Forma Therapeutics Holdings, Inc.
Q4 2020 Earnings Call Transcript

Published: 30 Mar 2021

[Operator:]

Welcome to the Forma Therapeutics Fourth Quarter and Year End 2020 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, March 30, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

[Mario Corso:]

Thank you, Josh. This is Mario Corso, Senior Director of Investor Relations at Forma. Good morning to our listeners, and welcome to today's call to review fourth quarter and year end 2020 financial results and business update.

[Frank Lee:]

Thank you, Mario. Good morning, everyone and thank you for joining us. I'm excited to host Forma’s first quarterly call and to provide an update on the strong progress we've made over the course of 2020, as well as our plans for 2021. Before I get started, I'd like to express my deep gratitude to our patients, investigators, healthcare workers and employees. Throughout the pandemic so many have made tremendous sacrifices and demonstrated remarkable resilience to advance our science and to advance our mission to transform the lives of patients living with rare hematologic disorders and cancers.

[Patrick Kelly:]

Thank you, Frank and good morning everyone. I'm delighted to provide updates on two of our programs, FT-4202 for treating patients with sickle cell disease and olutasidenib for treating patients with relapsed or refractory AML with an IDH1 mutation. FT-4202 is our oral once-daily pyruvate kinase or PKR activator for which a pivotal Phase 2/3 trial in more than 300 patients living with sickle cell disease is presently enrolling. As Frank mentioned, today we are providing an update on the initial results from the patients who have completed the second two-week daily dose cohort in our randomized placebo-controlled Phase 1 trial of FT-4202. As a reminder on the trial design, each two-week dosing cohorts can enroll up to 12 patients with sickle cell disease. However, based on a blocked randomization strategy, a blinded analysis can be performed after nine patients have completed a three-week study participation, or a safety analysis that enables dose escalation decisions or to allow patients to enroll directly into our 12-week open-label dose cohort.

[Dave Cook:]

Thanks, Pat. I'm going to spend the next few minutes discussing how oral CBP/p300 inhibitor FT-7051, which earlier this year began rolling a Phase 1 trial in Metastatic Castrate-Resistant Prostate Cancer, or MCRPC. CBP/p300 is a required core activator of androgen receptor driven gene expression. FT-7051 has been shown the decrease expression of AR and it also inhibits AR dependent gene expression. Additionally, CBP inhibition has been observed to inhibit prostate cancer cell proliferation in vitro and in an in vivo patient-derived xenograft model. There is significant unmet need in MCRPC, as the majority of patients eventually progress, while in androgen deprivation therapy in combination with the adrenal androgen synthesis inhibitor abiraterone acetate or the androgen receptor agonists – antagonists, such as enzalutamide and apalutamide. Upon failure of one or more of these regimens, the therapeutic regimen leads to untargeted chemotherapy and the five year survival rate for MCRPC patients progressing on or after first line chemotherapy is estimated at only 1.6%. The mechanism of action of FT-7051 is applicable to a broad range of resistance mechanisms, including the AR-v7 splice variant, which lacks the hormone binding domain, and for which there are no approved drugs. The median survival for men with AR-v7 variant expression has been reported to be 10.8 months, as compared to 27.2 months for AR wild-type tumors. We believe that AR-v7 may be prevalent in approximately 20% to 40% of men after second or third line treatment and this indication could represent an accelerated path to market. In addition, we intend to explore FT-7051 in MCRPC with other mutation profiles, and earlier lines of therapy, as well as other AR dependent tumors, such as triple negative breast cancer. Following preclinical studies showing the FT-7051, reduced histone acetylation and AR positive prostate cancers, inhibited growth in prostate cancer cell line and show the anti-tumor activity in both enzalutamide sensitive and resistant prostate cancer, PDX mouse models, we began our first inhuman trial earlier this year. This trial will enroll up to 46 men with MCRPC, who have progressed following one or more regiments, with an adrenal androgen synthesis inhibitor, AR antagonist or chemotherapy. The crowd utilizes an adaptive design, starting with a dose of 25 milligram with titration to as many as five higher dose levels on a three week on, one week off cycle, based upon predefined safety and tolerability measures. Mutational status of circulating tumor cells will be profiled, including AR-v7 splice variant expression and genotypic markers, with clinical assessment, including PSA levels and radiographic progression. Depending upon enrollment rates, we intend to have initial clinical results from this trial in the second half of this year in a subset of patients, primarily focused on safety, tolerability, PK/PD, and preliminary biomarker data, more results from the trial are anticipated in the first half of 2022. Given the high unmet need in this population of men and a small number of innovative compounds with novel mechanisms in development, we are very intrigued by the promise of FT-7051 and we look forward to sharing initial data later this year. I'll now turn the call over to our Chief Financial Officer, Todd.

[Todd Shegog:]

Thank you, Dave and thank you to everyone for joining us on today's call. I wish to spend the first few minutes discussing our financial results for the fourth quarter and full year 2020, and then discuss our cash position and outlook. Our net loss for the fourth quarter of 2020 was $28.6 million and $70.4 million for the year ended December 31st, 2020. This compares to a net loss of $24.7 million and $34.8 million for the quarter and year ending December 31st, 2019. The increase in net loss during the year of 2020 was largely attributable to the absence of collaboration revenue, reflecting the completion of -- in 2019 of the performance obligations under our license agreements with Celgene, now BMS. Research and development expenses were $24.9 million and $93.4 million for the quarter and year ending December 31st, 2020 versus $27.0 million and $111.3 million for the quarter and year ending December 31st, 2019. This spending supports progress with all three of our compounds in development, FT-4202, olutasidenib, and FT-7051, including the start of our Phase 1 and Phase 2/3 trials for FT-4202 in sickle cell disease, the olutasidenib pivotal Phase 2 trial in AML, and Phase 1/2 trial in glioma, and the progression of FT-7051 into the first human trial in metastatic prostate cancer. These items were offset by a decrease in spending on internal research and development expenses, primarily due to restructuring in January of 2019. G&A expense in the quarter and year ending December 31st, 2020 was $7.9 million and $30.8 million, as compared to $6.8 million and $24.4 million in the quarter and year ending December 31st, 2019. This increase reflects the costs related to being a public company, including stock compensation expense, professional fees and insurance and aforementioned staff and additions to manage the expansion in clinical activities. Our cash, cash equivalents, and marketable securities balance as of December 31st, 2020 was $645.6 million compared to $173.2 million at year end 2019. This includes net proceeds of $293.3 million received from our initial public offering in June of 2020 and $258.6 million net proceeds from our follow-on offering completed in December 2020. Our current cash runway extends to the third quarter of 2024, which includes ongoing clinical trials, as well as planned commencement of FT-4202 development in thalassemia, and the pediatric population. Overall, we ended 2020 in a strong financial position, and are well financed through important upcoming clinical milestones. Josh, we can now take questions.

[Q - Tiago Fauth:]

Great. Thanks for taking my question. So, are there any noticeable relevant differences to baseline characteristics or genotypes between two subjects enroll in the 300 milligram cohort versus a 600 milligram cohort. I remember at least one patient in 300 milligram cohort have a slightly different presentation of sickle cell. And the follow-up to that perhaps related to the open label’s affinity. I understand it's a small sample size in a shorter period of time, but should there be an expectation of seeing the signals related to potential benefits in the events or VOCs, I understand that's not really what the trial is designed to show, but wondering if we should – could see any signals better early? Thanks.

[Frank Lee:]

Thanks for the questions Tiago. It’s Frank Lee here. First of all, these data are still blinded so we can comment as best we can on the baseline characteristics and other questions there. So let me turn it over to Pat to have him respond to that.

[Patrick Kelly:]

Yes. I think, in general the baseline characteristics of the patients is very similar to the 300 milligram cohort, predominantly hemoglobin SS genotype and most patients being on hydroxyurea beyond. So really, I would say, once we unbind or understand treatment effect more specifically, but at this time, really nothing that stands out for your question related to the different patient populations. And then in terms of the long-term aspects for VOC. I think as we've always expressed that the 12-week will give us a lot more detail where with our additional exploratory studies that have been built into this protocol. As we mentioned, some of the efforts to look at adhesion markers or inflammatory markers, over time we would expect that that's going to be helped inform more about the impact of what happens with such a profound reduction in the haemolytic markers, in particular. Does this translate in the background of a relatively short treatment period of 12 weeks? Does this continue to support our hypothesis that a less inflamed state has to contribute to improve vaso-occlusive outcome.

[Tiago Fauth:]

Got it. Understood. Thank you so much.

[Frank Lee:]

Thanks, Tiago.

[Operator:]

Thank you. Our next question comes from Biren Amin with Jefferies. You may proceed with your question.

[Jeet Mukherjee:]

Yes. Hey, good morning guys. This is Jeet Mukherjee on for Biren. Thanks for taking the questions and congrats on the progress today. I was just hoping you could talk us through some of the haem parameters you presented on the 600 mg cohort today. I think we noticed there was slightly fewer patients that were hemoglobin responders at 600 mg versus 300, and it seemed as though LDH reduction was slightly lower as well. So I was just hoping you could maybe share a little perspective on that and also just on randomization, I believe from your previous design you said, it was either seven to two or nine to three, so just wanted to check if it was consistent between the 300 mg and 600 mg cohorts? Thanks.

[Frank Lee:]

Yeah. Thanks for the question. And before I turn it over to Pat, I just want to step back and say, it's really important to look at the totality of the data that we've been able to generate on 42 to the 700 milligram single dose. The 300 milligram multiple ascending dose, and the 600 milligram now multiple ascending dose, and all in a very rigorous and controlled way with placebo controls, multicenter. And so I want to give that as context and, overall, we're very pleased as we noted earlier about the totality of the data, as well as the improvement in response that we're seeing over the 14 days of treatment. So let me, with that, turn it over to Pat.

[Patrick Kelly:]

Yeah. So, yeah, just quickly to the randomization scheme is the same, so with the minimum of nine, the randomization is seven to two, and with a maximum of 12 enrolled, the randomization would be nine to three. So it's equivalent analysis to the -- with the 300 milligram first line patients dose there. Yeah, I think just touching on what Frank said, it's hard. We don't -- yeah, it's difficult to with small numbers to take to this fact on the individual patient level. We, of course, will when we un-blind will do that. But -- in the general trends of everything, everything's pointing in the right direction. Again, this is a two week study to just intended to look at safety and understand some biology signals, and what we're continuing to see is that even with just two weeks, we're seeing significant improvements in these parameters, and many of them at the end of treatment, which again our conclusion with the 300 is that it's quite likely we haven't actually reached the steady state in terms of biologic response in this population, and that -- the 400 milligrams for 12 weeks it's going to give us much more insight in terms of where they -- were the individual patient ultimately lands from a chronic treatment perspective, which of course is the goal here. This is intended to be a foundational therapy that patients will take for extended periods of time.

[Jeet Mukherjee:]

Got it. Thank you for the perspective. And maybe just turning to the olutasidenib program, could you just maybe talk about your partnership efforts for that? And in your view, what an ideal partnership looks like? Thanks.

[Frank Lee:]

Sure. Thanks for that question. So, first, as we mentioned earlier, we're very pleased with the olutasidenib data that we reported in October. In many ways, because of ASH and everything else, we didn’t get as much visibility out there with -- to those data. But as you heard recently now from Pat, it's really impressive to see the survival data, 18 months and so we're I think -- agents and good discussions, we can't comment on any of those at this point in time, because of the nature of those kinds of conversations. But I come back to the strength of the data, and certainly a partner that has an existing heme infrastructure already with portfolio products. This one would be a nice one to put in there.

[Jeet Mukherjee:]

Thank you very much.

[Operator:]

Thank you. Our next question comes from Emma Nealon with Cantor Fitzgerald. You may proceed with your question.

[Emma Nealon:]

Hi. Thank you. Could you just walk us through you are confident here and the accelerated approval pathway based on hemoglobin responses 24 weeks based on your FDA interactions? And then a follow-up on the 12-week OLE update, what will be included in that initial update in the second quarter versus later in 2021? And should we then expect to continue to get updates with longer term follow-up, maybe later this year and into next year as well?

[Frank Lee:]

Yes. Thanks for the question. So let me turn it to Pat. There have been some questions about this accelerated approval process. So Pat maybe you can comment on that.

[Patrick Kelly:]

Sure. Yes. As we highlighted the study design for the Hibiscus Study was put together last year with FDA input. So, certainly -- as well as European input. The scope of the trial design is ultimately intended to generate full approvals for the vaso-occlusive event rate over a year for both US and the EU. We've continued to have conversations with the FDA around this program and they've been very supportive, even from the get-go that they wanted to work with us on the studies, particularly, as we've discussed with them our thalassemia trial as well as our pediatric plans. And we've had very direct conversations with them around the scope of this study and there's no indication from our conversations on this that an accelerated approval pathway is closed in this indication. Certainly, Oxbryta, Global Blood achieved an accelerated approval path, based on a hemoglobin response at 24-weeks, and that path is still open, because there's no full approval in that space. And so, we are continuing to proceed with that. And nothing has changed that direction, particularly with discussions with the FDA. In terms of the 12-week open label data set, it's a -- we're rolling up to 20 patients. It's directly enrolling as we indicated. We will provide an update at -- in June on the current -- patients who are enrolling up to that point. Since its open label, it's less difficult in terms of data cuts and looking at the data, but you could expect that by the end of this year that, that trial will be complete with full follow-up. And so, I would expect that at the end of this year, we would also provide a complete update on the totality of that data.

[Emma Nealon:]

Thanks very much.

[Operator:]

Thank you. Your next question comes from Mark Breidenbach with Oppenheimer. You may proceed with your question.

[Mark Breidenbach:]

Hey. Good morning and thanks for taking our questions. Just touching on one of the previous questions on both slightly decreased antihemolytic parameters in the 600 milligram versus 300 milligram MAD cohorts. I'm wondering if this could potentially be indicative of CYP autoinduction as we've seen with one of the other PKR activators out there. Any thoughts on potential mechanistic basis for the decrease or is it really just in your mind they -- a small numbers effect at this point?

[Patrick Kelly:]

Yes. No. Thanks for the question. It's definitely not related to any autoinduction. Our pharmacology, or the PK profile clearly showed an expected Cmax and AUC that's dose proportional. So no clearance issues with the drug. Yes, I think, it's literally just the small numbers and the potential variability that you might see amongst patients with just a two-week of dosing. The 12-week with a larger sample size is more likely to give us insights into where each of these patients end-up ultimately from a biologic response.

[Mark Breidenbach:]

Okay, totally fair. Also, could you maybe give us an update on progress with opening clinical sites in the Hibiscus trial and are there plans to provide any patient enrollment updates throughout the year.

[Frank Lee:]

Mark thanks for the question. So, we are actively opening sites as we speak. We haven't provided all the site numbers or enrollment numbers as of yet, but we are actively opening sites and enrolling patients.

[Mark Breidenbach:]

Okay. Fair enough.

[Frank Lee:]

Just as a reminder -- just as a quick reminder on that. So, as we talked about earlier, we are proceeding with the 200 and 400-milligram doses for that registrational Phase 2/3. So, the 600 that we reported out today certainly gives us a good, I would say, look at the characterizing the safety margin, which is what 50% over the top dose that will be studying in the Phase 2/3.

[Mark Breidenbach:]

Understood. Thank you so much for taking the questions and congrats on the progress.

[Frank Lee:]

Thanks Mark.

[Operator:]

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back over to Frank Lee for any further remarks.

[Frank Lee:]

Well, thank you everyone for taking some time to participate in today's call. 2020 was a year of remarkable accomplishments, pro forma, and as evidenced by our news today, on the second dose cohort in our multiple ascending dose trial of FT-4202 and sickle cell disease, 2021 holds a lot of promise for our continued strong momentum in our R&D pipeline, and that's focused on rare hematologic diseases and cancers. So, we look forward to sharing our progress on these quarterly calls over the course of this year, and have a good day. Thank you all.

[Operator:]

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.