Fulcrum Therapeutics, Inc. (FULC) on Q2 2022 Results - Earnings Call Transcript
Operator: Good morning, and welcome to the Fulcrum Therapeutics Second Quarter 2022 Conference Call. Currently all participants are in a listen-only mode. There will be a question-and-answer session at the end of this call. Please note today's conference is being recorded. I would now like to turn the call over to Stephanie Ascher from Stern Investor Relations. Please proceed.
Stephanie Ascher: Thank you, Rocco. Good morning, and welcome to the Fulcrum Therapeutics conference call. Please be reminded that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about our future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent our views as of today, they should not be relied upon as representing our views in the future. We may update these statements in the future, but we are not taking on an obligation to do so. Please refer to our most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business. With me on today's call are Bryan Stuart, President and Chief Executive Officer; Judy Dunn, our President of Research & Development; and Esther Rajavelu, our Chief Financial Officer. In addition, Paul Bruno, our Executive Director of Corporate Development will be available for Q&A. Let me quickly run through this morning's agenda. Bryan will begin the call with a corporate overview and key updates, Judy will review our clinical program. Esther will cover our financials and then Bryan will open the call for Q&A. With that, it's my pleasure to turn the call over to Bryan.
Bryan Stuart: Thank you, Stephanie. Good morning, everyone and thank you for joining us today. At Fulcrum, our mission is to treat the root cause of rare genetic diseases. And in the second quarter of 2022, we have made significant progress in advancing two clinical-stage assets that support that mission. The first is our FSHD program, which is now in Phase III, positioning losmapimod to be the first-to-market therapy for an untreated patient population. The second is FTX-6058, a once-daily HbF inducer with the potential to be the first oral therapy that can broadly improve outcomes in sickle cell disease and other hemoglobinopathies. I'll start with an update on FTX-6058. HbF induction is the only mechanism which has been shown to broadly improve outcomes and reduce both the frequency and severity of sickle cell disease symptoms such as VOCs, anemia, pain, fatigue and acute chest syndrome. A wide-body of evidence has demonstrated that increasing HbF by 5% to 10% above baseline levels produces benefits that could be transformative for patients with sickle cell disease, an oral therapy that can produce robust increases in HbF has been a therapeutic goal in sickle cell disease for some time, which is why our initial data from our Phase Ib trial are so exciting. In June, at the European Hematology Association Conference, we showed compelling proof-of-concept that FTX-6058 rapidly induces HbF protein in sickle cell disease patients and demonstrated that it is able to achieve absolute HbF increases within the 5% to 10% range that clinicians have targeted as the future standard of care. These initial data underscore the potential of FTX-6058 to disrupt the sickle cell disease treatment paradigm. They have also provided valuable insights to inform our path forward for the program and the Phase Ib trial, where we expect to complete enrollment in three cohorts including a new higher dose cohort by year-end. We are also making rapid progress in our FSHD program. In the second quarter, we announced the enrollment of our first patient in the Phase III REACH trial. Although FSHD is the second most common form of muscular dystrophy, until now no potential FSHD treatments have progressed to late-stage clinical development. Data from our Phase II ReDUX4 trial indicate that losmapimod has the potential to slow or stop disease progression and in some cases even improve function in FSHD patients. The REACH trial will enroll 230 patients at over 30 sites in the US, Canada, UK and the European Union. As a landmark trial for this disease, REACH has already received a tremendous amount of enthusiasm and interest from both patients and clinicians and we expect to complete enrollment in 2023. The progress that we have made with our clinical programs positions Fulcrum to move into the next phase of our growth, as we prepare to potentially have two registrational candidates within the next year. This is a pivotal moment for our company and in order to facilitate this transition and to ensure that we are aligned, as an organization to deliver near-term value for our clinical program. This morning, we laid out our strategic plan to realign our internal investments and operations to focus resources, on our two lead programs losmapimod for FSHD and FTX-6058 for sickle cell disease, while streamlining our discovery efforts. Esther will provide additional details on our plans. However, I would like to highlight that changes that we have instituted, extend our cash runway into mid-2024, enabling us to achieve key milestones in both clinical programs. As part of these organizational changes, we have made changes at the leadership levels. Mel Hayes, who joined Fulcrum in 2021 as Chief Commercial Officer, has been promoted to the role of Chief Operating Officer. In this new position, Mel will help guide execution of the day-to-day operations of the company in addition, to its current commercial responsibilities. Additionally, we have expanded the role of Curt Oltmans, our SVP and General Counsel. Curt will now take on the role of Chief Legal Officer. This is a very exciting time for our company. The strategies we are implementing, are designed to enable us to deliver on our near-term business imperatives, while we forge ahead with our mission of building a leading biopharmaceutical company, poised to bring transformative therapies to patients with genetically defined rare diseases. And with that, I'll turn it over to Judy, to talk more about our clinical programs. Judy?
Judy Dunn: Thank you, Bryan. As Bryan noted, last quarter we made significant advances in our two clinical stage programs. I'd like to begin by reviewing our 6058 program and the ongoing Phase 1b trial in sickle cell disease. There are significant unmet needs in sickle cell disease treatment landscape. We're all familiar with the efficacy, safety and tolerability challenges associated with hydroxyurea. Even the newer treatment options, only address the symptoms of the disease, rather than targeting its broad symptomatology. Other therapies in development such as gene editing approaches, present challenges due to the invasiveness and inaccessibility of the treatment. A safe and tolerable, oral small molecule that produces robust HbF increases, would be the new standard of care for sickle cell disease patients. As a once daily, oral HbF inducer, 6058 has tremendous potential to deliver life-changing benefits for people living with sickle cell disease. 6058 originated through our Fulcrums discovery engine, and is a potent and highly selective EED inhibitor, with a clean off-target profile. We have strong preclinical evidence, and now clinical evidence in sickle cell disease subjects, demonstrating that 6058 produces rapid and durable HbF induction. The ongoing Phase 1b study is designed to be a dose-ranging, multiple cohort study. Each cohort can enroll up to 10 subjects and is comprised of a 28-day initial treatment period. At the end of the treatment period, all subjects are offered the opportunity to participate in an eight-week treatment extension, resulting in a total of up to three months of exposure. The goal of the Phase 1b study was to first and foremost established that 6058 inducive HbF protein, in people with sickle cell disease. The data from initial patients that we presented at EHA, shows not just protein induction within 14 days of treatment initiation, but at the six mg dose, we were already able to achieve absolute increases in HbF within that 5% to 10% range that provides broad clinical benefits. In addition to HbF increases, we also observed meaningful changes in other biomarkers absolute reticulocyte count, total hemoglobin and total bilirubin that were indicative of clinical improvement through decreased hemolysis and less . Consistent with our healthy volunteer data, initial data from the 1b study indicates that 6058 was generally well tolerated with no serious, treatment-emergent adverse events. No SAEs were reported on study drug and there were no discontinuations recorded, due to treatment-emergent adverse events. Currently, we continue to enroll patients who are receiving HU as well as those who are not into the six mg and two mg dose cohorts of this Phase 1b study. It's important to understand the efficacy and safety of these drugs in combination, because although 6058 is intended to be used as a monotherapy, patients not fully responsive to hydroxyurea, may receive 6058 concomitantly. Our preclinical data indicates that there may be an additive or synergistic effect between these two drugs. Additionally, we plan to initiate a third higher-dose cohort this fall. The combined data from these cohorts will be critical as our aim is to move as efficiently as possible and selected optimal dose for the Phase 2/3 trial which we intend to be registrational. We expect to complete enrollment in three dose cohorts by the end of the year and anticipate initiating registrational trial in 2023. We've learned a lot from the early days of enrolling sickle cell patients into this study and we've used these learnings to refine our clinical execution and site operations. Specifically, as we have better understood some of the challenges around adherence, we implemented observed dosing. We've already seen a benefit. So, we're confident that as we complete the remainder of this study, we're collecting high-quality data that accurately represents the effects of 6058 in sickle cell disease patients. Moving on to FSHD and our losmapimod development program. This is another area where we are working to address a clear and critical unmet need. As Bryan mentioned, FSHD is the second most prevalent form of muscular dystrophy. It's estimated that there are 16,000 to 38,000 FSHD patients in the US alone and approximately 0.5 million patients worldwide, but there are currently no available therapies. The continually progressive nature of FSHD, a disease in which basic motor functions and quality of life begin to decline in a patient's second decade of life, emphasizes the urgent need for a disease-modifying therapy, as well as the value of our losmapimod program, which is the most advanced treatment in development for this disease. In the Phase 2 ReDUX4 trial, we looked at the effect of losmapimod in 80 FSHD patients over a 48-week treatment period. In addition to assessing the safety and tolerability of losmapimod, we also wanted to understand how to best study FSHD as our trial was the first of its kind for this disease. We looked at everything from the length of time needed to show an effect on disease progression to the appropriateness assessments for detecting changes. After 48 weeks, losmapimod demonstrated clinically meaningful benefits such as preservation of muscle health as measured by MRI, muscle function as measured by reachable workspace, and patient quality of life assessed by patient global impression of change. Importantly, losmapimod was very well-tolerated with no serious treatment-related adverse events. The extensive work that was done as part of the ReDUX4 trial has enabled us to design the Phase 3 REACH trial in a very efficient manner reaches a 48-week double-blind placebo-controlled trial. Reachable workspace a quantitative measure of function is its primary endpoint. The secondary endpoints of the REACH trial include muscle fat infiltration, the Neuro-QoL, a qualitative measure of function, and the patient's global impression of change. As we prepare for commercialization, we'll also be probing health care utilization and other economic and outcomes research metrics. As the first ever Phase 3 trial in this disease, REACH represents an enormous milestone for the FSHD community. Since enrolling our first patient in June, we have been moving quickly to begin enrolling at sites across North America and Europe and we are on track to complete that process next year. We are incredibly proud of both our clinical programs and we look forward to sharing more in the future. With that, I'll turn it over to Esther to walk through the financials. Esther?
Esther Rajavelu: Thank you, Judy. Following up on Bryan's comments about our organizational changes, I'd like to first provide more detail on our strategy and focus going forward and then provide an update on our financial performance in the second quarter. As you heard from both Bryan and Judy, our two clinical stage programs have gained momentum and the business realignment that we announced today, reflects our confidence in the progress we have made and expect to make in the near-term with both programs. Fulcrum is well-positioned to transition from an early-stage clinical company to a pivotal stage company with two assets potentially in registration-enabling trials within the next year. We intend to build on our success by prioritizing execution on these clinical stage assets. Consequently, we have taken steps to realign our internal investments and organizational structure to prioritize these key value-driving programs, while streamlining our research and discovery efforts. In our clinical programs, we are focused on rapidly generating value-enhancing data from our Phase Ib sickle cell disease and Phase III FSHD programs. While in discovery, we are now scaled appropriately to efficiently identify targets and generate an IND in 2023. As part of the realignment towards our lead clinical programs, we are delaying the planned initiation of the Phase Ib trial in beta-thalassemia and other non-sickle hemoglobinopathies, as well as some ongoing discovery and preclinical projects that are not core to our areas of focus. A key consideration of our strategy is the desire to remain nimble and adaptable. So, even as we plan to deliver on key value-driving clinical programs, our discovery engine is enabled to be flexible and opportunistic towards ongoing and future collaborations. The changes we have implemented are expected to result in savings of $40 million to $50 million, which includes a 25% planned reduction in our workforce. This realignment of internal investments and organizational structure to realize near-term value from both our clinical programs also extends our cash runway into mid-2024. As you can see, these changes allow us to operate from a continued position of financial strength, as we end the second quarter with $169 million in cash, cash equivalents and marketable securities. Now, I will briefly review the financials for this quarter. During the second quarter of 2022, we recognized collaboration revenue of $1.9 million compared to $4.4 million recognized during the second quarter of 2021. Second quarter '22 R&D expenses were $25 million compared to $17.4 million for the second quarter of 2021. G&A expenses for the second quarter of 2022 were $11.1 million compared to $6.7 million for the second quarter of 2021. And our net loss for the second quarter of '22 was $34.1 million compared to a net loss of $19.6 million for the second quarter of 2021. With that, I'll turn it back to Bryan.
Bryan Stuart: Thanks, Esther. Before we close today, I want to thank our incredible team at Fulcrum, including those employees who have been impacted by our recent organizational changes, whose contributions we value greatly. I would also like to thank our patient communities, clinical trial partners and shareholders for their continued support. Operator, you may now open the line for questions.
Operator: Thank you. We will now begin the question-and-answer session. Today's first question comes from Judah Frommer with Credit Suisse. Please go ahead.
Judah Frommer: Hi. Thanks for taking my question and for all the updates. A couple from us. First, can we just start with the high dose cohort for the Phase Ib in sickle cell? Can you remind us, why you went low dose first and are now adding the high dose? And then, also for the Phase Ib, can you give us any more color on how compliance has improved and what you're seeing as you enroll patients in what I think are some incremental sites versus the initial data cut.
Bryan Stuart: Yes. Sure, Judah. Happy to and let me turn it over to Judy and we can speak both to our approach to dosing and then some of the changes that we implemented in the clinical trial.
Judy Dunn: Yes. Good morning, Judah. So as you know, our Ib trial was designed as a dose ranging study. And so we started somewhere in the middle of that range at six milligrams because we wanted to choose a dose that if we were going to see HbF, we felt confident that we would. And that's exactly what happened in six milligrams. We already achieved that 5% to 10% increase that we're looking for. So now in the dose ranging, what we really need to do is to explore that range in the trial, it's two mgs to 20 mgs and that's really based on our experience from healthy normal volunteers. And we're also going to get some experience with HU. And so we're on track to deliver those three cohorts, and select a dose that enables us to go into a registration trial next year. In terms of the execution, it's a great question, and we're in really good shape in terms of how this trial is being executed currently. We've made some significant changes into how we operationalize it. So we do have more sites. And what that allows us is, to access a broader base of sickle cell disease patients. And also, we've implemented observed dosing. So we have patients showing up on video be a computer or cell phone, every morning, and the site witnesses the dosing. And that's proven extremely effective. We have a really great rate of compliance in terms of patients showing up very regularly. And I think this puts us in a good position to ensure that, we're going to deliver a robust data set of high-quality data when we finished enrollment.
Judah Frommer: Okay. That's great. A quick follow-up to that and then one for Esther, have you identified the high dose, or are you still deciding on exactly what it will be? And then just for us on the $40 million to $50 million in savings, do you have a cadence I think you said it would be kind of over the next it sounds like 18 months to 20 months or so?
Judy Dunn: Yeah. I'll start Judah with naming that high dose. We continue to enroll patients as I said in the two mg and six mg and you know we're using quantitative pharmacology modeling to name that high dose. So when we have that data we'll start the high dose. But we haven't shared that information yet and we're still examining that data.
Esther Rajavelu: Yes. And Judah, to answer your question on the $40 million to $50 million savings that extends our runway into mid-2024, so that's the time frame for that.
Judah Frommer: Okay. Thank you.
Operator: And our next question today comes from Matthew Harrison of Morgan Stanley. Please go ahead.
Unidentified Analyst: Hi. Thanks for taking our questions. This is Yuzhong Ma on behalf of Matthew. So we have one question on 6058 and one question about the cash. So for the SCD program, how have the changes you have made to the clinical program impacted the enrollment rate of the new patients for SCD? And when will you estimate for additional data updates? Do you still think an accelerated approval still possible? And for the cash, do you still think you could extend the cash runway further with the current strategic change? Are you considering potential partnership for the FSHD program, if the phase 3 study extends beyond 2024? Thanks.
Bryan Stuart: Yeah. So great question and let me just make sure we're addressing all of those. Maybe we'll start with 6058. And the question is being about enrollment based on some of the changes and progress that we've made, as well as the potential for accelerated approval. And I'll turn it over to Judy.
Judy Dunn: Sure. First I'll speak to the enrollment question. And as I said in my earlier comments we've made significant changes to how we operationalize this trial. So you always start out with a fewer number of sites. We've increased our number of sites. We've increased that patient base that we can draw from and then on top of enrollment, as I said that other really important piece of operationalizing this program is that, observed dosing. So we are enrolling at a rate that gives us confidence that we'll be able to complete enrollment by the end of this year. So the second part of your question was around accelerated approval and that's really a question for what we're going to do in that registrational trial. So we're on track to complete enrollment in the Ib this year. At that point, we'll look at the data. We'll select the dose. We'll have a conversation with the regulators. But we really think that HbF is such a â it's an important biomarker. It's an important driver of efficacy. And so we will have that conversation, in terms of could it be HbF surrogate for an accelerated approval followed by a clinical outcome. But those conversations haven't occurred yet, and we'll start that study. Our plan is to start that study in 2023.
Bryan Stuart: Great. I think the second part of your question, we can turn it over to Esther, and talk about FSHD timing and how we think about runway.
Esther Rajavelu: Yeah. Sure. So the current run rate guidance is into mid-2024. And that includes completing enrollment in the Phase 1b trial the start of a registration-enabling Phase 2/3 in 2023 for the sickle program and also includes completing enrollment in our Phase III REACH program. So we are funded into mid-2024 with that as an operating plan in addition to an IND in 2023. With regards to your question on flexibility to extend it beyond mid-24, look, we're a company that is moving from a clinical stage to a pivotal stage. And we have built-in enough flexibility in there to be nimble and flexible as our plans evolve.
Bryan Stuart: And maybe just one other point and just to reemphasize this, we've spoken about this a lot as it relates to FSHD. I think, one of the things we were very encouraged by was how quickly we enrolled the Phase IIb trial. And that's just due to the severity of the disease, unfortunately the tremendous unmet need that exists. Obviously, we were very enthusiastic about the data that we generated in the Phase IIb. And as we transition now into our registrational trial, as we mentioned, there's a lot of enthusiasm from patients and clinicians and caregivers for the opportunity to participate in the trial and we're excited to get that up and running and look to enroll as quickly as it's feasible.
Unidentified Analyst: Thanks. Just a very quick follow-up. Do you have an estimate of the time line of data report for the Phase Ib trial in SCD? So when are you expecting additional data for all the three doses cohort?
Judy Dunn: Yes. So what we've guided to is completing enrollment by year-end in all three cohorts. And we've also indicated that our next data update will be a comprehensive update with the full data set from all three cohorts in the Phase Ib.
Unidentified Analyst: Okay. Cool. Thanks a lot.
Operator: And our next question today comes from Ted Tenthoff with Piper Sandler. Please go ahead.
Ted Tenthoff: Great. Thank you, very much. And thanks for the update. Obviously, lots of questions on 6058. So I had a question more on the continued discovery efforts. I'm really pleased to see, that is, continuing to invest in FulcrumSeek and advancing additional differentiated pipelines. Can you tell us about where sort of the lead efforts are there and maybe give us somewhat of a sense of what might be sort of a lead program that could emerge as the next IND? Thanks.
Bryan Stuart: Yes, absolutely, Ted. I'll turn it over to Judy. And I think we -- from our perspective, obviously, we remain extremely enthusiastic about FulcrumSeek and our discovery approach. And both of these programs came from FulcrumSeek. And I think one of the particularly powerful elements of the engine is, as we discover targets it gives us the ability to either in-license chemical matter or create our own and move very quickly into the clinic. So this still remains a very important focus and investment in the company. And in terms of exact areas of focus, I'll let Judy go from there.
Judy Dunn: Yes. Good morning. Thanks for the question. As Bryan said, FulcrumSeek really offers us a lot of optionality. We are identifying targets in our main therapeutic areas of interest and those are hem, muscle and cardio. It also gives us the opportunity to do collaborations. We have a number of late-stage discovery programs and projects right now in the pipeline and we have guided to an IND in 2023 and we're on track for that. And because we have a couple of things that we're considering, what I can say is, it will be one of those key areas for us hem, muscle or cardio. But beyond that we're not going to provide any other information until we're that further along.
Ted Tenthoff: Understood. And would this be something that the goal would be to take forward more yourself, or do you also see as additional partnering opportunities emerging from FulcrumSeek? Thanks.
Bryan Stuart: Yes. I would say both, Ted, I think, as we referenced our next IND and as Judy spoke to 2023, that's something that we intend to move forward ourselves. But as we've shown in the past with the collaborations that we've done, there is broad applicability to the product engine. We feel like it's certainly been validated both with our collaborations, but more importantly with our clinical programs and the data we've been able to generate. So we intend to continue to follow the same strategy that we've done, move programs forward ourselves in our areas of focus and look for collaborations outside of those areas and we hope to continue to do both.
Ted Tenthoff: Great. Thank you.
Operator: And our next question today comes from Dae Gon Ha with Stifel. Please go ahead.
Dae Gon Ha: Great. Good morning. Thanks for taking my questions and congrats on the progress. I wanted to revert back to the 6058 program. And I'll just cut it short with two questions. On the 6058 data that we saw at EHA, appreciating the need to establish the minimally efficacious dose or a minimally safe dose, we also saw that there was about 25% to 30% lower exposure in SCD patients versus healthy volunteers. So I guess just thinking about the cohort three enrollment plan for the fall, would it make sense to start sort of earlier on at say, like a 10-milligram collect all the data from six, two and perhaps a little bit of the 10 and then think about perhaps opening a fourth dose that could really help on the triangulation of that final registration trial level dose. That's question one. And then on the second question, just wanted to clarify the ongoing trial, I guess, Cohort 1 it sounds like you're enrolling now both HU Experience and HU-Naive. I wanted to clarify that. And once that's clarified if you can comment on sort of the preclinical assessments that you saw, what the sort of transitional gap might be once you move into the clinic you mentioned additive or potentially synergistic, but any other confounders that we should be thinking about as you dose the patients. Thanks so much.
Bryan Stuart: Yeah. Thanks for the question Dae Gon. I'll turn it both over to Judy. One, in terms of how we're thinking about the different doses in the cohorts and maybe what data we want to get out of that? And then, two, as we are gaining this additional HU Experience, what -- as you said are there any gaps? What is the value of that data as we put together our plan moving forward?
Judy Dunn: Yeah. Hi Dae Gon, as you know, we designed this experiment to help us select that dose for registration. And we designed it with three cohorts in mind, because based on our experience in healthy normal volunteers that's likely sufficient. That said, we have the flexibility, if we need to do a fourth cohort to do that. We would like to enroll these three cohorts. And your question about exposure is a really important one. We continue to collect data at six milligrams and two milligrams. We'll understand that exposure. And then, we can take that difference in exposure into consideration as we select our next dose. And that's what the quantitative pharmacology modeling does. It's really not based on dose it's based on exposure. And so we can select the dose hopefully based on three, but your question is a good one. And we have that flexibility. So we think we need four. I think the second part of your question is, are we seeing hydroxyurea patients and not? And yes, we are enrolling patients both on and off hydroxyurea. And that's simply because people may be on hydroxyurea. It's standard of care. And we want to understand that interaction. And then, from a preclinical perspective, I'll hand it over to Paul to give us some information on what we saw mechanistically.
Paul Bruno: Yeah. And Dae Gon, as you probably recall the CD34 assay for us has been highly predictable at least of HbF clinical response. And in our hands combinations of 6058 and hydroxyurea have been additive or synergistic. And so our assumption based on this asset is that we would see similar additivity or synergy in the clinic.
Operator: Thank you. Ladies and gentlemen, today's next question is from Matt Biegler with Oppenheimer. Please go ahead.
Matt Biegler: Great. Hye guys. Thanks for the update. Great news to hear that you're planning to explore the higher 6058 cohort, can you tell us whether that decision was based on any new safety data that's emerged at EHA? And is the goal still 5% to 10% HbF or might you even be able to push that higher? And then I have a follow-up?
Bryan Stuart: Yeah. Maybe let me start Matt and thanks for the question. Maybe I'll start with the second question, and then I'll turn it over to Judy for the first question. In terms of our goal and as we've talked about we have the benefit here of there being so much data about HbF and the benefits of HbF. And that's from systematic literature reviews, hereditary persistence of fetal hemoglobin real-world evidence and now gene editing data. So I think that very consistently shows. And we continue to hear from the KOLs that, because HbF broadly impacts all of the symptoms of the disease, the data shows when you can get to those levels of 5% to 10% can really have a transformational benefit. And the feedback is that at those levels that 6058 would be standard of care for sickle cell disease. So that remains our therapeutic goal. Certainly, as we explore different doses, different combinations, obviously we'll want to understand whether we can achieve that goal maybe even in some cases go beyond that goal. But at that 5% to 10% level, the feedback is because of all of the benefits that this drug would be standard of care. So that's where our focus is. And let me turn it back over to Judy now.
Judy Dunn: Sure. In terms of that Ib trial, it was always our plan to dose higher. So we haven't seen anything whether that's clinical tolerability or anything in our ongoing toxicology program that has changed our plan in any way. I think in terms of that 5% to 10% range Bryan has already spoken earlier particularly about why we have such confidence in that. But I think what we need to remember is, if you think back to our 6-milligram data, that HbF level was still increasing. So we don't know how we would need to go or if we would need to go higher and that's exactly why we're doing this study.
Matt Biegler: Right. Okay, that makes sense. And then I just â I wanted to just have a follow-up about the delay or the decision to delay the beta-thal indication. Is there a higher bar for what's needed in terms of HbF induction in that indication? And I mean should we be reading into that as to think of that maybe that's why you're choosing to delay it or is there something else in terms of competitive landscape that is right now it doesn't make sense to you? Thanks.
Bryan Stuart: Yes. Thanks, Matt. So I mean nothing's changed at least with regards to our conviction around beta-thal. I think the thing to highlight here is that the dose ranging that we're doing in the sickle study we can actually leverage those insights for beta-thal. And so we just see this as a more efficient way to go into the beta-thal trial rather than doing dose range in that study as well.
Matt Biegler: All right. Thank you.
Operator: And our next question today comes from Joseph Schwartz at SVB. Please go ahead
Joseph Schwartz: Hi, everyone. Thanks very much. I was wondering if you could talk a little bit more about your clinical affairs organization, the people that are the boots on the ground, any liaisons, any other initiatives you have in order to ensure that you can generate an adequate quantum of data for the community with sickle cell for 6058. And do you have any goals you can share in terms of numbers of patients and at certain time points and maybe even for certain durations for 6058 as a mono and combo in your ongoing effort in the Phase Ib that you can share? For example, what will we learn by the end of the year? And that's really the crux of my main question. Thank you.
Bryan Stuart: Yes. And Joe maybe we can â we'll split those up and Judy can broadly speak to just some of the clinical initiatives and the things that we've been undertaking which is also a meaningful part of the broader announcement today is that we are ensuring that we are really investing sufficiently in this program because of our enthusiasm about its potential and the data that we've already generated. And then Esther can guide just a little bit more to what we've shared in terms of enrollment and data disclosure.
Esther Rajavelu: Sure. I'll start out with our outreach into the sickle cell community. We have what we think is a really robust on-site presence here in our clinical organization. And what we have been able to do is very quickly integrate ourselves into working with the community-based organizations in the sickle cell community. It's a really important group within this community and one that our patient advocacy group has been working closely with. So in terms of that that's really kind of where we are from a clinical perspective. Your question around the Ib study, we're going to enroll as we said up to 10 patients per cohort. A couple of those in each cohort will be on HU. And that's really just to help us to understand that potential synergy and we'll have this enrolled all three cohorts enrolled by the end of the year.
Joseph Schwartz: Thanks. Will we get an update on the first patient exposed to 6058 perhaps at ASH or a press release at any point?
Bryan Stuart: Yes. I think Joe at this point, what we've guided to and I think one of the reasons that we chose to share the initial data at EHA is, we had made a commitment to do so. And we were very enthusiastic about the fact that we were seeing HbF increases. We were seeing them very quickly. We were already seeing robust increases. And that, obviously, gives us a lot of conviction for the program. Moving forward, what we want to do now is to get all three dose cohorts enrolled and then be able to share a complete data set rather than on a piecemeal basis. We feel like we've certainly established proof of concept. And now moving forward we want to share the complete data set, which is really going to inform what dose we take into our registrational trial.
Joseph Schwartz: Understood. Thank you.
Bryan Stuart: Thanks, Joe.
Operator: Today's next question comes from Yatin Suneja with Guggenheim. Please go ahead.
Yatin Suneja: Hey, guys. Thank you. A quick question for me on the sickle cell program. Can you just talk about what is your estimation of peak time to HbF induction? Are you thinking about perhaps a little bit longer Phase 1b longer duration just to get a better idea of when you are reaching the peak and is the next cohort that you're starting acute for that? Thanks.
Bryan Stuart: Yes, it's a great question. I think that was really one of the key questions that we wanted to understand going into the Phase 1b was both how quickly are we seeing HbF increases knowing that there will be patient benefit that will follow? And then what does that curve look like? One of the things that we talked about as we looked at other HbF-inducing mechanisms is typically maximal occurred within three months to five months, but we wanted to understand these curves. As Judy referenced, we've been encouraged that based on the early data that we shared at EHA, HbF was still increasing at the three-month time point and it was already getting into this 5% to 10% range. So both of those were highly encouraging. At this point, I think, we need to gather more data which we will during the course of the trial to understand these curves do the curves vary based on dose. But the fact that we're already seeing robust increases, we're seeing the increases occur within weeks. I think it's all very encouraging and more data will better inform this.
Yatin Suneja: Thank you.
Operator: Thank you. This concludes the question-and-answer session for today. I would like to turn the call over to Bryan Stuart for closing remarks.
Bryan Stuart: Great. Thank you. Thanks everybody for joining us. We very much appreciate the support of Fulcrum. And have a great day.
Operator: Thank you, sir. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.
