Fulcrum Therapeutics, Inc.

Good morning and welcome to Full Chrome Therapeutics fourth quarter and full year 2024 financial results and business update conference call. Currently all participants are in listen-only mode. This call is being webcast live and can be accessed on the investor section of Full Chrome's website at www.fullchrometx.com and is being recorded. Please be reminded that remarks during this call may contain forward-looking statements within the meaning of 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 because not taking on and any applications to do so. These refer to Wilkrom'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 Wilkrom. Joining Alex on the call are Alan Musil, Chief Financial Officer, and Dr. Ian Frazier, Senior Vice President of Early Development. After providing updates on the company's key programs, there will be a brief Q&A in which Alex, Allen 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 so much, Marvin. Good morning, everyone, and thank you for joining us today. The latter part of 2024 and early 2025 has been an exciting period for Fulcrum, with notable progress for our lead program, Pociridae, currently in development for the treatment of sickle cell disease. With the team we have in place, a year-end cash position of $241 million, and lastly, two data readouts over the next 12 months. 2025 is poised to be an important year for Fulcrum, and more critically, for patients with sickle cell disease and other benign hematological conditions. So let me get into some of the details, and I'll begin by giving an update on Pociridir, our oral HBF inducer for the treatment of sickle cell disease. Now, as many of you know, sickle cell disease is a lifelong inherited blood disorder that severely impacts quality of life for approximately 100,000 people in the US and 4.4 million people worldwide. Historically, the standard treatment for sickle cell disease has involved blood transfusions, pain medications, and hydroxyurea, focusing primarily on symptom relief. And despite the approval of gene editing therapies and their ability to increase fetal hemoglobin levels to transformational levels for patients, there remains a significant unmet need for safe and accessible oral therapeutic options that are broadly protective of sickle cell symptomatology. This unmet need is further underscored by the recent global withdrawal of Oxbrita. And as the first in class oral small molecule HBF inducer, we believe POSIRIDER has the potential to address this high unmet need. In our phase 1B trial of POSIRIDER, which we call the pioneer trial, we have made good progress in enrolling patients and activating sites. And I am pleased to report that we recently enrolled our 10th patient in the 12 milligram cohort with the potential to enroll additional patients currently in screening prior to the next cohort, the 20 milligram cohort, being open for enrollment. Based on the progress that we've made with enrollment, we remain committed to share data from the 12 milligram cohort in mid 2025 and the 20 milligram cohort by year end. Now, just as a quick reminder, patients enrolled in cohort three are receiving 12 milligrams of Posteriori once daily, while patients in cohort four will receive 20 milligrams once daily. Each cohort has a dosing duration of three months, followed by a one-month follow-up visit by the patient. We believe that inducing fetal hemoglobin is the optimal strategy for treating sickle cell disease. Evidence for the benefits of fetal hemoglobin continues to grow, as highlighted by the recent data presented at ASH last December, showing that even modest increases in HBF correlate to reduce disease severity. Specifically, each 1% increase in HBF was shown to provide a 4% to 8% reduction in painful and at times debilitating vaso-occlusive crises, or VOCs. Furthermore, once HBF levels reach into their mid-20s, patients experience a near-abolition of VOCs. Based on Posirider's mechanism of action, and the data that we have previously disclosed, we believe that POSIRADIR has the potential to provide a differentiated therapeutic option for patients living with sickle cell. Beyond POSIRADIR, we continue to make progress in other rare benign hematological conditions. In particular, we are currently conducting IND enabling studies for an oral compound we believe has the potential to treat inherited aplastic anemias such as Diamond Black Fan Anemia, or DBA for short, Schwachmann Diamond Syndrome, and Fanconi Anemia. And we plan to submit an IND for Diamond Black Fan Anemia in the fourth quarter of this year. With that, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials. Alan, over to you.

Thanks, Alex. I'll now go over our results for the fourth quarter. and for the full year ended December 31, 2024, beginning with results for the quarter. We had no collaboration revenues in the fourth quarter of 2024, compared to $900,000 for the fourth quarter of 2023. The decrease was due to the completion of our research services under our myocardial collaboration agreement during the fourth quarter of 2023. Our research and development expenses were $11.7 million for the fourth quarter of 2024, compared to $19 million for the fourth quarter of 2023. The decrease of $7.3 million was primarily due to decreased costs associated with the discontinuation of our Los Mapamod program and global development cost-sharing reimbursements under the collaboration with Sanofi, partially offset by increased costs related to the advancement of the Phase 1b pioneer trial. General administrative expenses were $7.7 million for the fourth quarter of 2024 compared to $9.9 million for the fourth quarter of 2023. The decrease of $2.2 million was primarily due to decreased employee compensation costs resulting from the workforce reduction implemented in the third quarter of 2024. Our net loss was $16.6 million for the fourth quarter of 2024 compared to a net loss of $24.8 million for the fourth quarter of 2023. I'll now review the results for the full year ended December 31, 2024. Collaboration revenue was $80 million for the year ended December 31, 2024, compared to $2.8 million for the same period in 2023. The increase of $77.2 million was primarily due to recognition of the $80 million upfront license payment received from Sanofi during 2024. The research and development expenses were $63.4 million for the year ended December 31, 2024, compared to $71.8 million for the same period in 2023. The decrease of $8.4 million was primarily due to global development cost-sharing reimbursements under the collaboration with Sanofi, partially offset by increased costs related to the advancement of the Phase 1b pioneer trial. General administrative expenses were $36.4 million for the year ended December 31, 2024, compared to $41.7 million for the same period in 2023. The decrease of $5.3 million was primarily due to decreased employee compensation costs as a result of the workforce reduction implemented in the third quarter of 2024. Our restructuring expenses were $2.1 million for the year ended December 31, 2024, compared to no restructuring expenses during the same period of 2023. The increase was due to the workforce reduction implemented in the third quarter of 2024, primarily related to severance costs. And our net loss was $9.7 million for the year ended December 31, 2024, as compared to $97.3 million for the same period in 2023. And now turning to the balance sheet, we ended 2024 with cash, cash equivalents, and marketable securities of $241 million, compared to $236.2 million as of December 31st, 2023. The increase in our cash position was due to the $80 million upfront payment we received from Santa Fe in the second quarter of 2024, partially offset by the cash used to fund our operating activities in 2024. And finally, turning to cash guidance, Based on our current operating plans, we continue to 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 Alan.