Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Territic's first quarter 2025 financial results and business update conference call. Currently all participants are on 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 Meaning the meaning of the Private Securities Litigation and Form 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 Farcom's view as of today, they should not be relied upon as representing the company's views in the future. Farcom may update these statements in the future, but is not taking on an obligation to do so. Please refer to Farcom's most recent filings 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. After providing updates on the company's key programs, there'll be a brief Q&A in which the Fulcrum management team will be available for questions. With that, it is my pleasure to turn the call over to Alex.

Thank you, Livia, and good morning, everyone, and thanks for joining us today. So before jumping into the updates for the quarter, I just wanted to take a moment to welcome Dagon Ha, the newest member of the Fulcrum management team, as our senior vice president, head of strategy and business development. Now, Dagon is no stranger to Fulcrum, nor to the sickle cell space. For the past five years, Dagon was an equity research analyst at the banking firm Steeple covering Fulcrum. Dagon, whose first day with the company is today, will be focused on overall corporate strategy and business development here at Fulcrum as we continue our efforts in sickle cell disease and other benign hematological conditions. So now, let's turn to the updates for the quarter. The past several months have been an exciting period for Fulcrum as we've continued to make good progress with our lead program, Pociradir, which is currently enrolling in a phase 1B trial, a trial that we call Pioneer, for the treatment of sickle cell disease, an inherited blood disorder afflicting approximately 100,000 people in the US and approximately 4.4 million people worldwide. I am pleased to announce that we've completed enrollment in the 12 milligram cohort, cohort three, with a total of 16 patients enrolled and plan to share results of this cohort in early Q3. These data will include key baseline patient characteristics, adverse events, magnitude of HBF induction, and changes in other important hematological parameters measured throughout the study. Let me spend a bit of time providing some details on these 16 patients. The majority of these patients have come from sites in the U.S., with the remainder coming from a single site in South Africa. Their median fetal hemoglobin level at the start of the study was 7.7%, with a mean value of 7.6%. To date, no patients have discontinued from the study, and we continue to see greater than 90% adherence to the once-a-day oral drug regimen. Furthermore, we're pleased to report that the data monitoring committee for the Pioneer study, after reviewing interim data from the 12-milligram cohort, recommended that we continue the study as planned with the initiation of the 20 milligram cohort, cohort 4, which is now underway and currently screening patients. We remain on track with our plans to report data from cohort 4, the 20 milligram cohort, by the end of 2025. Now, we continue to believe that inducing fetal hemoglobin is the optimal strategy for treating sickle cell disease, Evidence for this approach continues to grow as highlighted by not only the recently approved gene therapies, but recent data analysis showing that even modest increases in fetal hemoglobin correlate to reduced disease severity. Specifically, a recent data analysis that was presented at ASH last December shows that for every 1% increase in HBF, there was a 4% to 8% reduction in vaso-occlusive crises, or VOCs. These VOCs occur when sickled red blood cells prevent oxygenated blood from getting to the tissues, resulting in debilitating pain, often requiring hospitalization or visits to the emergency room. Additionally, fetal hemoglobin levels in the mid-20% range have shown a near abolition of these VOCs that I spoke about. Based on Poseradir's mechanism of action and the data that we have previously disclosed, we believe that Poseradir has the potential to provide a differentiated therapeutic option for people living with sickle cell disease, and we look forward to providing important clinical data this year to further validate our potentially transformative approach with Poseradir. At the upcoming European Hematology Association meeting, or EHA for short, which is being held in June in Milan, we have two abstracts that have been accepted for poster presentation. Those abstracts include preclinical target engagement and reversibility of gene expression data with POSIRIDER, as well as clinical data from our previously completed phase one healthy volunteer study. Now, beyond posterior deer, we continue to advance our earlier stage development program for the potential treatment of inherited aplastic anemias, such as Diamond Black Fan Anemia, or DBA, Schwachmann Diamond Syndrome, and Fanconi Anemia. We plan to submit an IND for DBA in the fourth quarter of this year. And with that overview, I will now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials. Over to you, Alan.

thanks alex i'll now go over our results for the quarter ended march 31st 2025. our research and development expenses were 13.4 million for the first quarter of 2025 compared to 19.8 million for the first quarter of 2024. the decrease of 6.4 million was due to the discontinuation of our los mapamad program and the global development cost sharing reimbursement under the santa fe collaboration partially offset by increased costs related to the advancement of the Phase 1b pioneer trial of the SEERDIR. The general administrative expenses were $7 million for the first quarter of 2025, compared to $10.1 million for the first quarter of 2024. The $3.1 million decrease was primarily due to decreased employee compensation costs as a result of the reduction in workforce implemented in the third quarter of 2024. Net loss was $17.7 million for the first quarter of 2025, compared to a net loss of $26.9 million for the first quarter of 2024. And turning to the balance sheet, we ended the first quarter of 2025 with cash, cash equivalent, and marketable securities of $226.6 million, compared to $241 million as of December 31, 2024. The $14.4 million decrease is primarily due to cash used to fund the operating activities. 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, I'll turn the call over back to you, Al.