Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics' first quarter 2021 conference call. Currently, all participants are in a listen-only mode. There will be a question and answer session at the end of this call. I would now like to turn the call over to Christy Warwick, Director of Investor Relations and Corporate Communications at Fulcrum. Please proceed.

Thank you, Operator. Good morning and welcome to the Fulcrum Therapeutics conference call to discuss our first quarter 2021 financial results and recent corporate highlights. Earlier today, we issued a press release. For those of you who don't have a copy, you can access it in the investor relations section of our website at fulcrumcx.com. 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 our future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent our views as of today, they should not be relied upon as representing our views in the future. We may update these statements in the future, but we are not taking on an obligation to do so. Please refer to our most recent filing to the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with our business. With me on today's call are Brian Stewart, President and CEO, Chris Moxon, Chief Scientific Officer, Peter Thompson, Vice President, Finance and Accounting, and Judith Dunn, President, Research and Development. Let me quickly run through this morning's agenda. Brian will begin the call with a corporate overview, Chris will provide a more detailed review of our program in sickle cell disease and our product engine, and Peter will cover our financials. With that, it's my pleasure to turn the call over to Brian. Brian?

Thank you, Christy. Good morning, everyone, and thank you for joining us today. It's been an exciting and fast-moving quarter for Fulcrum. We continue to make important progress across our clinical development programs, discovery collaborations, and product engine, and expect to have meaningful updates from multiple key initiatives in the near term. I'd like to first start with our product engine, FulcrumSeq, which is a powerful and differentiated approach that serves as the innovation backbone for our company. FulcrumSeq has allowed us to rapidly identify novel, Thank you for joining us. Fulcrum C creates an unparalleled opportunity to efficiently grow our pipeline of therapeutics and develop root cause treatments for genetically defined rare diseases. With this in mind, our goal is to bring forward two INDs over the next 24 months. The full-lose MAPIMOD data from Redux 4 and FSHD will be presented next month at the FSHD International Research Conference. I'll have more to share on that in a few minutes, but these data will provide new insights that will inform the clinical path forward in FSHD. Following data availability, we'll meet with the FDA to discuss the path to registration. And with FDX 6058, we'll have data from the Phase 1 trial in healthy adult volunteers mid-year, and we anticipate initiating dosing in people living with sickle cell disease by the end of the year. Additionally, we have further enhanced our leadership team with the appointment of Dr. Judith Dunn as our President of Research and Development, and today we announced the appointment of Dr. Chris Morabito as our Chief Medical Officer. Both Judy and Chris have extensive experience in drug discovery and clinical development. Judy has held multiple roles in global research and development, including leadership roles at Roche and Pfizer, and Chris also has extensive leadership experience at biotech companies, including most recently as Chief Medical Officer at Cardurian. Prior to Cardurian, Chris held leadership roles at Takeda, Sanofi, and Merck. We are thrilled to have both of them as part of our team. Now let's turn to Liz Mappamod for FSHD. As a reminder, FSHD is a rare progressive and disabling disease characterized by severe muscular degeneration that occurs as skeletal muscle is replaced by fat. We estimate there are approximately 16,000 to 38,000 patients in the U.S. and similar incidents worldwide, leading to an estimated global patient population of 300,000 to 780,000 patients. There are currently no approved therapeutics for FSHD, and Fulcrum is advancing the only known industry-sponsored clinical trial evaluating a potential treatment. Our development program in FSHD builds on the established safety of losimethamide demonstrated in approximately 3,600 subjects. We have made tremendous progress with our integrated FSHD clinical development strategy, evaluating molecular biomarkers as well as structural and functional measures, and patient-reported outcomes. This strategy includes natural history studies to better understand disease progression, preparatory studies to establish a biomarker and clinical endpoints, as well as studies that have demonstrated muscle penetration and target engagement for losmethamide. Recently, at the virtual Muscular Dystrophy Association Conference in March, We presented new data related to the use of imaging biomarkers and clinical outcome assessments for FSHD. Presentations included development of a whole body muscle skeletal MRI protocol. Data show this can capture heterogeneity and provide important information about disease severity. Meaningful composite MRI measurements demonstrated correlation with relevant FSHD functional endpoints. Specifically, These data were the first to demonstrate strong correlations of muscle fat infiltration and muscle fat fraction with timed up-and-go, FSHD timed up-and-go, and reachable workspace, which measure impact on function. This work has helped to inform the design of fulcrum's current ongoing studies of losamapamide in patients with FSHD, which include a single-site Phase II open-label study, as well as Redux IV. As a reminder, REDUX4 is an international, Phase IIb, double-blind, placebo-controlled trial of losmaphimodin in approximately 80 subjects with genetically confirmed FSHD. We are on track to report results from this trial next month. We and others in the field have demonstrated that Dux4 expression occurs on a spectrum, and we believe that all people with FSHD will have muscles that exhibit high Dux4-driven gene expression. Biomarker data reported from Redux4's interim analysis indicated that muscles with the highest Dux4-driven gene expression in pretreatment biopsies showed larger reductions following treatment with losmethamide compared to placebo. We look forward to the Redux4 data readout, which will include the entirety of the biomarker data, as well as outcomes from structural, functional, and patient-reported measures. We'll be encouraged if we continue to observe evidence of trends similar to the interim analysis and high-expressing muscle biopsies from Los Mapamon-treated patients. Additionally, we'll be encouraged if we observe trends of benefit in secondary endpoints like muscle skeletal MRIs, clinical outcome assessments, or patient-reported outcomes. We believe Los Mapamon has the potential to establish a new treatment paradigm for people living with FSHD and reflects our continued commitment to research that targets genetically-defined rare diseases with high unmet needs. I would like to now turn the call over to Chris.