Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics second quarter 2023 financial results and business update conference call. Currently all participants are in a listen-only mode. This call is being webcast live on the investor section of Fulcrum's website at www.FulcrumTX.com and is being recorded. 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 the company's future expectations and plans, including the clinical hold on FTX-6058 clinical development timelines and financial projections. While these forward-looking statements represent Fulcrum's view 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 a discussion 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 today are Dr. Ian Frazier, Interim Chief Medical Officer, and Greg Tarangio, Fulcrum's Principal Accounting Officer. After providing updates on our key programs, there will be a brief Q&A in which Alex, Ian, and Greg will be available to answer your questions. With that, it is my pleasure to turn the call over to Alex. Please go ahead.

Thank you, operator, and thanks to all of you for taking time to join us today. It's truly an honor for me to have the opportunity to lead Fulcrum at this important time and to build on the company's strong foundation. as we work towards advancing our pipeline and delivering on our commitment to improve the lives of patients with rare genetic diseases. So what I'd like to do this morning is to provide a brief update on our two key programs, losmapamod for fascioscapulohumeral muscular dystrophy, or FSHD for short, and FTX6058 for sickle cell disease. After that, I'll provide a couple of corporate updates and then turn it over to Greg for financial highlights, and after Greg, we'll open it up for questions. So let's start with losmapamod, our most advanced program. As a quick reminder, losmapamod, a selective P38 alpha-beta MAP kinase inhibitor, is currently in phase three development for the treatment of FSHD, a form of muscular dystrophy with an estimated patient population of 30,000 in the U.S. Now, FSHD is characterized by relentless and accumulating loss of muscle function over many years, resulting in the inability to perform daily life activities like putting away the dishes or lifting a cup of coffee, activities that you and I take for granted. Now, even more sobering is the fact that these patients have no approved treatment options for their disease. These are the factors that drove us to embark on this journey to find options for these patients that had none. So in June of 2022, we initiated our phase three trial for losmaphobon, which we call the REACH study. Let me give a bit of background on REACH. It's a 48-week trial intended to be registration enabling, both in the U.S. and in ex-U.S. geographies. The primary endpoint for the study is the change from baseline in reachable workspace, or RWS, a quantitative measure of upper extremity range of motion and function that specifically evaluates shoulder and arm mobility using 3D motion sensor technology. Now, preserving this upper extremity function is critical for these patients to maintain their independence and their ability to perform some of these activities of daily living that I talked about earlier. As part of this study, we'll also be looking at some other important secondary endpoints like muscle fat infiltration or MFI, which is an important marker of disease pathology, as well as self-reported quality of life measures and healthcare utilization questionnaires that will really help inform our thinking on our payer strategy as we prepare for our commercial launch. I'm really excited to share that screening in the REACH Study has now closed. and we expect enrollment to complete later this quarter. And with this being a 48-week study, we plan to report top-line data in the fourth quarter of 2024. For us, and more importantly, for the patients, this brings us one step closer to delivering the first-ever FDA-approved therapy for patients with FSHD. Let me now move on to 6058. 6058 is our oral HBF inducer for the potential treatment of patients with sickle cell disease. As previously announced, we received a clinical hold letter from FDA on February 24th, and at that point, immediately suspended dosing and paused enrollment in the Phase 1B trial for 6058. In the initial feedback provided by FDA, they stated that the hold was related to preclinical data that we submitted in April October and December of 2022, as well as other non-clinical and clinical evidence of hematological malignancies observed with other PRC2 inhibitors. In order for us to restart the Phase 1b study, the agency has requested that Fulcrum further define the patient population where the potential benefit of continued treatment with 6058 outweighs potential risk. I do think it's important to mention that at this stage, the FDA has not requested any additional preclinical or clinical data as a prerequisite to restarting the Phase 1B study in patients. Based on preliminary clinical data that we obtained prior to the clinical hold, 6058 has demonstrated dose-dependent increases in total fetal hemoglobin, or HBF, of a magnitude that we believe has the potential to lead to a meaningful improvement in disease severity. We believe that 6058 as an oral HBF inducer has the potential to provide a differentiated therapeutic option for patients living with sickle cell disease, and that the clinical and preclinical data generated to date demonstrate a favorable benefit risk profile. Overall, our interactions with FDA have been productive and collaborative, and we look forward to continuing our interactions as we work toward resolving the clinical hold as quickly as possible. I will provide an update once we have more clarity on the regulatory path forward, and I intend to provide specifics regarding this more narrowly defined patient population once we have agreement with FDA. So, that covers the updates on our two key clinical programs. Before turning it over to Greg, let me give a quick update on two other important topics. As we remain committed to delivering groundbreaking therapies for underserved communities, in July of this year, we obtained an exclusive global license from Camp 4 Therapeutics to acquire intellectual property arising from Camp 4's preclinical research program in Diamond Black Fan Anemia, or DBA for short. Under the terms of this agreement, Fulcrum will research investigational oral compounds for the potential treatment of DBA, a congenital rare blood disorder that affects an estimated 5,000 individuals worldwide. Our agreement with CAMFOR further strengthens our discovery pipeline, and we are excited to expand on CAMFOR's foundational preclinical work, which we believe has potential broad applications and a unique opportunity for growth. Additionally, solidifying our leadership team is one of my key priorities, and I am pleased to announce the appointment of Alan Musso to the position of Chief Financial Officer, effective August 7th. I have known Alan for some time now and thus have firsthand knowledge of his financial acumen, his keen strategic insights on a range of complex financial decisions that face a company of our size, and most importantly, his character. His leadership experience within the biopharma industry will be invaluable as the company enters its next stage of development. Welcome aboard, Alan. And so with that, let me turn it over to Greg to give an update on our financials. Greg?

Thanks, Alex. We ended June 30th, 2023 with cash, cash equivalents, and marketable securities of $278.2 million as compared to $202.9 million as of December 31st, 2022. We continue to operate from a strong financial position, and we expect our cash equivalents and marketable securities to fund our operating expenses into mid 2025. This projection assumes a timely resolution of the FTX 6058 clinical hold. Collaboration revenue was $0.9 million for the second quarter of 2023 as compared to $1.9 million for the second quarter of 2022. Research and development expenses were 17.8M dollars for the second quarter of 2023 as compared to 25M dollars for the second quarter of 2022. The decrease of $7.2M was primarily attributable to a $5M milestone due to GSK that we achieved during the second quarter of 2022 upon the initiation of REACH, as well as decreased costs as a result of the clinical hold for FTX 6058. General and administrative expenses were $10.3M for the second quarter of 2023 as compared to $11.1M for the second quarter of 2022. The decrease of $0.8 million was primarily due to decreased professional services costs. Net loss was $23.8 million for the second quarter of 2023 as compared to $34.1 million for the second quarter of 2022. And with that, let me turn it back over to Alex.