Forma Therapeutics Holdings, Inc.

Welcome to the Form of Therapeutics year-end 2021 financial results and business update conference call. All participants are currently in listen-only mode. Following management's prepared remarks, we'll hold a Q&A session. To ask a question at that time, please press the star key followed by one on your touchstone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this call is being recorded today, March 1st, 2022. I would now like to turn the conference over to Mario Corso. Please go ahead.

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 a 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 this conference call include certain statements that are estimates, beliefs, forward-looking, and are subject to various risks and uncertainties. Any statements made during this call that are not statements of historical or current facts are intended to be forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We want to emphasize that such forward-looking statements reflect our current expectations and assumptions regarding timing, enrollment, success and data announcements of our current and ongoing clinical trials, therapeutic potential and clinical benefits and safety of our product candidates, planned regulatory submissions, our financial condition and capital requirements, our business operation 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 business. reports on Form 10-K for the year ended December 31st, 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 law. Before turning the call over to Frank, I'd like to mention two upcoming activities as outlined in today's press release. We'll be participating virtually in the Oppenheimer Healthcare Conference, March 15 to 16, and we'll 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. Thank you, Mario.

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 former's purpose is to transform the lives of patients living with 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, EtablaPVAP for people living with sickle cell disease and FT7051 for men living with metastatic castration-resistant prostate cancer. These clinical data formed the building blocks for expanded development in 2022 and beyond. In the latter part of 2021, we completed the Phase I trial of our once-daily PKR activator, Etabopivac. This molecule has the potential to be a foundational therapy for sickle cell disease via its multimodal mechanisms 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 I 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 red blood cell health. Pat will review the impressive results here shortly. While we completed the Phase 1 trial and continued to enroll the Phase 2-3 hibiscus study, we also furthered our commitments to improving access to care, with the recent announcement of our Form-a-Bridge program to aid in pediatric to adult transition, as well as the addition of a renowned leader in sickle cell disease, Dr. Ed Fiasunco, 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 under-appreciated. 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 the community 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 was achieved with our CBP P300 inhibitor FT7051. With the presentation in October at the triple meeting of the first in human results from our ongoing phase one trial in 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 Etabla PVAT and expanding FORMA's pipeline to position the company for longer-term success. We continue to enroll the Global Phase 2-3 Hibiscus Study and expect the interim analysis 1 dose selection decision towards the end of this year. We're also broadening our ETAVA PBAT development in sickle cell disease to include the transfusion-dependent and pediatric populations. We are also progressing in new areas such as thalassemia 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 FT7051 in metastatic castration-resistant prostate cancer later in the year, including its safety, tolerability, profile, and activity. This data will enable us to discuss the clinical development approach for FT7051 and positioning in the current treatment landscape. Finally, this year, with respect to our third development compound, the IDH1 inhibitor, the ludicidinib, 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 and beyond. We're building a company that is positioned for success with multiple clinical stage assets and 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 working very closely with the clinical sites as well as the sickle cell community. With that, I'd like to acknowledge those who have 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 to discuss recent Etabla PVAT and the ludicide NIV results in more detail. Pat.

Thank you, Frank, and good morning, everyone. I will provide a brief overview of our development programs for Atavo PVAT and elutisidinib, including clinical results that were presented at the ASH annual meeting in December. Atavo PVAT 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 of our Phase I Etabo-PVEC 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 etavopivet administration. Key findings from the 15 patients with sickle cell disease treated up to 12 weeks included the following. Etavopivet dosing of 400 milligrams daily was well tolerated with a safety profile that was consistent with the underlying sickle cell disease. All patients experienced an improvement in hemoglobin levels with 11 out of 15, or 73% of patients, achieving a greater than one gram per deciliter hemoglobin improvement, with a maximal mean increase of 1.5 grams per deciliter. An increase in the lifespan of the RBCs was observed based on the increase in the hemoglobin and a concomitant reduction in the absolute reticulocyte count. There was reduced intravascular hemolysis, a key driver of sickle cell pathology, which was shown by decreases in indirect bilirubin and lactate dehydrogenase. Improved sickle RBC deformability was demonstrated as measured by the oxygen scan with a shift in the point of sickling to lower oxygen pressures. Improved RBC hydration was observed with a decreased intracellular hemoglobin concentration and a decrease in the number of dense cells. There was a reduction in systemic markers of inflammation, coagulation, and hypoxia, showing the potential to reduce these downstream measures of sickle cell disease pathophysiology. In terms of vaso-occlusive crises, in the 15 patients dosed for up to 12 weeks, there was only one VOC requiring hospitalization reported while on treatment, which was precipitated by a COVID-19 infection. Notably, that patient remained on etavopivet and did well. In the four weeks post-etavopivet treatment, there were three reports of VOC, which we believe is consistent with that seen in other sickle cell disease trials and largely reflects the removal of a therapy that was having a positive clinical impact. We also conducted an analysis of patient-reported VOC rates in the prior 12 months prior to trial enrollment. and compared it to the VOC rate we observed during the treatment period, which totaled over three years of patient exposure. There was a 68% reduction in the annualized rate of VOCs resulting in hospitalization, an interesting finding in the context of the benefits we observed in the aforementioned measures of sickle cell disease and RBC health. Overall, we are very pleased with the Phase I Etavo PVET results. gaining significant insights into the consistent PK-PD properties of etalopivet and the importance of RBC health. The results strongly support our ongoing Phase II-III hibiscus study and provide a rationale for our ongoing and planned expansion into other areas, including transfusion-dependent sickle cell disease, thalassemia, myelodysplastic syndrome, and pulmonary diseases. Now turning to elutacitinib. our mutant IDH1 inhibitor, being evaluated in patients with relapsed or refractory acute myeloid leukemia, or AML. Following the presentation of the positive registrational Phase II results at the ASCO annual meeting last June, new results from the trial were presented at the ASH annual meeting in December. Patients were enrolled into a ludicidinib plus azacitidine combination cohorts based on their disease status and prior therapy, and were evaluated for their best response with a primary endpoint of a composite complete remission plus complete remission with partial hematologic recovery, or a CRCRH rate. The group of patients who had not yet received therapy for AML were candidates and more candidates for azacitidine as a single first-line treatment had a CRCR rate of 45%. The other groups enrolled were relapsed refractory patients who had had prior hypomethylating agent or an IDH1 inhibitor or were candidates for azacitinib. The CRCRH rates in these groups ranged from 30% to 47%. We believe these findings support the potential of elutacitinib as the basis of combination therapy in patients with AML who have not achieved a durable response from prior therapies. With that, I'm going to now turn the call over to Dave, who will provide an update on the FT7051 program for prostate cancer.

Thanks, Pat. I'm going to spend the next few minutes discussing our CBP P300 inhibitor, FT7051, 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 FT7051 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 ARV7 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 FT7051. We began enrolling a phase one 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 2 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 FT7051 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 was 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 We'll 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.

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.

If you'd like to ask a question, please press star, then 1. If your question hasn't been answered and you'd like to remove yourself from the queue, press the pound key. Our first question comes from Tiago Fall with Credit Suisse. Your line is open.

Hey, thanks for taking your question. So I wanted to get more detail on recent discussions with the FDA on the potential regulatory fast-forward. So we've discussed this in the past on the potential 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 timelines between a potential accelerated approval based on the hemoglobin response at 24 weeks, then you have the final VOC endpoint at 52 plus 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? Thank you.

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 we're studying, 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 linking the 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 endpoint. And so what we plan on doing, what we are doing is, you know, collecting data, mechanistic data, epidemiologic data, as well as our own clinical data, which, you know, 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 timelines, I'd say broadly speaking, we're in alignment with you that to the extent that we can pursue accelerator approval, that would likely mean an approval about a year earlier than the traditional path.

Got it. Perfect. Thank you so much. Okay.

Thanks for the question, Tiago.

Our next question comes from Alicia Young with Cancer Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my questions, and congrats on the progress so far. I got two from me. One, can you just talk a little bit, maybe furthering on the Tiago's question, you know, kind of from a commercial setting? Let's say, you know, you are able to get approved without the VOCs and with the hemoglobin. You know, how do you think that sets you up, or do you think that physicians 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, you know, upcoming data and how, what are the gating factors for success there, you know, as you read out more data? Thanks.

Thanks for the question, Lydia. First, on the question of, you know, 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, you know, isn't as optimal as launching with both hemoglobin and, let's say, other clinically meaningful endpoints like VOCs. That said, you know, we'd be launching a year ahead of time, roughly speaking, and so, you know, I think there's a tradeoff there. It just depends on what we see in the data as we unblind the results at IA2. So, I think it really depends, but, you know, to your point, I think there are the tradeoffs of launching early with, let's say, not the complete data set versus launching a year later with a complete data set. So it'll all eventually depend on the data. With respect to the prostate cancer program, what to expect roughly mid-year is just an update to what we presented at the triple meeting last year. So more patients followed for a longer period in 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 mid-year.

Great, thank you.

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

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

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

Sure. Thanks, Maury. Relative to combo options, we're clearly evaluating multiple possibilities in the setting of phase two. And I think there's a case to be made for looking at combos early, but also continuing to evaluate as 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 ARB7 expression variant. And I'll remind you that our One patient who had a PSA response in the first eight 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.

And, Mario, 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 a presentation is accepted. So right now, we're not commenting on any sort of submissions on any abstracts.

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 II Transfusion-dependent sickle cell disease study, the one in beta-thal, how enrollment's going for that study as well, if you can provide any more granularity.

Yeah, Mario, 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, you know, 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, you know, 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. Got it.

Okay. Thanks for taking my questions.

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

Hey, good morning, and thanks for taking the questions. You know, just following up on 7051, it sounds like we shouldn't be expecting a recommended Phase II dose to be announced midyear, if I'm understanding correctly. And also, is it correct to assume we shouldn't expect those expansion cohorts to be initiated later this year? Is that more of a 2023 goal?

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 are relative to drug supply. And so the company's 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 one and a phase two dose expansion.

Okay, fair enough. Maybe one for Pat. Can you just remind us if the Hibiscus protocol allows for resizing of the Phase III component based on the magnitude of signal you're seeing in Phase II? Is there any chance for altering the size, you know, maybe to go after the VOC endpoint with statistical significance? Thanks.

Yeah, no, thanks, Mark. You know, the protocol is – It is fairly set, but these can change based on, you know, conversations with the FDA. If there's opportunity to take learnings, we'll do that. But remember that this is blinded analysis, so it'll be difficult for us to do anything in the current design other than, you know, follow the data as it gets unblinded.

Okay, understood. All right, thanks for taking the questions. Sure. Thanks, Mark.

As a reminder, to ask a question, please press star, then 1. Our next question comes from Andrew Behrends with SPB. Your line is open.

Hi, thanks. My question is, we're going to move aside a bit. You guys are moving the assets forward, it seems, in the regulatory process. I was wondering if the plan is still to divest it, and if 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, but is the Servier IGS field 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 a sign that you're considering going forward with the IGS program alone?

Andy, you were breaking up on me a little bit there, but I think I caught your questions. So first on eliticide nib, Our partner strategy has not changed, so we remain committed to the partner strategy and we're furthering the NDA. So that's number one. With respect to, let's say, comps relative to, you know, the Lewis-Sideneb and the Servier deal, I think these are very different kinds of deals. As you might recall, the deal involving Servier involved not only but it also involves 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 CRCRH responders. Hopefully that answers your question about comps. And finally, with respect to the Chief Patient Officer, and let me just say that we're absolutely delighted to have Dr. Ippy on board. She's a remarkable clinician, investigator, leader, and a champion for patients. And her primary mandate is to make sure that we bring the patient 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 in the other therapeutic areas that were involved. So hopefully that answers your question. I'm really proud of the fact that, you know, in many ways we're leading the way here with regard to a position like this reporting directly into the CEO's office. And, you know, she's been on board just a few short weeks, and I'm already seeing the impact that she's making.

Great. Now that does answer the questions. Thanks, Frank. Thanks, Andy.

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

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 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.

This concludes the program. You may now disconnect.