Forma Therapeutics Holdings, Inc.
Q1 2021 Earnings Call Transcript

Published: 14 May 2021

[Operator:]

Welcome to the Forma Therapeutics First 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, May 14, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

[Mario Corso:]

Thank you, operator. This is Mario Corso, Senior Director of Investor Relations at Forma. Good morning to our listeners, and welcome to today's call to review first quarter 2021 financial results and business update.

[Frank Lee:]

Thank you, Mario. Good morning, everyone. And thank you for joining us on today's call. I'm pleased to say we continue to make strong progress in the first quarter with our R&D pipeline. And I'll share some high level thoughts with you before turning it over to Pat and Dave for more detailed remarks. I'd like to first acknowledge the time, effort and contributions made by patients, investigators, healthcare workers and our employees, who are navigating challenges posed by the COVID-19 pandemic and make it possible for us to pursue our purpose and that is to transform the lives of patients living with rare hematologic disorders and cancers.

[Pat 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. As Frank mentioned, we are very pleased with the completion of the two week MAD dosing cohorts for the FT-4202 program demonstrating that 4202 was well tolerated with a favorable safety profile. We also saw a hemoglobin increase of one gram or greater at the end of the 14 day treatment period in 71% of the patients and nearly all patients experienced benefit in other important surrogate markers. These include the reticulocyte counts, the LDH, and the bilirubin, indicating improvement in red blood cell health. Looking forward, we will disclose a complete analysis of the unblinded two week MAD cohorts and for the first time we will be providing an analysis of the initial patients receiving FT-4202 beyond the two weeks of dosing from the open label 12 week extension cohort. These results will be presented at the EHA annual meeting taking place June 9 through the 17th. We expect to have additional data on RBC health, which combined with the improved red cell functional studies supports the potential for reduction in the rate of VOC's. Altogether, we are pleased with the emerging profile of FT-4202 indicating potential benefits beyond haemoglobin improvement. We would also like to take this opportunity to reiterate that our ongoing Phase 2/3 trial, the hibiscus study is designed to be consistent with FDA guidance and reflects regulatory feedback. The Hibiscus study design includes two separate primary endpoints, hemoglobin change following 24 weeks of treatment in support of an accelerated regulatory approval and a 52 week rate of VOC's in support of a full regulatory approval is positive. Finally with respect to FT-4202, our planned trials in thalassemia and pediatric sickle cell disease are progressing well, with enrollment anticipated to begin in the second half of this year for thalassemia and the first half of 2022 in pediatric patients with sickle cell disease. Now turning to olutasidenib, our mutant IDH one inhibitor being evaluated in patients with relapsed or refractory acute myeloid leukemia our AML. In October of last year, we announced that the interim analysis successfully met the primary endpoint of a durable complete response rate in this registrational phase 2 trial. We are pleased to announce that these data have been accepted for oral presentations at both the annual ASCO and EHA meetings in June. In addition, our work continues on preparing a filing of a new drug application or an NDA, to the US FDA.

[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 antigen receptor pathway by a novel mechanism that has the potential to address many of the resistance mechanisms seen for standard of care AR signaling inhibitors. In tumor cell lines, FC-7051 has been shown to decrease AR expression and also decrease AR dependent gene expression. In addition, FT-7051 has been observed to inhibit prostate cancer cell proliferation in vitro and in a patient-derived xenograft model in vivo. We believe the mechanism of action of FT-7051 is applicable to a broad range of resistance mechanisms, including the AAR-v7 splice variant, which lacks the AR hormone binding domain, and for which there are no approved treatments. Published data suggests that AR-v7 may be detectable in approximately 20% to 40% of men after third-line treatment, and it correlates with substantially shorter overall survival. Activity in AR-v7 expressing cancer could represent an accelerated path to market. In addition, 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. Our phase 1 trial began enrolling early in the first quarter of this year. This trial is planned to enroll up to 45 men with metastatic castrate resistant prostate cancer, who will fail one or more lines of standard of care, it utilizes an adaptive design, starting with a dose of 25 milligrams, 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 will be profiled including AR-v7 expression and genetic markers of resistance and clinical assessments will include PSA levels, and radiographic measurements of tumor burden. We expect to have initial clinical results in the fourth quarter of this year in a subset of patients. These results may include safety, tolerability, PK/PD, and preliminary biomarker data. More complete results from the trial are anticipated in 2022, including an assessment of tumor response rates and underlying genetic characteristics of responders. Given the high unmet need in this population of men, and the novel mechanism of our molecule, we are enthusiastic regarding the promise of FT-7051, and look forward to sharing data as they become available.

[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 first quarter of 2021 and then discuss our cash position and outlook. Our net loss for the first quarter of 2021 was $36.0 million, which compares with net income of $11.2 million for the quarter ending March 31, 2020. The year-over-year change in net loss was attributed - largely attributable to a one time gain on the divestiture of our Hit Discovery capabilities and income tax benefits in the first quarter of 2020. Research and development expenses were $26.3 million in the quarter versus $23.2 million for the quarter ending March 31, 2020. This increased spending supports progress with our two compounds in development, including the Phase 1 and Phase 2/3 trials for FT-4202 in sickle cell disease and the start of the Phase 1 trial for FT-7051 in metastatic prostate cancer. General and administrative expense in the quarter was $9.9 million, as compared to $8.9 million in the quarter ending March 31, 2020. This increase reflects the costs related to being a public company, including stock compensation expense, professional fees and insurance and increased compensation expense. Our cash, cash equivalents and marketable securities balance as of March 31, 2021 was $603.7 million, compared to $645.6 million at year end 2020. Cash used in the first quarter reflects the net loss, as well as changes in working capital. Our current cash run rate continues to extend through third quarter of 2024, which includes ongoing clinical trials, as well as planned commencement of FT-4202 development in thalassemia, and the pediatric sickle cell population. Overall, we continue to be in a strong financial position and are well financed through important upcoming clinical milestones. Operator, we can now take questions.

[Operator:]

Thank you. First question comes from Emma Nealon with Cantor Fitzgerald. Your question please?

[Emma Nealon:]

Hi, good morning. So for 4202, can you just speak to the trend toward increasing hemoglobin response that you saw over the 14 day treatment periods for the first two cohorts? And whether you expect to see potentially a better response over this longer treatment period in the open label data at EHA?

[Frank Lee:]

Hi, Emma. Thanks for the questions. Frank Lee, here. And let me just provide some high level remarks and turn it over to Pat for some additional thoughts. Certainly, the data we have now is primarily for the first two weeks of treatment. And we're certainly looking forward to the open label extension data which will provide a look at various cuts of patients, some will have completed 12 weeks, and some will have completed anywhere from two to 12 weeks. And so we'll have a spectrum of patients. And certainly we're encouraged by what we saw in the early data from the two MAD studies.

[Pat Kelly:]

Great. Thanks, Frank. Yeah, I think he said it. Well, we - you know, key here is as people are aware from the 600 milligram or MAD two cohort, patients participating in that group were allowed to rollover into the 12 week open label. And as we previously disclosed six out of the first nine patients enrolled in the MAD two did rollover into the 12 weeks. So we will be able to have, you know, a comparadent comparison, if you will, in that population, based on their two week experience in the MAD two versus their two week or greater exposure experience in the in 12 week cohort.

[Emma Nealon:]

Okay. That’s helpful. Thanks.

[Operator:]

Thank you. Our next question comes from Andrew Berens with SVB Leerink. Your question please?

[Andrew Berens:]

Hi. Good morning, guys. A couple from me please. I was wondering if you could give us some color on the decision to go into the hemolytic anemias, would these be acquired or inherited, chronic or acute treatment? And I guess, how many do you think are addressable by 4202 and the PKR class? And then I do have a question on the prostate cancer program afterwards. If that's okay.

[Frank Lee:]

Sure. Thanks for the question, Andy. So we're looking through, you know, and going through our analysis, and we'll share more of that in the second half the year. Certainly, there are other PKR agonists one in particular that is looking at PKD. Certainly, that's one of the areas we'll look at, but we haven't made any decisions yet. And so, at the current time, we're doing our analysis, so to speak, and we'll have more information to share in the second half of the year, but we certainly think there's more potential than just be - just to be focused on sickle cell disease and thalassemia.

[Andrew Berens:]

Okay. And more than potentially PKD also, because it's a very broad area?

[Frank Lee:]

Yes, potentially. So I don't want to make any comments at this point until we've completed our analysis, but certainly there's potential beyond two initial indications that we talked about in PK…

[Andrew Berens:]

Okay. Okay. And then on the prostate cancer program. Well, the upcoming data set that's presented include AR-v7 patients only or all comers. And then just what's the pathophysiological rationale for targeting AR-v7 with 7051?

[Frank Lee:]

Sure, let me answer that. And then turn it over to Dave for some additional comments. And so we'll share what data we have around about the fourth quarter of this year, it'll be the initial COVID data. And certainly right now, we're enrolling all comers, late-line patients, and some of whom will be AR-v7. And so we'll have those cuts of the data. That will be at the initial analysis. Let me turn it over to Dave for some additional comments.

[Dave Cook:]

Yeah. Hi, Andy. So I think as Frank said, we're really kind of doing an all comers commerce study in Phase 1. We don't want to make assumptions about where the drug may have efficacy or not. That being said, given the - what we know about AR-v7, we expect to have a number of patients with AR-v7 phenotype. The rationale there is twofold. One, we know that these splice variants, what they do is they tend to delete the protein domains that include the ligand binding domain, so meaning the C-terminus is where you have truncation, and the N-terminus where CPB and p300 interact, is intact. So we think the mechanism of our drug by disrupting that should continue to be useful. The second really is empirical, is that we can show for instance, that AR-v7 expressing cell lines which are resistant to enzalutamide, for instance, are sensitive to FT-7051.

[Andrew Berens:]

Okay, thanks. Appreciate the color.

[Operator:]

Our next question comes from Tiago Fauth with Credit Suisse. Your question, please?

[Tiago Fauth:]

Thanks for taking the question. So just a follow up on RBC health data that we might see, we get some questions on the Osmo scan data. So just want to understand a little bit better forecasting trends or patient variability for that specific measurement and how well established it is in sickle, so it's not something that you see for every single program. So any color there would be helpful. Thanks.

[Frank Lee:]

Thanks for the question, Tiago. Let me first ask Dave to give a little bit of color on the Osmo scan and maybe perhaps, Pat and talk a little bit further after that. So Dave?

[Dave Cook:]

Sure. Well, first of all, that measurement has been around for 40 years, or so was developed in the early 80s. And it's been well validated as to what it indicates, although it is a complex measurement. It's not typically used in clinical labs, because commercial devices have only been available fairly recently. What is it - what it indicates are several things. It indicates critical hemolytic volume, meaning, it has to do with the surface to volume ratio of red cells. And it also indicates elements of membrane function. For instance, under high osmotic pressure, when ions are leaking in water, water also tend - when ions is leaking out, water tends to leak out. And the ability to restore ion gradients is a key element of having appropriate ATP levels. And so when we're able to show that we can handle these osmotic gradients, we think it demonstrates the health of the red cell and its ability to maintain hydrodynamic balance.

[Frank Lee:]

Pat?

[Pat Kelly:]

Yeah, I think the other piece of that is, these are complex assays that can be a bit challenging, as each lab we've learned has different parameters. But what's important for what we've done is we centralize the analysis of all samples are sent to one lab. So there's a consistency in that analysis. And based on that work, in the MAD cohorts, we've come to appreciate that, yes, between the patients there might be variability just based on the phenotypes of the individual patient, but there's consistency within the patient's themselves. So having a patient and certainly our experience with patients who have enrolled in both the MAD and the open label, that we see a very consistent phenotype for the individual patient, you know, over a period of time where they're not receiving treatment. So what we'll have is, as part of our complete analysis of the MAD cohorts is all the information in those groups in total.

[Tiago Fauth:]

Great, very helpful. Thank you.

[Operator:]

Thank you. We have a question from the line of Mark Breidenbach with Oppenheimer. Your question please?

[Mark Breidenbach:]

Hey. Good morning, guys. And congrats on getting enrollment started in hibiscus. You know, we've seen a little bit of data suggesting there was a substantial dip in healthcare provider visits by sickle cell patients during the COVID pandemic. And I'm just wondering if your clinical sites are seeing traffic starting to normalize in terms of sickle cell patients coming back to the clinic. And I'm also wondering if you have any plans to open clinical sites in x-US territories, especially in Africa, to potentially help accelerate enrollment in hibiscus?

[Frank Lee:]

Thanks for the question, Mark. I guess, let me talk about the impact of the pandemic broadly, and then turn it over to Pat in terms of the steps we've been taking to navigate the pandemic. First, I'll say that, certainly the pandemic has had an impact on our efforts. And so we've had to really double down and think about not only the traditional ways, but non-traditional and innovative ways to enroll patients. And so based on that, and the team's efforts, we've been able to deliver the data that we've been talking about so far. And so we'll see how this plays out as we move forward, but so far, we've been able to navigate COVID and the pandemic. Pat, why don't you talk a little bit more about specifically what we're seeing at the sites?

[Pat Kelly:]

Sure. Yeah, I think, you know, really, the activities globally have been in parallel, not just US-focused, but also x-US in terms of getting countries up and running. But like what you can read in the papers, you know, the activity at various countries and centers is really been impacted based on how the severity of COVID is hitting, or impacting those hospitals and countries. So, you know, what we're seeing really is more activity in the US, as you can imagine, as the vaccines have rolled out, and sites are starting to catch up in terms of clinical research. These are coming online, certainly. And that's, you know, for our benefits in the sense that we're already there, we've already have the approvals and contracts. So as COVID, and the vaccine in the US has kind of diminished and the vaccine is improved, healthcare activity this is starting to, you know, open up, so we're looking - we're hopeful, I guess, is how we would put it.

[Mark Breidenbach:]

Okay. In terms of plans to open sites in Africa, where there are high concentrations in sickle cell patients?

[Frank Lee:]

Yeah, we're looking - you know, we have a number of countries that we've been - we've approached, and we're working on, and it's really dependent on availability, and resources, both from our own internal activities, our CRL, as well as the countries themselves at this point, but we're not disclosing specific countries, but we're looking everywhere, right.

[Mark Breidenbach:]

Okay, got it. And one follow up on the prostate cancer program, the data we're expecting in fourth quarter, just to be clear that will include some of the CTC profiling data. So AR-v7 status and specific point mutations conferring resistance, they are targeting therapies, that sort of thing, or is that going to come later in 2022?

[Frank Lee:]

Dave, go ahead and take that one.

[Dave Cook:]

Yeah. Mark, I don't think we've been specific yet. And part of that's going to depend on our strategy for doing the analysis and how it gets batch. So I don't want to commit for the genotype data at the end of the year, but obviously that's really important to interpret the results globally. So we're going to be working hard at that, but I don't think we're yet have a specific commitment around whether that data will be available by the end of the year.

[Mark Breidenbach:]

Got it. Okay. Thanks for the clarification, and congrats on the progress.

[Operator:]

Thank you. And this concludes our Q&A session. I would like to turn the call back to Frank Lee for his final remarks.

[Frank Lee:]

Well, thank you, everybody. We just want to thank everyone for taking the time to participate in today's call. The first quarter brought some important progress in our R&D pipeline that's focused on rare hematologic disorders and cancers. And we're executing our strategy to bring these new medicines to patients and look forward to sharing more progress during the course of the year. So have a great day, everybody. Thank you.

[Operator:]

Thank you. And this concludes today's conference. Thank you for your participation and you may now disconnect. Good day.