Forma Therapeutics Holdings, Inc.
Q4 2021 Earnings Call Transcript

Published: 1 Mar 2022

[Operator:]

Welcome to the Forma Therapeutics Year End 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, March 1, 2022. Now, I like to turn the conference over to Mario Corso. Please go ahead.

[Mario Corso:]

Thank you, Michelle. This is Mario Corso, Senior Director of Investor Relations at Forma. Good morning to our listeners and welcome to today’s call to discuss year end 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 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, enrollment, success and data announcements of our current and ongoing clinical trials, therapeutics, potential and clinical benefits and safety of our product candidates, planned regulatory submissions, our financial conditions and capital requirements, our business operations, development plans, 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 reports on Form 10-K for the year ended December 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. Before turning the call over to Frank, I would like to mention two upcoming activities as outlined in today’s press release. We will be participating virtually in the Oppenheimer Healthcare Conference March 15 to 16. And we will also be holding our first R&D Pipeline Review in May 2022. Further information on these events will be made available on our website www.formatherapeutics.com. With that I will now turn the call over to Frank, our President and Chief Executive Officer.

[Frank Lee:]

Thank you, Mario. Good morning everyone. It's my pleasure to review Forma’s significant accomplishments in 2021 and outline our plans for 2022 as well as the longer-term vision for the company. As you know, Forma’s purpose is to transform the lives of patients living with the rare hematologic diseases and cancers. In support of our mission, 2021 was a year to generate early stage clinical trial results on our two active clinical development programs, It to have a etavopivat for people living cell disease and FT-7051 for men living with metastatic castration-resistant prostate cancer. These clinical data formed building blocks for expanded development in 2022 and beyond. In the latter part of 2021, we completed the Phase 1 trial of our once daily PKR activator etavopivat. This molecule has a potential to be a foundational affair with sickle cell disease via its multimodal mechanism of action. Results were presented from the open label extension of the trial at the ASH Annual Meeting in December. And we believe this was the most rigorous and comprehensive Phase 1 program conducted in people living with sickle cell disease. Not only assessing the typical measures of hemoglobin and hemolysis but also analyzing numerous biomarkers of health. Pat will review the impressive results here shortly. While we completed the Phase 1 trial and continue to involve the Phase 2/3 Hibiscus study, we also furthered our commitments to improving access to care with the recent announcement of our former Forma program to aid in pediatric to adult transition, as well as the additional – the addition of a renowned leader in sickle cell disease, Dr. Ify Osunkwo, in the newly created role of Chief Patient Officer. Unlike similar orphan diseases, such as hemophilia and cystic fibrosis, sickle cell disease remains underfunded, under resourced and underappreciated. As a result, sickle cell patients must endure barriers to quality of care, like no other disease. We believe every sickle cell patient deserves high quality care, and we're working closely with it to make this happen. Being a trusted partner to the communities we serve is important for rare orphan diseases, but it's particularly the case with sickle cell disease. Another important 2021 milestone we achieved with our CBP/p300 inhibitor FT-7051 with the presentation in October at the triple meeting of the first inhuman results from our ongoing Phase 1 to metastatic castration-resistant prostate cancer. We're encouraged by the safety profile and the early data suggesting that CBP/p300 inhibition may provide a novel approach for patients who have failed standard of care. Dave will detail the results shortly. Now, looking ahead, 2022 is a year of advancing the clinical development of etavopivat and expanding Forma’s pipeline, position the company for longer-term success. We continue to enroll the global Phase 2/3 Hibiscus study and expect the interim analysis one, dose selection decision towards the end of this year. We're also broadening our etavopivat development in sickle cell disease to include the transfusion dependent and pediatric populations. We are also progressing in new areas, such as thalasemia and low-risk myelodysplastic syndrome or MDS, while also evaluating other disease areas. In order to bring all that we have learned about PKR mechanism and red blood cell health to additional areas with substantial unmet patient need. We expect to provide updated data for FT-7051 in metastatic castration-resistant prostate cancer later in the year, including its safety tolerability profile and activity. This data will enable us discuss the clinical development approach for FT-7051 and positioning in the current treatment landscape. Finally, this year with respect to our third development compound, the IDH1 inhibitor, olutasidenib for relapsed/refractory AML, we're progressing a new drug application as we continue a partnering strategy for this molecule. I'm proud of all that we accomplished at Forma last year and enthused about our plans for this year. We're building a company that is positioned for success with multiple clinical stage assets in development, research capabilities to sustain our strategy and with substantial capital to achieve our near term and long term objectives. As we discussed before the COVID-19 pandemic has created substantial ongoing challenges for both the clinical trial sites and for patients. We're observing conditions, improving over time and are very closely with the clinical sites as well as a sickle cell community. With that, I'd like to acknowledge those who've helped navigate the ongoing challenges posed by the COVID-19 pandemic, including patients, investigators, healthcare workers, and our employees. As we pursue our purpose to transform the lives of patients living with rare hematologic disorders and cancers. I'll now turn over the call to Pat Kelly, who has go recent etavopivat and olutasidenib results in more detail. Pat?

[Patrick Kelly:]

Thank you, Frank. And good morning, everyone. I will provide a brief overview of our development programs for etavopivat and olutasidenib, including clinical results that were presented at the ASH Annual Meeting in December. Etavopivat is our once-daily selective PKR activator with a distinct multimodal mechanism of action that improves oxygen binding and reduces hemoglobin S polymerization by decreasing 2,3-DPG. And also repairs, the damaged sickle RBC membrane by increasing ATP. We believe that the effects of decreased 2,3-DPG and increased ATP can improve the sickle RBC health and lifespan thus potentially modifying the course of sickle cell disease. In December at the ASH Annual Meeting complete results were presented from the 12-week open label extension or Phase 1 etavopivat study, which we believe is the most comprehensive characterization of any novel agent in sickle cell disease. We presented conventional measures of response, including hemoglobin, reticulocytes and hemolysis, and also presented critical RBC parameters, such as deformability, oxygen binding and hydration. We also looked at systemic markers of inflammation, coagulation, and hypoxia, and analyzed VOCs prior to during and following etavopivat in administration. Key findings from the 15 patients with sickle cell disease treated up to 12 weeks included the following

[Dave Cook:]

Thanks, Pat. I’m going to spend the next few minutes discussing our CBP/p300 inhibitor, FT-7051, which is in development for the treatment of metastatic castrate-resistant prostate cancer. Because CBP/p300 modulates AR via the N-terminal domain, we believe FT-7051 may be able to address a broad range of resistance mechanisms that limited the utility of standard of care AR signaling inhibitors. In addition, tumors expressing the AR-V7 splice variant, which lacks the C-terminal AR hormone binding domain and for which there are no approved treatments is a potential therapeutic target for FT-7051. We began enrolling a Phase 1 trial last year in up to 45 men with metastatic castrate-resistant prostate cancer who 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. The trial utilizes an open-label adaptive design, starting with a dose of 25 milligrams given on a three-week on, one week off cycle, and dose escalation is performed based on predefined safety and tolerability criteria. Initial results in eight patients were presented at the triple meeting in October, showing an encouraging safety profile and biologic effects consistent with the inhibition of the CBP/p300 pathway. Importantly, the 150-milligram dose achieved drug concentrations that approached the predictive efficacious dose based on modeling with preclinical data. In addition, skin biopsies demonstrated a reduction in histone acetylation, a marker of inhibition of this pathway. All but one of the treatment emergence events were grade two or lower with no events leading to treatment discontinuation. One patient in the highest 150-milligram dose cohort experienced a Grade 3 hyperglycemia which was medically managed and the dose of FT-7051 was reduced. This patient was the first in the trial who was evaluable at 12 weeks for the standard surrogate marker of disease progression prostate-specific antigen level, which declined by greater than 50% and then greater than 80% at 16 weeks. His nodal tumor, which is progressing prior to enrollment, was classified as stable disease and confirmed by radiography. We are encouraged by these initial results and dose escalation in the trial has continued since the October update. We look forward to providing updated trial results toward the middle of this year. Future results from the trial will inform our next steps with respect to potential combinations, lines of therapy and mutational status of patients. With that, 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 first spend a few minutes discussing our financial results for the quarter and year ended December 31, 2021, and then discuss our cash position and outlook. Our net loss for the quarter and year ended December 31, 2021 was $50.1 million and $173.0 million which compares to a net loss of $28.6 million and $70.4 million for the quarter and year ended December 31, 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 $37.0 million and $125.7 million for the quarter and year ended December 31, 2021 compared to $24.9 million and $93.4 million for the quarter and year ended December 31, 2020. The increase was primarily attributable to costs of our clinical and preclinical development programs, manufacturing activities, R&D staffing and equity-based compensation. General and administrative expenses were $13.2 million and $48.3 million for the quarter and year ended December 31, 2021 compared to $7.9 million and $30.8 million for the quarter and year ended December 31, 2020. The increase was primarily attributed to equity-based compensation, staffing costs and professional fees and insurance. Our cash, cash equivalents and marketable securities balance as of December 31, 2021 was $490.3 million compared to $645.6 million at year-end 2020. Cash use reflects operating expenses and working capital requirements to support our operations. Overall, we continue to be in a very strong financial position with funding through the third quarter of 2024. I’d like to thank you, and we can now take questions.

[Operator:]

Our first question comes from Tiago Fauth with Credit Suisse. Your line is open.

[Tiago Fauth:]

Thanks for taking my question. So I wanted to get more detail on recent discussions with FDA on the potential regulatory path forward, right? So we’ve discussed this in the past on the potential of approval, and it sounds like you would have to provide some additional evidence that correlates increasing hemoglobin with a relevant clinical endpoint. So I’m curious what that could look like. And perhaps just taking a step back, what would be the difference in time lines between a potential accelerated approval based on the hemoglobin response at 24 weeks, then you have the final VOC endpoint of 52 or last a few months of additional regulatory review. So our estimate is about a nine- to 12-month difference between the two options potentially, but are we missing something there?

[Frank Lee:]

Hi, Tiago. Good morning. Thanks for the question. So let me take a step back. What’s important to note here is that our Hibiscus trial, which is our study which is the Phase 2/3 has always included the ability to pursue accelerated and also the traditional path. And so as we’ve mentioned before, we’ve been working very closely with the FDA to make sure that we can provide the data required. And that specifically is being able to demonstrate that because this is a unique mechanism of action, PKR, that we’re able to correlate hemoglobin response to a clinically meaningful end point. And so what we plan on doing, what we are doing is collecting data, mechanistic data, epidemiologic data as well as our own clinical data, which – much of which we shared at our ASH presentation at the end of last year. And so that’s the overall plan. And the key thing here is that we’re generating this information because the PKR mechanism is, in fact, very unique and different. So that’s an important point. Second, with respect to time lines, I’d say, broadly speaking, we’re in alignment with you to the extent that we can pursue accelerated approval that would likely mean an approval about a year earlier than the traditional path.

[Tiago Fauth:]

Got it. Perfect. Thank you so much.

[Frank Lee:]

Okay. Thanks for the question, Tiago,.

[Operator:]

Our next question comes from Alethia Young with Cantor Fitzgerald. Your line is open.

[Alethia Young:]

Hey guys. Thanks for taking my question. And congrats on the progress so far. I guess two for me. One, can you just talk a little bit maybe furthering on Tiago’s question kind of from a commercial setting, let’s say you are able to get approved without the VOCs and with the hemoglobin, how do you think that sets you up? And do you think that the missions will want to see the VOCs nonetheless? Or do the evidence you have may be able to bridge that? And then just on the prostate cancer program, can you just frame a little bit more detail, like what we should expect as far as like kind of upcoming data? And how – what are the gating factors for success there as you read out more data? Thanks.

[Frank Lee:]

Thanks for the question, Alethia. First, on the question of the approval and what that might look like to the extent that we can get accelerated approval versus, let’s say, a traditional path that would be a year later. Certainly, launching with hemoglobin only isn’t as optimal as launching with both hemoglobin and, let’s say, other clinically meaningful endpoints like VOCs. That said, we’d be launching a year ahead of time, roughly speaking. And so I think there’s a trade-off there and just depends on what we see in the data as we unblind the results at IA2. So I think it really depends. But to your point, I think there are the trade-offs of launching early with, let’s say, not the complete data set versus launching a year later with a complete data set. So it will all eventually depend on the data. With respect to the prostate cancer program, what to expect, roughly midyear is just an update to what we presented at the triple meeting last year. So more patients followed for a longer period of time. And I would expect that we wouldn’t see the complete data set until towards the end of this year, early next year, and we’re aiming to recruit or enroll 45 patients in total. So we continue to have actually very strong demand for the clinical trial, and it’s progressing nicely. We are dose escalating, and so we should have a reasonable update midyear.

[Alethia Young:]

Great. Thank you.

[Operator:]

Our next question comes from Maury Raycroft with Jefferies. Your line is open.

[Maury Raycroft:]

Hi, good morning, and thanks for taking my questions. I’ll start off with prostate cancer for 7051. Just wondering if you can talk a little bit more on your latest thinking on combo options and mutation status and how that’s going to factor into the midyear update. And then also, I just wanted to know if you can say if you’ve submitted an abstract to ASCO at this point.

[Frank Lee:]

So Dave, why don’t you maybe talk about 7051?

[Dave Cook:]

Sure. Thanks, Maury. Relative to combo options, we’re clearly evaluating multiple possibilities in the setting of Phase 2, and I think there’s a case to be made for looking at combos early but also continuing to evaluate as a monotherapy depending on the data that we see. So we’re looking at the broad range of options. Regarding mutation status, as we have done in the past, we’ll be fairly transparent about the data that we get, and we are doing both genetic analysis of AR as well as looking at the AR-V7 expression variant. And I’ll remind you that our one patient who had a PSA response in the first cohort actually had an AR mutation associated with enzalutamide resistance. So we’ll continue to build that data set and report it as the data comes out.

[Frank Lee:]

And Maury, to your question about submission of abstracts, we typically don’t comment on that. We’ll comment on that once an abstract is accepted or presentation is accepted. So right now, we’re not commenting on any sort of submissions on any abstracts.

[Maury Raycroft:]

Okay. Okay. Thanks. And maybe just a quick question. You probably can’t say too much, but just with the impact of COVID recently. Just wondering if you can comment on enrollment status for Hibiscus. And also for the Phase 2 transfusion-dependent sickle cell disease study and the one in beta-thal, how enrollment is going for that study as well, if you can provide any more granularity.

[Frank Lee:]

Yes, Maury. Thanks for that question. It's an important one. And as we've said before, I mean, we've been working very, very closely with the sites, both here and abroad. And what I can tell you is that we maintain our guidance, which is for Hibiscus to have the IA1 interim analysis-1 towards the end of this year. And with respect to the thalassemia and also the transfusion-dependent trial that's on track as well for early results at the end of this year. So no change in guidance. That said, as I mentioned earlier, we've been working very, very closely with the sites. The team has really been making sure that we're trying to help the sites as much as possible, help the patients as much as possible. It is a difficult situation. We do see it, I would say, improving over time. And so fingers crossed that we continue to see that trend. But right now, I can again confirm the guidance that we provided before with respect to how we're progressing on both of those trials.

[Maury Raycroft:]

Got it. Okay, thanks for taking my questions.

[Operator:]

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

[Mark Breidenbach:]

Hey, good morning and thanks for taking the question. Just following up on FT-7051. It sounds like we shouldn't be expecting a recommended Phase 2 dose to be announced mid-year if I'm understanding correctly? And also is it correct to assume we shouldn't expect dose expansion cohorts to be initiated later this year? Is that more of a 2023 goal?

[Dave Cook:]

So we don't expect to make an RP2D midyear, but that's really an objective for the end of the year. The team is actively planning for expansion cohort, and we'll announce that at the right time, but some of the early investments that one makes at risk relative to drug supply. And so the company has got a planned timing for making those investments as the data matures. So we should have – we expect no gap between the end of Phase 1 and a Phase 2 dose expansion.

[Mark Breidenbach:]

Okay. Fair enough. And maybe one for Pat. Can you just remind us the Hibiscus protocol allows for resizing of the Phase 3 component based on the magnitude of signal that you're seeing in Phase 2? Is there any chance for altering the size maybe to go after the VOC endpoint with statistical significance? Thanks.

[Patrick Kelly:]

Yes. Thanks, Mark. The protocol is fairly set, but these can change based on conversations with the FDA if there's opportunity to take learnings. We will do that. But remember that this is blinded analysis. So it will be difficult for us to do anything in the current design other than follow the data as it gets unblinded.

[Mark Breidenbach:]

Okay. Understood. All right, thanks for taking the question.

[Patrick Kelly:]

Thanks Mark.

[Operator:]

Our next question comes from Andrew Berens with SVB. Your line is open.

[Andrew Berens:]

Hi my question is on olutasidenib. You guys are moving the assets forward, it seems, in the regulatory process. I was wondering if the plan is still to divest it. So how should we think about the ability to monetize it and what that deal could look like, probably not a good apples-to-apples comparison to the Servier-Agios deal good analog? And then as a corollary, you announced the hiring of Chief Patient Officer. Is that really more for the sickle cell program? Or is this the time that you're considering going forward with the IDH program alone?

[Frank Lee:]

Andy, you're breaking up on me a little bit there, but I think I caught your questions. So first on olutasidenib, our partner strategy has not changed, so we remain committed to the partner strategy and we're forging the NDA. So that's number one. With respect to, let's say, comps relative to olutasidenib and the Servier deal, I think these are very different kind of deals. As you might recall, the deal involving Servier involved, not only TIBSOVO, but it also involved a broad array of other pipeline molecules in addition to the infrastructure and people. And so this is a very different kind of a deal. That said, I mean, this is a differentiated molecule. If you look at this molecule, we believe that it does have the potential to be best-in-class based on the duration of response that we've seen, which is an impressive 18 months for the CR/CRh responders. So hopefully, that answers your question about comps. And finally, with respect to the Chief Patient Officer, let me just say that we're absolutely delighted to have Dr. Ify on board. She's a remarkable clinician investigator leader and the champion for patients. And her primary mandate is to make sure that we bring the patient's voice into everything that we do here internally and also help to champion access, reimbursement, funding and care for patients broadly speaking. And so this includes sickle cell patients. It includes patients and the other therapeutic areas that we’re involved. So hopefully, that answers your question. I'm really proud of the fact that in many ways, we're leading the way here with regard to a position like this, reporting directly into the CEO's office. And she's been on board just a few short weeks, and I'm already seeing the impact that she's made.

[Andrew Berens:]

Great. Well, that does answer the question. Thanks Frank.

[Frank Lee:]

Thanks Andy.

[Operator:]

There are no further questions at this time. I'd like to turn the call back over to Frank Lee for any closing remarks.

[Frank Lee:]

Well, we'd like to thank everyone for taking the time to participate in today's call. As we outlined today, 2021 was a year of significant progress and accomplishments for Forma. And in 2022, we have the plans to do even more in pursuit of our purpose to transform the lives of people living with rare hematologic diseases and cancers. In closing, I'd like to thank our patients, investigators and employees for their substantial contributions in 2021. And so I'd like to say thank you again, and this concludes today's call. Have a great day.

[Operator:]

This concludes the program. You may now disconnect.