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

Ladies and gentlemen, the program is about to begin. Reminder that you can submit questions at any time via the Ask Questions tab on the webcast page. At this time, it is my pleasure to turn the program over to your host, Greg Harrison. You may begin.

Hi, and welcome to the Bank of America SMID Biotech Virtual Conference. I'm Greg Harrison, one of the biotech analysts here at BoA. And today, we're lucky enough to have Agios joining us. Thanks for joining us, everybody. And for those of you out there watching, if you want to send questions, I'm happy to ask on your behalf. At this time, I'll turn it over to the CEO, Brian Goff, to introduce the team. Brian, if you want to do introductions and start off with some opening remarks, then we can jump into Q&A.

Yes, that's great. And Greg, thanks a lot for hosting us and for the people who have dialed in, thanks so much for your interest in Agios. This is a really exciting time for us, and so we're happy to share our story. Sitting to my left is our Chief -- Chief Medical Officer and Head of R&D, Sarah Gheuens. And then in another room, but paired up is Richa Poddar, our Chief Commercial Officer; and then next to her is Cecilia Jones, our recently added Chief Financial Officer. And again, we're really excited to be able to have some time with all of you. I'll start by just reiterating that this is a very exciting period for Agios. We're particularly proud of the fact that we are the inventors of and the leaders in PK activation. And right now, we're very pleased that not only are we the pioneers, but we now have a commercialized product, mitapivat, known commercially as PYRUKYND, which launched back earlier in this year in February for an ultra-rare condition called PKD, Pyruvate Kinase Deficiency, we're happy to talk more about that launch as well. We also right now are working towards maximizing our therapeutic opportunities across a few other meaningfully larger rare diseases that all share common underlying pathophysiology and biology. And that's an important point that we should talk about because what we believe ultimately is that the data that we're building is compelling. It's also consistent and subsequently because of the underlying pathophysiology, it's derisking in a sense as we move into these meaningfully larger opportunities. To give you a state of where we are right now as an organization, as I mentioned, we launched PYRUKYND in February of this year. And so that means as of our third quarter call, we reported out on our second full quarter of launch. We continue to learn dynamically from that launch. We have a lot of conviction and excitement about the opportunity to serve PKD patients who have had no therapeutic option prior to PYRUKYND in the more than 60 years that PKD has been known about as a disease. We're also, though, sitting next to me, as I mentioned, Sarah, we're really pleased to have 5 registrational quality studies underway with 2 focused on expansion of PKD into the pediatric population. We have 2 studies known as ENERGIZE and ENERGIZE-T focused on moving into the totality of thalassemia, which we'll talk about more. And then we have 1 study known as RISE UP, which is a Phase II study in sickle cell disease, but that really is the seamless Phase II/III study that could give us a pathway forward to the finish line of sickle cell. So the last thing I'll just say is I'm looking at Cecilia right now on the screen. Cecilia, as our CFO knows very well that we're in a strong, uniquely strong cash position as an organization. And that gives us the opportunity to not only carry forward all of these pivotal programs that I've talked about and to move us through proof-of-concept in low-risk MDS with AG-946, our other PKR activator, but it also gives us a way to continue to work on business development, where we have ambition to deepen and diversify our pipeline and portfolio, and we'll do that in a very disciplined way. So maybe, Greg, I'll stop there, that's a little preamble about why we're so excited about closing out this year strong in the year ahead, but we would welcome your questions.

Great. Yes. That's a great overview. And it is a very exciting time for you guys. And I think that's reflected in some way by the huge number of abstracts you have at ASH this coming weekend. Maybe we can start off with that. Maybe what's the most impactful there? You have long-term outcomes for PYRUKYND. So maybe how that could benefit the launch as you see the durability of effect, and maybe anything else that you'd like to highlight?

Yes, great question. I'll just start because I just want to brag about Sarah and the team that she works with first, and then I'll let Sarah talk to the characteristics of the data. First, I'll make a quick advertisement that next Monday at ASH, we have another investor event, and I would encourage everybody to listen in on that. We're really excited about the opportunity to talk about the 22 abstracts that we have at ASH, which is amazing for a company of our size. And frankly, it's not just the quantity, it's the quality of the data, which Greg, you just alluded to. And we will be showcasing in particular long-term data that I think Sarah should talk about now.

Thanks. So we have long-term data for pyruvate kinase deficiency that is being presented at ASH, but also for thalassemia. And then we're very excited about it because one for pyruvate kinase deficiency, we're continuously showing that hemoglobin improvement is sustained and maintained over time, transfusion reduction responses as well and that this is accompanied by hemolytic improvement. So this is great to see because when people take a therapy like this, it's important to highlight that responses are maintained over time, and that you don't like get used to a therapy and kind of have to wean off. So that's that. What we're also very excited about is that we actually have iron overload data that we cannot show for ACTIVATE in our long-term extension data. This is important because this goes beyond just treating hemolytic anemia, but actually highlights how it is a therapy that can be beneficial for the longer-term consequences of having a hemolytic anemia because iron overload is a huge problem in these conditions. And so we're super excited about that data. And then we also have a patient-reported outcome data that we can highlight for pyruvate kinase deficiency. This is important because I think we are the first hemolytic anemia drug that actually has highlighted that hemoglobin improvement is statistically and significantly linked to a PRO and that, that PRO also is clinically meaningful over time. So a lot to look at, at ASH. We're super excited about next weekend and more to come at our ASH IR Event as well.

And I'll just add, too, that with the PKD launch underway, the long-term data only reinforces and mirrors what we've expected thus far in the launch, that patients in the early going appear to be responding well. We're very pleased every time we get an unsolicited anecdote from a patient who's enthusiastic about how they're doing on PYRUKYND. And we see this as really important because this is a chronic disease. And so to have that long-term data to be reinforcing to both clinicians and patients alike about the safety profile, the efficacy profile is great. The PKD launch itself for us is also not just important from the perspective of the launch into serving the patients with PKD who have not had a therapeutic option up until this point, but it also is foundational for us as we build commercial capabilities for these other indications that we're pursuing sequentially.

Great. That's helpful. And maybe we can build off of that and talk a little bit about the launch. And maybe could you provide an update on the launch? And how has it been tracking versus your expectations to this point? I know it's a launch that has some unique aspects to it, and obviously, it's a very rare disease. So just wanted to get your thoughts there?

Yes, correct. Very rare. It will be a long but very important journey for us. I don't think about the launch as being slow and steady. And as I mentioned, really important continued dynamic learnings that we'll look to leverage as we build these capabilities for other launches. Richa, do you want to give a little more color on that?

Sure. So as we talked about at the end of Q3, this is, and as you alluded to, Greg, a disease that is ultra-rare. It is a diffuse patient population. It's poorly understood. So there's no centers of excellence here. So what we're really expecting and we're expecting prior to launch and are seeing play out in this post launch phase is a slow and steady launch, which we expect will continue throughout the phase of the launch itself. The story overall is that of breadth, breadth in terms of physicians that are prescribing the drug and breadth in terms of the kinds of patients that are being prescribed drug. The patients that are on therapy right now are representative of the adult PKD patient population, which is very similar to our indication statement as what we would like to see. And what we reported in Q3 was 84 patients that have been prescribed PYRUKYND, which was a 64% increase over where we were at the end of Q2. And then 56 patients of those have navigated through the access hurdles and are currently on therapy as of the end of Q3 again. So that's a 50% increase relative to where we were in Q2. So both of those are important metrics and things that we would continue to highlight because they highlight the slow and steady momentum of the launch. And as Brian highlighted, this continues to be a dynamic learning environment for us, because all of the learnings here are directly applicable to future indications, especially thalassemia, where you have the same customer base and the learnings that we have here can then directly be applied to those indications as well. So our goal continues to be around improving the diagnostic efficiency because we continue to want to raise awareness of the disease and get more and more patients diagnosed while also activating patients to take a more thoughtful and deliberate approach to the diagnosis and treatment.

Great. Maybe could you run us a little bit through the logistics of getting patients on therapy? What are the steps that they have to go through? And what trends you're seeing there so far?

Yes. So there's sort of 3 buckets that I'll talk about. The first one is diagnosis. So as we've highlighted before, it's really, really important that we continue to educate the physicians as well as the patients on the fact that there is both a disease that has a lot of burden that needs to be treated, so that they can diagnose these patients. We have a tool, Anemia ID that we've talked about, that is really important in helping with improving the diagnostic efficiency and getting more and more patients tested through genetic testing program. It's, again, not specific to pyruvate kinase deficiency, but does help a hematologist determine what the underlying cause of hemolytic anemia may be for that patient, and therefore, serving as an important tool in helping improve differential diagnosis overall. So that's step 1. Once the patient is diagnosed, our goal, again, is to highlight the burden of disease and the importance and relevance of ensuring that the patient should be treated as long as they're within label, which would be an adult PKD patient. So that's again an element of like both the disease education and the data that Sarah and her team have continued to generate but also highlighting the benefits of the drug itself. So that's where the 84 patients come in that we had at the end of Q3 that have all been prescribed PYRUKYND. And then each prescription gets enrolled into what we call a myAgios Patient Support Program, which is the third step, which is around access. And that allows these patients to be helped through a patient support manager in navigating their access, their prior authorization criteria. And we are able to get those patients, therefore, then on therapy, which is the 56 patients that we reported at the end of last quarter as the ones that have received at least one pack of the drug. So that's how the step-wise edit is happening. But overall, we're generally seeing most physicians that get -- most patients that get a prescription are getting access to therapy, we're able to navigate through that process pretty seamlessly.

Okay.

And Greg, maybe I'll just drop in then a fourth point adding to Richa's list is continuation of therapy. And so we're now in an important point in the PYRUKYND launch, where some of the patients are starting to move through that first 6 months of therapy. And that will be important for us to determine and work with payers to continue the support for appropriate patients so they can continue successfully on their therapy. But again, that's also a capability because all of the diseases we're pursuing are chronic rare diseases. That will be a capability that we'll also look to enhance, particularly as we build a larger base of patients who are beyond that 6-month mark.

Great. I guess the other aspect of the launch, obviously, is when people are around that 6-month mark on treatment, you have to look at which patients are responding, and which are not. I know it's early to have a lot of assumptions around what discontinuation could look like. But maybe just what factors are you guys considering that could make the real-world responder rates either higher or lower than what we thought in the trial?

So fortunately for us with the work that the clinical team had done, we have language in our label that we can speak to commercially that entails looking at not just the hemoglobin and transfusion burden, but also the impact that the drug is having on chronic hemolytic parameters. So the focus for the team as those patients sort of reach that 6-month mark and are going through that re-authorization process is to ensure that we have all the baseline parameters, not just for hemoglobin and transfusion burden, but also for the chronic hemolytic parameters, so that the totality of the data can be taken into consideration as a decision on continuing therapies made. So still very early days as you highlighted, Greg, more to come in the next few quarters as more patients get to that 6-month mark. But our goal is to make sure that it's not just limited to hemoglobin or transfusion burden.

Okay. That makes sense. The other topic I wanted to hit on the launch here is now you have EMA approval. How should we be thinking about commercialization within the EU and ex U.S. generally as far as your strategy?

Yes, [ Miss ], do you want me to take that one?

Yes, please.

Yes. So first of all, we're really pleased that we have approval from the European authorities because that's a mark of credibility for PYRUKYND. And that's important not only for the PKD launch, but it's important for the investigators and the patients who are involved in PYRUKYND further pursuits in, for example, thalassemia and sickle cell disease to give them further confidence. Job one from our perspective as a company that's really oriented culturally around the patients is to make sure that patients outside the U.S., i.e., in Europe have access to PYRUKYND as appropriate for adult patients on a label with PKD. And so I'm really proud of the fact that Sarah and her team have put in place what we refer to as the Global Managed Access Program or GMAP. And we've made that available non-commercially, so again, those appropriate patients can have access. Looking at the point about when would we commercialize, the dynamics are very different in ex U.S., especially in Europe relative to the U.S. in ultra-rare diseases. One example of that is this is a diagnostically intense disease. And with patient privacy dynamics different between the U.S. and Europe and of course, everything that we do, we want to respect patient privacy, but claims database analysis, for example, to guide us efficiently on high-potential clinicians who are likely to have a PKD patient. We exercised that in the U.S., that would not be an option for the most part in Europe. So that's one challenge. Secondly, pricing itself will be very different, and then the pathway to reimbursement takes a long time in Europe. So where we are right now is we're continuing to pursue partnerships as appropriate. But I would say that we're really going to be motivated towards further commercialization at a point where we have further data in one of our other subsequent meaningfully larger diseases like thalassemia, and then we'll be able to have a platform of commercialization likely not on our own but with a partner that we could amortize more effectively across multiple options, not just PKD itself.

Okay. That's helpful. Maybe moving on to thalassemia and sickle cell. This is more of a general question. As we see some of these curative -- treatments of curative intent getting closer to the market, where do you see the advantages of a treatment like mitapivat? When you also have curative type therapies on the market? And where do you see mitapivat fitting in with that treatment landscape?

Yes. I think Sarah should weigh on this one, too. But I will start with a comment that we, as a company, applaud everyone who's in these rare disease spaces that we're pursuing, whether it's PKD or thalassemia or sickle cell disease. These are complex diseases. They'll require a lot of scientific pioneering. That said, if you pick an oral small molecule focused on the pyruvate kinase specific point of action in the glycolytic pathway and then you look at gene therapy, those are on polar opposites of the spectrum. And so we really see that as another option, but not necessarily a real competing option in the broad sense. But Sarah should talk about the scientific aspect.

No. And I think this is truly about benefit risk profiles being generated on those different components in the context of the diseases that we're targeting to treat. And I think for some of the or part of the populations that currently is not on any treatment to have an option of taking an oral in the comfort of your home without having to go through conditioning regimens, et cetera, is very meaningful, especially now that we are also highlighting more of the disease-modifying data that we see with our impact on iron overload. So I think we're, to Brian's earlier point, very hopeful that everybody can move forward successfully because the diseases that we are working on deserve several treatment options.

And I guess one last point would be this sort of goes back right to your question about ASH and the data that we'll see. Across the board with gene therapy, it's important, but it's early. We're generally talking about a handful of patient data that we've seen of clinical data with PYRUKYND. And so that's important as well from a confidence safety standpoint, efficacy for sure, but especially as we proliferate across other therapeutic diseases.

Yes. Yes.

Brian, can I just, one last point as well, which is just around like the thalassemia, in particular, like the gene therapies are only approved and are only being studied for the transfusion-dependent beta-thalassemia population. So you still have 60% of the patient population that is currently massively underserved with no therapeutic options available at all other than transfusions for the few that might still need them. So when we think about our overall thalassemia program, in particular, it addresses all aspects of thalassemia, alpha-thalassemia, beta-thalassemia regularly transfused and non-regularly from a benefit risk standpoint and oral treatment that can address the entirety of thalassemia, so that makes us unique and different as well.

Thanks for that, Richa.

Yes. Yes. No question. There's a place for both approaches. So we have about 1 minute left before they give us the hook. So maybe we could just finish off with a question on when you're looking ahead to the next wave of R&D and maybe business development, what's the strategy there as far as how you deploy your balance sheet, which is, as mentioned, very strong? And where should we expect to see future investments being made?

Cecilia, do you want to tackle this one?

Yes, I'll start with that. So like Brian said, we are fortunate to be in a very strong position from a capital perspective, sorry, in order to support our clinical development of all the programs that we just mentioned in addition to when we didn't get to talk much, which is AG-946 for MDS is a proof-of-concept there and our earlier programs. And then the second prong to that is BD as well, that's a critical part of our strategy. We're reinforcing our BD team to get strong on research and evaluation. And we will balance that with a very disciplined approach in terms of looking for profound unmet needs, strategic fit from a science perspective and R&D perspective and obviously, value creation.

Great. Well, with that, our time is up. So I'd like to thank the team from Agios for joining us. And thank you, everyone out there for watching. And take care, everyone. We'll see at ASH.

Thanks a lot, Greg. Yes. And Monday the 12, we have another investor event. Thanks so much.