Forma Therapeutics Holdings, Inc.

Welcome to the FORMA Therapeutics first quarter 2021 financial results and business update conference call. All participants are currently in a listen-only mode. Following management prepared remarks, we will hold a question and answer session. To ask a question at this time, please press the star followed by the one on your touchtone phone. If anyone has difficulty hearing the conference, please press star zero for operator's assistance. As a reminder, this call is being recorded today, May 14, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

Thank you, Operator. This is Mario Corso, Senior Director of Investor Relations at FORMA. Good morning to our listeners, and welcome to today's call to review first quarter 2021 financial results and business update. On this call, I'm joined by Frank Lee, our President and Chief Executive Officer, Pat Kelly, our Chief Medical Officer, Dave Cook, our Chief Scientific Officer, and Todd Shegog, our Chief Financial Officer. Before we begin, I'd like to caution listeners that comments made and financial information provided during this conference call include certain statements that are estimates, beliefs, forward-looking, and are subject to various risks and uncertainties. Any statements made during this call that are not statements of historical or current facts are intended to be forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We want to emphasize that such forward-looking statements reflect our current expectations and assumptions regarding timing, success, and data announcements of our current ongoing clinical trials, therapeutics potential, and clinical benefits, and safety thereof, planned regulatory submissions, our financial condition, our business operations, development efforts, and the potential impact of COVID-19 on our business and clinical development, and relationships with third parties and collaborators, and are neither predictions nor guarantees of future events or performance. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business. including those under the heading entitled Risk Factors in our annual report on Form 10-K for the year ended December 31, 2020, and our quarterly report on Form 10-Q for the quarter ended March 31, 2021, that will be filed with the SEC today, and in subsequent reports, including our current reports on Form 8-K. The company disclaims any obligation to update or revise any forward-looking statements except as required by applicable law. I will now turn the call over to Frank, our president and chief executive officer.

Thank you, Mario. Good morning, everyone, and thank you for joining us on today's call. I'm pleased to say we continue to make strong progress in the first quarter with our R&D pipeline, and I'll share some high-level thoughts with you before turning it over to Pat and Dave for more detailed remarks. I'd like to first acknowledge the time, effort, and contributions made by patients, investigators, healthcare workers, and our employees who are navigating the challenges posed by the COVID-19 pandemic and make it possible for us to pursue our purpose, and that is to transform the lives of patients living with rare hematologic disorders and cancers. I'm proud of our talented employees and how they live our guiding principles and values every day. in pursuit of our purpose, and I believe our patient-focused culture is a key strength which differentiates pharma. During the first quarter, we achieved important milestones for our two development programs, FT4202, our oral PKR activator being developed for sickle cell disease, and FT7051, our oral CBP P300 inhibitor for metastatic castrate-resistant prostate cancer. starting with FT4202, a potential foundational therapy with the potential to provide benefits in both hemoglobin and vaso-occlusive crisis in a once-daily pill. We disclosed that the Phase 2-3 hibiscus study began enrolling patients in the first quarter. In addition, we disclosed initial blinded results in the two-week from the second two-week cohort in our randomized multicenter placebo-controlled phase one trial, which successfully completed the MAD portion of the trial. The key takeaways were as follows. Number one, no dose-limiting toxicity or significant treatment-related adverse events have been identified. Number two, hematologic and or hemolytic responses indicated a consistent biologic effect and improvement in red blood cell health. And responses were typically best at the end of the 14-day treatment period, suggesting patients may benefit from longer duration of treatment beyond the 14 days. Importantly, completion of the MAD cohorts allowed us to continue moving forward with the next phase of this trial, the ongoing 400 milligram, 12-week open-label extension. And finally, results from the MAD cohorts together support the 200 milligram, and 400-milligram doses being evaluated in the ongoing Phase 2-3 trial to hibiscus study. The next steps of this program will be the presentation of the combined unblinded MAD cohorts, as well as initial open-label extension results to date at the European Hematology Association, or EHA, meeting taking place virtually June 9th through the 17th. Building on the ongoing sickle cell program and the thalassemia trial getting underway later this year, we see potential for FT4202 to benefit other patient populations with high medical needs, including hemolytic anemias and rare diseases. We're taking a review internally and expect to provide more specifics during the second half of the year. With respect to FT7051, our oral CBP-P300 inhibitor for metastatic castrate-resistant prostate cancer. We reported the first patient dosed in the ongoing phase one trial early in the first quarter and are pleased with the initial interest in the trial among both the centers and patients. We look forward to the initial results from this trial in the fourth quarter of this year, and in particular, the data for patients with ARV7 splice variants for which there are no currently available treatments. I'll now turn over the call to Pat to discuss FT4202 as well as elutisidinib in more detail. Pat?

Thank you, Frank, and good morning, everyone. I'm delighted to provide updates on two of our programs, FT4202 for treating patients with sickle cell disease and elutisidinib for treating patients with relapsed or refractory AML with an IDH1 mutation. As Frank mentioned, we are very pleased with the completion of the two-week MAD dosing cohorts for the FT4202 program, demonstrating that 4202 was well-tolerated with a favorable safety profile. We also saw a hemoglobin increase of one gram or greater at the end of the 14-day treatment period in 71% of the patients. And nearly all patients experienced benefit in other important therapy markers. These include the reticulocyte count, the LDH, and the bilirubin. indicating improvement in red blood cell health. Looking forward, we will disclose a complete analysis of the unblinded two-week MAD cohorts. And for the first time, we will be providing an analysis of the initial patients receiving FT4202 beyond the two weeks of dosing from the open-label 12-week extension cohort. These results will be presented at the EHA Annual Meeting taking place June 9th through the 17th. We expect to have additional data on RBC health, which, combined with the improved red cell functional studies, supports the potential for reduction in the rate of VOCs. Altogether, we are pleased with the emerging profile of FT40202, indicating potential benefits beyond hemoglobin improvement. We would also like to take this opportunity to reiterate that our ongoing Phase 2-3 trial, the Hibiscus study, is designed to be consistent with FDA guidance and reflects regulatory feedback. The Hibiscus study design includes two separate primary endpoints, hemoglobin change following 24 weeks of treatment in support of an accelerated regulatory approval, and a 52-week rate of VOCs in support of a full regulatory approval, if positive. Finally, with respect to FT4202, our planned trials in thalassemia and pediatric sickle cell disease are progressing well, with enrollment anticipated to begin in the second half of this year for thalassemia and the first half of 2022 in pediatric patients with sickle cell disease. Now turning to alutacidamib, our mutant IDH1 inhibitor, being evaluated in patients with relapsed or refractory acute myeloid leukemia, or AML. In October of last year, we announced that the interim analysis successfully met the primary endpoint of a durable complete response rate in this registrational phase two trial. We are pleased to announce that these data have been accepted for all presentations at both the annual ASCO and EHA meetings in June. In addition, our work continues on preparing a filing of a new drug application or an NDA to the US FDA. With that, I'm going to now turn the call over to Dave, who will provide an update on the FT7051 program for prostate cancer.

Thanks, Pat. I'm going to spend the next few minutes discussing our clinical stage CBP P300 inhibitor, FT7051. FT7051 targets the antigen receptor pathway by a novel mechanism, that has the potential to address many of the resistance mechanisms seen for standard of care AR signaling inhibitors. In tumor cell lines, FT7051 has been shown to decrease AR expression and also decrease AR-dependent gene expression. In addition, FT7051 has been observed to inhibit prostate cancer cell proliferation in vitro and in a patient-derived xenograft model in vivo. We believe the mechanism of action of FT7051 is applicable to a broad range of resistance mechanisms, including the ARV7 splice variant, which lacks the AR hormone binding domain and for which there are no approved treatments. Published data suggests that ARV7 may be detectable in approximately 20 to 40 percent of men after third-line treatment, and it correlates with substantially shorter overall survival. Activity in ARV7 expressing cancer could represent an accelerated path to market. In addition, we believe FD7051 has potential for use in earlier lines of prostate cancer therapy, as well as other AR-dependent tumors, such as triple negative breast cancer. Our Phase I trial began enrolling early in the first quarter of this year. This trial is planned to enroll up to 45 men with metastatic castrate-resistant prostate cancer who have failed one or more lines of standard of care. It utilizes an adaptive design, starting with a dose of 25 milligrams, with titration to as many as six higher doses on a three-week on, one-week off cycle, based upon predefined safety and tolerability criteria. Circulating tumor cells will be profiled, including ARV7 expression and genetic markers of resistance. And clinical assessments will include PSA levels, and radiographic measurements of tumor burden. We expect to have initial clinical results in the fourth quarter of this year in a subset of patients. These results may include safety, tolerability, PKPD, and preliminary biomarker data. More complete results from the trial are anticipated in 2022, including an assessment of tumor response rates and underlying genetic characteristics of responders. Given the high unmet need in this population of men and the novel mechanism of our molecule, we are enthusiastic regarding the promise of FT7051 and look forward to sharing data as they become available. I will now turn the call over to Todd, our Chief Financial Officer.

Thank you, Dave, and thank you, everyone, for joining us on today's call. I will first spend a few minutes discussing our financial results for the first quarter of 2021 and then discuss our cash position and outlook. Our net loss for the first quarter of 2021 was 36.0 million, which compares with the net income of 11.2 million for the quarter ending March 31, 2020. The year-over-year change in net loss was largely attributable to a one-time gain on the divestiture of our hit discovery capabilities and income tax benefits in the first quarter of 2020. Research and development expenses were $26.3 million in the quarter versus $23.2 million for the quarter ending March 31, 2020. This increased spending supports progress with our two compounds in development, including the Phase I and Phase II-III trials for FT-4202 in sickle cell disease and the start of the Phase I trial for FT-7051 in metastatic prostate cancer. General and administrative expense in the quarter was $9.9 million as compared to $8.9 million in the quarter ending March 31, 2020. This increase reflects the costs related to being a public company, including stock compensation expense, professional fees and insurance, and increased compensation expense. Our cash, cash equivalents, and marketable securities balance as of March 31, 2021 was $603.7 million compared to $645.6 million at year-end 2020. Cash use in the first quarter reflects the net loss as well as changes in working capital. Our current cash runway continues to extend through third quarter of 2024, which includes ongoing clinical trials as well as planned commencement of FT4202 development in thalassemia and the pediatric sickle cell population. Overall, we continue to be in a strong financial position and are well financed through important upcoming clinical milestones. Operator, we can now take questions.

Thank you. And as a reminder, to ask a question, simply press star 1 on your telephone. To withdraw your question, press the pound or hash key. One moment while we compile the Q&A roster. Our first question comes from Emma Nealon with Cantor Fitzgerald. Your question, please.

Hi, good morning. So for 4202, can you just speak to the trend toward increasing hemoglobin response that you saw over the 14-day treatment periods for the first two cohorts, and whether you expect to see potentially a better response over this longer treatment period in the open-label data at EHOF?

Hi, Emma. Thanks for the questions, frankly, here. Let me just... provide some high-level remarks, and turn it over to Pat for some additional thoughts. Certainly, the data we have now is primarily for the first two weeks of treatment, and we're certainly looking forward to the open-label extension data, which will provide a look at various cuts of patients. Some will have completed 12 weeks, and some will have completed anywhere from two to 12 weeks, and so we'll have a spectrum of patients. And certainly we're encouraged by what we saw in the early data from the two MAD studies. So let me turn it over to Pat for some additional thoughts there.

Great. Thanks, Frank. Yeah, I think you said it well. The key here is, as people are aware, from the 600 milligram or MAD2 cohort, patients participating in that group were allowed to roll over into the 12-week open-label. And as we previously disclosed, six out of the first nine patients enrolled in the MAD-2 did roll over into the 12 weeks. So we will be able to have, you know, a comparison, if you will, in that population based on their two-week experience in the MAD-2 versus their two-week or greater exposure experience in the 12-week cohort.

Great. That's helpful.

Thank you. Our next question comes from Andrew Behrens with SVB. Your question, please.

Hi. Good morning, guys. A couple from me, please. I was wondering if you could give us some color on the decision to go into the hemolytic anemias. Would these be acquired or inherited, chronic or acute treatment? And I guess how many do you think are addressable by 4202 and the PKR class? And then I do have a question on the prostate cancer program afterwards, if that's okay.

Sure. Thanks for the question, Andy. So we're looking through, you know, and going through our analysis, and we'll share more of that in the second half of the year. Certainly there are other PKR agnes, one in particular that is looking at PKD. Certainly that's one of the areas we'll look at, but we haven't made any decisions yet. And so at the current time, we're doing our analysis, so to speak, and we'll have more information to share in the second half of the year. But we certainly think there's more potential than just to be focused on sickle cell disease and thalassemia.

Okay, and more than potentially PKD also because that's a very broad area.

Yeah, it's potentially. So I don't want to make any comments at this point until we've completed our analysis, but certainly there's potential beyond the two initial indications that we talked about and PKD.

Okay, okay. And then on the prostate cancer program, will the upcoming data set that's presented include ARV7 patients only or all comers? And then just what's the pathophysiological rationale for targeting ARV7 with 7051?

Sure. Let me answer that and then turn it over to Dave for some additional comments. And so we'll share what data we have around about the fourth quarter of this year. It'll be the initial code of the data. And certainly right now we're enrolling all comers late line. patients, some of whom will be ARV7. We'll have those cut to the data, albeit the initial analysis. Let me turn it over to Dave for some additional comments.

Hi, Andy. I think as Frank said, we're really doing an all-comers study in Phase 1. We don't want to make assumptions about where the the drug may have efficacy or not. That being said, given what we know about ARV7, we expect to have a number of patients with the ARV7 phenotype. The rationale there is twofold. One, we know that these splice variants, what they do is they tend to delete the protein domains that include the ligand binding domain, so meaning the C-terminus is where you have truncation, and the N-terminus, where truncation where CBP and P300 interact is intact. So we think the mechanism of our drug, by disrupting that, should continue to be useful. The second really is empirical, is that we can show, for instance, that ARV7-expressing cell lines, which are resistant to enzalutamide, for instance, are sensitive to FT7051.

Okay. Thanks. Appreciate the color.

Our next question comes from Tiago Falls with Credit Suisse. Your question, please.

Thanks for taking the question. So just to follow up on RBC health data that we might see, we got some questions on the OsmoScan data. So just want to understand a little bit better what's the intra-interpatient variability for that specific measurement and how well established it is in sickle cell. It's not something that you see for every single program. So any color there would be helpful. Thanks. Thanks.

Thanks for the question, Tiago. Let me first ask Dave to give a little bit of color on the OSMA scan, and maybe perhaps Pat can talk a little bit further after that. So, Dave.

Sure. Well, first of all, that measurement has been around for 40 years or so. It was developed in the early 80s, and it's been well validated as to what it indicates, although it is a complex measurement. It's not typically used in clinical labs because commercial devices have only been available fairly recently. What it indicates are several things. It indicates critical hemolytic volume, which has to do with the surface-to-volume ratio of red cells. And it also indicates elements of membrane function. For instance, under high osmotic pressure, When ions are leaking in, water also tends to leak out. And the ability to restore ion gradients is a key element of having appropriate ATP levels. And so when we're able to show that we can handle these osmotic gradients, we think it demonstrates the health of the red cell and its ability to maintain hydrodynamic balance. Pat?

Yeah, I think the other piece of that is, yeah, these are complex assays that can be a bit challenging as each lab we've learned has different parameters. But what's important for what we've done is we've centralized the analysis. So all samples are sent to one lab, so there's a consistency in that analysis. And based on that work in the MAD cohorts, we've come to appreciate that, yes, between the patients there might be variability, just based on the phenotypes of the individual patient, but there's consistency within the patients themselves. So having a patient, and certainly our experience with patients who have enrolled in both the MAD and the open label, that we see a very consistent phenotype for the individual patient over a period of time where they're not receiving treatment. What we'll have as part of our complete analysis of the bad cohorts is all the information in those groups in total.

Great. Very helpful. Thank you.

Thank you. And as a reminder, if you have a question, simply press star 1 on your telephone. We have a question from the line of Mark Breidenbach with Oppenheimer. Your question, please.

Hey, good morning, guys, and congrats on getting enrollment started in Hibiscus. You know, we've seen a little bit of data suggesting there was a substantial dip in healthcare provider visits by sickle cell patients during the COVID pandemic. And I'm just wondering if your clinical sites are seeing traffic starting to normalize in terms of sickle cell patients coming back to the clinic. And I'm also wondering if you have any plans to open clinical sites in ex-U.S. territories, especially in Africa, to potentially help accelerate enrollment in hibiscus.

Thanks for the question, Mark. I guess let me talk about the impact of the pandemic broadly and then turn it over to Pat in terms of the steps we've been taking to navigate the pandemic. first I'll say that certainly the pandemic has had an impact on our efforts and so we've had to really double down and think about not only the traditional ways but the non-traditional and innovative ways to enroll patients and so based on that and the team's efforts we've been able to deliver the data that we've been talking about so far and so we'll see how this plays out as we move forward, but so far we've been able to navigate COVID and the pandemic. Pat, why don't you talk a little bit more about specifically what we're seeing at the sites?

Sure. Yeah, I think, you know, really the activities globally have been in parallel, not just U.S. focused, but also ex-U.S. in terms of getting countries up and running. But like what you can read in the papers, you know, the activity at various countries and centers has really been impacted based on how the severity of COVID is hitting or impacting those hospitals and countries. So, you know, what we're seeing really is more activity in the U.S., as you can imagine, as the vaccines have rolled out and, you know, Sites are starting to, you know, catch up in terms of clinical research. These are coming online, certainly. And that's, you know, for our benefit in the sense that we're already there. We already have the approvals and contracts. So, as COVID and the vaccine in the U.S. has kind of diminished and the vaccine has improved healthcare activity, This is starting to, you know, open up, so we're looking, or we're hopeful, I guess is how we would put it.

Okay, in terms of plans to open sites in Africa where there are high concentrations of sickle cell patients?

Yeah, we're looking, you know, we have a number of countries that we've been, we've approached and working on, and it's really dependent on availability and resources both from our our own internal activities our CRO as well as the countries themselves at this point but we're not we're not disclosing specific countries but we're looking everywhere right okay got it and one one follow-up on the prostate cancer program the data we're expecting in fourth quarter

Just to be clear, that will include some of the CTC profiling data, so ARV7 status and specific point mutations conferring resistance to AR targeting therapies, that sort of thing, or is that going to come later in 2022? Dave, go ahead and take that one.

Yeah, Mark, I don't think we've been specific yet, and part of that's going to depend on our strategy for ARV7. we're doing the analysis and how it gets batched. So I don't want to commit for the genotype data at the end of the year, but obviously that's really important to interpret the results globally. So we're going to be working hard at that, but I don't think we're yet have a specific commitment around whether that data will be available by the end of the year.

Got it. Okay. Thanks for the clarification and congrats on the progress.

Thank you. And this concludes our Q&A session. I would like to turn the call back to Frank Lee for his final remarks.

Well, thank you, everybody. We just want to thank everyone for taking the time to participate in today's call. The first quarter brought some important progress in our R&D pipeline that's focused on rare hematologic disorders and cancers. And we're executing our strategy to bring these new medicines to patients and look forward to sharing more progress during the course of the year. So have a great day, everybody. Thank you.

Thank you. And this concludes today's conference. Thank you for your participation, and you may now disconnect. Goodbye.