Fulcrum Therapeutics, Inc. (NASDAQ:FULC) Q4 2021 Earnings Conference Call March 3, 2022 8:00 AM ET Company Participants Christi Waarich - Director of Investor Relations Bryan Stuart - President and Chief Executive Officer Judy Dunn - President of R&D Esther Rajavelu - Chief Financial Officer Chris Morabito - Chief Medical Officer Conference Call Participants Dae Gon Ha - Stifel Joseph Schwartz - SVB Securities Matthew Harrison - Morgan Stanley Judah Frommer - Credit Suisse Ted Tenthoff - Piper Sandler Discl ...

Financial Performance - The company reported a net loss of $80.8 million for the year ended December 31, 2021, and an accumulated deficit of $302.5 million as of the same date[16]. Clinical Trials and Product Development - The ongoing clinical trials for losmapimod and FTX-6058 are critical to the company's future financial results and product development plans[11]. - The Phase 2b clinical trial, ReDUX4, involved 80 patients and aimed to evaluate the change in DUX4-driven gene expression, with secondary endpoints including muscle health and patient-reported outcomes[22]. - The Phase 3 trial, REACH, is expected to enroll approximately 230 adults with FSHD and will evaluate the efficacy and safety of losmapimod over a 48-week treatment period[25]. - The company plans to initiate a Phase 3 trial for losmapimod in FSHD in Q2 2022, aiming for rapid development and regulatory approval[42]. - The ongoing ReDUX4 open label extension allows long-term treatment with losmapimod, including clinical assessments every three months[73]. - The Phase 1b clinical trial for FTX-6058 in people with SCD was initiated in Q4 2021, with initial data expected in Q2 2022[37]. - The Phase 1 trial included various dosing cohorts, with healthy volunteers receiving doses ranging from 2mg to 60mg[28]. - The company plans to nominate its next development candidate by the end of the first quarter of 2023[19]. Drug Candidates and Mechanisms - Losmapimod targets p38α/ß and aims to treat FSHD, with an estimated patient population of 16,000 to 38,000 in the U.S. and 300,000 to 780,000 globally[20]. - FTX-6058 is an investigational oral HbF inducer in development for SCD and other hemoglobinopathies, designed to upregulate fetal hemoglobin[26]. - FTX-6058 demonstrated robust HbF elevation, reaching approximately 30% of total hemoglobin in preclinical studies, significantly higher than hydroxyurea[27]. - FTX-6058 showed a greater than mean 2-fold induction in HBG mRNA starting with the 6mg dose, which is associated with significantly improved outcomes in SCD[32]. - Losmapimod, the lead product candidate, demonstrated a 38-fold decrease in DUX4-driven gene expression in patients with the highest baseline levels compared to a 5.4-fold decrease in the placebo group[67]. Regulatory Engagement and Designations - The company has engaged with regulatory agencies to align on the design of the Phase 3 trial for losmapimod[25]. - The FDA granted orphan drug designation to losmapimod in January 2020, and fast track designation in May 2021 for the treatment of FSHD[61]. Manufacturing and Development Challenges - The company relies on contract manufacturing organizations for product candidate manufacturing, which could impact development timelines[16]. - The ongoing COVID-19 pandemic may continue to affect the company's clinical trials and overall business operations[17]. - The company has engaged a contract manufacturing organization to produce losmapimod tablets and has sufficient quantities for ongoing Phase 2 clinical trials[182]. Market Landscape and Competition - The biotechnology and pharmaceutical industries are characterized by intense competition, with competitors having greater financial resources and expertise[186]. - The company faces competition from existing therapies and new therapies that may become available, which could impact its market position[188]. - There are currently no approved therapies for the treatment of FSHD, and the company is not aware of any product candidate in clinical development with the same mechanism of action as losmapimod[190][191]. - FTX-6058 faces competition from various therapeutic approaches for sickle cell disease (SCD) including gene therapies and PKR activators in clinical trials[194]. Collaborations and Agreements - The company has entered into a right of reference and license agreement with GlaxoSmithKline, which includes milestone payments aggregating up to $37.5 million and royalties ranging from mid single-digit to low double-digit percentages based on annual net sales[153]. - A collaboration and license agreement with Acceleron includes an upfront payment of $10 million and potential milestone payments of up to $145 million based on sales milestones for products directed to identified targets[162]. - The collaboration with MyoKardia aims to identify biological targets relevant to genetically defined cardiomyopathies, granting MyoKardia an exclusive worldwide license for research and development[164]. Research and Development Initiatives - The company is leveraging FulcrumSeek to discover drug targets for rare genetic diseases, with a focus on muscular, hematologic, and neurologic disorders[38]. - The company has made significant enhancements to its FulcrumSeek platform, enabling drug target screening at scale in physiologically relevant assay systems[134]. - The company is focused on drug target validation to establish a robust link between identified drug targets and modulation of root cause gene expression, utilizing diverse pharmacological tools[143]. - The company has initiated medicinal chemistry and drug discovery activities to advance development candidates suitable for clinical trials, optimizing characteristics such as potency and safety[144]. Patient Population and Disease Prevalence - The estimated prevalence of Facioscapulohumeral muscular dystrophy (FSHD) in the U.S. is between 16,000 to 38,000 patients, with a significant portion potentially undiagnosed due to the lack of approved treatments[54]. - The estimated prevalence of SCD in the U.S. is around 100,000 individuals, with a global incidence of approximately 300,000 births annually[99]. - β-thalassemia affects approximately 40,000 babies born worldwide each year, with 25,000 requiring blood transfusions due to severe anemia[108]. Safety and Efficacy Data - In the Phase 1 clinical trial, FTX-6058 was well-tolerated with no serious adverse events reported, supporting once-daily dosing with a mean half-life of approximately 6-7 hours[30]. - The MAD cohorts exhibited a 75-95% reduction in H3K27me3 after 14 days of treatment, indicating robust target engagement[30]. - Secondary endpoints indicated non-statistically significant trends of slower progression and meaningful improvements (12-27%) in muscle strength for losmapimod-treated patients compared to placebo[69]. - The MAD cohorts showed time- and dose-dependent HBG mRNA induction, with persistent induction observed for 7-10 days post-treatment[120].

Fulcrum Therapeutics, Inc. (NASDAQ:FULC) Q3 2021 Earnings Conference Call November 4, 2021 8:00 AM ET Company Representatives Bryan Stuart - President, Chief Executive Officer Chris Morabito - Chief Medical Officer Peter Thomson - Vice President of Finance & Accounting Judy Dunn - President of R&D Paul Bruno - Senior Director of Corporate Development Naomi Aoki - Senior Vice President of Corporate Communications, Investor Relations Conference Call Participants Dae Gon Ha - Stiefel Ted Tenthoff - Piper Sandl ...

WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 UNITED STATES SECURITIES AND EXCHANGE COMMISSION For the transition period from to Commission File Number: 001-38978 FULCRUM THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Delaware 47-4839948 (State or other j ...

Fulcrum Therapeutics, Inc. (NASDAQ:FULC) Q2 2021 Earnings Conference Call August 10, 2021 8:00 AM ET Company Participants Christi Waarich - Director, IR & Corporate Communications Bryan Stuart - President & CEO Chris Moxham - CSO Chris Morabito - CMO Conference Call Participants Ted Tenthoff - Piper Sandler Dae Gon Ha - Stiefel Joseph Schwartz - SVB Leerink Matthew Harrison - Morgan Stanley Tazeen Ahmad - Bank of America Judah Frommer - Credit Suisse Operator Good morning, and welcome to the Fulcrum Therape ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38978 FULCRUM THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Delaware 47-4839948 (State or other jurisd ...

Fulcrum | --- | --- | --- | --- | |-------------------------------------------------------------------------|-------|-------|-------| | | | | | | | | | | | Regulating Gene Expression to Treat the Root Cause of Disease May 2021 | | | | | | | | | Disclaimer and Notice This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Com ...

Fulcrum Therapeutics, Inc. (NASDAQ:FULC) Q1 2021 Earnings Conference Call May 6, 2021 8:00 AM ET Company Participants Christi Waarich - Director, Investor Relations & Corporate Communications Bryan Stuart - President & Chief Executive Officer Chris Moxham - Chief Scientific Officer Peter Thomson - Vice President, Finance & Accounting Conference Call Participants Kelly Girskis - SVB Leerink Ted Tenthoff - Piper Sandler Kostas Biliouris - Morgan Stanley Tazeen Ahmad - Bank of America Operator Good morning, a ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38978 FULCRUM THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Emerging growth company ☒ If an emerging ...

Fulcrum | --- | --- | --- | --- | --- | |---------------------------------------------------------------------------|-------|-------|-------|-------| | | | | | | | | | | | | | Regulating Gene Expression to Treat the Root Cause of Disease March 2021 | | | | | | | | | | | Disclaimer and Notice This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the dev ...