Fulcrum Therapeutics, Inc.

Good morning and welcome to Fulcrum's Therapeutics Second Quarter 2024 Financial Results and Business Update Conference Call. Currently, all participants are on a listen-only mode. This call is being webcast live and can be accessed on the investor section of Fulcrum's website at www.fulcrumtx.com and is being recorded. Please be reminded the remarks during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. May include statements about the company's future expectations and plans, timelines, and financial projections. While these forward-looking statements represent full-time views 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 discussion of certain risks and uncertainties associated with the company's business. Meeting today will be Alec Sapir, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer, Dr. Pat Horn, Chief Medical Officer, and Dr. Lynn Fazer, Senior Vice President of Development. After providing updates on our key programs, there will be a brief Q&A in which Alex, Alan, Pat, and Lane will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex.

That's great. Thank you, Lisa. And good morning, everyone. And thanks to all of you for joining us for our second quarter conference call. We've organized today's call to provide you with updates on recent progress and upcoming milestones for our two clinical stage assets, Los Mapamad and Pociradir. And after a brief introduction, we'll segue into our pipeline. I'll then ask Alan to review the financials. And finally, we'll end by taking your questions. I am happy to report that we are on track to report top-line data for the Phase III REACH trial of Los Mapamad by the end of October, compared to our previous guidance of the fourth quarter. As we advance toward this important inflection point, we continue to build out the team and add talent as we prepare for the potential NDA filing and the U.S. commercial launch of Los Mapamad. In parallel, we are working with Sanofi in preparation for regulatory filings and the launch of Los Mapamad outside of the United States. As a reminder, in May of this year, we announced our collaboration and license agreement with Sanofi for the development and commercialization of Los Mapamad for fascio scapulo humeral muscular dystrophy, or FSHD for short, for all territories outside of the U.S. We believe we selected the best possible partner for Los Mapamad as this collaboration combines Fulcrum's expertise in FSHD with Sanofi's deep regulatory development and commercial capabilities in neuromuscular markets around the world. Together, we look forward to delivering on our shared commitment to address the high unmet need of patients in the FSHD community. Let me spend a bit more time on losmapamod, which, as many of you know, is an oral small molecule selective P38 alpha-beta map kinase inhibitor that inhibits Dux4 expression and many of its downstream transcripts, and thus prevents muscle cell death in patients with FSHD. An estimated 30,000 patients in the U.S. have FSHD, which is characterized by a slow but relentless loss of muscle function year after year, resulting in significant impairment of upper extremity muscle function and mobility. And while there is a degree of heterogeneity in the onset and disease progression of FSHD, this relentless loss of muscle function means that approximately 20% of patients become wheelchair bound. I think it's important to remind everyone that there are currently no approved therapies for FSHD and No drugs used off-label to help these patients. Now, let's turn our attention to our Phase 3 registrational trial called REACH, which I spoke about earlier. As a reminder, REACH is a 48-week Phase 3 trial intended to be registration-enabling both here in the U.S. and in ex-U.S. geographies. In September of last year, we completed enrollment in REACH with a total of 260 patients. As presented at the 31st Annual FSHD Society International Research Congress in June of this year, baseline characteristics of the REACH study population are similar to those of our Phase II Redux IV study population. Building on the encouraging clinical benefit and favorable tolerability observed in our Redux IV trial, the primary endpoint for the REACH study is the change from baseline in the relative surface area, or RSA, which is a quantitative assessment of reachable workspace and has been shown to correlate with disease severity and progression. RSA is a measure of upper extremity range of motion and muscle function that specifically evaluates shoulder and arm mobility using 3D motion sensor technology and is indicative of the ability to perform activities of daily living. Based on collaborative interactions with the Clinical Outcomes Assessment or COA group at FDA, we are further assessing the extent to which a specific change in the RSA score is meaningful to patients. I'm pleased to report that we are on track to complete the activities agreed upon with the FDA at the time of reporting the REACH top line data. Additional key secondary endpoints in REACH include muscle fat infiltration, or MFI, which is a marker of disease pathology measured by whole body MRI, shoulder dynamometry, and patient global impression of change, or PGIC for short. We believe that the implementation of self-reported quality of life measures and healthcare utilization questionnaires will help inform our payer strategy as we begin preparing for a commercial launch to deliver the first FSHD treatment for patients. We are now progressing toward the completion of the 48-week treatment phase of the trial for all enrolled patients. As of June 30, 2024, of the 234 out of the 260 who completed the 48-week treatment phase, 232 of those patients, or 98%, chose to enroll in part b the open label extension of the study in which all patients receive drugs this very high percentage of patients opting to move into the open label phase is similar to what was observed in our phase 2 clinical trial and we believe is indicative of the high unmet need for patients with fshd again we are on track to report top line data by the end of october which will bring us one step closer to delivering the first ever FDA-approved therapy for FSHD patients. Now let's talk a little bit about Poseradir, which is our oral HBF inducer for the potential treatment of patients with sickle cell disease. The elevation of HBF, or fetal hemoglobin, is a clinically validated therapeutic rationale for sickle cell disease, a lifelong inherited blood disorder that severely impairs quality of life for approximately 100,000 people in the U.S. and approximately 4.4 million people worldwide, making sickle cell disease one of the most prevalent non-malignant hematologic diseases. Historically, the standard treatment for sickle cell disease has included blood transfusion, pain medications, and hydroxyurea that focus only on symptom relief. While exciting scientific progress has enabled the advancement and, more recently, the approval of gene editing therapeutic approaches, we believe there remains a high unmet need for an oral therapeutic option that is broadly protective of sickle cell disease symptomatology. As a first-in-class oral small molecule HBF inducer, we believe posterior dare has the potential to address this unmet need. Turning now to our Phase 1B clinical trial, the Pioneer trial, we continue to make progress. Given that many of the sites we are newly activating are academic sites here in the U.S., as well as outside the U.S., both of which have long site activation lead times, together with our narrower inclusion-exclusion criteria, it is taking longer than initially expected. We expect to have study data to share with everyone in 2025. As a reminder, cohort three of the phase 1B trial will evaluate Posteriori at the 12 milligram once daily dose with a dosing duration of three months, followed by cohort four at the 20 milligram once daily dose also for three months. Both cohorts are expected to enroll approximately 10 patients each. We look forward to building on the encouraging clinical data obtained prior to the clinical hold which demonstrated that Poseradir increased total fetal hemoglobin of a magnitude that could translate into a meaningful improvement in disease severity. These interim results of the Phase 1b trial involving 16 patients were recently reported in June at the IHA conference in Madrid and were very well received by the medical community. We believe that Pocirida as an oral HPF inducer has the potential to provide a differentiated therapeutic option for people living with sickle cell disease. And addressing the significant unmet need in the sickle cell disease community remains a key priority for us. So with that update on the business, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials. Alan, over to you.

Thanks, Alex. I'll now go over our results for the second quarter ended June 30th, 2024. Let me start with our cash position. As of June 30th, 2024, cash, cash equivalents and marketable securities were $273.8 million as compared to $236.2 million as of December 31st, 2023. The increase in our cash position is due to the $80 million upfront payment received from Sanofi in the second quarter of 2024, partially offset by cash used to fund operating activities in the first half of the year. Collaboration revenue was $80 million for the second quarter of 2024, compared to $0.9 million for the second quarter of 2023. The increase of $79.1 million was primarily due to recognition of the $80 million upfront license payment received from Santa Fe during the second quarter of 2024. Our research and development expenses were $17.3 million for the second quarter of 2024, compared to $17.8 million for the second quarter of 2023. The decrease of $0.5 million was primarily due to the Los Mapamad Global Development cost-sharing reimbursement from Sanofi, partially offset by increased costs related to the advancement of the REACH trial. The general administrative expenses were $10.2 million for the second quarter of 2024, compared to $10.3 million for the second quarter of 2023, and the 0.1 million decrease was primarily due to lower employee compensation costs. For the second quarter of 2024, we had net income of $55.4 million compared to a net loss of $23.8 million for the second quarter of 2023. For the foreseeable future, excluding the potential for future milestone payments under our Santa Fe collaboration, we expect to be in a lost position, including for the year ended December 31st. And finally, turning to our cash runway guidance, based on our current operating plans, we continue to expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operating requirements into 2027. And with that, let me turn the call back over to Alex.