Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics third quarter 2024 financial results and business update conference call. Currently all participants are in a listen only mode. This call is being webcast live and can be accessed on the investor section of Fulcrum's website at www.fulcrumtx.com and is being recorded. Please be reminded that remarks during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, may include statements about the company's future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent Fulcrum's views as of today, This should not be relied upon as representing the company's views in the future. Fulcrum may update these statements in the future, but is not taking on an obligation to do so. Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for discussions of certain risks and uncertainties associated with the company's business. Leading the call today will be Alex Sapir, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer, Dr. Pat Horn, Chief Medical Officer, and Dr. Ian Fraser, Senior Vice President of Development. After providing updates on our key programs, there will be a brief Q&A in which Alex, Alan, Pat, and Ian will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex.

That's great. Thanks, Michelle, and good morning, everyone. I appreciate you joining us for our third quarter conference call. Today, I'll provide you with updates on recent progress and upcoming milestones. I'll then hand the call over to Alan to review financials, and finally, we'll end by taking your questions. I'll begin with a very brief review of the update we provided on the Los Mapamod program back in September. As you'll recall, we reported that Los Mapamod did not show separation from the placebo group on the primary or key secondary endpoints in the Phase III REACH trial. In light of these results, we suspended the development of Los Mapamod and announced a workforce reduction of approximately 40% in order to focus our research and development efforts on advancing post-serodere and our preclinical pipeline. This included a reduction of positions across both research and development, as well as general and administrative functions. I do want to take a moment to express my gratitude to the patients, physicians, and clinical coordinators who participated in our trials. to the FSHD Society and to the broader FSHD community. We sincerely appreciate all of your support in advancing the Los Mapamad program, and we remain fully committed to sharing the full results of the REACH trial for the benefit of the FSHD community. Although we were disappointed that the Phase 3 results did not replicate what was shown in Phase 2, the entire Fulcrum organization remains deeply committed to our mission of improving the lives of patients with genetically defined diseases in areas of high unmet need. To that end, we are excited to continue advancing Posterior Dare, our oral HBF inducer, for the potential treatment of patients with sickle cell disease. Sickle cell disease is a lifelong inherited blood disorder that severely impacts quality of life for approximately 100,000 people in the US and approximately 4.4 million people worldwide. Historically, the standard of treatment for patients with sickle cell disease has involved blood transfusions, pain medications, and hydroxyurea, focusing primarily on symptom relief. Despite the recent approval of gene editing approaches, we believe there remains a significant unmet need for safe and accessible oral therapeutic options that are broadly protective of sickle cell symptomatology, which is further underscored by the recent global withdrawal of Oxprita. As a first-in-class oral small molecule HBF inducer, we believe that Pociradir has the potential to address this unmet need. Now, in our Phase 1b trial of Posterior Dear, which we call the Pioneer Trial, we continue to make progress in enrolling patients and activating sites. We are focused on progressing the development of Posterior Dear as expeditiously as possible and remain on track to provide data from the Pioneer Trial in 2025. Based on our progress in site activation and current enrollment trends, we intend to provide more detailed guidance on our plans to share data early in the new year. As a reminder, cohort three of the trial is evaluating Posteriori at the 12 milligram once daily dose with a dosing duration of three months. And this will be followed by cohort four at the 20 milligram once daily dose also for three months. Both cohorts are expected to enroll up to 10 patients. In addition to the ongoing pioneer trial, we are also pleased to report that we are initiating phase one clinical trials of Posterior Dare in healthy volunteers following recent interactions with the FDA. These studies are intended to support the comprehensive development program for Posterior Dare. The literature supports that any increase in fetal hemoglobin is beneficial for patients with sickle cell disease. And most importantly, when sickle cell patients achieve fetal hemoglobin levels in the mid to high 20s, their disease presentation may become asymptomatic. We believe that as a novel inducer of fetal hemoglobin, POSIRIDER has the potential to provide a differentiated therapeutic option for people living with sickle cell disease. We look forward to building on the encouraging clinical data generated prior to the hold, which demonstrated that POSIRIDER increased total fetal hemoglobin of a magnitude that could translate into meaningful improvements in disease severity. Now, beyond posterior deer, we are also focused on advancing our early-stage development programs in inherited aplastic anemias, such as Diamond, Black-Fand anemia, or DBA, Schwachmann-Diamond syndrome, or SDS, and Fanconi anemia under our licensing agreement with CAMP4. We anticipate sharing additional information regarding a development candidate and plans for IND-enabling studies in the near future. I also wanted to provide some updates on the management and board of directors front. This morning we announced that Rachel King has joined our board of directors. Having served as the CEO at Bio, executive in residence at NEA, as well as CEO of several early stage biotech companies, Rachel's experience is well aligned with Fulcrum's needs given where we are in our evolution. She currently serves on the board of Novavax and Glycomimetics. Rachel will be replacing Jim Collins, who will be transitioning to an advisory role on our Science and Technology Committee. I am personally excited to have Rachel joining us and also pleased that we will continue to benefit from Jim's deep scientific acumen and sound judgment. Now, on the management front, Dr. Thomas Winkler joined us in September as our Vice President of Hematology Clinical Development. and has assumed responsibility for our hematology program, but also for the Pioneer study. Thomas has a distinguished career within the hematology branch of the NIH before transitioning to industry, where he focused on developing numerous hematology assets at both Agios and AstraZeneca. Additionally, Pat Horn, our chief medical officer, has decided to retire at the end of this year. Pat joined Fulcrum earlier this year and was instrumental in leading clinical development for the REACH study, hiring key talent like Thomas, and building out the medical team as we prepared for the launch of losmapamide. I would like to personally thank Pat, who is here with us in the room today. Thank you, Pat. As well as express my appreciation to Thomas for bringing his strong hematology background to Fulcrum at such a critical time. And with that, I will now turn it over to our Chief Financial Officer, Alan Musso, to run through the numbers. Alan, over to you.

Thanks, Alex. I'll now review our financial results, starting with our cash position. As of September 30, 2024, cash, cash equivalents, and marketable securities were $257.2 million, compared to $236.2 million as of December 31, 2023. The increase in our cash position is due to the $80 million upfront payment that we received from Sanofi in the second quarter, partially offset by cash used to fund our operating activities in 2024. We had no collaboration revenue in the third quarter of 2024 compared to $0.8 million for the third quarter of 2023. The decrease of $800,000 was due to the completion of our research services under our collaboration agreement with Myocardia. during the fourth quarter of 2023. Our research and development expenses were $14.6 million for the third quarter of 2024, compared to $18.2 million for the third quarter of 2023. The decrease of $3.6 million was primarily due to the global development cost-sharing reimbursement under our collaboration with Sanofi for Los Matamad, partially offset by increased costs related to the advancement of our Phase 1b pioneer trial. General administrative expenses were $8.4 million for the third quarter of 2024 compared to $10 million for the third quarter of 2023. The decrease of $1.6 million was primarily due to decreased employee compensation costs as a result of our reduction in workforce implemented in the third quarter of 2024. The net loss was $21.7 million for the third quarter of 2024 compared to a net loss of $24 million for the third quarter of 2023. Finally, turning to our cash guidance, we expect to end 2024 with approximately $240 million of cash, cash equivalents, and marketable securities. And we expect that in 2025, our cash burn will be approximately $55 to $65 million. Based on current operating plans, we expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operating requirements into at least 2027. And with that, let me turn the call back over to you, Alex. Okay, great.