Welcome to the 2023 RBC Global Healthcare Conference. My name is Greg Renza, one of the senior biotechnology equity research analysts here at RBC. We're pleased to kick off our first fireside chat session today with Agios Pharmaceuticals. Joining us from the team is the Chief Executive Officer, Brian Goff, and the Chief Medical Officer and Head of R&D, Dr. Sarah Gheuens. Which we just went over pronunciations and I managed to botch that one. Without further ado, it's great to have you, especially to kick off our session for today.
Brian, maybe we can just begin with allowing you to give us a quick intro for those who aren't familiar with the Agios story, and just provide us with not just an intro, but also maybe some updates on-
Sure
... on the mid-program.
Well, thanks a lot for hosting us. First off, Greg, we're delighted to be here. I'll begin with just a snapshot of Agios, who we are and where we're headed. We're a company where our mission is exclusively focused on developing therapeutics, transformative therapeutics for patients with rare diseases. We're building a PK activation franchise, which is pyruvate kinase activation.
This focuses on hematologic conditions that have common underlying pathophysiology, high unmet need and very limited treatment options for patients. Now, in the beginning of last year, the first quarter of 2022, we launched PYRUKYND, mitapivat, for adult patients with PK deficiency, again, pyruvate kinase deficiency. This is the first and only really transformative therapy available to these patients for the more than 60 years that PKD has been known as a disease.
It's truly disease modifying. Since then, we've made progress on the launch. We also have continued to see very consistent and compelling data across a range of diseases, which I'm sure we'll talk about this morning. We have a balance sheet that is well-capitalized, we talk about it as an enviable balance sheet, particularly in this environment, where at the end of Q1 of this year, we landed with approximately $1 billion. Now it's enviable, but we're very careful to also note that we don't walk around just with an enviable balance sheet. We're very disciplined with our OpEx as well as our capital deployment. We are coming up on some very important milestones for this year and beyond, that's where, Greg, you alluded to perhaps some updates.
I'll give one really important update since our earnings call that we had just a couple weeks ago, and that is that we have a program where we're pursuing thalassemia, and it's known as the ENERGIZE and ENERGIZE-T program. Those are the trial names. The update is that as of today, we have completed enrollment with both programs, and this is for the totality of thalassemia, alpha thalassemia, beta thalassemia, transfusion-dependent, as well as non-transfusion-dependent patients. We're really pleased with that update, and that puts us on a path where we would have readouts in 2024, first half for ENERGIZE and second half for ENERGIZE-T. If successful, that would put us on a path towards launch in 2025. That's one.
As we proceed through the balance of this year, of course, a lot of folks are very interested in our sickle cell disease pursuits. We have a operationally seamless phase II/III study known as RISE UP, and we're expecting at the midpoint of the year a readout on the phase II portion, which will guide us go, no-go for the operationally seamless phase III part. If successful there, phase III we would expect to be completed in 2025, putting us on a path towards launch in 2026. A couple of other milestones that we're targeting for this year. At the end of the year, we would look to have more than half of the patients in the pediatric PK deficiency phase III programs known as ACTIVATE and ACTIVATE-T. We'd look to have more than half enrolled.
We also have another PK activator known as AG-946, and we're looking for full enrollment by year-end in our phase IIa proof of concept study in low intermediate risk MDS. The last thing is, out of the Agios research organization, we also have a PAH stabilizer that we're pursuing for PKU or phenylketonuria, and the goal there is to have an IND by year-end. We are stacked with very important readouts, a lot of activity, and I think hopefully the takeaway will be that Agios is poised for growth and significant value creation for shareholders. That's the snapshot of all we have going on.
That's it. That's great, Brian. Appreciate the update and also congrats on the enrollment. I know that was something we were looking for, mid-year, and it also reminds me of several months ago, when you had that strong engagement on getting the sickle cell trials up and enrolled and completed there.
Can I interject too?
Yeah
... just to say, since Sarah Gheuens is sitting to my left, I just want to brag about Sarah and her team. I should have mentioned that that achievement of enrollment says an awful lot about the excellence from Sarah and her clinical development team. Equally, we think it gives a strong signal about, from investigators and from patients alike, about the potential profile that we have to offer in thalassemia.
Yeah. Certainly some readers there. Maybe Brian, just to help on the broader context and taking a step back, you've been on board in the seat for about a year now. I've certainly have seen an evolution of your leadership, many appointments in place. How are the operational and strategic plans evolving the overall company outlook as you and your team have really been on the ground running?
Yeah, thanks for the question. I do want to comment and again, brag a bit about the team and the evolution. As I had mentioned, we're focused on rare diseases. What we need is rare disease expertise and experience. That was my attraction for joining Agios is I've spent more than a decade in hematologic rare diseases with Baxter, Baxalta, then Alexion, and then now Agios. About a month after I joined, we brought on board Cecilia Jones as our CFO. Cecilia most recently came from LogicBio, which is a company that was also focused on very rare diseases. Before that, she was at Biogen, before that, many years at Genzyme. We thought that was a very important addition to the team.
At the beginning of this year, Tsveta Milanova joined as our new Chief Commercial Officer, and Tsveta and I worked together for many years at Alexion. I would describe Tsveta as a world-class, with no exaggeration, world-class expert in reimbursement and global access, and all the complexities that come with that, and quite a rare disease experienced leader, having led the U.S. organization at Alexion most recently. She joined us, and of course, I mentioned Sarah has been with Agios already for many years, has quite a track record with really delivering on these, the clinical progress that we're making. The takeaway is that we are stacked with the right rare disease experience for what we need right now at this really important period for Agios.
I think what you're starting to see is the fruits of that expertise and experience.
Great. Great. The team's in place. We've got some nice readouts coming up. Maybe before we get into how we should think about some of that catalyst flow, let's focus a bit about PYRUKYND in the market with PKD. I know Brian and Sarah, we talk about the consistency of the data. There's also an execution story here, not just about development, but actually delivering and treating patients on market. Maybe just since the approval and launch of PYRUKYND in PKD in February, as you mentioned, what are you observing as far as new Rx trends, many dynamics going into the commercial picture that are important to learn? How should we think about some of those dynamics and what you're learning there?
I think the first thing is big picture is that PKD adult patients is an ultra-rare condition. If we're picking launches that will help us build all the capabilities that we need to scale up from here, meaning getting ready for meaningfully larger, more prevalent launches to come, as I mentioned, thalassemia potential in 2025, sickle cell disease in 2026. You know, I'm pleased with the fact that we continue to make progress. We've just lapsed the first year, and we reported out in the first quarter, we have 89 patients on therapy. We've generated 127 prescription enrollment forms or PEFs, as we call them. Every one of those is a significant effort involved because this is the first-ever therapy for these patients.
We're the only ones who are educating on PKD, which is where most of our efforts are focused, is on awareness and activation of patients. We continue to make steady progress in that regard. One aspect that we're particularly encouraged by is that as we've transitioned from the clinical pivotal phase three programs with mitapivat or PYRUKYND, as it's known, to real-world experience, persistency has really played out in an encouraging way. All of the diseases that we're pursuing, Greg, are chronic rare diseases where it's not just the beginning of experience for the patient, it's feel and function. Do they want to continue?
That's where we've been encouraged with what we've seen recently with PKD, and that gives us a signal that as we transition with potential launches in thalassemia and sickle cell disease, that persistency, we think, is quite an important attribute.
Yes. Certainly, the adherence is key, and I know areas of focus, for us and investors can be just around the 6-month mark, around the discontinuations, which you're alluding to, any potential reauthorization. What are you observing there? It sounds like you're seeing that traction and continuity, but maybe just more specifically, how those are perhaps faring in accordance to your expectations.
So far so good. As we expected, I must say, again, the product performance, which is an immovable characteristic, right? We're really pleased that PYRUKYND is performing well in the real world at the patient level, and that's why the persistency that we're achieving is so important. With respect to the mechanics of payer reauthorizations, that's not been a headwind. We didn't expect it to be so. This is an ultra-rare disease, first ever available treatment option. Payers have been supportive. There are nuances where payers can require things like a reassessment of hemoglobin at the front end, genetic testing to confirm that the patient actually has PKD, but those have not been barriers. Our focus is really heavily front-loaded on identification efficiently of high-potential providers who are likely to have a patient with PKD.
As I mentioned, awareness, education, and eventually activation of the patient to transition onto a prescription enrollment form.
Okay. With the form to, say, the script to maybe even revenue flow through, what is that patient flow or even that timeline look like? Maybe how is that evolving with the levels of engagement that you set and the team are undergoing?
Generally, I mean, if we just pick, there's education upfront, and it's hard to define how much that requires, and for how long to get a patient to start on a prescription enrollment form. If we pick the PEF until start of therapy, generally that's four-six weeks. I wouldn't expect that to change markedly one way or the other. That can be gated by the need for a genetic confirmation on the part of the payers and the reimbursement dynamics. As I said, you know, we're making good progress. We're always going to work on how we can tweak that for efficiency on the patient's behalf, but generally that's the timeframe. Our focus is across the whole sequence in rare diseases of awareness, reimbursement dynamics, and activation, moving into adherence, and ultimately persistency.
Great. Well, maybe we can now pivot to thalassemia and certainly.
Darryl would be delighted.
Yes. Yes. Yeah. Yeah. Well, yeah, I mean, I think certainly there's so much to cover, but certainly with the, with the thalassemia program ...
Yeah
Net now enrolled, looking towards next year with readout. We, of course, have the sickle cell prior to this. Why don't we stay on thalassemia and just share a little bit about these two trials, the benchmarks, and just your confidence on achieving those levels of benefit in transfusion-dependent patients as well as non-transfusion-dependent patients?
Sure. As Brian mentioned, we're super excited that the trials have completed enrollment because that means we're on track for our next milestones in the program. The thalassemia program has two clinical trials, and that is meant to really encompass the entire spectrum of thalassemia. We have ENERGIZE and ENERGIZE-T. ENERGIZE is focused on non-regularly transfused patients, and ENERGIZE-T is focused on regularly transfused patients. The beauty about the program is that this is the first program that includes all genotypes. Instead of just focusing on beta thalassemia, we also include alpha thalassemia patients that also have hemolytic anemia and have, you know, severe comorbidities. And the trials have enrolled globally to be able to focus on both genotypes, but also on having that spread of transfusion burden.
The fact where we are now is obviously people are continuing in the trial, moving towards the last patient, last visit. That is our next big goal. What is important to understand is that if you're designing a program that is meant to encompass the whole spectrum of thalassemia, is that the trials reflect relatively that population and that spread. I think we can say that we have that right now, which is great. Now it's really focusing on the execution and on the regulatory strategy, you know, implementing further that, and we'll take it from there.
What is the composition of the alpha and beta thal patients in the trials?
Well, we have not disclosed the baseline characteristics, but it is generally reflective of the real-world population. It's really good to see that the execution of the trials without having to place caps or doing, you know, specific things that the population enrolled is reflective of the thalassemia population overall. I think that is important for multiple reasons. One, for the validity of the trial, but also it speaks to the unmet need. You know, the fact that we can enroll a non-regularly transfused patient population is important because similarly to PKD, you know, if you don't have transfusions, do you feel sick enough to actually want to participate in a trial? The answer is yes, because we were able to enroll that trial.
Also similarly to PKD, we're working very hard to highlight the burden of the disease in the non-regularly transfused population. We have abstracts at EHA, speaking specifically to that as well. Brian also already mentioned it earlier, like the lessons learned from PKD are very valuable across the board for thalassemia as well.
Mm-hmm. putting just the addressable market and the opportunity in context, just based on that landscape, how should we think about that?
Yeah, it's pretty interesting in thalassemia, and I would say even unique across the translation of rare diseases in the U.S. to other geographies. We describe it as geographically concentrated as an addressable market. Between the U.S. and EU5, think of it as 18,000-23,000 patients, and that breaks down to about 8,000 in the U.S., roughly 13,000 or so in EU5. The interesting component is that, and we address this on our earnings call, by the way, there's a really important slide, that if you look at the Middle East, the Gulf region, the prevalence is actually about eight to nine times greater, i.e., about 70,000 patients addressable market in that region alone. In fact, it's so much so that in that region, in Saudi Arabia, for example, it's not described as a rare disease.
The prevalence is so dramatically different because of the population and the family connections and so on genetically. For us, as a company, that geographic concentration is very appealing because we're looking at commercializing, as I mentioned, potentially in 2025 in the U.S. As we seek partners or a partner, what we'll be looking for is someone who has the expertise to be able to concentrate on that addressable market, specifically in the Gulf region and potentially in areas within Europe as well. That covers most of it. We think it's a tremendous opportunity for us. Of course, we have to wait for the data, but that is next in line as our potential launch, and we're thrilled about the opportunity.
Okay. Maybe this is just a good segue just on PYRUKYND in PKD and the commercialization strategy outside of the U.S. What is the latest there?
Yeah, it's sort of the same setup as. We're going to be guided a little bit on our progress in thalassemia. If we have the potential for PKD and thalassemia as a nearer-term opportunity, again, we're going to be looking for partners or a partner where we have a high bar. They'll have to match our values the way we believe commercialization should occur for patients with rare diseases. We would look for localized expertise, and ultimately it's about do we believe that that partner can create the value that we're looking for for any of our launches to come.
Great. Maybe we're saving the nearest term event for last here, but just on sickle cell, and I'm sure there's little you can say, but I'm going to try. When it comes to the timeline and the venue of disclosing the top line that's upcoming, what is the latest that you're sharing? Maybe even for Sarah Gheuens, just reminding us of the benchmarks that we and others are and you are setting for this readout and certainly building on that hemoglobin response dynamic that you talk about.
You want to start?
Sure. To the first part, we've guided to a data readout mid-year. We are on track to meet that. The way we would be disclosing this is in a press release, and we'll give enough detail for people to find comfort in the data. However, we also really do want to present data at medical meetings, so it's always a balancing act between those two. The trial itself, we're excited about the trial for, you know, multiple reasons. One, it's the first randomized control clinical trial in sickle cell disease, so it will give us really good insight in the data because it's treated versus placebo. It's a 12-week trial, so we're looking at hemoglobin response first and safety, consistent with like a phase two trial in, you know, in any clinical development plan.
There are secondary endpoints of which, you know, there's always interest in VOCs, so we are capturing that data, and people have an opportunity to roll over into an open label extension study. We'll continue to follow those patients. We, you know, we have our predefined criteria to determine go, no-go, both at a program level, but then also to call success within the specific trial. There is another component within the trial, which is a dose finding, because we're testing two doses against placebo. Our goal is to take one dose forward into phase three. The hemoglobin response story, we believe that is important because, you know, hemoglobin has been used as for an accelerated approval for voxelotor, for instance.
We really are trying to deliver with our program on a hemoglobin response, meaning that we are examining hemoglobin and VOCs as primary endpoints in the phase three. The strategy in the program allows us, if one or both endpoints are positive, to move on to secondary endpoint testing, which includes endpoints that are highlighting how patients feel and function. That is where the hemoglobin response story comes from, with the goal to shoot on this trifecta of data, but allowing us to speak to more than hemoglobin by itself. We believe that is a valid strategy. We have applied a strategy like that in thalassemia as well. Like, our non-regularly transfused patient population has an endpoint that speaks to hemoglobin response, you know, how patients feel.
We have applied that strategy in PKD as well, and believe that that is a really important thing to highlight to the patients, the physicians, the regulators, the payers, to tell the full story.
That's great. Very helpful. We could certainly go into more detail, but we are running out of time. Maybe what I can do is just Brian, just have you follow up on your mention of your balance sheet, the strength there, the discipline you're applying. How do you see putting that to work in addition to your trial execution and the building value with PYRUKYND in the market?
I mean, I'll use the word that I think everybody's used to hearing with companies like ours, which is we will be disciplined. I mentioned Cecilia has joined us as our CFO. She is really tough on our capital allocation and our OpEx deployment. We'll continue in that regard. From a business development standpoint, equally so, we have a filter that we look at. It has to be rare disease, which is our area of expertise and core capability, as I mentioned. We look for transformative potential. We look for value creation ultimately, and opportunities to de-risk early are sort of the highlights in that regard. As I mentioned, we're well capitalized.
We'll be very disciplined in that approach, and we are super excited about everything we just talked about with these devastating conditions and the potential for Agios to make a real impact.
That's great. Brian, Sarah, we'll leave it there.
Thanks a lot, Greg. Thanks, everyone.