Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics' first quarter 2022 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 Naomi Aoki, Senior Vice President of Corporate Communications and Investor Relations at Fulcrum. Please proceed.

Thank you. Good morning, and welcome to Goldcombe Therapeutics conference call. 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 timeline, 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 with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business. With me on today's call are Brian Stewart, President and Chief Executive Officer, Judy Dunn, our president of R&D, and Esther Rajavallu, our CFO. Chris Moravito, chief medical officer, and Paul Bruno, our executive director of corporate development, will also be available for Q&A. Let me run quickly through this morning's agenda. Brian will begin the call with a corporate overview, key updates, and review of upcoming milestones. Judy will review our FTX 6058 programs. Esther will cover our financials, and then Brian will open the call for Q&A. With that, it's my pleasure to turn the call over to Brian.

Thank you, Naomi. Good morning, everyone, and thank you for joining us today. At Fulcrum, our mission is to treat the root cause of rare genetic diseases, and we are advancing two important clinical stage assets that support that mission. The first is our Phase III FSHD program that is positioned to be a first-to-market therapy for an untreated patient population. The second is our program for sickle cell disease and other hemoglobinopathies, a once-daily HBF inducer with the potential to be the first oral therapy that can broadly improve outcomes for these diseases. We have made significant progress across these programs in the first quarter. start with an update on FTX 6058, our oral HBF inducer for sickle cell disease and other hemoglobinopathies. 6058 shows great promise in addressing critical unmet needs in these patient populations. The current treatment landscape consists of therapies that only target select symptoms of sickle cell disease. HBF is the only mechanism that has been shown to broadly improve clinical outcomes, including anemia, VOC events, pain, fatigue, and acute chest syndrome. As the only agent in development with the potential to induce HBF, we believe that 6058 is uniquely positioned in the current and emerging landscape. In January, we announced that we had dosed our first patient in our Phase 1b trial at a starting dose of 6 milligrams. We plan to share initial data from the ongoing 6 milligram dosing cohort including measures of HBF induction at the European Hematology Association Congress, taking place from June 9th through 12th. We also plan to open the next dosing cohort in the Phase 1b trial this quarter, and we'll have more details to share on that cohort along with the data at EHA. Notably, this update will be the first look at HBF protein induction in people living with sickle cell disease receiving 6058. Based on data from other HBF mechanisms and the process of erythropoiesis, we would anticipate seeing signs of protein induction after one month of treatment with potentially maximal protein induction at three to five months. As a reminder, our Phase Ib trial is an early proof-of-concept study that is designed to provide evidence over a range of doses that 6058 increases HBF. For this initial data, we would consider evidence of HBF induction as a proof of concept for this program. Typically, people with sickle cell disease have HBF levels of 5 to 10%. However, a subset of people with sickle cell trait have additional mutations that result in elevated levels of HBF, a condition known as hereditary persistence of fetal hemoglobin. These individuals have little to no symptoms of sickle cell disease. These clinical and genetic data clearly demonstrate that increases in HBF improve outcomes. Based on this well-understood data, KOLs consistently state that an absolute 5% to 10% increase in HBF beyond baseline levels would be transformative for patients and would be used as standard of care. Our robust preclinical data and our Phase I data in Healthy Volunteers give us reason to believe that we can achieve these absolute 5% to 10% increases that will be life-changing for people with sickle cell disease. We also believe that 6058 could be a transformative therapy for other hemoglobinopathies, including beta thalassemia, and we are committed to developing 6058 in these patient populations as well. This morning, we updated the anticipated timings, of the initiation of the trial in non-sickle cell hemoglobinopathies to the second half of the year. This shift in timing allows us to focus on expeditiously advancing our development plans in sickle cell disease while remaining well-positioned to successfully execute a trial in other hemoglobinopathies. Moving on to losmapamon, our phase three candidate for FSHD, which is the second most common form of muscular dystrophy. We remain on track to begin dosing patients in our Phase III REACH trial this quarter. As the first-ever Phase III trial in FSHD, REACH is a landmark study that brings us one step closer to delivering a potentially life-changing therapy to people with this severe and debilitating disease. Los Matamatas is positioned to be the first-to-market therapy for FSHD, and based on the data to date, we believe it has the potential to slow or stop disease progression, and in some cases, even improve function. REACH will evaluate losmapamide compared to placebo in adults with FSHD over a 48-week treatment period with reachable workspace, or RWS, as the primary endpoint. The trial design reflects key learnings from the REDUX-IV Phase IIb trial, most notably that we can show a measurable clinical benefit in 48 weeks and that RWS is a quantitative measure of function that is sensitive to disease progression in that timeframe. Based on these insights and the data from Redux 4 demonstrating clinical benefit, we aligned with regulators on key aspects of the design of REACH. In March, we presented data supporting RWS as a quantitative and relevant measure of function at the Muscular Dystrophy Association Clinical and Scientific Conference. That same month, we hosted an event with leading KOLs to discuss the unmet need in FSHD key measures of disease progression, and the design of the REACH trial with a focus on RWS. Together with the FSHD Society, we also hosted a webinar on REACH for the patient community. Additionally, in April, at the American Academy of Neurology annual meeting, we presented clinical data supporting the potential of losmapamide as well as the design of REACH. We are proud of the progress that we have made with losmethamide. REACH marks an important milestone for fulcrum and for the FSHD community. There are currently no approved drugs for FSHD and nothing else in the clinic. People with FSHD lose strength, function, independence, and mobility as the disease advances. There is an urgent need for a drug that can slow or stop disease progression. The data we reported last year from Redux IV demonstrate Los Mapamot's potential to do exactly that, showing delayed progression and improvement in measures of function. Los Mapamot is also supported by an extensive safety and tolerability database. In addition to our progress with initiating REACH, we've also made significant gains in preparing for the potential of commercial launch. Beyond building internal infrastructure needed for success, we have progressed the commercial formulation of Los Mapamot Additionally, we continue to engage with patients, care partners, and care providers to ensure Los Mapamad has the maximal potential to meet the community's expectations. 6058 and Los Mapamad, as well as our ongoing collaborations, are a testament to the power of FulcrumSeq, our product engine and the innovation backbone of our company. FulcrumSeq has allowed us to rapidly identify novel, high-quality targets that modulate the root cause of rare genetic diseases, and it continues to power our pipeline. We remain on track to nominate our next development candidate by the end of this year and submit what will be Fulcrum's fourth IND by the end of the first quarter of 2023. As we advance two potentially life-changing therapies through clinical development while expanding our pipeline, we are well positioned to establish Fulcrum as a leading rare disease company supported with a strong financial foundation and a cash runway into 2024. With that, I'll turn it over to Judy.