Forma Therapeutics Holdings, Inc.

Welcome to the Formal Therapeutics Second Quarter 2021 Financial Results and Business Update Conference Call. All participants are currently in listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press the star key followed by 1 on your touchtone phone. If anyone has difficulty hearing the conference, please press star 0 for operator assistance. As a reminder, this call is being recorded today, August 13th, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

Thank you, Gigi. This is Mario Corso, Senior Director of Investor Relations at Forma. Good morning to our listeners and welcome to today's call to review second quarter 2021 financial results and business update. On this call, I'm joined by Frank Lee, our President and Chief Executive Officer. Patrick Kelly, our Chief Medical Officer, Dave Cook, our Chief Scientific Officer, and Todd Shigog, our Chief Financial Officer. Before we begin, I'd like to caution listeners that comments made and financial information provided during the conference call include certain statements that are estimates, beliefs, forward-looking, and or subject to various risks and uncertainties. Any statements made during this call that are not statements of historical or Recurrent 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 and ongoing clinical trials, therapeutic potential and clinical benefit and safety of our product candidates, planned regulatory submissions, our financial condition and our business operations, development efforts, 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 quarterly report on Form 10-Q for the quarter ended June 30, 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 those required by applicable law. I will now turn the call over to Frank. our President and Chief Executive Officer.

Thank you, Mario. And good morning, everyone, and thank you for joining us on today's call. The second quarter marked FORMA's one-year anniversary as a public company, and I'm extremely proud of all that we've accomplished while at the same time recognizing that we have much work left to do on our mission to improve the lives of patients living with rare hematologic diseases and cancers. Before turning the call over to Pat and Dave for more detailed review of our pipeline, I'd like to provide some high-level thoughts on our second-quarter achievements. First, our lead development program, the once-daily PKR activator, now called ETAPA-PVAP, formerly FT4202. We believe that the new Phase I results in sickle cell disease presented at the EHI meeting in June provide growing evidence that etabopevat has a highly differentiated profile and the multimodal mechanism of action may be able to modify the course of this complex and multifactorial disease. More specifically, initial etabopevat results show sustained hemoglobin increase in nearly all patients and improvement in red blood cell health and lifespan as measured by metabolic and systemic markers. Altogether, These data support the potential of Atabipivac to improve important clinical outcomes, such as vaso-occlusive crisis or VOCs. And our goal is to have Atabipivac approved as a first sickle cell treatment that can improve both hemoglobin and VOCs. As we advance our ongoing pivotal Phase II-III sickle cell trial, the Hibiscus Study, we We're also partnering closely with the sickle cell community to improve patient access and care. And I'm very proud to say that we've assembled a talented group of people who are all in to make a difference in the lives of patients living with sickle cell disease. Looking forward, we plan to start the phase two thalassemia trial later this year and a sickle cell pediatric trial in the first half of next year. Furthermore, we're evaluating a tab of PVAP for study in other populations where improving red blood cell health and lifespan could benefit patients. Turning to our prostate cancer program, we began enrolling at phase one trial earlier this year of the oral CBP P300 inhibitor, FT7051, in men with metastatic castration-resistant prostate cancer. This is a population of men whose cancer has either progressed while on current standard of care antiandrogen treatment and or for whom chemotherapy has not been successful. So the unmet need is significant. CBP-P300 is a novel pathway, and we're very interested in the potential to address a broad range of AR-driven cancers, and in particular, patients with ARV7 splice variant, for which there are no approved therapies. Dave will shortly provide an update on our FT7051 development program. With respect to our third development compound, the IDH1 inhibitor, olivacidinib, or relapsed refractory AML, the registrational results presented at EHA and ASCO show that we believe it's a very competitive profile in terms of response rate, duration of response, and survivability. And based on these results, we're preparing a new drug application for regulatory submission. In addition, I'm very pleased to welcome John Bishop, our new chief technology officer to the executive team. John will lead chemistry, manufacturing, control, CMC-related functions, and quality, encompassing FORMA's early pipeline through commercial. John's background includes extensive experience in CMC development, in oncology and hematology, and we're very excited to have them on board. Before turning the call over to Pat for a more in-depth review of Atavapivac and Alucidinib, I'd like to once again this quarter recognize the contributions made by patients, investigators, healthcare workers, and our employees as they navigate the challenges posed by the COVID-19 pandemic. and help us pursue our purpose to transform the lives of patients living with rare hematologic diseases and cancers. I'll now turn over the call to Pat.

Thank you, Frank, and good morning, everyone. I'm delighted to provide an update on our Etavo PVET development program and outline the eluticidinib results that were recently presented at scientific conferences. Etavo PVET is a once-daily, highly-selective PKR activator with a distinct multimodal mechanism of action. This multimodal mechanism is important in that decreased 2,3-DPG improves oxygen binding to hemoglobin S, which decreases polymerization, thereby reducing the sickling and the hemolysis of sickle RBCs caused by the rigid structures formed by deoxygenated hemoglobin S. The increase in ATP allows the cells to repair damage to the membrane that is incurred through multiple cycles of cell sickling. Together, the effects of decreased 2,3-DPG and increased ATP improves the sickle RBC membrane function, which can lead to improved cellular hydration, membrane repair, and ultimately deformability. From the beginning of our Etabo-PVAC clinical development, our goal has been to generate clinical data that would support an improvement in both the anemia and the vaso-occlusive events that characterize sickle cell disease. We've also sought to elucidate the effects of Etavo PVET on the sickle RBC as measured by numerous markers of red blood cell health. We designed a rigorous and comprehensive Phase I program, and we are very pleased with the updated data that was presented during the EHA meeting in June. We believe Etavo PVET has the potential to reduce the hemolysis and the anemia of sickle cell disease, by improving RBC health and lifespan. These direct effects on the sickle RBC may then reduce the inflammation and hypercoagulability risk that's associated with sickle cell disease, and ultimately through chronic daily dosing of atavopetate may significantly reduce the debilitating vaso-occlusive events that characterize sickle cell disease. In terms of our phase one results thus far, The following key data were observed from the multiple ascending dose cohorts that administered Etabo PVAT for two weeks and the initial open-label extension results administrating Etabo PVAT for up to 12 weeks. Sustained increases in hemoglobin levels were observed. 73% or 11 out of 15 patients treated for two weeks achieved an increase in hemoglobin of one gram per deciliter or greater. And data from the open label extension show that 88% of patients, or seven out of eight, experienced a greater than one gram per deciliter increase that was sustained for up to 12 weeks. We also observed improvements in RBC oxygenation and deformability. Red blood cells from sickle cell patients treated with the TAVO-PVET for two weeks had increased oxygen affinity with a significant shift in the point of sickling and improved deformability when compared to the predosing level functions. We also saw significant reduction in hemolysis, with markers approaching normal levels in some patients. With just two weeks of dosing, 100% of patients showed a reduction in their reticulocyte counts, with some patients normalizing by the end of treatment. The majority of patients also demonstrated a marked decrease in LDH and indirect bilirubin levels as compared to their baseline levels. Reduction in systemic biomarkers related to inflammation and hypercoagulability. The initial results from patients receiving up to 12 weeks of the TAVOP, that treatment, indicated that in addition to the improvements in the metabolic markers of red blood cell health, there were improvements in systemic markers of inflammation and coagulation, and these can be observed with chronic daily dosing of Atavo P-Vet. Finally, Atavo P-Vet was well-tolerated even at doses up to 600 milligrams daily, which is 150% of the maximum dose currently being evaluated in the Hibiscus study. and that with this dose and schedule, it had a safety profile that was consistent with underlying sickle cell disease. I have summarized for you today the key results presented during EHA, and more detailed information can be found in the poster available on our website. Later this year, we expect to present at a scientific conference updated results from the open-label extension trials. in which up to 20 patients will be dosed with 400 milligrams of Atavo PVET daily for 12 weeks. With respect to our planned trials, we are on track to begin enrollment prior to the end of this year for thalassemia and the first half of 2022 in pediatric patients with sickle cell disease. Now turning to elutacitinib, our mutant IDH1 inhibitor being evaluated in patients with relapsed or refractory acute myeloid leukemia, or AML. In the fourth quarter of last year, we announced that the interim analysis successfully met the primary endpoint of a durable complete response rate in our Registrational Phase II trial. These data were presented at both the annual ASCO and EHA meetings in June. The primary efficacy of valuable population was comprised of 123 relapsed or refractory AML patients who received 150 milligrams of Alutacideinib twice a day for at least six months prior to the interim analysis last year. The key data points were as follows. The primary endpoint was achieved with a complete remission or a complete remission with partial hematologic recovery at a rate of 33.3%, with the majority of patients having a complete response. The duration of CR or CRH for people on treatment was greater than 13.8 months. The median overall survival was 10.5 months for all treated. The median overall survival for the non-CR or CRH responders was 15 months. And the median overall survival has not been reached for those patients with a CR or a CRH with an 18-month survival estimate of 87%. Also among patients with a complete remission who were transfusion-dependent at baseline, the 56-day transfusion independence was achieved in 100% of patients who required platelet transfusions at study entry and 80% of patients who required red blood cell transfusions at study entry. Moreover, alutacidin was well-tolerated with adverse events consistent with late-stage disease and the heavily pretreated populations. At present, our work continues preparing an elutisidinib new drug application, or NDA, for regulatory filing. With that, I'm going to now turn the call over to Dave, who will provide an update on the FT7051 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 androgen receptor pathway by a novel mechanism that we believe 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 expression of AR and also decrease the expression of AR dependent genes. Additionally, FT7051 has been observed to inhibit prostate cancer cell proliferation in vitro and in a patient-derived xenograft mouse model in vivo. We believe the mechanism of action of FT7051 is applicable to a broad range of resistance mechanisms, including the ARB7 splice variant, which lacks the AR hormone binding domain and for which there are no approved treatments. Published data suggests that ARB7 may be detectable in approximately 20% to 40% of men after third-line treatment, and its presence correlates with substantially shorter overall survival. Activity in ARB7 expressing cancer cells could represent an accelerated path to market. Additionally, we believe FT7051 has potential for use in earlier lines of prostate cancer therapy, as well as other AR-dependent tumors, such as triple-negative breast cancer. We began enrolling a Phase I trial of FT7051 in the first quarter of this year in up to 45 men with metastatic castrate-resistant prostate cancer. These men had failed at least one line of therapy and are typically heavily pretreated, receiving one or both of abiraterone and enzalutamide, and in many instances, also chemotherapy prior to experiencing disease progression. The trial utilizes an open-label, adapted design starting with a dose of 25 mg 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 are profiled, including ARV7 expression and genetic markers of resistance. Clinical assessment will include PSA levels and radiographic measurements of tumor burden. This trial is presently in the dose titration phase, and we are pleased to announce today that an abstract has been accepted for presentation at the AACR NCI EORTC virtual international conference on molecular targets in cancer therapeutics, taking place October 7th to 10th. Results will be presented at the conference that will include data from a small number of patients encompassing primarily PK, PD, and tolerability and safety information, although some may remain on therapy for a duration sufficient to assess preliminary clinical response. More comprehensive results from the trial are anticipated in 2022, including tumor response rates and underlying genetic characteristics of responders. We look forward to results from this study to clarify our next steps in development, given the high unmet need in this population of men, as well as the compound's novel mechanism of action and positive preclinical data. I will now turn the call over to our Chief Financial Officer, Todd.

Thank you, Dave, and thank you, everyone, for joining us on today's call. I will now spend a few minutes discussing our financial results for the second quarter of 2021 and then discuss our cash position and outlook. Our net loss for the quarter ended June 30, 2021, was $43.6 million, which compares with the net loss of $25.4 million for the quarter ending June 30, 2020. The increased net loss was driven by increased spending in support of our preclinical and clinical development programs, as well as employee hiring to support our operations. Research and development expenses were $31.6 million for the quarter ended June 30, 2021, compared to $20.5 million for the quarter ended June 30, 2020. The increase was primarily attributable to a TAVO-PVET development, the ongoing Phase I and Phase II-III trials in SCD or sickle cell patients, and startup costs for the thalassemia trial, as well as increases in staff and stock-based compensation. General and administrative expenses were $12.5 million for the quarter ended June 30, 2021. compared to $6.4 million for the quarter ended June 30th, 2020. The increase was primarily attributable to increased equity-based compensation, executive and staff hiring, professional fees, and insurance. Our cash equivalents and marketable securities balance as of June 30th, 2021 was $570.8 million, compared to $645.6 million at the year-end 2020. Cash use in the second quarter reflects operating expenses and working capital requirements to support operations. Overall, we continue to be in a very strong financial position with funding through the third quarter of 2024. Gigi, we can now take on questions.

Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Emma Nealon from Cantor Fitzgerald. Your line is now open. Hi. Thanks for taking the question.

In the Phase II SAL study, I guess just curious what the rationale is for including sickle cell patients who are receiving chronic transfusions and then not including dial patients who are receiving transfusions.

Sure. Hey, good morning, Emma. Thanks for the question. Let me turn this over to Pat.

Yeah, so the thalassemia trial, the pilot 201 trial that we are initiating includes both a transfusion dependent and non-transfusion dependent thalassemia. as well as a cohort of sickle cell patients on chronic transfusions as well.

Got it. Okay. And then just for the sickle cell cohort, what you're trying to learn versus what you're looking at in the Hibiscus study?

So the endpoints of that will look at hemoglobin response in both the transfusion-dependent populations as well as the, you know, pre-transfusion as well as non-transfusion-dependent thalassemia patients. And in those patients receiving chronic transfusions, look at the impact on reducing the transfusion burden in those patients. Great. Thanks, Cliff.

Thank you. Our next question comes from the line of Tiago Foss from Credit Suisse. Your line is now open.

Hi. Thanks for bringing the question. So, one follow-up on 7051. So, again, just to set expectations correctly for the October update, I'm assuming we're probably not going to get sufficient biomarker data across the patients. So, just want to clarify that that is the case. Again, we're generally going to try to disrupt from an efficacy perspective. But regardless of the data coming in October, perhaps next year, what are you looking for given a trial design situation? and the novel mechanism of action is really PSA response at a certain level indicative of what you're looking for. I'm just trying to understand how to interpret the data given the novelty of the approach. Thank you.

Thanks for the question, Tiago. Just a high-level thought, and let me turn it over to Dave and Pat for further comments. As we've got it before, we're on track to deliver safety and some PKPD results for the triple meeting later this year. And the full results, the final results, will be sometime mid-next year. So that's the broad sort of, I would say, expectation. And certainly, depending on how the trial goes, we may have some other endpoints. But Dave, why don't I turn it over to you?

Sure. Hi, Tiago. Yeah, you're correct. It's a limited number of patients that will be at a dose this year that we expect to be in the therapeutic range. And remember that the way PSA response is defined, it's a 90-day PSA response. So the patient not only has to be treated at a therapeutic dose, but have been on treatment for 90 days in order to assess that. So we think that's We'll have a much more robust data set in the sort of middle of next year timeframe. In addition to looking at PSA response, which is really a very typical parameter that's looked at in these early patients, we will be looking at radiographic response. And so we can correlate the two of those.

I've got to appreciate the details there. Thank you.

Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Your line is now open.

Hi. Good morning, everyone, and thanks for taking my questions. First one is on TAVO. Your update at EI showed it can improve overall sickle RBC functional health and increase hemoglobin production, but we're just wondering if you can help set expectations for ASH on what to be looking for on VOCs if it if the update will be robust enough to get some perspective there, or at what point should we be able to learn more about that?

Hey, Mari. Good morning. Thanks for the question. Just at a high level, what we presented at EHA just recently in June, basically if you look at what we're planning to present at ASH, it's basically those endpoints, albeit with more patients that have completed now the 12-week dosing regimen. So that's what to expect. So when you take a look at the EHA data and the types of data that we presented, I would just think about that with a full 12-week course of therapy for more patients. And with respect to VOCs, we won't definitively have the VOC data until we conduct the Hibiscus trial. But in the meantime, there are some, I would say, markers that we're looking at that may be associated with VOCs. And certainly, Dave, you might want to talk a little bit more about that.

Sure. Hi, Maury. So we know that VOCs represent a complex process that starts with sickling but translates into things like coagulation at the site of vascular damage and inflammatory responses. And so the study is actually carefully looking at a number of innate immune cytokines. We're looking at factors, the activation of the coagulation pathway, which actually is quite activated typically at baseline for these patients. So we're actually looking at the ability to reduce that activation. And then some other more systemic biomarkers, for instance, the reduction in the reticulocyte drive. So those are the kinds of systemic biomarkers that I think will build confidence that we're going to see a difference in VOCs in the Hibiscus trial. I'll just point out... If you look at, for instance, the one approved drug that we have that reduces VOCs, well, two now with chrismozumab, patients still experience VOCs, and that's why it's very challenging in the absence of a placebo and a blinded study to positively say that you're seeing a reduction of VOCs in a small sample open-label study, and that's where there's a need for a hibiscus study. But we think these precursors of coagulation immune activation, red cell deformability are all very strong precursors that we will have a benefit for DOCs.

Got it. That's all really helpful perspective. And then also just wanted to check on, you mentioned during the prepared remarks, the potential to explore TAVO and other indications. And so just wondering if you can talk a little bit more about the plan there and when we can learn more about that strategy.

Yeah, Mari, we're hard at work looking at the possibility of some other indications and populations. Outside of the ones we've already talked about, that is the VAL program and the peat sickle cell, we are considering a number of other indications and populations. We won't be ready to share that until likely towards the end of the year. So that's the timeline that we're operating under.

Got it. And last question for me, just for the triple meeting update, is there anything else you can say on baseline characteristics? And just wanted to clarify if you'll have perspective into whether patients are ARV7 or not at baseline at that point.

Sure. Dave, you want to, or Pat, you want to speak to that?

Sure. I'll just say, obviously, this is a heavily pretreated population. while they only have to have failed one line of therapy, typically they've had multiple lines and may in fact have had chemotherapy. We are doing circulating tumor cell and CT DNA analysis. So we'll have both the ARV7 status and mutational data. However, that data is batched. So we don't get the data, for instance, with each patient, but we batch it. So The amount of data that would be available will depend on, in some sense, on timing of when patients enter the study and what batch they end up in. So that's why I think it's really worth keeping in perspective that this will be early data. We'll share what we can, as we always do, but by no means should we think this as being comprehensive since we're still in the dose escalation phase.

Got it. That's helpful. Thanks for taking my questions.

Thank you. Our next question comes from the line of Mark Bredenbach from Oppenheimer. Your line is now open.

Hey, good morning, guys. Congrats on the progress. I'm just wondering if the early success of Servier's Agile trial of Tibsovo in a newly diagnosed AML setting has had any positive impact on your partnering discussions for Ola I'm wondering if it's inspired plans for FORMA to run a randomized trial in a similar setting.

Hey, Mark. Good morning. Yeah, we're very excited about the LUCIDINIB program, as we've talked about before, and the data presented are actually pretty remarkable results. That said, we're committed to a partner strategy that we've talked about before, and we're in partnering discussions. And so I can't comment on those and what the partnership will entail, but what I can say is we're very encouraged by the program and also the interest in the hearing.

Okay. And just a quick follow-up on the sickle cell program. It might be a little early, but it maybe you can give us a sense for what the pediatric sickle cell trial might look like in terms of size and if we can expect any pediatric-specific efficacy endpoints, things like transcranial Doppler flow velocities, things like that.

Yeah, let me just say at a high level, we're still in, of course, discussions with the regulatory authorities, so nothing definitive, but certainly we have some thoughts. I mean, Pat, maybe you can share some initial thoughts.

Yeah, I think we're looking at all opportunities in this setting. But, you know, the heart of this study and intent is to look at the pharmacology, the pharmacodynamics, and the safety, you know, as a careful exploration of Etavo PVET in young patients. The additional efficacy or clinical benefit endpoints are part of that discussion, as Frank mentioned.

Got it. Thanks for taking the questions.

Thank you. Our next question comes from the line of Robin Garner from Craig Hallam. Your line is now open.

Congratulations on the advances in the quarter. I have a question for you on ETAVO. Looking at the upcoming studies in thalassemia in pediatric patients, how could we expect the hemoglobin response to ETAVO to differ given the underlying differences in these populations versus... adults with sickle cell disease.

Hey, Rob, and thanks for the question. Pat, you want to take this one?

Yeah, I think it's part of the questions we're asking to characterize the activity of the TABO-PVAT in these particular patient populations. Mechanistically, the activity of the TABO should be active in all red cells and, as such, The activity that we're seeing in sickle patients' red cells, including patients under 18, already is giving us confidence that this mechanism should benefit younger patients with sickle cell disease as well as thalassemia patients with unstable hemoglobin.

Would you expect to see more of an effect in pediatric patients who typically have very different responses than adults to sickle cell therapeutics?

Well, you know, we're very pleased with the results we've seen to date in the sickle cell adult patients, you know, with a very robust hemoglobin response generally across the entire patient population. It'll be hard to improve on that, I suspect. And we'll see. I think you're right, you know, that patients younger have done better with standard of care in terms of those therapies, you know, generally healthier without more of the accumulated morbidity. So that gives us, you know, confidence that what we see in adult patients will translate to better or, you know, nearly equivalent or better responses in the younger population.

Okay. Thank you for answering my question.

Thank you. At this time, I'm showing no further questions. I would like to turn the call back over to Frank Lee for closing remarks.

All right. Well, we thank everyone for taking the time to participate in today's call. The second quarter of 2021 brought important new data for our lead compound etabo in sickle cell. as well as progress on FT7051 in prostate cancer, as well as eluticide in AML. And it's really continuing our mission to bring new therapies to patients with rare hematologic disorders and cancers. We look forward to sharing more progress on our development programs prior to the year end. And this concludes today's call. Thank you all. Have a great day.

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