Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics First Quarter 2026 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 Investors 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 security's litigation reform Act 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, they 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 files 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, and Dr. Ian Frazier, Senior Vice President, Clinical Development. After providing updates on the company's key programs, there will be a brief Q&A in which the Fulcrum management team will be available for questions. With that, it's my pleasure to turn the call over to Alex.

That's great. Thanks, Shannon, and good morning, everyone. We appreciate you all joining us today. The first quarter of 2026 was an important and exciting period for fulcrum, highlighted by the positive clinical data we reported from the Phase 1b pioneer trial of posterior dare in sickle cell disease. Now, as a reminder, sickle cell disease is a serious genetic blood disorder with a significant unmet need affecting approximately 120,000 patients in the United States and millions more globally. Patients with sickle cell disease face a substantial disease burden, including chronic pain and fatigue, as well as serious complications such as vaso-occlusive crises, stroke, and progressive end-organ damage, all of which result in a substantial reduction in life expectancy of over 20 years. Now, we have known for decades that increasing levels of fetal hemoglobin, or HPF, in patients with sickle cell disease leads to improvements in anemia and reductions in vaso-occlusive pain crises. And so it was for that reason that we were so pleased with the data that we reported in February, demonstrating that after only 12 weeks of treatment, 20 milligrams of Pociradir taken once daily demonstrated a robust and clinically meaningful increase in HBF from 7.1% at baseline to 19.3% at week 12, along with improvements in markers of hemolysis and improvements in anemia. We also observed continued progression toward pancellular expression of HBF, which we believe is critical for achieving meaningful clinical benefit. And importantly, we saw a reduction in the number of VOCs we would have expected in this severe patient population with seven of the 12 patients experiencing no VOCs during the 12-week treatment period. And importantly, Pociridae has continued to be generally well tolerated with no treatment-related serious adverse events reported to date. And so taken together, these data reinforce our conviction in Pociridae's potential to address the underlying biology of sickle cell disease and support our belief that Pociridae has the potential to represent a differentiated, once daily, oral treatment option for patients. Now, during the quarter, we also initiated an open-label, long-term dosing trial for patients in the Pioneer study, and we recently enrolled our first patient in this new study. All patients in this long-term dosing study previously completed 12 weeks of treatment as part of the Pioneer trial, We also continue to support initiatives aimed at improving the care journey for people living with sickle cell disease, including our recent collaboration with MedicAlert, and the Sickle Cell Disease Association of America, or SCDAA, to help improve access to patient-specific care information in the emergency department setting. Looking ahead, we are now focused on the next stage of clinical development for Procedure and we expect to provide an update in the design of our next trial later this quarter following our upcoming end-of-phase meeting with the FDA and receipt of the final meeting minutes. Pending FDA feedback from that end-of-phase meeting, we plan to initiate a potential registration-enabling trial in the second half of 2026. And so with a strong balance sheet that provides cash runway into 2029, we are well-positioned to advance procedure through the next phase of clinical development. Now, before turning it over to Alan, I want to cover the two other important corporate updates. First, I want to welcome Josh Lurer to our Board of Directors. Josh brings to Fulcrum a deep experience and passion for sickle cell disease, as well as a strong track record in advancing transformative therapies in this space, including his role in the development and approval of Oxbrita. We are honored to have Josh join Fulcrum at this important stage. Secondly, I would also like to thank Alan for his years of dedication and leadership as he looks towards retirement later in the year. Alan has played a critical role in strengthening our balance sheet and instilling financial discipline across the organization, and we are grateful for his continued commitment to fulcrum as he remains in his role until a successor is named to ensure a smooth transition. And so with that, I'll turn it over to Alan to review our financial results. And again, Alan, thanks for all you've done for Fulcrum.

Thanks, Alex, and thank you for the kind words. It's been a privilege to be part of Fulcrum's progress, and I'm proud of what we've accomplished together. With the impressive results from the Pioneer trial, a talented and motivated team, and a strong capital base, the company is well-positioned to deliver transformative therapy for sickle cell patients. I look forward to continue working with the team over the coming months and ensuring a successful transition. And with that, I'll now go over our results for the first quarter ended March 31st, 21-26. The research and development expenses were $14.1 million for the first quarter of 2026 compared to $13.4 million for the first quarter of 2025. The increase of $700,000 was primarily driven by higher employee compensation costs including $400,000 of increased stock-based compensation expense. General and administrative expenses were $8.1 million for the first quarter of 2026 compared to $7 million for the first quarter of 2025. The increase of $1.1 million was primarily driven by higher employee compensation costs, including $300,000 of increased stock-based compensation expense as well as higher professional services costs. The net loss was $22.2 million for the first quarter of 2026 compared to a net loss of $20.4 million for the first quarter of 2025. Now, turning to the balance sheet, we added the first quarter of 2026 with cash, cash equivalents and marketable securities of $333.3 million compared to $352.3 million as of December 31st, 2025. The $19 million decrease was primarily due to cash used to fund our operating activities. And based on our current plans, we expect our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operating requirements into 2029, providing runway to advance the zero-year through the next phase of clinical development. And with that, I'll turn it back over to you all.