Agios Pharmaceuticals at Barclays Conference: Strategic Advances in Rare Disease Treatments

On Wednesday, 12 March 2025, Agios Pharmaceuticals (NASDAQ: AGIO) presented at the Barclays 27th Annual Global Healthcare Conference, outlining its strategic focus on rare diseases. The company highlighted both its promising pipeline developments and challenges, such as the need for increased monitoring due to potential hepatocellular injury in thalassemia patients.

Key Takeaways

• Agios is advancing treatments for rare diseases, with Pyrocaine already approved for pyruvate kinase deficiency (PKD).
• The company anticipates a U.S. approval decision for thalassemia by September 7, 2025.
• Phase 3 RISE UP study data for sickle cell disease is expected by the end of the year.
• Agios ended 2024 with $1.5 billion in cash, focusing on maximizing upcoming launches and expanding its pipeline.
• A disciplined approach to business development excludes gene therapy but seeks transformative rare disease treatments.

Financial Results

• Agios closed 2024 with a robust cash position of $1.5 billion.
• The company prioritizes cash allocation to maximize upcoming launches, advance its pipeline, and explore new business development opportunities.

Operational Updates

• Thalassemia Program:

- Filed for approval in the U.S., Europe, Saudi Arabia, and UAE.

- U.S. PDUFA goal date set for September 7, 2025.

- Sales team expansion planned to support the launch.

- Distribution agreement with Newbridge targets the Gulf region’s 70,000 thalassemia patients.

• Sickle Cell Disease Program:

- Phase 3 RISE UP study is fully enrolled; results expected by year-end.

- Study focuses on hemoglobin response and reduction of sickle cell pain crises.

• TevaPIVID (AG946) Program:

- Phase 2b study in lower-risk MDS is ongoing, with completion expected by year-end.

- A Phase 2 study in sickle cell disease is planned to start mid-year.

Future Outlook

• Agios aims for back-to-back launches in thalassemia (2025) and sickle cell disease (2026), pending successful trial outcomes.
• The company is building a multibillion-dollar franchise with Pyrocaine.
• Business development will focus on acquiring early-stage assets with transformative potential in rare diseases.

Q&A Highlights

• FDA Interaction on Thalassemia:

- Review is ongoing; no advisory committee meeting has been scheduled.

• Label Change Impact (PKD):

- New warnings require monthly monitoring for hepatocellular injury in thalassemia patients.

• Sickle Cell Phase III Trial (RISE UP):

- Co-primary endpoints include hemoglobin response and sickle cell pain crisis reduction.

For a detailed understanding, readers are encouraged to refer to the full transcript below.

Full transcript - Barclays 27th Annual Global Healthcare Conference:

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. Good afternoon, everyone. My name is Gina Wen. I’m a clinical biotech analyst at The Barclays. It is my great pleasure to introduce our next presenting company, Allios Pharmaceuticals.

Sitting on the stage with me, we have Sarah Hewins, Chief Medical Officer and Head of R and D. We also have Cecilia Jones, Chief Financial Officer. Before we dive into the questions, maybe I will let you guys give a quick overview of other companies and then we can discuss.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Thanks, Gina, for having us and thanks everybody for listening in. So for those of you that might not be as familiar with our story, our mission at ADGIS is to develop transformative treatments for patients living with rare diseases. And our main focus right now is on diseases that result in either the dysfunction or due this destruction of red blood cells. And we have programs in pyro mechanistic deficiency or PKD, thalassemia, sickle cell disease and lower risk MDS. Our lead program is called Pyrokind or metapivat, and it has a unique mechanism of actions called PK activation that allows it to help the metabolism of the red blood cells.

So it improves their hydration, longevity and the energy of the cell that then helps these patients. Pyrocaine is approved today and commercialized today in The U. S. For adults with PK deficiency. And we’re hoping to extend into new indications in thalassemia and sickle cell.

Twenty twenty four was a super exciting year for Agios. We had we set up the year, the beginning of the year with a lot of corporate milestones, which we hit on all either on or ahead of schedule. And one of the highlights that we had in 2024 was on our thalassemia program, where we presented the data of our two Phase three studies. One was called Energize, which was for non transfusion dependent patients. And the second one is Energize T for transfusion dependent patients.

So between the two studies, we covered the totality of the patient population of thalassemia and that those results enabled us to five simultaneously by the end of the year in four regions, The U. S, Europe, Kingdom Of Saudi Arabia and United Arab Emirates. For The U. S, particularly, we have a PDUFA goal date set for September seven of this year. So the commercial team is really gearing up to that date.

We’ve been increasing our sales reps and everybody surrounding the launch from PKD, which was ultra rare into still rare, but much bigger indication for us in thalassemia. So we’re very excited for that. Another highlight of the year was for the sickle cell part of the program, we have a Phase three study called RISE UP. And in October of last year, we announced the full enrollment of the study. It’s a fifty two week study.

So we expect to have top line data for that study by the end of this year. On the next program or the next molecule we have is also a PT activator that’s called teva pivot or used to be AG946. And we have two paths for TevaPIVID. The first one is in lower risk MDS. And for that one, we’re well underway on a Phase 2b study.

And we expect to complete enrollment for that study by the end of the year. That’s a very exciting area with high growth, and we’re looking forward to having the data for that study as well. And then the second part of that will be also is to have a second PK activator in sickle cell. So we’re planning to initiate a Phase two study by midpoint of this year, and that will allow us to eventually hopefully have a franchise for sickle cell, which is a disease with very high unmet need. And then lastly, I would say, we have a very strong balance sheet, which was bolstered last year through the monetization of the vorasidenib royalty that we had kept from the transaction we did with Servier back in 2021.

So we ended up the year with $1,500,000,000 in cash and equivalents. And the way we think about the priorities for cash allocation or capital allocation is, first and foremost, be able to maximize the launches, hopefully back to back launches. If we’re successful on sickle cell, we would have Palacin in 2025, sickle cell in 2026. And we’re hoping to build a franchise, a multibillion dollar franchise with Pyrocoyne. The second priority is to advance the pipeline, so Teva pivot like I described, and we also have some earlier programs in phenylketinuria, PKU and Polycythemia vera.

And the third bucket would be to expand our pipeline, and that could be both on internal organic options and opportunities we’re looking for as well as external opportunities through business development. So we have a very exciting year ahead of us for 2025 and we look forward to continue to share our progress.

Gina Wen, Clinical Biotech Analyst, The Barclays: Sounds great. So maybe starting with your PKD program, how have the interaction with the FDA proceeding in recent weeks since your supplementary NDA just was accepted and PDUFA was assigned?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes. So we’re indeed building upon our PKD story. We’re now with the thalassemia program. And so we have a supplemental NDA that was submitted. And as Cecilia mentioned, the PDUFA action goal date for September 7.

So right now, the review is actively ongoing and progressing as expected. And we’re very excited about the potential opportunity to deliver this therapy for patients with thalassemia.

Gina Wen, Clinical Biotech Analyst, The Barclays: Any comments regarding potential ADACON?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So to date, we have not been informed that there will be an advisory committee. But as we’ve mentioned in the past, if we would be informed at any time point, then we will of course let the community know.

Gina Wen, Clinical Biotech Analyst, The Barclays: What could be the latest time that FDA that you know that there would not be any add on?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Well, there is not really a specific time point by which you are truly in the clear. However, as we are continuing to progress, the chances of something like that continue to decrease. Okay.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: So maybe

Gina Wen, Clinical Biotech Analyst, The Barclays: the regarding the label change, what is in the community with the increased monitoring, what is the feedback there?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So you are referring to the label change that we have made for pyruvate kinase deficiency. So that was we’ve added a warning and precaution based on an observation made in the thalassemia program, in which we had observed hepatocellular injury in thalassemia patients. And so we’ve updated the label language in for pyruvate kinase deficiency to reflect that observation. And so that warning and precaution has led to a request to monitor on a monthly basis for the first six months of exposure to pyrokines, both for PKD and then across all of our clinical programs. And so in regards to how has that been perceived, it has been perceived as part of normal routine care really.

So patients when they are starting on a new therapy, when they have hemolytic anemia, they are routinely being monitored both for efficacy, but also for safety. So physicians are used to actually routinely monitor for liver function, for kidney function in the context of these diseases. Especially the liver is an organ that often gets damaged in the context of these hemolytic anemia or also is in the context of iron collator something that needs to be monitored.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And then regarding the potential timing for approvals in Philadelphia in The U. S, EU and other parts of the world?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So those regulators, they do not give you like an action date like The U. S. Does, but those filings are progressing as normal and as anticipated. So we are looking forward to getting to progressing those further.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And then for the commercialization, what kind of maybe preparation you have done and regarding the sales outreach?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Yes. So for the our main focus is The U. S. Right now. So we are commercializing that directly and we have started obviously building an infrastructure with PKD, but because it’s ultra rare, it was much smaller.

As we move into thalassemia, it’s a broader patient population. We are expanding. The nice thing is PKD gave us the opportunity to build the foundation on things like market access, patient services, and now we’re leveraging that and enhancing. We had about 18 to 20 reps when we were just PKD, and we doubled that as we get to prepare for thalassemia. And sales reps is only one part of the ecosystem, if you want, of the support that we have.

In terms of outside of Ex U. S, we’re not building direct presence. And what we’ve done is for the Gulf countries where there’s a big prevalence, if you think The U. S. Is our first market, the second one or the second group would be the Gulf countries.

There’s about seventy thousand patients with Talaisina in those countries. So that’s where you see we filed into Saudi Arabia and UAE as well as Europe and U. S. There we signed an agreement with a company called Newbridge, and this is like a specialty for a company that does distribution of products for a lot of different pharmaceutical companies. They’re very well known in the region.

They understand the region. They basically are your feet on the ground. So they carry all the costs and investment, but we still keep the strategic decisions and the strategic control of the asset as well as managing with pricing. And so our teams work very closely with them, but we leverage their expertise in the region and we’ll probably do something very similar in Europe.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And regarding the safety profile, do you think beta thalassemia and the sickle cell has a different like a threshold that what patients are willing to take?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So each patient has to make their own individual decision, right? So this dependent on we’re still working to generate the benefit risk profile in sickle cell disease because our Phase III is still ongoing.

Gina Wen, Clinical Biotech Analyst, The Barclays: But

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: then once that is available and if we can deliver to the target product profile that we are looking for, then that will be always an individual discussion between patients and physicians.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. So I think that’s a good transition to sickle cell. Okay. So maybe the Phase III trial, remind us the primary endpoint and what is your goal for the Phase three trial?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So as Cecilia mentioned in the beginning, we are indeed studying pyrokines in sickle cell disease. We believe that because of the mechanism of action of the drug, this drug has the potential to deliver an improvement both on hemolytic anemia and on vaso occlusion in the context of sickle cell disease. And both those components are very important for patients living with sickle cell disease. Hemolytic anemia obviously has all of the complications of anemia, makes people really feel very, very bad, very fatigued. This is not I’m tired.

This is like bone crushing fatigue that is really limiting what people can do. And the hemolysis and the hemolytic anemia ultimately leads to end organ damage as well. And then the vaso occlusion part of the disease is basically acute ischemia that leads to pain and can lead to organ damage as well and ultimately can also lead to death. So very horrible disease, big unmet need and our Phase III program is designed in such a way that we’re trying to deliver one therapy that can address the totality of sickle cell disease. So that means we’re looking to improve hemolytic anemia.

So one primary endpoint is an hemoglobin response and then we’re looking to improve vaso occlusion. So the other primary endpoint is looking at sickle cell pain crisis reduction. We have done an alpha split on those endpoints because we would like to if one or both are positive, we would like to move on to secondary endpoint testing. And within that secondary endpoint bucket, we have other ways to look at how patients feel and function. As I just highlighted, fatigue is very important for patients living with sickle cell disease, so that is also something we are looking to improve.

And we have precedent on being able to deliver on that on an improvement of fatigue both in our thalassemia program and in our pyruvate kinase deficiency program.

Gina Wen, Clinical Biotech Analyst, The Barclays: So regarding the primary endpoint, what is the alpha allocation?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So it is 0.02 to the hemoglobin response and 0.03 to the sickle cell pain crisis rate.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And what is your assumption for the control arm?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So for the sickle cell pain crises rate, we were looking for the baseline of three sickle cell pain crises in the prior year that then we look to continue in the year that they are on drug and then the drug is hoping to reduce that from three percent to a little bit less than two percent.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. So basically thirty percent reduction?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes. Okay.

Gina Wen, Clinical Biotech Analyst, The Barclays: And then for the hemoglobin level, the percentage you define?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So for the hemoglobin level, we are looking to improve the average hemoglobin concentration by one gram per deciliter between week twenty four all the way to the end of the trial. It’s important that that is an average hemoglobin, not just the one time point in that time period, because we’re also looking to highlight maintenance of effects by doing this. The trial is 90% powered to look for that improvement of 35% in the on the hemoglobin response.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And for the BOE also is 90% power?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes. Okay. The one is 91% and the other 90%. Okay.

Gina Wen, Clinical Biotech Analyst, The Barclays: And then going to the secondary endpoint, also maybe remind us what you showed so far and why you designed the study this way?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes. So the study is designed this way to really try to deliver to the totality of the disease as highlighted, but we’ve based that also we have a Phase II obviously, which was a dose finding study. So we tested two doses against placebo with a primary endpoint of a hemoglobin response. And then we looked at hemolytic parameters as a secondary endpoint and also a trend in sickle cell pain crisis reduction. And so across the two doses, we were able to show an improvement when compared to placebo trends because we did not do statistical testing on the secondary endpoints based on the sample size and the shorter duration.

But we basically have a hemoglobin improvement, a hemolytic parameter reduction and a trend on sickle cell pain crises as well that allowed us to move on to Phase three.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. And then secondary endpoint, is there any hierarchy there or we just even split of the

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes, we are testing everything together.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. Good. That’s very good. And then maybe status phase three like the timing?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes. We’re very excited because the team really worked very hard

Gina Wen, Clinical Biotech Analyst, The Barclays: and very collaboratively with all of the different sites and they were able

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: to enroll the different sites and they were able to enroll the study fast. So we announced full enrollment last October, so one year observation period for this study. And so we

Gina Wen, Clinical Biotech Analyst, The Barclays: are one of our corporate milestones this year is delivery of the data of that

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: trial by the end of this year. And so we are phones this year is delivery of the data of that trial by the end of this year.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. So maybe going back to the primary endpoint, since you have a co primary endpoint? Well,

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: two primary endpoints with the alpha split, yes.

Gina Wen, Clinical Biotech Analyst, The Barclays: I see. So as long as you’re hitting one, that will be enough for approval?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Well, for approval, that is like you do need the risk profile and all that. Right.

Gina Wen, Clinical Biotech Analyst, The Barclays: So but then the FDA, what you define as a positive study, as long as you hit one of the primary endpoint that will be enough? Or if they want you to hit the both? So it’s

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: always so everything is always dependent on the totality of the data. So if you have you need to be able to speak to clinical meaningfulness in your data package. Obviously, sickle cell pain crisis reduction is considered a clinically meaningful endpoint.

Gina Wen, Clinical Biotech Analyst, The Barclays: Right.

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: But when you speak to patients, what they are really looking for as a solution is something that also improves their fatigue. So hence, we have designed that trial to be able to deliver to that. So in the context of hemolytic anemia, when you can actually hit on hemoglobin and have a patient reported outcome that is also statistically significant, that is also a clinical meaningful benefit. We have in that secondary endpoint bucket also other ways to look at sickle cell pain crises. So I think as always, a regulator will always look at the totality of the data, especially in the context of a disease that is horrible and has a huge unmet need with no options.

You really have to speak to the totality of the benefit risk profile.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. Just trying to understand. So have you agreed with FDA? Like, did FDA see anything that one is enough or you want to No.

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So an agency will like I have never heard of an agency committing proactively to what they will approve. Like even if you hit on if you have a positive trial

Gina Wen, Clinical Biotech Analyst, The Barclays: and

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: a positive primary endpoint, you really need to have the totality of it work out, right? So there’s plenty of precedence of drugs that did hit on a primary endpoint and ultimately did not get approved and other way around the like drugs that did not hit on the primary endpoint, but ultimately got approved because it’s really everything that matters.

Gina Wen, Clinical Biotech Analyst, The Barclays: Right. Okay. That makes sense. And then was the study design was based on the feedback from the FDA?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: Yes, of course. We always work with all of the different stakeholders with the different regulatory authorities across the globe. We work with our like patient advocates and advisory boards with patients and of course the physicians as well to make sure that we can deliver a drug that is not just going to hit on that you can claim a clinical trial is positive, but you really want to deliver something meaningful to all of those different audience. So we take feedback into account from all of those different stakeholders to come up with what we believe is the best plan forward.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. Quickly on your AG946, what

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: kind of data will we see later this year?

Sarah Hewins, Chief Medical Officer and Head of R and D, Agios Pharmaceuticals: So for September, it’s another PK activator that we’re currently studying in MDS and in sickle cell disease. And for MDS, we have a corporate milestone of enrolling full enrollment of a Phase 2b in lower risk MDS. So that is not data, but it’s actually an important step to be able to deliver data in that program. And for sickle cell disease, we have a corporate milestone of having first patient enrolled mid year.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay. Okay, good. And then for your PK franchise, you do have several assets there. And how do you see this coexist in the marketplace?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Yes. So like Sara said, sickle cell disease is a complex disease and we require a lot of options for these patients. They don’t all respond to the drug, to individual drugs. So first things, which year for everybody that’s trying to get therapies for these patients. For us, like you said, we have two PK activators, PyroCon, which Sarah was just talking about, which we expect to have the data readout this year.

And the second one is tepaperate, which is also a PK activator, but a more potent agent there. And our thinking is to be able to build a franchise to have the ability to address more patients down the road with our franchise and as well there’s also different patent lives in each of the products. So it allows us to have flexibility there. So we’re very excited to be able to go, but it’s earlier, right, that’s in entering into Phase two.

Gina Wen, Clinical Biotech Analyst, The Barclays: Okay, good. And so Sylvia, you did mention you have a $1,500,000,000 that’s a lot of cash for Valtar company. So how do you say from the BD perspective, how would you use this cash?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Yes. So what we’ve said for a while, we’re very disciplined in how we think about business development and we establish criteria in terms of we want something within rare. That’s kind of our core of what we are. We probably don’t want to go ultra rare again as we did with CKD, but still stay within the rare area where we’ve established very good capabilities on clinical development and now we’re building on commercial Transformative drugs that we don’t really don’t want to meet to or something that really doesn’t address an unmet need, something that has ideally a way to early derisk the program as we do kind of smaller bets before we put a lot of capital in it as well as good clear path to a regulatory approval. Our team has been amazing at being creative at designing studies, but we have to have an end in sight there.

And of course, something that’s value creative. In terms of what we’re looking at, probably we’re agnostic to modalities, I’d say probably not gene therapy that would be very much outside of our capability there, but we are agnostic otherwise in terms of modalities. And in terms of stage of development, probably towards the earlier side, where we can again apply all our capabilities to clinical development with potential back to back launches. We have the commercial team definitely busy there.

Gina Wen, Clinical Biotech Analyst, The Barclays: Very good. I think we have one minute left. So maybe, which are the key topics you wanted to emphasizing that you think investors were misunderstood?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Yes. So I think in a couple so we have a lot going on. So we’re very excited. I don’t want to pick a favorite child. But for one is I think we have an incredible potential with Pyrocyne as a franchise to build a multibillion dollar franchise there.

Hopefully with success in RISE UP that would mean back to back launches in thalassemia and in sickle cell after. And we also have an advancing pipeline with TEGAPIVID with the two programs. We didn’t get to talk a lot about the next ones, but we have another asset in PKU, which is in healthy volunteers right now. And we’re expecting to file an IND on the latest or the earliest asset, which is AG-two 36. And like you said, we have a very strong balance sheet, which allows us to move all these programs along.

Gina Wen, Clinical Biotech Analyst, The Barclays: Thank you very much.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Thank you and thanks for having us.

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