Forma Therapeutics Holdings, Inc.
Q2 2021 Earnings Call Transcript

Published: 13 Aug 2021

[Operator:]

Welcome to the Forma Therapeutics Second Quarter 2021 Financial Results and Business Update Conference Call. All participants are currently in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. As a reminder, this call is being recorded today, August 13, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

[Mario Corso:]

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; 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 the comments made and financial information provided during this conference call, includes certain statements that are estimates, belief, 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 of our product candidates, planned regulatory submissions, our financial conditions and our business operations, development efforts, the potential impact of COVID-19 on our business, and political 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.

[Frank Lee:]

Thank you, Mario, and good morning everyone. 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 call etavopivat, formally FT-4202. We believe that the new Phase 1 results in sickle cell disease presented at the EHA meeting in June provide growing evidence that etavopivat as a highly differentiated profile and the multimodal mechanism of action may be able to modify the course of this complex and multi-factorial disease. More specifically, in this etavopivat results show sustained hemoglobin increase in nearly all patients and improvement in red blood cell health and lifespan as you measured by metabolic and stomach markers. All together, these data support the potential of etavopivat to improve important clinical outcomes, such as vaso-occlusive crisis or VOC's, and our goal is to have etavopivat approved as a first sickle cell treatment that can improve both hemoglobin and VOC's. As we advance our ongoing pivotal Phase 2/3 sickle cell trial by Hibiscus Study, 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 make a difference in the lives of patients living with sickle cell disease. Looking forward, we plan to start the Phase 2 thalassemia trial later this year and a sickle cell pediatric trial in the first half of next year. Furthermore, we're evaluating etavopivat study in other populations where improving red blood cell health and lifespan to benefit patients. Turning to our prostate cancer program, we began enrolling a Phase 1 trial earlier this year of the oral CPB/p300 inhibitor FT-7051 in men with metastatic castration resistant prostate cancer. There's a population of men whose cancer has either progressed while on current standard of care, anti-androgen treatment and/or for whom chemotherapy has not been successful. So the unmet need is significant. CPB/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 AR-v7 splice variants for which there are no approved therapies. Dave will shortly provide an update on our FT-7051 development program. With respect to our third development compound, the IDH1 inhibitor, olutasidenib, for relapsed refractory AML, the registrational results presented at EHA and ASCO so that we believe it's a very competitive profile in terms of response rate, duration of response, and survival. 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 and 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 him on board. Before turning the call over to Pat for more in depth review of etavopivat and olutasidenib, 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.

[Pat Kelly:]

Thank you, Frank, and good morning everyone. I'm delighted to provide an update on our etavopivat development program and outline the olutasidenib results that were recently presented at scientific conferences. Etavopivat is a once daily highly selective PKR activator, with a distinct multimodal mechanism of action. This multimodal mechanism is important in the decreased 2, 3-DPG improves oxygen binding to hemoglobin S, which decreases polymerization, thereby reducing the sickling and the hemolysis sickle RBCs caused by the rigid structures formed by deoxygenated hemoglobin S. The increase in ATP allows the cell to repair damage to the membrane that is encouraged through multiple cycles of cell sickling. Together, the effects have decreased to 2, 3-DPG and increase ATP improves the sickle RBC membrane function which can lead to improve cellular hydration, membrane repair and ultimately deformability. From the beginning of our etavopivat 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 the etavopivat on the sickle RBC as measured by numerous markers of red blood cell health. We designed a rigorous and comprehensive Phase 1 program and we are very pleased with the updated data that was presented during the EHA Meeting in June. We believe etavopivat has the potential to reduce the hemolysis and the anemia 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 etavopivat may significantly reduce the debilitating vaso-occlusive events that characterize sickle cell disease. In terms of our Phase 1 results thus far, the following key data were observed from the multiple ascending dose cohorts that administered etavopivat for two weeks and the initial open-label extension results administrating etavopivat 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 1 g/dL or greater. And data from the open label expansion show that 88% of patients or 7 out of 8 experienced a greater than 1 g/dL 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 etavopivatfor for 2 weeks had increased oxygen affinity with a significant shift in the point of sickling and improved the formability when compared to the pre-dosing level functions. We also saw significant reduction in hemolysis with markers approaching normal levels in some patients. With just 2 weeks of dosing, 100% of patients showed a reduction in the 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 etavopivat 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 etavopivat. Finally, etavopivat was well tolerated even at doses up to 600 milligrams daily, which is a 150% of the maximum dose currently being evaluated in the Hibiscus Study. And 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 could 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 trial, in which up to 20 patients will be dosed with 400 milligrams of etavopivat daily for 12 weeks. With respect to our plan 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 olutasidenib, 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 2 trial. These data were presented at both the Annual ASCO and EHA meetings in June. The primary efficacy available population was comprised of 123 relapsed or refractory AML patients who received 150 milligrams of olutasidenib 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 4CRh, the 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 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 a 100% of patients who require platelet transfusion at study entry, and 80% of patients who require red blood cell transfusions at study entry. Moreover, olutasidenib was well tolerated with adverse events consistent with late-stage disease and the heavily pretreated population. At present, our work continues preparing an olutasidenib 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 FT-7051 for prostate cancer.

[Dave Cook:]

Thanks, Pat. I'm going to spend the next few minutes discussing our clinical stage CPB/p300 inhibitor FT-7051. FT-7051 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, FT-7051 has been shown to decrease expression of AR and also decrease the expression of AR dependent genes. Additionally, FT-7051 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 FT-7051 is applicable to a broad range of resistance mechanisms, including the AR-v7 splice variants, which lacks the AR hormone binding domain and for which there are no approved treatments. Published data suggests that AR-v7 may be detectable and approximately 20% to 40% of men after third line treatment and its prevalence correlate with substantially shorter overall survival. Activity in AR-v7 expressing cancer cells could represent an accelerated path to market. Additionally, we believe FT-7051 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 the Phase 1 trial of FT-7051 in the first quarter of this year and up to 45 men with metastatic castrate resistant prostate cancer. These men have 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 adaptive design, starting with a dose of 25-milligram 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 AR-v7 expression and genetic markers of resistance. Clinical assessment will include PSA levels and radiographic measurements of tumor burden. This trial was technically in the dose titration phase, and we're pleased to announce today that an abstract has been accepted for presentation at the AACR/NCI/EORTC Virtual International Conference on Molecular Targets and 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 high end unmet in this population of men, as well as the compounds novel mechanism of action and positive preclinical data. I will now turn the call over to our Chief Financial Officer, Todd.

[Todd Shegog:]

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 a net loss of $25.4 million for the quarter ending June 30, 2020. The increase 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 etavopivat development, the ongoing Phase 1 and Phase 2, 3 trials SCD for sickle cell patients and start-up 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 30, 2020. The increase was primarily attributable to increase equity-based compensation, executive and staff hiring, professional fees and insurance. Our cash, cash equivalence and marketable securities balance as of June 30, 2021, was $570.8 million compared to $645.6 million at the yearend 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.

[Operator:]

Our first question comes from the line of Emma Nealon from Cantor Fitzgerald. Your line is now open.

[Emma Nealon:]

Thanks for taking the question. In the Phase 2 thals study, I guess, just curious go through the rationale is for excluding sickle cell patients who are receiving chronic transfusions and then not including thal patients who are receiving transfusion?

[Frank Lee:]

Thanks for the question. Let me turn this over to Pat.

[Pat Kelly:]

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

[Emma Nealon:]

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

[Pat Kelly:]

So, the endpoints of that we'll look at hemoglobin responses in about the transfusion dependent populations, as well as the 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.

[Operator:]

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

[Tiago Fauth:]

Thank you for taking my 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, across the patients. So, just want to clarify that that is a case. Again, we're generally going to try some disrupt day from an efficacy perspective. But regardless of the data coming in October, perhaps next year, what are you looking for given a trial design? And then all the mechanism of action is really just a response at a certain level indicative of what you're looking for? I'm just trying to understand how to interpret that data given the novelty of the approach? Thank you.

[Frank Lee:]

Thanks for the question, Tiago. Just a high level thought and let me turn it over to Dave and Pat for further comment. As we've guided before, we're on track to deliver safety and some PK/PD results for the triple meeting later this year. And the full results, as a final result will be sometime mid next year. So, that's the broad sort of expectation. And certainly, depending on how the trial goes, we may have some other endpoints, But Dave, I want to turn it over to you.

[Dave Cook:]

Sure, hi, Tiago. You're correct, we will be -- it's a limited number of patients that will be at a dose this year that we expect to be in a 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 therapeutic dose, but have been on treatment for 90-days in order to assess that. So, we think that we'll have a much more robust data set in 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.

[Operator:]

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

[Maury Raycroft:]

Hi, good morning, everyone, and thanks for taking my questions. First one is on, etavo, your update at EHA show that, 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 and what to be looking for on VOC's. 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?

[Frank Lee:]

Maury, good morning. Thanks for the question. Just at a high level, what we've 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 today 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 the full 12-week course of therapy for more patients. And with respect to VOC's, 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 VOC. And certainly Dave, you might want to talk a little bit more about that.

[Dave Cook:]

Sure. Hi, Maury. So we know that, the VOC is represented 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 VOC and Hibiscus trial. I'll just point out that, if you look at, for instance, the one approved drug that we have that reduces VOC's well two now with patients still experience VOC's, and that's why it's very challenging in the absence of a placebo and a blinded study to positively, I would say, that you're seeing the reduction of VOC's in a small sample open-label study, and that's where there is Hibiscus study. But we think these precursors of coagulation immune activation of red cell dependability for all very strong precursors that we will have a benefit for VOC's.

[Maury Raycroft:]

Got it. That's all really helpful perspective. And then, also just wanted to check the on, you mentioned during the prepared remarks potential to explore etavo in 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?

[Frank Lee:]

Yes. Maury, 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 program and the P sickle cell. We are considering a number of other indications in 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.

[Maury Raycroft:]

Got it. Last question for me. Just for the triple meeting updates. Is there anything else you can say on baseline characteristics? And just want to clarify, if you'll have perspective into whether patients are AR-v7 or not at baseline at that point?

[Frank Lee:]

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

[Pat Kelly:]

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 they may in fact have had chemotherapy. We are doing -- circulating tumor cell and ctDNA analysis. So, we'll have both the AR-v7 status and mutational data; however, that data is batched. So if you 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 one patient end of the study and what batch they end up in. So, that's why I think it's really worth keeping a perspective that this'll be early data. We'll share what we can as we always do, but by no means should -- you should be thinking as being comprehensive since we're still in the dose escalation phase.

[Operator:]

Our next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open.

[Mark Breidenbach:]

Hey, good morning, guys. Congrats on the progress. 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 olutasidenib? And I'm wondering if it's inspired plans performance in one randomized trial in a similar setting?

[Frank Lee:]

Hey, Mark. Good morning. We're very excited about olutasidenib program as we've talked about before in the data presented are actually pretty remarkable. That said, we are committed to the 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 year end.

[Mark Breidenbach:]

Okay. And just quick follow-up on the sickle cell program, might be a little early, but 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 velocity things like that?

[Frank Lee:]

Yes. 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. Pat, may you can share some initial thoughts.

[Pat Kelly:]

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

[Operator:]

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

[Robin Garner:]

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

[Frank Lee:]

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

[Pat Kelly:]

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

[Robin Garner:]

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

[Frank Lee:]

We're very pleased with the results we've seen to date in the sickle cell adult patients 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. The patients younger have done better with standard of care in terms of those therapies generally healthier without more of accumulated morbidity. So that gives us confidence that what we see in adult patients will translate to better or nearly equivalent or better responses in the younger population.

[Robin Garner:]

Okay. Thank you for answering my question.

[Operator:]

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.

[End of Q&A:]

[Frank Lee:]

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 etavo in sickle cell as well as progress on FT-7051 in prostate cancer as well olutasidenib in the AML. And truly continue 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.

[Operator:]

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