Forma Therapeutics Holdings, Inc.

Welcome to the former 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. To ask a question at that time, please press the star key followed by the one on your touchstone telephone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this call is being recorded today, March 30th, 2021. I would now like to turn the conference over to Mario Corso. Please go ahead.

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. 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, assumptions, and currently available data regarding, among other things, our business operation, development efforts, regulatory strategy, and relationships with third parties 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 annual report on Form 10-K for the year ending December 31, 2020, being filed today, and in subsequent reports, including our quarterly reports on Form 10-Q and our current reports on Form 8K. In addition, today we will make a number of comments about our expectations for the COVID-19 pandemic on our business. We provide these comments to give investors insights into what we're observing. However, given the dynamic nature of the pandemic, there is a high degree of uncertainty around any forward-looking statements made. The company disclaims any obligation to update or revise any forward-looking statements except as required by applicable law. I will now turn the call over to Frank, our President and Chief Executive Officer.

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. Today, we'll provide updates on three development stage programs. Following my opening remarks, our Chief Medical Officer, Pat Kelly, will provide an update on FT4202, a PKR agonist being studied in sickle cell disease, and elutacidinib, an IDH1 inhibitor being studied in acute myeloid leukemia and glioma. Afterward, our chief scientific officer, Dave Cook, will provide an update on FT7051, a CBP P300 inhibitor being studied in metastatic castration-resistant prostate cancer. Following a brief financial review from our Chief Financial Officer, Todd Chagag, we'll be happy to answer any of your questions. In 2020, we made strong progress in three important areas. Number one, advancing our pipeline. Number two, building our organizational capabilities. And number three, funding our future activities. With regard to advancing our pipeline, we reported at Ad Ash in December. initial phase one results for lead compound, FT4202, in people living with sickle cell disease. These data exceeded our hopes for the emerging profile of this potential foundational therapy. In October, we reported positive results from our pivotal trial for ludicidinib in patients with relapsed refractory AML with an IDH1 mutation. Notably, these results included compelling survival benefit in such a heavily pretreated patient population. Lastly, we progressed FT7051 into the clinic with a phase one trial in late-line patients with metastatic castration-resistant prostate cancer. This trial will broadly enroll late-line patients, including those with ARV7 splice variant identified by genetic mutation analysis. In January of this year, we reported first patient dose in this trial. With regard to building our organizational capabilities, we've strengthened our board of directors with three new appointments and also attracted top quality talent into the organization and collectively established a culture centered on three guiding principles. Patients are our purpose, people are why we succeed, and science drives us. I'm proud of our culture and believe it will differentiate FORMA over the long term. With regard to our funding of future activities, we completed our successful initial public offering in June and a subsequent follow-on equity offering in December. This extends our current cash runway through the third quarter of 2024. When I joined FORMA two years ago, we sharply focused our vision on being a leader in rare hematologic disorders and cancers. And it's been very gratifying to see the vision take shape. We now stand with three potentially transformative molecules in development, with a talented organization, as well as a well-capitalized company. I'd like to now turn to 2021. I'm pleased to say 2021 is off to a strong start for FORMA. We reported today in a separate press release the latest clinical data from our randomized multicenter placebo-controlled trial, Phase I trial, of FT4202 in people living with sickle cell disease. These initial top-line blinded results from the 600-milligram multiple ascending dose cohort are being reported as planned in the first quarter of this year, despite the challenges associated with the COVID pandemic. We're pleased with the initial 600-milligram results. and plan to report the full unblinded analysis at an upcoming scientific meeting this summer. I'd like to touch on some key points. Number one, while treatment assignment remains blinded, the initial results of the 600-milligram MAT2 cohort support the 200-milligram and 400-milligram doses being evaluated in our ongoing Phase 2-3 trial, the Hibiscus study. Number two, Doubling the dose to 600 mg once a day for 14 days was well-tolerated in patients with sickle cell disease with no dose-limiting toxicity or treatment-related adverse events identified. Number three, hematology and chemistry parameters in the 600 mg dose cohort were comparable to that observed with the 300 mg dose previously. Of note, hematologic and hemolytic responses were typically best at the end of the 14-day treatment, suggesting patients may benefit from longer duration of treatment beyond 14 days. Importantly, these data with the 600-milligram dose cohort have allowed us to continue moving forward with the next phase of this Phase I trial, the ongoing 400-milligram 12-week open-label extension. I'll now turn over the call to Pat to discuss our FT4202 results in more detail. as well as review elutisidinib for relapsed refractory AML and glioma.

Thank you, Frank, and good morning, everyone. I am delighted to provide updates on two of our programs, FT4202 for treating patients with sickle cell disease and elutisidinib for treating patients with relapsed or refractory AML with an IDH1 mutation. FT4202 is our oral once-daily pyruvate kinase, or PKR, activator, for which a pivotal Phase II-III trial in more than 300 patients living with sickle cell disease is presently enrolled. 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 I trial of FT4202. As a reminder on the trial design, each two-week dosing cohort 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 for a safety analysis that enables dose escalation decisions or to allow patients to enroll directly into our 12-week open-label dose cohort. Blinded data from the first nine patients enrolled in the 600 milligram cohort is the basis for our update today. We are very pleased that this higher dose cohort supports a favorable tolerability profile, similar to what we reported in the first 300 milligram multiple dose cohort as disclosed at the ASH meeting in December. No treatment-related adverse events or dose-limiting toxicities were observed. Based on these results, the 12-week open label cohort is now enrolling patients directly as the dose escalation portion of our phase one study has closed to further patient enrollment. It should be noted that based on the safety profile observed, we could have continued to dose escalate if the protocol allowed us to do so. However, our previous studies in healthy volunteers and in patients with sickle cell disease had led us to predict that the doses of FT4202 greater than 400 milligrams daily would not provide any additional PKR activation, which is the target of FT4202. Indeed, the PKPD results from the 600 milligram cohort have confirmed these observations. While we doubled the dose of FT4202 to 600 milligrams daily over the previous 300 milligram daily dose, and saw a near-dose proportional pharmacokinetic response, we did not see a meaningful increase in the pharmacodynamic response. Specifically, the increase in ATP levels in the sickle cell red cells was equivalent to what we saw in the 300 milligram dose cohort, and there was only a modest decrease in the 2,3-DPG levels compared to this prior experience. These results further support the 400 milligram daily dose of FT4202 as the top dose we are evaluating in the dose range portion of our ongoing Phase 2-3 registration trial. While a more in-depth per patient analysis can be anticipated once the 600 milligram cohort is formally unblinded, we are able to look at the treatment effect of FT4202 based on an analysis of those patients with detectable FT4202 PK while continuing to maintain the study blind. In the patients who were randomized to FT4202, we saw a similar level of clinical activity based on improved hematologic and hemolytic parameters as compared to the 300 milligram dose cohort. This finding reflects the clear overlap of pharmacodynamic responses between the two treatment groups. Specifically, all seven patients showed an increase in hemoglobin over baseline, with four patients achieving a one gram or greater increase. Equally important, all seven patients showed a reduction in their reticulocytes compared to baseline, with a median 45% decrease. Similar to the prior 300 milligram results, all seven FT4202 treated patients had a reduction in bilirubin levels and LDH levels. Overall, we continue to be pleased by the observed safety and tolerability profile at a dose level well above our intended phase two dose range. The hematologic and hemolytic improvements observed with just two weeks of FT4202 dosing is supportive of the concept that this mechanism of action can increase red blood cell health, supporting the potential for clinical for clinical benefit beyond hemoglobin improvement. The hemoglobin response, coupled with the decline in reticulocytes, is early evidence supporting improved oxygen delivery to the tissues. The reduction in markers of intravascular hemolysis is also encouraging. We believe that these are leading indicators supporting the potential for a reduction in vascular damage and immune activation, since it is well known that the intracellular products released by hemolysis stimulate endothelial cell and immune cell activation. Altogether, the effects that we have observed on multiple surrogate markers lead us to believe that FT4202 administration may lead to the reduction of vaso-occlusive crises, or VOCs, pain events that require medical attention or hospitalization. which is one of the two primary endpoints in our ongoing Phase 2-3 trial. Our Phase 2-3 trial design reflects regulatory feedback and includes two separate primary endpoints, including hemoglobin change following 24 weeks of treatment, which is expected to support an accelerated regulatory filing, and a 52-week rate of VOCs, which is intended to support full regulatory approval if positive. This Phase 2-3 trial is presently enrolling and we believe utilizes the optimal dose of FT-4202 as well as the appropriate trial design. In summary, FT-4202 was well tolerated and no safety concerns identified at an exposure of approximately 50% over the anticipated exposures planned in the ongoing phase two portion of our pivotal trial. There was similar levels of biologic activity in the 600 milligram daily dosing cohort compared to the previous 300 milligram dose cohort. Once again, supporting the selection of 400 milligrams daily as our top dose in our phase two dose ranging study, as well as the dose we are studying in the ongoing open label 12-week dosing cohort. As a reminder, this cohort will enroll up to 20 patients with sickle cell disease and has allowed patients participating in the 600-milligram two-week dosing cohort to roll over, for which six of the initial nine patients in the 600-milligram cohort have done so. A more detailed summary of all patients enrolled in the two-week dose escalation cohorts, as well as the initial observations from the 12-week 400-milligram open-label extension of FP4202 are expected to be disclosed in June, likely at a scientific conference. Now turning to elutisidinib, our mutant IDH1 inhibitor being evaluated in patients with relapsed or refractory acute myelogenous leukemia or AML. In October of last year, we announced the interim analysis was successfully met in this registrational phase two trial in an efficacy-evaluable population of 123 patients. We believe that the rates of complete remission or complete remission with hematologic recovery of 33% compares favorably to the current standard of care. And while a median duration of the CR or CRH population has not been reached, based on a sensitivity analysis, we know the median duration of the CR-CRH response group be at least 13.8 months, which we believe is a very differentiating factor, a feature of alutacitinib. In addition, among the CR or CRH responders, the 87% survival rate at 18 months in this heavily pretreated patient population is gratifying, and we believe more closely resembles results reported for earlier lines of AML treatment. The most common reported adverse events were primarily gastrointestinal, nausea, and constipation, with lab values indicating increases in anemia, neutropenia, or thrombocytopenia, as well as transient liver enzyme elevations. Differentiation syndrome, an adverse drug reaction in this class of targeted therapies, was also observed at a similar rate and with outcomes as observed with other therapies. Based on these data, we are preparing a new drug application for an NDA to the U.S. FDA. Pharma has previously announced our intention to partner this program with a company having an established commercial capability and a sales force in place. In the interest of time, I will not spend a great deal of time on the glioma development for alutacidamide, but suffice it to say that we are as excited about this potential indication as we are for AML. The Phase I-II data presented at ASCO last year demonstrated a preliminary disease control rate of approximately 50% in a heavily pretreated patient population that was predominantly enhancing recurrent IDH1 mutant glioma. Importantly, PKPD results have indicated that alutacidinib successfully penetrates the brain crossing the blood-brain barrier, which is a necessary element for impacting tumor burden and response. We believe that enhancing glioma represents a large potential commercial upside for elutacitinib due to the high penetrance of the IDH1 mutation in this patient population and the high unmet medical need. With that, I am going to now turn the call over to Dave, who will provide an update on FT7051, or prostate cancer.

Thanks, Pat. I'm going to spend the next few minutes discussing our oral CBP P300 inhibitor, FT7051, which earlier this year began enrolling a phase one trial in metastatic castrate-resistant prostate cancer, or MCRPC. CBP 300 is a required co-activator of androgen receptor-driven gene expression. FT7051 has been shown to 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 abiriderone acetate, or the androgen receptor 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 FT7051 is applicable to a broad range of resistance mechanisms including the ARV7 splice variant which lacks the hormone binding domain and for which there are no approved drugs. The median survival for men with ARV7 variant expression has been reported to be 10.8 months as compared to 27.2 months for AR wild type tumors. We believe that ARV7 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 FT7051 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 that FT7051 reduced histone acetylation in AR-positive prostate cancers, inhibited growth in prostate cancer cell lines, and showed 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 regimens with an adrenal antigen synthesis inhibitor, AR antagonist, or chemotherapy. The trial utilizes an adaptive design, starting with a dose of 25 milligrams 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 ARV7 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-end net need in this population of men and the small number of innovative compounds with novel mechanisms in development, we are very intrigued by the promise of FT7051, and we look forward to sharing initial data later this year. I'll now turn the call over to our Chief Financial Officer, Todd.

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 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 31, 2020, versus $27.0 million and $111.3 million for the quarter and year ending December 31, 2019. This spending supports progress with all three of our compounds in development, FT-4202, alutacitinib, and FT7051, including the start of our Phase I and Phase II-III trials for FT4202 in sickle cell disease, the elutisidinib pivotal Phase II trial in AML, and Phase I-II trial in glioma, and the progression of FT7051 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 31, 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 31, 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 31, 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 following offering completed in December 2020. Our current cash runway extends through the third quarter of 2024, which includes ongoing clinical trials as well as planned commencement of FT4202 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.

Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Tiago Falk with Credit Suisse. He may proceed with your question.

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

Thanks. Thanks for the question, 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.

Yeah, 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. So really, I would say once we unbind, we'll understand treatment effect more specifically. But at this time, really nothing in, you know, 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, the 12-week will give us a lot more detail 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 help inform more about the impact of What happens with such a profound reduction in the hemolytic markers in particular? Does this translate in the background of, you know, a relatively short treatment period of 12 weeks? Does this continue to support our hypothesis that a less inflamed state has to contribute to an improved vaso-occlusive outcome?

Got it. Understood. Thank you so much. Thanks, Tiago.

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

Yeah, hey, good morning, guys. This is Jeet Mukherjee on for Byron. Thanks for taking the questions, and congrats on the progress to date. Was just hoping you could talk us through some of the heme parameters you presented on the 600-meg cohort today. I think we noticed there were slightly fewer patients that were hemoglobin responders at 600-meg versus 300-meg. 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 and the 600 meg cohorts. Thanks.

Yeah, thanks for the question. And before I turn it over to Pat, you know, 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 4202, 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, multi-centered. So I want to give that as context and, um, You know, 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, you know, over the 14 days of treatment. So, let me, with that, turn it over to Pat.

Yeah. So, yeah, just quickly, 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 an equivalent analysis to the 300 milligram first nine patients dose there. Yeah, and I think just touching on what Frank said, you know, it's hard. We don't, yeah, it's difficult to, with small numbers, to take, you know, to dissect on the individual patient level. We, of course, will, when we unblind, we'll do that. But in the general trends of everything, everything's pointing in the right direction. You know, 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 a steady state in terms of biologic response in this population, and that the 400 milligrams for 12 weeks is going to give us much more insight in terms of where 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.

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

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

Thank you very much.

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

Hi, thank you. Could you just walk us through your confidence here in the accelerated approval pathway based on hemoglobin response 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 long-term follow-up maybe later this year and into next year as well.

Yeah, 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.

Sure, yes. You know, as we highlighted, the study design for the hibiscus study was put together last year with SBA input. as well as the 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 U.S. and the EU. You know, 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 Oxybride or 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, you know, we're enrolling up to 20 patients. It's directly enrolling as we indicated. We will provide an update in June on the current patients who are enrolling up to that point. Since it's 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 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.

Thanks very much.

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

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

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

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?

Yeah, 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. Okay, fair enough. And just as a reminder, just as a quick reminder on that, so as we talked about earlier, we are proceeding with the 200 and the 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 characterizing the safety margin, which is, what, 50% over the top dose that we'll be studying in the phase 2-3.

Understood. Thank you so much for taking the questions in, and congrats on the progress. Thanks, Mark.

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.

Well, thank you, everyone, for taking some time to participate in today's call. 2020 was a year of remarkable accomplishments for FORMA, and as evidenced by our news today on the second dose cohort in our multiple ascending dose trial of FT4202 in sickle cell disease, 2021 holds a lot of promise for our continued strong momentum in our R&D pipeline 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.

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