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

Good morning, and welcome to day 3 of the 2024 Bank of America Healthcare Conference. Thanks for joining this session with Agios. My name is Alec Stranahan. I'm Vice President and senior biotech analyst covering Agios here at BofA. And I'm pleased to be joined by Brian Goff, Chief Executive Officer of Agios; and Sarah Gheuens, Chief Medical Officer and Head of R&D. Thanks for being here, guys.

Happy to be here, Alec. Thanks very much for the invite, and good morning, everyone.

Perfect. I believe Brian is going to run through some prepared remarks to start, and then we'll jump into Q&A. So with that, Brian, over to you.

Yes. Thanks a lot. I mean this is really good timing to have a discussion like this. It's a really exciting time at Agios. We have a lot of momentum. And for those who are new to our story, as a snapshot, Agios is a company that is really focused exclusively on rare diseases. And at the core of that focus is red blood cell health. And that really points towards our industry-leading mechanism of PK activation, pyruvate kinase activation. And our flagship product, mitapivat, which is known commercially as PYRUKYND, we were really pleased to have launched PYRUKYND back in early 2022 for an ultra-rare indication called PKD or pyruvate kinase deficiency and that has served as a wonderful platform for us to build up commercial capabilities in rare but secondly, also to see how PYRUKYND performs in the rare space, in the real world. And that's a great setup for the next indications that we're working on, where we're late stage in development right now, and that's thalassemia and sickle cell disease. 2023 was a fabulous year for us. We delivered on all of our corporate objectives to advance our clinical pipeline. And we started 2024 in a real high note. In January, we reported out our ENERGIZE pivotal Phase III study and ENERGIZE is focused on the non-transfusion-dependent thalassemia patients and why that's important is because in the U.S., that's about 2/3 of the population. So we start from a real position of strength. We were very pleased that we hit on the primary endpoint, statistical significance that's hemoglobin improvement. But I think what surprised a lot of folks was both key secondary endpoints were also significant. And the most important of which was fatigue, FACIT-fatigue, a patient PRO measure. And that is essential because that's one of the devastating symptoms of thalassemia. It also is across the board for hemolytic anemia as a real challenge for patients. I will note as a quick advertisement that 2 days ago when the EHA abstracts were announced, we were really proud with the fact that ENERGIZE will be featured as a plenary session. So for the folks listening in, we encourage you to take note of that, and you'll have a chance to see the full data set. The next study, the second study in the thalassemia program is what we call ENERGIZE-T. And the only difference there is that's focused on transfusion reductions in the transfusion-dependent population. So the other 1/3 of the population. And we announced earlier this month that we're expecting that top line data set actually Q2, the quarter that we're in right now. So lots of momentum. Last year also was a great year for us with sickle cell disease. We announced the top line results of RISE UP Phase II data for sickle cell, we hit with both doses tested, statistical significance in hemoglobin improvement. And again, there was a real aha! coming out of that study, which is a positive trend in sickle cell pain crisis reduction. So I must say, looking to my left here, Sarah Gheuens and her team did a fabulous job of moving very quickly from that data into the start of enrollment in our Phase III RISE UP study. And I'll just note that our goal for that is to be fully enrolled by the end of this year. So we have a great setup where thalassemia will get data this year for the second of the 2 studies. Our intent is to package those up together, filed by the end of this year. That gives us a potential launch in 2025. And sickle cell fully enrolled is the target for this year, data next year and a back-to-back launch scenario in 2026 with sickle. So all in all, it's just a super exciting time. And the last thing I'll just note is from a balance sheet perspective, again, a real position of strength. We ended the first quarter with approximately $714 million on the balance sheet. And that includes a $200 million milestone that we will receive upon approval of vorasidenib which is now owned by Servier that was part of the divestiture that we did in 2021. What's not included in our cash runway, very importantly is a 15% royalty on vorasidenib U.S. net sales. So that gives us, obviously, a lot of optionality. So all in all, great momentum. We have opportunities for first-in-class, best-in-class launches and we're working on building a multibillion-dollar franchise.

Fantastic. Well, definitely a lot going on, and I hope we can drill down into each of those areas. But -- so now we'll jump into the Q&A. I've got a few here, but I welcome those in the audience if you do have a question, just raise your hand and someone will be around with a microphone. But Brian, maybe just to start at a high level, mitapivat is looking like it could be sort of a pipeline in a drug, so to speak. Could you maybe talk at a high level, and you did touch on this, but how you're thinking about developing this asset not just in PK, but also already approved [ where ] it's already approved, but also thalassemia and sickle cell. What is sort of the grand vision for this asset?

Yes. A couple of points. One, we actually like the phrase pipeline in a product, but it's a little cliche. So we try to avoid it and talk more in grand terms. So 2 aspects. One is that I noted that we're the industry leaders with pyruvate kinase activation. And that is, of course, with mitapivat and the great progress we're making in PKD, in thalassemia, as I talked about, and in sickle cell disease. And I should note, we have 4 pivotal Phase III studies that we'll be reading out by the end of next year. So great momentum there. But we also have another PK activator. And the main difference there is it's more potent. And we refer to this as AG-946, and we have 2 different pathways that are underway right now. One, which is the most advanced is in low-risk MDS. Late last year, we reported positive data, positive proof-of-concept data in low-risk MDS in a Phase IIa study. We got a lot of learnings out of that study, and I'm sure Sarah would be happy to talk about that. And now we're preparing for commencement of a Phase IIb mid this year in MDS. And that's another growing market, high unmet need. So we're looking to extend PK activation as far as we can take it. The other area where we're doing research with 946 is in Phase I in sickle cell disease. And the main point there is to obtain data in a hemolytic anemia with our other PK activator.

Fantastic. And congrats on the plenary for ENERGIZE at EHA. I think that's a huge win for the program, and we'll definitely elevate it at least within the physician community. What can we expect from the talk, this is your non-transfusion-dependent study?

No, I know Sarah would be proud to talk about it.

Yes. We're very happy that ENERGIZE was selected for a plenary at EHA. As you can expect from -- in line with what we have previously done, our first big presentation is always our intent to treat analysis of the primary endpoint, secondary endpoint safety. But we're also very happy that there is an additional poster presentation the day before that goes into more detail about our patient reported outcomes and also performance measures. So we'll be highlighting an improvement in FACIT-fatigue there, but also a 6-minute walk test, adding to that totality of the data and feel and function for patients. So EHA, we're very excited to go and can't wait to get there.

Yes. Great. And maybe we can actually drill down further into beta thalassemia. So the next update beyond EHA is going to be ENERGIZE-T, which I think everyone is eagerly looking forward to. I think you've got it to middle of this year. Could you maybe walk us through the expectations for this readout, it's a slightly different patient population. So how would you define success from this study?

Well, obviously, we're hoping to hit on the primary endpoint, and that would be the statistical significance piece. That being said, we look at these 2 trials together and the unique components of our development program is that this is truly for all of thalassemia. So alpha and beta thalassemia, nonregularly transfused and regularly transfused with the hopes to be able to deliver a label that no matter where you fall as a thalassemia patients, you can benefit potentially from this treatment. In regards to the energized population, so the 2/3 of the thalassemia population where we now have data, we are very pleased with those results because it does cover the biggest part of the population. And we've also highlighted already that based on our prespecified subgroup analysis, there is not a single group that is driving the overall efficacy, meaning we see efficacy in all of the genome types. In regards to ENERGIZE-T, so where we are blinded and we don't know yet. It's also an all-commerce population. The difference is there that these people participating are regularly transfused. And therefore, we're measuring hemolytic anemia improvement via a transfusion reduction response. Success on a clinical trial basis would be the statistical significance, of course, but -- there is a lot of data there that can support clinical meaningfulness because what we hear from -- for the real world in the context of this product profile and the way it is used that any transfusion reduction can be meaningful for an individual patient.

Okay. Yes. Can I just add, Alec, too that it's -- these 2 studies together for people who are just learning about thalassemia. This is a historic period because in the case of the U.S. population out of the 6,000 patients, as I noted, 2/3 of those are non-transfusion dependent. They have no approved treatment option in the U.S., none. And there's another dimension to alpha and beta thalassemia Sarah has alluded to, alpha thalassemia patients have largely been ignored from pharmaceutical development, and they have no approved treatment options. So you can imagine if you're in the thalassemia community, and you hear about the data that we reported in January, and now we're going to feature in a plenary session at EHA with ENERGIZE, that's a breakthrough. And this is oral therapy, which makes it that much more convenient for patients. And now to have the kind of sister study of ENERGIZE-T. And we don't know the data, of course, but we're excited to see what that looks like because that package is a breakthrough historically for -- or has the potential to be a breakthrough historically for these patients.

Yes. Great. And definitely having a broad -- regardless of transfusion dependency that would be a first of its kind, right?

That's right. That's right, particularly also is an oral therapy.

Yes. How does ACTIVATE-T -- this is your transfusion-dependent PKD study. How does this provide potential read-through to ENERGIZE-T?

So the -- I think it's the overall program that we compare to the thalassemia program because we took a very similar development approach. Basically having those 2 trials, one non-regularly transfused and one regularly-transfused trial complement each other and highlight that we can improve hemolytic anemia as measured via a hemoglobin response in people who are not regularly transfused, but then a transfusion reduction response in people who are regularly transfused because hemoglobin, you can't reliably measure because of the transfusions. And so we took that exact same approach now for thalassemia. And of course, now we have the first part of the puzzle, as Brian mentioned. The second part of the puzzle we're still blinded to, but it's the same principle. Examining the disease as a whole as 1 disease independent of transfusion burden. And the drug, the mechanism of action is really focused on that red blood cell health, which is also independent of the transfusion.

Okay. And I think I know the answer to this next question since you mentioned that you saw same responses across genetic subtypes and it's an oral therapy. But I guess what patients with thalassemia would be best suited for mitapivat? I guess where do you see this fitting into the current treatment paradigm?

Well, we're always obviously subject to the data and how it specifically reads out. But if I sort of invert it a little bit and talk about what is our goal. Our goal is that all patients with thalassemia would have an opportunity to be on mitapivat. And again, if you just break it down, the fact that it's oral therapy makes it very convenient for the patients. We've -- we're already in a position of strength because of the ENERGIZE data, which covers 2/3 of the population. And this is a population, by the way, where they and their clinicians, they will need to be educated because they've never had a therapeutic option. So we need to help them understand what the potential looks like. Likewise, for investigators -- or for clinicians rather, there is a misnomer that non-transfusion-dependent patients are somehow less at risk than the transfusion-dependent patients. It may be the inverse because the ones with transfusions, they're actually -- they're in treatment, they're getting active transfusions, but all patients are undergoing ongoing chronic hemolysis. And that's the part that in the long term can be deadly for these patients. So it's really all types. And that is the beauty of the ENERGIZE program is all dimensions we've designed to be covered in our clinical program.

Okay. Okay, great. And Brian, you mentioned the U.S. market is being roughly 6,000 patients. Could you maybe talk about what the global opportunity could look like and how you would approach commercialization ex-U.S.

Yes. We're very focused on 2 specific regions, which have a very significant opportunity. The U.S., for sure, with the 6,000 patients and again, 4,000 of those are non-transfusion-dependent. The other big geography where we have a lot of focus is the Gulf or GCC region. And what is interesting and creates a tremendous opportunity is on a per capita basis, the prevalence of thalassemia is a significant multiple of the U.S. There are approximately 70,000 patients in the Gulf region who have thalassemia and the setup is the same. They have very limited treatment options. It's generally well known, particularly in the Gulf, that this is a more ubiquitous disease than we see even in the U.S. And so that's why our commercialization efforts are such that we're actively pursuing partners. And you can imagine when the ENERGIZE data read out, we got a lot of attention from people who are interested in partnering for this opportunity, and that's where we are right now is preparing for that. Beyond that could take beyond those regions could also take the form of other partnerships as well.

Right. And especially being an oral therapy, it could be easier to break into these other geographies?

Yes. And what's great right now in thalassemia and sickle cell diseases, we're seeing a lot of different modality approaches. And so the gene therapies, of course, have ex vivo have made really good progress. That's beneficial because that is also educating these markets about the opportunity, but we're on the opposite end of the spectrum, as you note. And to have an oral therapy married up with other potential options is really healthy for a biopharmaceutical ecosystem.

And I think there also our clinical trials are present in the region. So there is local experience with the product and engagement from key opinion leaders there as well. So I think that is definitely an important attribute to the programs.

That's a good point. And maybe along the lines of the regulatory path from here, I think, obviously, we'll see what ENERGIZE-T looks like, but I think you've guided to a filing expected by the end of this year. Could you maybe walk us through your discussions with regulators or your regulatory strategy?