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

All right. Thank you so much for joining our next session here. My name is Kennen MacKay. I'm one of the Senior Biotechnology Analysts here at RBC, and it's my great pleasure to have with us on this next session, Agios. And from Agios, we have Dr. Jackie Fouse, Agios' Chief Executive Officer. Jackie, thanks so much for joining.

Happy to be here, being late is my fault you can tell them that. So...

I'll shoulder the blame of the technical difficulties. Thank you, again, for joining. Thank you again for doing a video. Before we dive in with some fireside chat questions Agios is really at sort of a pivotal point in terms of the company's history now with really some potentially major rare disease programs very close on the horizon. Maybe you can just give us sort of a quick overview of the company, the decision to issue some longer-term guidance earlier on in the year. And really just how you are thinking about the strategy from here out?

Yes. Thanks for that and thanks for having me again today. So the -- just to your point of where the company is today in our maturity cycle and all the things that we've had in terms of how the portfolio has evolved that's exactly why we felt it was the right moment to give some vision for where we could be in 2025. And that vision is based on mostly on assets that are already in the clinic. So they've been derisked to a certain standpoint, and we really like where we are. We like how the portfolio could evolve. And we wanted to put some stakes in the ground because we know that now being a company that's going into now its 12th year of existence, we've employed a lot of capital over time. We wanted to show where we are as a result of that, so that investors have an appreciation of all the things that can come along out of the pipeline and the portfolio and go ahead and put those stakes in the ground with those commitments to where we think we can go with things. So there -- we're very happy with how we see things evolving even with the bizarre set of circumstances that we all find ourselves in today. We still see that we're on track to hit the goals in our Agios 2025 vision, and we feel like we've put out there some minimum guidelines that we think we can hit, maybe there's upside potential associated with those. So we're very excited about where we are.

And some of that upside potential, like you mentioned, could potentially come from mitapivat in beta thalassemia as well as potentially some other indications like potentially sickle cell disease. Obviously, we are very focused on beta thal going into the now virtual EHA Congress. The abstract was sadly, just a place holder. But maybe can you help sort of guide us to really what would be exciting, would it be sufficient to really push that board in beta thalassemia and talk about sickle as well.

Yes. So we wanted you to tune in into the presentation. So I didn't give you everything in the abstract. So we got you keep you honest. So we're really excited about mitapivat for a whole host of reasons. So the same scientific platform that allowed us to leverage our expertise in cellular metabolism and bring the IDH inhibitors into cancer is the platform that has allowed us to elucidate what we think are unique molecules in the PKR activation space. And now with mitapivat this is a drug that we've studied for almost 6 years. It's been in humans, including healthy volunteers for about 5 years, 4 of those in PKD and now building up a nice data set in thalassemia and it's [ about ] alpha thalassemia and beta thalassemia. So I want to remind everybody of that because the number of alpha thal patients is not small, it's about 1/3 of the thalassemia market. And then we also look forward to sharing some disclosures around sickle cell disease potentially. So this is a drug that activates both the mutant enzyme for PKR as well as wild-type PKR. So we will -- and what you saw in the EHA abstract was essentially what we disclosed last December where we declared proof-of-concept for the drug in thalassemia, what you -- and that was 8 patients worth of data with 7 responders at that time, just as a reminder. What you will see in the presentation at EHA, the trial has now enrolled 20 patients. We had an original goal of 17 and as of the data cutoff, there will be 13 patients worth of results presented at EHA. We'll have safety, we'll have PK/PD, we'll have efficacy, we'll talk about the totality of the data set and it's going to be very interesting. And included in those 13 patients are some alpha thalassemia patients, and we will break out the alpha thal and beta thal patient subsets, so everybody can see those as well. The 8 patients that you saw data on back at ASH were all -- they just all happened to be beta thal patients who had made it through the dosing period at that point in time. We also sometime around the middle of the year are going to disclose our -- where we think we are with sickle cell disease and we would expect that to be in mitapivat. And we would expect that to be a similar type of disclosure that we did back when we declared proof-of-concept for thalassemia at ASH of last year. So proof-of-concept declaration, some data, just to give you an idea of how we made the proof-of-concept decision. So very excited about that. And the next-gen molecule, the IND has cleared. So we've got a portfolio of drugs in the PKR activation space to work with as we take the programs forward.

And just thinking about beta thalassemia versus alpha thalassemia versus sickle cell to your point, mitapivat is something that can activate really both wild-type as well as mutant pyruvate kinase as is the case in pyruvate kinase deficiency. And it's really remarkable how rate-limiting this is in terms of energy production for a number of different diseases, not just pyruvate kinase deficiency. So is the way to look at this, to look at potential for mitapivat to enable change or enable efficacy in some of these indications, the sort of energy burden that the disease inhales on the red blood cells, for instance, comparing alpha versus beta thal versus sickle cell?

So we know -- or we hope that what we will show in the data as it evolves is that the drug lowers 2,3-DPG, it increases ATP. It improves red blood cell health, the integrity of the red blood cell membrane, oxygenation, hydration, all of those things. And so we think that we've got a unique mechanism here that may come at these diseases in different ways, but in ways that should allow us to address both the hemolytic anemia component of these diseases, which, as I think you were alluding to is a common thread across all of PKD, alpha or beta thal as well as sickle cell disease. So even though there are different diseases that hemolytic anemia is a common thread, but we know that with the disease like sickle cell, for example, there are other issues, whether it's vaso-occlusive crisis and the pain associated with those, all of those sorts of things. So we're keeping our fingers crossed that this is a drug that can have application in a clinically meaningful way across a broad range of hemolytic anemias, and we're very excited about that on behalf of patients and on behalf of the company and our stakeholders.

Okay. Maybe thinking about some of these rare diseases, especially some of these hemolytic anemia and hematologic rare diseases. Can you maybe talk a little bit about how these trials have sort of held up throughout the COVID-19 pandemic. That's really been a focus of ours as it relates to ACTIVATE and ACTIVATE-T with those data sets coming up towards year-end or potentially early next year.

So I think the good news in this situation is the ACTIVATE trial for non-transfusion-dependent PKD patients, the ACTIVATE-T trial for transfusion-dependent PKD patients as well as the Phase II thalassemia trial were all enrolled as the pandemic situation started to escalate. So that is very good news. In our Q1 results call, a week or so ago, we talked about how our original goal of having to ACTIVATE-T trials readout and be able to talk about those was the end of the year. We're still keeping that as a possibility. But we are acknowledging that maybe we don't know what we don't know about exactly how things are going to go with respect to accessing the clinical trial sites to be able to clean data and make sure all the data is there and then it's entered and there's no entry errors and all the things that you have to do before you can lock your database. And maybe we're being a little bit conservative. As a C-suite executive, I've been through a couple of other sort of dramatic situations. As I said to somebody earlier today, not a pandemic, I'm not that old, but I was a CFO during the 9/11 stop and everything else. And all I can tell you is you -- in a situation like this, so you want to just at least acknowledge that there may be things that you don't know. So that's what we were trying to do, so that later you guys wouldn't yell and scream at us if we did have a little bit of a delay. But we've got people working very hard on this. We're literally following every patient on an individual basis in these trials along the way. The beauty of oral modalities is you can deliver drug to patients' homes if they don't want to leave their homes, you can do blood draws from their homes and still monitor them in conjunction with the protocol requirements and things like that. And we've been on this way early in the game. So we think we're in relatively good shape. Any trial that was underway during this pandemic is going to have some impact on it, and it very much depends on the modality of the drugs being used, the indications and where the trial was in terms of its particular dynamic. So we're grateful with those 3 that they were fully enrolled at the time this all started to escalate.

Sure. And maybe moving towards mitapivat in PKD and just thinking about the PKD population, it seems one of the biggest uncertainties isn't really whether or not mitapivat is going to have a profound effect in these patients. I certainly think it will from the DRIVE PK trial that we saw in the Phase II. But it's really on sort of the size of this patient population and the population is obviously segregated into transfusion dependent, transfusion independent. And as I look at the ACTIVATE and ACTIVATE-T trials, ACTIVATE-T enrolled incredibly rapidly. Obviously, those transfusion-dependent patients are in clinics. They're coming in to see their providers and quickly going into a clinical trial that could benefit them, but not so much with ACTIVATE -- or I shouldn't say not so much. It just took longer to enroll. And I think that's the bigger uncertainty. Can you maybe talk a little bit about the current estimates around how many PK patients there -- PKD patients that are out there? And how many transfusion-independent patients there are out there?

So what we believe, and we've done extensive literature reviews on this. And then our ongoing work with our Phase II -- Phase I, Phase II programs, our PEAK Registry, our ongoing interactions with physicians as well as patients themselves is allowing us to have a view on this. So it's still, in our mind, a relatively broad range. We think that there are at least 3,000 to 8,000 patients out there with PKD. As you observed, the transfusion-dependent ones clearly have more serious disease. They're seeing their physicians more regularly. So it was no surprise really to us that, that trial enrolled faster. That being said, as you bring a therapy along for an indication that has no approved therapies, what you start to see is even with the non-transfusion-dependent group, we've seen physicians actually figure out that they may have PKD patients that had heretofore only been diagnosed with a general hemolytic anemia. And the physicians may not have even necessarily tested them for these mutations to figure it out because they didn't have an approved treatment to go put them on. And so we're finding that raising the patient awareness is one thing. There hasn't been up to now a -- and still isn't a very well-organized patient support group. We're supporting that effort, and I think that will happen over time, but we're finding a very enthusiastic response from the patients that we've been interacting with in the context of our trials and the registry and the experience that we're getting. So the best thing we can say is we feel good about this 3,000 to 8,000 number. It's hard for us to narrow that just yet. We think it's an underdiagnosed disease. And that when there's an approved treatment option that the awareness will help to improve the diagnosis. We have found about 1,000 of these patients so far in our patient-finding efforts. And we think that actually is really pretty good for this type of disease that we already feel like we found 1,000 of those patients. So hopefully, that bodes well for the uptake of the drug, as we get it approved and everything.

And there have been several analogies in a number of rare diseases where these patients essentially don't exist to health care providers ahead of a drug approval for the treatment of their rare disease. One analogy that I sort of look at, and I think about is another hemolytic anemia here and it's PNH. And it's what Soliris have really been able to do in that setting. Is that in your view sort of the appropriate example for a drug approval in one of these rare diseases with patient estimates really, really dramatically increasing after approval?

So I don't want to go into that analogy necessarily to make a whole lot of promises. So I do think we believe that PKD is underdiagnosed. We think that the lifelong implications associated with the disease may be more profound than is what is widely recognized including by payers. That being said, we know we've got some work to do, especially with that non-transfusion-dependent population to continue to show what the burden of the disease is, work with patients, work with physicians. And frankly, then when you can come out with an oral drug that's safe and efficacious, it's the type of modality that's the perfect profile for treating a disease that patients could be on for that drug for a very long period of time. So let's keep our fingers crossed, but we know that we're going to do great things for these PKD patients. However, many of them, they are out there. And I think there's probably more than we fully appreciate.

And with your commercial experience, I can only imagine how excited you and the team are to hopefully get this across the finish line.

Well, we've got a great commercial team, too. So...

Well, maybe with commercialization of mitapivat in mind, can you tell us -- help us understand a little bit how you're thinking about this next-generation PK activator. Is that going to be aimed at these PKD patients or really much more relevant for some of these other indications, either much larger indications or other rare diseases?

So I think the good news is we have choices. I think it's always great when a company can have multiple compounds in a potential portfolio to have optionality around how you take those forward. We know that 946 does have some differentiating characteristics compared to mitapivat. If the only thing we did was take mitapivat forward in a broad range of hemolytic anemias that we're already very happy with that. So we don't need 946, but the great news about 946 is for PKD, it does hit some mutations that mitapivat does not work in. R510Q is one very notable one. We know that in our preclinical work, that 946 works there and 348 mitapivat does not. Also, though, 946 seem to be more potent in terms of its activation of wild-type PKR, which would potentially make it relevant also in thalassemia or sickle cell disease, it has the potential for once-a-day dosing. Even though from a clinical standpoint in all the years that we've studied mitapivat, there's -- we see no impact from the aromatase inhibition. Mitapivat does have mild aromatase inhibition, 946 has none. So I think the IND cleared in the first quarter we need to get 946 into the healthy volunteer study, get the data, see what's there and then make some decisions about where we take it next. But it could be that these 2 compounds play in different indications in a portfolio. They could potentially play in different patient segments within an indication. It could be -- 946 could be part of a life cycle management plan. We've got, I think, some choices that we're going to have there. We just need to get some data in humans for the molecule first. And we'll be very mindful of our capital efficiency as we take all of these things forward.

That obviously was very clear on the Q4 call as well. Well, we spent almost all this time talking about PK and your PK activators. I'd be remiss if I didn't congratulate you on the TIBSOVO publication just today in The Lancet Oncology. We are almost running up against the top of our time here. So maybe as we think about the IDH platform, I would just love to ask what you're most excited about either as it relates to the TIBSOVO, potentially IDHIFA or vorasidenib as well some of the deeper IDH-targeted drugs.

I love them all. So I would say, I think just on TIBSOVO, we're extremely happy with where we are even in the commercial space today. The drug has held up very well, as you saw in the first quarter performance and so far in Q2. Again, I think that speaks to the advantages of oral oncolytics that are safe and efficacious in a time like this, but the drug has been gaining traction, increasing duration of treatment and doing very well in its labeled indications. We're excited about the potential in cholangio. We are reopening, as you know, the MDS arm of the Phase I trial. So we think that TIBSOVO has got a lot of future potential with the ongoing label expansion work, and we're building on what's been a successful launch and so far successful experience in the commercial space. So we love it, and we're very happy to have it. We like IDHIFA too. Bristol's still got IDHIFA. We co-promote with IDHIFA so we love them both. I am quite excited about vorasidenib. I think the glioma trial is a long trial. So we know that people are saying, "Oh, it's going to take a while" and all that sort of thing. But you've probably seen the ASCO, we have an oral presentation there. I would pay some attention to that just because the data updates are particularly relevant for that non-enhancing glioma patient population. And every time we've done an update on that Phase I vorasidenib data, it's continued to look encouraging in terms of how we might think about the potential success for the Phase III trial, which initiated late last year, enrollment has been a little slowed down because of the pandemic, but we've got a ways to make up some of that time. And we're -- I think that would be a terrific indication. And I think the mechanism of vorasidenib is well suited to potentially treat a disease like this grade II non-enhancing glioma. So...

Yes. Absolutely. Well, that's a perfect stopping point for us. We are, I think, at the end of our time. And I think we'll leave it at that and just say very excited about what's to come at ASCO, at EHA. And later on in the year, both I'm assuming the virtual ESMO as well as ASH.

Well, we will see you in whatever forum we can see. So thank you so much for having me today.

Well, thank you, again, Jackie. I appreciate it. Okay, and thank you all for joining.