Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum Therapeutics third 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 like now to turn the call over to Stephanie Asher from Stern Investor Relations. Please proceed.

Thank you, Caroline. Good morning and welcome to the Fulcrum 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 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 filings 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, and Esther Rajavelu, our CFO. Paul Bruno, our Senior Vice President of Corporate Development, will also be available for Q&A. Let me quickly run through this morning's agenda. Brian will begin the call with a corporate overview and key updates, including on our clinical programs. Esther will cover our financials, and Brian will open the call for Q&A. With that, it's my pleasure to turn the call over to Brian.

Thanks, Stephanie. Good morning, everyone, and thanks for joining us today. At Fulcrum, our mission is to treat the root cause of genetically defined rare diseases, and this quarter, we have continued to make progress towards bringing transformative therapies to patients. Currently, we have two clinical programs with the potential to dramatically transform the treatment paradigm in sickle cell disease and FSHD. We are committed to moving both programs through the development and regulatory process as rapidly as possible to address the significant unmet needs that we know exist in these patient populations. We are also continuing to invest in our research engine and expect to file our next IND in 2023. At our last update, we announced a strategic realignment to prioritize our internal investments and our two key value driving clinical programs intended for the treatment of FSHD and SCD. This extended our runway into mid 2024 at that time. In August, we closed an underwritten public offering that resulted in net proceeds of approximately $81 million that has extended our runway further, and we are in a strong cash position that enables us to continue to execute on our mission. Esther will provide details on our financials later in the call. Moving on to our clinical programs, starting with our Phase 1B Sickle Cell Disease Program. STD is a debilitating disease that for far too long has lacked effective and tolerable treatment options. HBF induction is the only mechanism which has been shown to broadly improve outcomes and reduce both the frequency and severity of STD symptoms such as VOCs, anemia, pain, fatigue, and acute chest syndrome. FDX6058 is an HBF-inducing agent that has the potential to address the unmet need in sickle cell disease, including symptoms not addressed by current therapies. Several independent lines of evidence, including human genetics and emerging gene editing data, support our therapeutic goal that a 5% to 10% increase in HBF above baseline can reduce both mortality and morbidity associated with SCD. An oral therapy that can produce robust increases in HBF has been a therapeutic goal in sickle cell disease for some time, which is why the initial data from our FTX6058-1B trial are so exciting. We have shown compelling proof of concept that FTX6058 rapidly induces HBF protein in sickle cell disease patients and demonstrated that it is able to achieve absolute HBF increases within the range that clinicians have targeted for a potential future standard of care. As our work on the Phase 1B trial continues, we will continue to focus on understanding the effect of 6058 across multiple dose cohorts and the consistency in response with 6058, both as monotherapy and in combination with hydroxyurea. In addition to our ongoing six milligram and two milligram dose cohorts, we have selected 12 milligrams as the dose for our next cohort and plan to continue enrollment into 2023. Our goal is to have high quality data across multiple cohorts to inform our plans for a registration enabling trial in 2023. We have been focused on clinical trial operations and trial conduct. During the second half of the year, we have increased the number of sites that are participating in the program and have targeted our recruitment efforts in areas with meaningful populations of people living with sickle cell disease. We are focused on building connections and partnerships with the SCD community because we understand that local community-based organizations have been on the front lines of the fight to treat sickle cell disease. The feedback that we have received from the community has been clear, the accessibility and ease of use of a new SCD therapy is extremely important. Our approach of developing an oral small molecule that can be taken once a day and deliver robust HBF induction has been met with very positive response from patients and healthcare providers. Now moving on to our FSHD program, where we are currently enrolling the Phase III REACH trial. REACH was designed as a highly efficient 48-week trial and is intended to be registration enabling both in the U.S. and in ex-U.S. geographies. We continue to be well positioned to bring the first-to-market therapy for this relentless and devastating disease that is the second most common form of muscular dystrophy. People with FSHD lose strength, function, independence, and mobility as the disease advances, seeing their quality of life decline as a result. there is an urgent need for a disease-modifying therapy that can help patients with FSHD maintain their quality of life. Data from our Phase II Redux IV trial indicates that Losmapamod has potential to slow or stop disease progression, and in some cases, even improve function in FSHD patients. In October, at the World Muscle Society meeting in Halifax, Nova Scotia, we shared 96-week data from our open-label extension trial in the ongoing Phase IIb Redux IV. Over 97% of patients in the initial 48-week trial decided to remain in the study during the open-label extension. Top-line results show that participants in the initial treatment arm who continued to receive losmepamod demonstrated maintenance of effect through a 96-week period, as measured by change in reachable workspace, or RWS, from baseline. Notably, those who crossed over from placebo to losmapamide after the initial 48-week trial period demonstrated slowed disease progression based on the same measures. Losmapamide also continued to maintain its favorable safety profile and was generally safe and well-tolerated. We have strong conviction in this program, and our interactions with patients and the clinical community continue to reinforce the potential for losmapamide to become the standard of care for FSHD. We expect to complete enrollment for the phase three trial in 2023. As we continue to make progress on our two lead programs, we are very excited to welcome two additions to our executive leadership team. Dr. Santiago Arroyo joined Fulcrum yesterday as our chief medical officer. Dr. Arroyo is a neurologist by training with two decades of experience in drug development. He most recently served as the chief medical officer of Momenta Pharmaceuticals through its acquisition by Johnson & Johnson. We have great confidence in Dr. Arroyo's experience and leadership and are incredibly pleased to have him at the helm of our clinical organization as we look towards having two registration enabling trials in 2023. We have also appointed Dr. Jeff Jacobs as our chief scientific officer. Dr. Jacobs has more than 25 years of experience in drug discovery, and has led, co-led, and mentored multiple discovery programs from concept stage to IMD enabling studies. Dr. Jacobs was most recently the chief scientific officer at Goldfinch Bio and will be joining Fulcrum as of December 1st. We are thrilled to have both on board to lead our efforts towards filing our next IMD in 2023. With that, I will hand the call over to Esther to review our third quarter financial results.