rise Up phase three, pivotal study, and it’s a fifty two week study. So if you do the math, that means we’ll be fully prepared to read out that data by the end of this year, which is a really important milestone for Agios and even more importantly for patients who very much need new therapeutic options.

Cecilia also, I must say, did a great job last year strengthening our balance sheet through a royalty monetization. So we ended the first quarter of the year with approximately $1,400,000,000 on the balance sheet. So all in all, a great year and some important milestones and again, we’re only three point five months away from our very important PDUFA date for thalassemia. So I’ll stop there and happy to field your questions.

Greg Renzo, Biotech Analyst, RBC: That’s great, and it is so important to to demonstrate how you’re coming into 2025 with such a a running start, not just with the accomplishments, the transformations you’re talking about in in ’24, but also historically with with the molecule and and and your pipeline. And, I mean, we we we like how you you do characterize ’25 as this this breakout year Right. When it comes to having commercial traction, in PKD, having regulatory interactions with with thalassemia as well as, frankly, pivotal and important data, those are aspects that just one of them would be coveted by by a company in in in your peer group. But certainly eyes on on thalassemia, great deal of chatter about regulatory friction or not when it comes to transitions there. You’ve recently provided an update about the supplemental NDA.

So just give us a state of where you are with that acceptance in January with respect to having a September action action day. So we’re sort of in that mid range now, where we should have some sense of, advisory committee. You’ve you’ve said no, but you have healthy interactions. So just just give us the state of the state, please,

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: on the filing. Yeah. Happy to. And you already mentioned one important feature, which is this is an sNDA. So, mitapivat is well characterized.

And as I noted, we’ve been commercialized with real world experience with, pyrokine since the beginning of, 2022. With respect to the FDA, we get a lot of questions about, have you felt dynamics in terms of staffing and so forth? The way we refer to it is if we were not watching the news, I’m not sure that we would notice any difference. And the the project manager is consistent, has been all the way through our other regulatory files. And as you also noted, we reported in our first quarter earnings call that the FDA has communicated to us that at this time they’re not planning an advisory committee.

I think that was an important update, but of course, the review is ongoing. And so, calendar wise, we’re just a few months away and we’re very well prepared, and I think this speaks to the strength of the package that we’ve submitted. Sure. Sure.

Greg Renzo, Biotech Analyst, RBC: And other sponsors are are preparing for early approvals, others are preparing for delays. Maybe just speak to the versatility or the flex that you have in the launch preparedness that you, Sveta, the team are embarking on.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: So, again, Sveta is very much on top of this. Job one as a commercial leader is always be prepared for an early scenario. Mhmm. And frankly, we are ready now. We actually from an efficiency of capital deployment, we waited last year until we had the very positive readout of the first of the two pivotal studies, ENERGIZE Mhmm.

Beginning of last year. And at that point, that’s when we scaled up, and when I say scaled up, this is still rare, but we appropriately adjusted the sizing of our commercial field teams to make sure that we would be ready. So since essentially the middle of last year, we’ve had that team in place. They’re fully trained, fully ready to go, and very focused on disease state education, but prepared for an early scenario.

Greg Renzo, Biotech Analyst, RBC: Okay. That’s helpful. And investors certainly focus on the full profile of mitapivat, but with recent areas of scrutiny on the safety and tolerability side, when we think about the liver findings thalassemia, you’ve updated the label, the current marketed label. You’ve discussed how you’re framing that up with respect to thalassemia. And maybe talk a little bit, Brian, about any ability to decipher the underlying mechanism behind the hepatocellular injury, how that’s managed, certainly when it comes to, discontinuing the drug.

You’ve had some interesting findings there. What is the latest, with the views on on the liver findings?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. Let’s do we’ll do a two parter. I’ll start and talk about the findings themselves, and then Cecilia can talk about what’s been so encouraging is, the read from clinicians who treat patients with hemolytic anemias and specifically PKD or thalassemia. First, just as a as a reminder to everybody, in December of last year, when we were presenting the full results of the ENERGIZE T study at ASH, we also disclosed that we’d identified a risk of hepatocellular injury. The totality of what we disclosed was there were five patients who were identified with this risk, four of the five had confounding factors, one did not, and there were essentially one each from each of the two pivotal studies and three from the crossover in the open label extensions going from placebo to mitapivat.

What’s important about that is all those patients, were identified. They had this event in the first six months and they were all identified through monthly monitoring, which was a standard part of our clinical trial protocols. So that in essence and I should note, they all returned back to their baseline upon drug discontinuation. So that in essence, already tells us a lot. One is it would be difficult to identify the exact mechanism because we’re talking about five patients, four of whom had confounding factors.

Secondly, the fact that all those patients returned back to baseline, has given clinicians quite a bit of comfort that they would already anyway go through, these patients would go through normal testing starting on a new drug for a hemolytic anemia treatment. And maybe Cecilia can comment on some of the learnings we’ve had from the So

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: both from the clinical trials and the real world on the commercial side, we haven’t seen anything as a concern from clinicians. Like these physicians are very used to monitoring patients, especially when they initiate these type of treatment. So monitoring for them wasn’t an issue from a burden perspective. This is a test you can get in a lab kind of near your home. You don’t have to even go into the office, so we haven’t seen that.

From a numbers perspective, our Q1 we reported two thirty four prescription enrollment forms to date, which is consistent with the growth we’ve seen on the prior quarters, and that resulted in net one hundred and thirty six patients on therapy. So we really haven’t seen an impact on that. Physicians, like I said, are very comfortable with the monitoring. This is monitorable, manageable, so we haven’t seen that.

Greg Renzo, Biotech Analyst, RBC: That’s great. And so no disruptions based on the commercial metrics you’ve seen. Do you have a going in base case about what a label could look like to account for some of these scenarios? What types of warnings? Would it mimic PKD?

How should we frame up a THALT label and what that could look like?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: So right now we have what we were mentioning before. The PKD label was updated to reflect the thalassemia cases. So you see it’s in another condition at another dose because it’s not approved yet, but that means thalassemia at one hundred mg. So that’s in the warning and precautions, and it has what was observed and what needs to be done if you observe the elevated tests. Right now we think that is reflective of the cases and we had, like, you know, people ask if it’s a black box warning and things like that.

Usually those are more in cases where there’s a fatality or a liver transplant or more of a bad outcome. We haven’t seen those, so logically we would expect something similar. Again, papers are part of reviews and discussions, so we’ll know once we get there.

Greg Renzo, Biotech Analyst, RBC: That’s helpful. Brian, you discussed a little bit about the opportunity, the unmet need for the thal patients across the different types. Maybe talk a little bit about your conviction of this commercial opportunity with you and the team, and as we think about the potential white space and upside, maybe just weave in a little bit countering the bear case that just could become another sort of sluggish rare disease launch.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. You want me to take that?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: You can go.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. So, thanks for asking. That’s a question we get quite a bit. And I think, first of all, what’s been important with the PKD launch is, it’s admittedly ultra rare. Yeah.

Though we’ve we’ve really characterized that this will not be a needle mover with respect to revenue, but it’s been very important on two fronts. One is to get real world experience with pyrokine, and one of the key features that we’ve seen is the persistency that patients have had with PKD has been very encouraging. I think that’s a really strong indicator about the feel and function aspect, the fatigue benefit, for example, that patients experience. And secondly, it’s been a really nice platform for us to build up our commercial capabilities, getting ready for meaningfully larger launches to come, namely thalassemia, and potentially sickle cell disease as well. There are some key features that really make thalassemia a very different equation than, PKD.

One is that, we talk about six thousand adult patients in The US with thalassemia. That’s very well characterized because there are well established ICD-ten codes for thalassemia now, and frankly, even before for decades, there have been ICD-nine codes established. So that number is validated substantially through claims database analysis, and most patients are, diagnosed through newborn screening anyway. Number two is it’s been, a real challenge educating clinicians on the burden of PKD. Most clinicians have not even really heard of it.

Thalassemia is a very different situation. Burden is well understood, the burden on the patients. Most doctors know of thalassemia, and we certainly have seen that there’s more concentration of patients than we experience with PKD. And the third is that there are well established thought leaders in this space and, mirroring that, well established patient advocacy groups. A good example is internationally, there’s the Thalassemia International Federation or TIFF, and in The US, there’s Coolies Anemia Foundation, and both of those are very important communities that are also supplementing education for both patients and providers.

Greg Renzo, Biotech Analyst, RBC: That’s great. That’s great. Let’s turn to sickle cell disease as you’re thinking about the layering of expanding opportunities that you’re referencing. You’ve mentioned the trial enrollment data later this year. Maybe talk to us a little bit about what you’d like to see, what levels will start on the efficacy side when it comes to the Rise Up study.

What does mitapivat need see to be clinically adoptable in sickle cell, even potentially approvable with the dual endpoints and the success of the prior trials that you’re building on? What should we be seeing to be competitive?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Well, I think the first place we should start is the unmet need for this population, and it’s hard in a venue like this, it’s hard to even describe how profound that unmet need is. And in the last year, the unmet need has only grown because as most folks know, one of the therapeutic options, Oxbryta, Voxelotor was actually removed as a treatment option for patients, a very challenging period for the community. So the setup that, we have in the elegant design for Rise Up Phase three is, as you noted, these are not co primary endpoints, there are two primary endpoints. One is focused on hemoglobin increase of a gram per deciliter or better, and the other is focused on sickle cell pain crises or vaso occlusive crises reduction. Those are the two primary endpoints, and we believe very strongly in the powering assumptions that we’ve put behind those, but we also have set up they each have their own respective alpha.

And so for secondary testing, one of the really important measures that we’ll be looking at is fatigue. And again, fatigue is almost indescribable for somebody who doesn’t have sickle cell disease. It’s not tiredness, it’s fatigue, you cannot sleep away, and is one of the biggest impairments on the quality of life for patients. And the other complicating dynamic is chronic pain itself only adds to fatigue. So we think that that’s also a really important measure and the design has been set up as what we call hemoglobin plus, that’s the target for us.

So we’re looking for improvement in hemoglobin, which we’ve demonstrated now across three different hemolytic anemias, and the plus could be vaso occlusive crises improvement and or fatigue benefit as well. And of those permutations would be a very compelling package for patients.

Greg Renzo, Biotech Analyst, RBC: That’s helpful. And we talk about PK activators as a class and mitapivat just having several unique qualities. Maybe talk to us a little bit about some of those differentiators between mitapivat and others in this space. Now granted, you are many years ahead of the competition, namely the tavapivat. But as you think about not only demonstrating, what you need to for the phase three, but also how it compares and fares across the broader class, what are the key differences to point out?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Well, I think one is, very consistent data that we’ve had, again, across multiple hemolytic anemias, which shows the strength of the mechanism itself and the broad applicability of the mechanism. Mechanistically, what we’re talking about here, as I noted up front, is this is about increasing the throughput of the glycolytic pathway, which is the only source of energy for the red blood cell, ultimately increasing ATP, energy available for the cell. But in sickle cell disease, there’s also a dual benefit, which is lowering as a consequence of increasing that throughput, lowering two, three DPG, which is linked very much towards the sickling of these cells. So that, you you could think of that as well, that’s theoretical mechanistic, aspects, but we saw very strong data in our Rise Up phase two study that read out last year, and there we saw, of course, hemoglobin improvement. And importantly, we saw positive trends with both doses tested in vaso occlusive crises improvement.

The only changes that we made between our phase two and our phase three study is that we picked the higher dose, the one hundred milligrams BID, because that was consistently beneficial across hemoglobin, the trend that we saw, the positive trend in vaso occlusive crises, and all measures of markers of hemolysis. So the setup here is really unique and potentially very beneficial for a community that, again, has

Greg Renzo, Biotech Analyst, RBC: such limited treatment options. Yeah. And maybe going to the the value proposition with respect to the unmet need and the differentiation, talk a little bit, Brian and Cecilia, just about pricing strategies. With with pyrokin, we certainly have an established place for the ultra rare disease. We we know with thalassemia, multiple markets globally, sickle cell as well, larger market, also also global.

Such chatter about, most favored nation pricing, potential policies, maybe some mismatches, and and solving for disconnects. How is Agios thinking about, about the value proposition and how pricing works in these layered

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Well, there’s a lot in there.

Greg Renzo, Biotech Analyst, RBC: So if you wanna do that? All.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: So today, you’re right. We have a price of $335,000 annual WAC for for pyruvate kinase deficiency as we think in general, I’d say pricing for us is something we look at based on the value proposition, so we usually won’t comment until we know exactly the label, and in the case of sickle cell, the data as well. In general, the way we see thalassemia from a payer lens, it’s in the neighborhood of PKD. Still a rare disease. We don’t expect it to be a managed category.

The access team has done a tremendous job on PKD and has already started preapproval, like information exchanges with payers, and everything has gone really well there. So we expect thalassemia to be kind of similar to PKDS from a payer perspective on how to think about it. When you go into sickle cell, obviously a much bigger population. Again, we’ll wait to see the data when we see there and go from there. In terms of different countries, we’re in a kind of a different place than most companies are because today we only have a price in The U.

S, so there isn’t any other nations to compare to. So it’s a little different the way we’re thinking of international expansion as well as today our focus is The U. S. So when we think of thalassemia, that’s where we’re going. Like we said, we built the team, we have everything, that’s our main focus.

The second part is on the Gulf countries in The Middle East, where we established a partnership with a company named Newbridge, and as Brian said, we’ve also filed in Saudi and United Arab Emirates, so that’s kind of number two. And then Europe is kind of a third in the tiers there. We’ll probably do a similar partnership as we have for GCC, and even Europe is different because it’s certain countries in Europe, it’s not yet traditional pattern of where patients are located.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: So it’s really clear, U. S. Number one priority, the Gulf Region, and specifically Saudi Arabia, number two. And we can be from an MFN perspective or any other dynamic, we can be very selective and thoughtful about where we go from there. So it really is we’re in a unique position relative to nearly every other company.

Excellent.

Greg Renzo, Biotech Analyst, RBC: And the last moments we have, maybe just talking the broader portfolio and just extending to the to the sickle cell landscape and talking about other PK activators, you have another with with, tebapivot. So maybe just put that into context, profile of tebapivat in sickle cell based on the phase one profile that you’ve seen.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. I mean, we have a lot to learn with tebapivat. Unfortunately, we’re about to commence on the phase two aspect of that journey middle of this year. The goal here is that we’re in an advantageous position of having not one, but two PK activators. Tebapivat, the most prominent feature right now is it’s a more potent PK activator.

And, our target is, again, with this community in need of different therapeutic options, options that have been developed differently to tackle different aspects of the disease, puts us in a position of building a proper franchise for sickle cell disease. And so we’re excited about starting the journey of tebipivat in sickle cell disease in phase two. We’re equally excited about what’s already underway with tebipivat, which is our pursuit of low risk MDS, and we have a phase 2b study that we’re actively enrolling, and the target there is to be fully enrolled by year end. So the main message for everybody is there’s a lot coming. It’s been an exciting year in 2024, but 2025, as you said upfront, is a real breakout year for Agios.

Greg Renzo, Biotech Analyst, RBC: That’s great. Well, we’re just on time. We’ve always wanted to talk more pipeline and business development, but we’ll we’ll leave it there. It’s a great place to to close and best of luck, with with with the rest of the year.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks a lot, Greg. Thanks, everybody.

Greg Renzo, Biotech Analyst, RBC: Have a good

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