Agios Pharmaceuticals, Inc. Q1 FY2021 Earnings Call

Good morning, and welcome to Agios' First Quarter 2021 Conference Call. At this time all participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Holly Manning, Senior Director of Investor Relations.

Thank you, operator. Good morning, everyone, and welcome to Agios' First Quarter 2021 Conference Call. You can access slides for today's call by going to the Investors section of our website, agios.com. With me on the call today with prepared remarks are Dr. Jackie Fouse, our Chief Executive Officer; Dr. Chris Bowden, our Chief Medical Officer; Daren Miles, our Chief Commercial Officer; and Jonathan Biller, our Chief Financial Officer and Head of Legal and Corporate Affairs. Dr. Bruce Carr, our Chief Scientific Officer, will join for Q&A. Before we get started, I would like to remind everyone that some of the statements we make on this call will include Forward-Looking Statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. With that, I will turn the call over to Jackie.

Thank you, Holly. Good morning, everyone, and thanks for joining our first quarter 2021 results call. The first three months of this year were extremely productive. We closed the sale of our Oncology business, accelerated our late-stage clinical programs for mitapivat and prepared for our first regulatory filings and subsequent commercial launch in pyruvate kinase deficiency. Back in December, we announced our strategy to focus on genetically defined diseases, including accelerating and unlocking the full potential of mitapivat across its three initial indications in hemolytic anemias as well as leveraging our overall expertise in PK activation and our other research programs. To enable this focus, we also announced the decision to sell our oncology programs to Servier to facilitate and fund this strategy. Since that time, nearly a third of our organization has been actively involved in the important and complex process of ensuring a smooth transition of our assets and people to Servier. The transaction was approved by Agios shareholders on March 25, and on April 1st, we announced the closing of the sale. To each and every oncology employee who helped create truly meaningful differentiated therapies for patients over the past decade, we are grateful for your impassioned work at Agios, and we look forward to watching these programs develop with Servier. As we look ahead, Agios is poised for a bright and focused future that will build on the important progress we are making now in Q2. This includes finalizing our global regulatory filings for mitapivat and pyruvate kinase deficiency; preparing to initiate two Phase III trials of mitapivat in thalassemia and a Phase II/III trial of mitapivat in sickle cell disease.

Thanks, Jackie. I will start with our most advanced genetically defined disease program, mitapivat, our first-in-class PKR activator currently being evaluated across three distinct chronic hemolytic anemias: pyruvate kinase deficiency, thalassemia, and sickle cell disease. In pyruvate kinase deficiency, we reported top line data from the ACTIVATE and ACTIVATE-T Phase III studies, evaluating mitapivat in adults with pyruvate kinase deficiency who are not regularly transfused and those who were regularly transfused, respectively.

Thank you, Chris. Today, I will first briefly review consumer performance for Q1, which is the last period for which Agios is accountable for sales of the product. I will then summarize our progress on cross-functional launch preparedness in anticipation of the potential approval of mitapivat in 2022. TIBSOVO net sales in Q1 reached $37 million, largely driven by market increases in utilization across newly diagnosed and relapsed/refractory AML, partially offset by higher expenses related to Q1 Part D coverage gap seasonality and increased volume moving through the 40B institutions. Turning to mitapivat launch readiness. The team made progress on a number of fronts, including PK deficiency education, physician and patient profiling, and the ongoing field in build. In November, we announced the launch of the Anemia ID program, a partnership with PerkinElmer to offer free genetic testing to help patients and physicians reach a definitive diagnosis for patients with suspected hereditary anemia. The program has been well received and is increasingly utilized to help patients with their diagnosis by simplifying the testing requirements associated with reaching a definitive diagnosis of a patient's hemolytic anemia. The program also provides Agios with the identified patient-level information, which adds meaningfully to our understanding of the PK deficiency patient profile. Our experience with this program highlights the magnitude of unmet need in the community and the deepening sense of urgency to improve the diagnosis of patients with hemolytic anemias, like PK deficiency. As Jackie mentioned, in March, 23 & Me added a new PK deficiency carrier status report to their library of genetic insights and tools. Members who are either carriers or homozygous for the R486W variant in the PKLR gene, the most common Southern European PKR variant, are invited to receive the customized report with more information regarding their risk of developing PK deficiency and additional resources. The report included a summary of signs and symptoms of PK deficiency and other relevant clinical and genetic information. We expect that a number of patients who are carriers will seek genetic counseling for more robust testing, potentially through Anemia ID and other mechanisms resulting in a definitive diagnosis. We have also made good progress in expanding our ability to provide important information about PK deficiency to patients with questions. We intend to launch a robust PK deficiency patient education program by the end of the quarter, administered through existing Agios infrastructure, MyAgios Patient Support.

Thanks, Darrin. Our first quarter 2021 financial results can be found in the press release we issued this morning, which I will summarize. More detail will be included in our 10-Q filing later today. As Jackie mentioned, the sale of the Oncology business to Servier closed on March 31st, and as a result, the first quarter results related to our oncology business can be found in the discontinued operations note to our financial statements. I will first address our continuing operations for the business. Research and development for the first quarter was $57.7 million, an increase of $2.3 million compared to the first quarter of 2020. The modest year-over-year increase in R&D was driven primarily by start-up costs associated with the Phase III studies of mitapivat in thalassemia and sickle cell disease. Selling, general and administrative expenses for continuing operations were $33.1 million for the first quarter, representing a $1.5 million increase over the first quarter of 2020. The increase in SG&A expense was primarily due to certain one-time workforce expenses. For our discontinued operations, total revenue for the first quarter was $41.4 million, which included $37 million of net sales of TIBSOVO. Also included in discontinued operations is $50.2 million of operating expenses that were primarily attributable to professional fees and workforce expenses directly related to the Servier transaction. We ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion. We expect that this cash balance, together with anticipated interest income, future product sales of mitapivat, and royalties on TIBSOVO will fund our current operating plan through major catalysts and to cash flow positivity without the need to raise additional equity. As previously disclosed, our Board of Directors authorized the repurchase of up to $1.2 billion of our outstanding shares using the proceeds from the sale of the Oncology business. Earlier this month, we closed the repurchase of approximately 7.1 million shares of Agios’ common stock held by BMS and its affiliates for an aggregate purchase price of $344.5 million or $48.38 per share. In addition, we have put in place a 10b5-1 plan designed to efficiently repurchase a meaningful portion of the remaining shares by year-end. As is customary, we will report on repurchases made pursuant to these plans and any open market or privately negotiated repurchases in our future quarterly earnings reports. With that, operator, please open the line for questions.

Thank you. Our first question comes from Alethia Young with Cantor.

Congrats on all the progress. I just wanted to talk a little bit about maybe potential pipeline or indication expansion for both mitapivat and potentially 946, just kind of how you are thinking about some of the potential new indications that you might be moving forward with based on what you know about the biology here. Thanks.

Alethia, it is Chris Bowden here. We think about pyruvate kinase in two ways at this point. There is a PKR part of it, and I spoke in my remarks, and you are familiar with the advanced stage programs, where we are going after registration in pyruvate kinase deficiency, thalassemia, and sickle cell disease. There are a couple of other indications we are also considering where we can approach pyruvate kinase from activating wild type. This includes hereditary spherocytosis. We have some interest in myelodysplastic syndrome. The anemia of myelodysplastic syndrome can potentially be addressed through the activation of wild-type PKR, again, addressing and improving red cell health. We have been talking about the potential for activating PKM2 as well, which opens up a number of doors and other indications. Why don't I stop at that point and let Bruce Carr, who is on the call with us today, talk a little bit about PKM2? We look forward to the second half of the year and sharing more at Research Day. But Bruce, why don't you provide a little more color, please.

Yes. Thanks very much, Chris. So just by analogy, PKR is deficient in PK deficiency in red cells and is relatively deficient in many different hemolytic anemias. When one looks at the tissues that express PKM2, its generation of ATP and function is abnormal in many disease states as well. Since early last year, we have been studying tissue distribution and the involvement of PKM2 in a variety of different disease processes. Based on that work, we have identified several likely indications for PKM2. They are quite broad, depending on where it is expressed. It is expressed in the brain, in the retina, in regenerating muscle, and many other tissues in the gut wall. We have been conducting appropriate nonclinical models to evaluate the potential for these disease indications, and we are actually starting to get some very promising data in recent months, suggesting indications that we could possibly pursue, many of which would, of course, require partnering well outside of our hematology expertise. We hope to talk about these indications perhaps sometime later in the third quarter at an R&D Day. The work is going very well at the moment, and some of these indications are yielding spectacular nonclinical results to the extent we understand they are translatable. We are not sure yet, but there is a lot of promise for any additional indication for PKM2.

That is helpful. Thank you very much.

Thank you. Our next question comes from Mohit Bansal with Citigroup.

Thanks for taking my questions, congrats on the project. A couple of questions from my side. One is regarding the pricing, I may sound like a record because I have asked it in the past as well. But given you would be launching in an ultra-rare indication like PKD, how are you thinking about pricing right now because a rarer indication like sickle cell is still about four years away, four years after the PKD indication. And I will pause here.

This is Darrin. No record at all. Happy to address any questions on pricing. Now I won't tell you the pricing that we are considering, but I can give you some indications of how we are thinking about it. As you know, it is an ultra-orphan indication. We are going to price in a way that reflects the clinical value, particularly now that we have seen both of the Phase III studies, but we are pricing in a way that reflects the clinical value for this patient population. As we have shared in the past, our takeaway from engagements with the payer community is that we believe that pricing should also extend to thalassemia. Going to sickle cell, we have a different payer mix, a different mix of the patient population, and associated payer mix change as well. There is the potential that we would adjust price for the sickle cell market. But right now, we think the price that we launch with for PKD will carry over well into the future, and then we will revisit as we go into sickle cell.

Just to add one thing, Mohit, it is Jackie. As Darrin alluded to, I think we will also price for sickle cell based on the totality of the clinical data from the pivotal program for sickle cell. We will need to see what that yields in terms of both of the endpoints that we have built into that program.

Very helpful and one more question I may, probably for Jackie again. Given your strong balance sheet and even in the buyback plan, it leaves a lot of cash on hand. So when you look at your pipeline and cash at hand, do you think you could look at external opportunities as well, or do you think you have enough on your plate right now with the preclinical and clinical programs?

I think one of the things that is most exciting about where we are as we start the next chapter in our Agios life, is the number of things that we have in the pipeline and some of the opportunities that Bruce alluded to, where I think that we are going to start to see support for those and where we might be able to move with them, including also the indications that Chris highlighted for potentially mitapivat and 946, where you could move quite quickly into the clinic. We have a ton of things that we wholly own; we know the chemical matter very well and the biology. Those are our top priorities for the moment. That being said, we do keep our eyes on other things that are out there, and we don't want to miss anything that might be complementary or relevant for us. We always do that and we will continue to do that. So it is not out of the realm of possibility that we might do something on the early side because that has kind of been our sweet spot. But we have a ton of things that we think are very promising going on right now that are really what we have got the team focused on. Thanks.

Got it, thank you, Jacqualyn, I really appreciate it.

Thank you. Our next question comes from Peter Lawson with Barclays.

Hey, thanks for taking the questions. Just a question for Jonathan, just on the share repurchase and how quickly you think about doing that, and if you have got a goal in mind by year-end sort of share count and when that repurchase starts.

Sure. Thanks for the question. So as we have talked about, we made a nice start with our share repurchase program, successfully negotiating the repurchase of the 10% stake that Bristol owned. We think we got that at an attractive price. Around that same time, we put in place our own plans to be repurchasing in the market through 10b5-1 plans. I think we have disclosed that the current plan would buy up to $600 million, and the timing of that depends on stock price movements and other factors. We expect that by the end of the year, we would have, in combination with the Bristol stake, exceeded half or more of the repurchases that we intend to make. The exact amount is hard to predict because it does depend to some extent on the volatility that we will see in our stock price and macro volatility as well.

Great. And then just a quick question for Jackie or Chris maybe around. The work with 23 & Me on PK deficiency carrier status. Do you think that was going to help and has that led to any better understanding around both the incidence and prevalence of PKD?

Yes. I think Darrin is the best place to answer that. Do you want to jump in, Darrin?

Yes, sure. Happy to. I think it adds meaningfully to our understanding of the overall patient profile. It is important to note that the 23andMe chip looks at one variant. It is an important variant, what is most commonly referred to in the literature. But if you recall, we got upwards of 300 mutations or so for PKD. While important and it is giving us some very meaningful insights based on the population that has taken the 23andMe tests, certainly, it would not be sufficient. We are looking at multiple sources to be able to help us to better understand the true prevalence of the disease. But what we have seen thus far is very encouraging, at least in the 23andMe data set. The fact that those patients who are carriers or homozygous for the 486 mutation or variant are getting direct information to help them understand what they should do based on that, and we have created additional mechanisms or channels around those patients to help them pursue additional genetic testing potentially through Anemia ID. Eventually, once we launch the MyAgios PK or part of the kinase deficiency patient support program by the end of the quarter, potentially, those patients will then opt into our patient support program, which will allow them to get timely information about their disease and then after approval, access to medication.

Okay, thank you. Thank you so much for taking the questions.

Thank you. Our next question comes from Anupam Rama with J.P. Morgan. Your line is open.

Good morning, guys. This is Tessa on the call for Anupam. Thank you for taking our question. Just one from us. Can you remind us if there are any additional key analyses at EHA in June that we should be looking at specifically around the thalassemia or PKD programs? Thank you so much.

Yes. Hi, it is Chris Bowden here. I think that for pyruvate kinase deficiency, this is the first time the results from the pivotal studies, ACTIVATE and ACTIVATE-T, will be presented. The key analyses involve multiple components. There are, of course, the primary endpoints, the safety. One really important component of ACTIVATE is that it is a randomized trial. It will be the first time we will see the results - the safety results of mitapivat against a placebo-controlled trial where both patients and clinicians are blinded. This will give a much better and, I would say, balanced view of what the safety profile looks like over a substantial dosing period. Patient-reported outcomes in a placebo-controlled trial are also very important. There will be multiple components that will be critical. For thalassemia, we will build on the previous data that we showed on the durability of hemoglobin responses, which will be very important because this is another program that we are taking forward into Phase III. Mitapivat is a drug that continues to demonstrate a good safety profile and can be used for long periods, compatible with chronic dosing, so the durability of responses is vital. I think those are the key components. There will also be additional data on long-term safety with mitapivat and descriptions of the disease burden of pyruvate kinase deficiency. There will be many analyses and the overall picture will be extensive that we will present on mitapivat across those two diseases.

Okay, great. Thanks so much for taking the questions.

Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. Your line is open.

Just on the upcoming readouts from your academic collaborators working in sickle cell disease. I'm wondering if the NIH readout will include results from the extension study or if it will focus on the core study period? And also, what can we reasonably expect in terms of the number of efficacy evaluable patients from the Utrecht study? Could you also remind us of the main differences between the Utrecht and NIH trials in terms of study design? Thanks for taking the question.

I will take the back part first. The NIH study involves an eight-week dosing period with an eight-week continuous dosing period, including dose escalation starting at five milligrams to 20 to 50 to 100, followed by tapering, where patients are eligible to go into an extension study. The Utrecht study is enrolling up to 10 patients, starting at 20 milligrams, increasing to 50, and then 100, remaining on chronic dosing. Those are the major differences. In terms of what will be presented by the NIH, it depends on how many patients come into the extension and how much follow-up there is at the time they perform their data cut for submission. Remember, this is an investigator-sponsored study; they hold the IND and are the primary decision-maker on those issues. We collaborate with them, and things are going very well. However, they haven't finalized that level of detail yet. As for overall evaluable patients from the Utrecht study, their protocol dictates looking for at least up to 10.

Okay, got it. And very quickly on thalassemia, could you tell us the planned distribution between European versus U.S. clinical sites in the ENERGIZE trials and to what extent COVID is creating an obstacle for opening clinical sites, especially in Europe right now?

We will provide a site list, and we will disclose that during the trials in progress session. That information is forthcoming. We are not currently facing issues with activating the trial and getting it running related to the pandemic. However, we closely monitor that situation because it can change rapidly. But as of now, there are no problems.

Alright, sounds good. Thanks for taking the questions.

Our next question comes from Michael Schmidt with Guggenheim Securities.

It is Kelsey on for Michael. We had a couple on mitapivat in PKD. Now that we are almost a year out from launch, how are you thinking about the speed of uptake and how might the education efforts accelerate this? Have you received any initial feedback from physicians on the data so far, especially what has been presented in the top line press releases?

Got you. Darrin here. We are about a year out from approval, and we have been expanding the team to get ahead on patient profiling and physician profiling efforts. This will ultimately help with uptake post-approval. We have hired the full sales team, expecting them to be trained and in the field by the end of the quarter. We have also added clinical educators to engage practices and help with understanding and awareness of the disease. These expanded patient finding efforts will help ensure that we clearly understand the overall market, including potential diagnosed patients, by the time we reach approval.Regarding uptake post-approval, the identified patients and physicians will be at the top of the list for promotional efforts by the team. The key regulators on uptake will be physician inclination to prescribe and payer management. It may take a few months for policies to be written, which is not unusual and is customary in all approvals. As for early physician responses to the data set, we have been working with anonymized data to gauge physician and payer reactions to the overall profile, which has been encouraging for us. Our findings are consistent with what we have previously heard, and the overall profile of the patient population, as well as the quality of life data, has been even more encouraging in many respects. Overall, leading up to the approval, we feel we are in good shape to raise awareness and enthusiasm for prescribing mitapivat.

Great, that is super helpful. Thank you so much.

Thank you. Our next question comes from Salveen Richter with Goldman Sachs.

This is Elizabeth on for Salveen. Regarding the Anemia ID program, just wondering how many indications that might open up for you? Are you thinking of pursuing similar programs to the 23andMe initiative for other rare indications and potentially expanding for other variants of PKD?

This is Darrin here. I will address this first. For Anemia ID, as well as 23andMe, both focus on improving our understanding of PKD specifically. In Anemia ID, the panel used can help a physician identify any number of hemolytic anemias; however, we focus specifically on data associated with pyruvate kinase deficiency. We have not yet discussed how these programs may be helpful as we look ahead to the expanded indications for mitapivat. Given our success with PKD, however, these are likely viable options for us for additional indications.

Thank you.

Thank you. Our next question comes from Marc Frahm with Cowen & Company.

Hi, this is Mark. I have a follow-up question regarding your earlier comments about the thalassemia data presented at EHA. Would the data set be large enough to capture the impact of the improved hemoglobin level? Also, regarding the ENERGIZE trials, how long do you expect enrollment to take? Should we expect both trials to have similar timelines, or is one likely to take less time to complete besides the fact that they have different enrollment goals?

Yes, it is Chris here. Thank you for your question. Our initial presentation of the data presented at EHA last year illustrated what we define as proof of clinical concept, where we saw the majority of patients having a greater than one gram per deciliter increase. One important finding in this presentation is now, a year later, with 20 patients accrued and longer-term follow-up, the durability of those responses and the safety will be an important part of that presentation. As for timelines, it is too early to guide on the accrual of one trial versus the other. Our immediate goal is to initiate both studies in the second half of this year, and we are on track to do so, with anticipated approvals in the 2025 timeframe. More details will be provided as we progress. We are now entering the next stage of operations, dealing with IRBs, sites, and so forth. It is too early to guide on the timing of one trial over the other. We set our timelines based on detailed feasibility and track things along the way. If we see important movements in either direction, we are responsible for communicating that once we are confident. We are encouraged by how we are tracking towards starting the study and our anticipated approval guidance of 2025.

Okay, thank you for taking the call.

Thank you. I'm currently showing no further questions at this time. I would like to turn the call back over to Jackie Fouse for closing remarks.

Thank you, operator. I'm very excited about the progress we have made so far this year, including the transition of our Oncology business to Servier. We look forward to making a meaningful difference in the lives of patients with diseases that lie within our focus areas as we move into our future as a transformed Agios, starting with PK deficiency. To close, I would like to thank my Agios colleagues for their dedication and passion for making a difference for patients. I also want to thank all of the patients, caregivers, and physicians who participate in our clinical trials. Without them, we could not do what we do. Thank you all for joining us today. Take care.

This concludes today's conference call. Thank you for participating. You may now disconnect.