Exhibit 99.1 Fulcrum Therapeutics Announces Recent Business Highlights and Financial Results for First Quarter 2024 ― Entered into a collaboration and ex-U.S. license agreement with Sanofi for the development and commercialization of losmapimod ― ― On track to report topline data for Phase 3 REACH trial of losmapimod in facioscapulohumeral muscular dystrophy (FSHD) in the fourth quarter of 2024 ― ― Industry veteran, Patrick Horn M.D., Ph.D., appointed as chief medical of icer ― ― Conference call and webcast ...

― Sanofi receives exclusive rights to commercialize losmapimod in all territories outside the U.S.; Fulcrum retains full U.S. commercialization rights ― ― Fulcrum will receive an upfront payment of $80.0 million, and is eligible to receive $975.0 million in potential milestones, plus royalties on ex-U.S. product sales; parties will share future global development costs 50:50 ― ― Conference call and webcast scheduled for 8:00 a.m. ET today to discuss the collaboration and other recent corporate developments, ...

― Phase 2b ReDUX4 clinical trial indicates improvements in functional, structural, and patient-reported outcomes; findings informed the design and choice of efficacy endpoints in the ongoing Phase 3 clinical trial― ― Topline data for the Phase 3 REACH clinical trial of losmapimod in FSHD expected during 4Q'24― CAMBRIDGE, Mass., May 08, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically def ...

CAMBRIDGE, Mass., May 06, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (the "Company") (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced that its first quarter 2024 financial results will be released on Monday, May 13, 2024 before the U.S. financial markets open. Management will host a conference call and webcast at 8:00 a.m. ET to discuss the results and provide an ...

―Industry veteran with late-stage clinical development, medical affairs, and regulatory experience; well-positioned to advance losmapimod towards a potential regulatory submission and approval ― ― Interim Chief Medical Officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum's executive leadership team as senior vice president (SVP) of early development ― CAMBRIDGE, Mass., March 18, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (Fulcrum) (NASDAQ:FULC), a clinical-stage biopharmaceutical ...

CAMBRIDGE, Mass., March 08, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced that the company granted non-statutory stock options to two new employees. Fulcrum granted stock options to purchase shares of the company's common stock pursuant to the company's 2022 Inducement Stock Incentive Plan, as amended, or the plan, as ...

Fulcrum Therapeutics, Inc. (FULC) came out with a quarterly loss of $0.40 per share versus the Zacks Consensus Estimate of a loss of $0.44. This compares to loss of $0.50 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of 9.09%. A quarter ago, it was expected that this company would post a loss of $0.44 per share when it actually produced a loss of $0.39, delivering a surprise of 11.36%.Over the last four quarters, the company ha ...

Part I [Business](index=7&type=section&id=Item%201.%20Business) Fulcrum Therapeutics is a clinical-stage biopharmaceutical company developing small molecules for genetically defined rare diseases Clinical Pipeline Overview | Indication | Asset | Mechanism of Action | Preclinical | Phase 1 | Phase 2 | Phase 3 | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | **FSHD** | Losmapimod | DUX4 Reduction | | | | **✓** | | **SCD** | Pociredir | HbF Induction | | **✓** | | | - The company's primary focus is on developing small molecule therapies for rare genetic diseases with high unmet medical needs[20](index=20&type=chunk) - Losmapimod's Phase 3 REACH trial completed enrollment of **260 patients** in September 2023, with topline data anticipated in **Q4 2024**[20](index=20&type=chunk) - The FDA lifted a clinical hold on the IND for pociredir in August 2023, and the Phase 1b trial is being re-initiated at higher dose levels (12 mg and 20 mg) with revised criteria to target patients with higher disease severity[21](index=21&type=chunk)[79](index=79&type=chunk) [Losmapimod for FSHD](index=9&type=section&id=Losmapimod%20for%20FSHD) Losmapimod is being developed for Facioscapulohumeral Muscular Dystrophy (FSHD), a progressive muscle-wasting disease with no approved treatments - FSHD is a rare, progressive disease with no approved treatments, caused by the aberrant expression of the DUX4 gene in skeletal muscle[28](index=28&type=chunk)[31](index=31&type=chunk) - The pivotal Phase 3 REACH trial is a randomized, double-blind, placebo-controlled study evaluating a 15 mg twice-daily dose of losmapimod over 48 weeks, with the primary endpoint being the absolute change from baseline in Reachable Workspace (RWS)[51](index=51&type=chunk) - Previous Phase 2b (ReDUX4) trial data showed that while the primary biomarker endpoint was not met, losmapimod demonstrated **clinically relevant benefits** on functional measures like RWS and patient-reported outcomes compared to placebo at 48 weeks[37](index=37&type=chunk)[44](index=44&type=chunk) - Losmapimod has an extensive safety history, having been evaluated by its original developer, GSK, in nearly **3,500 subjects** across multiple non-muscle indications, where it was generally well-tolerated[36](index=36&type=chunk)[61](index=61&type=chunk) [Pociredir for SCD](index=17&type=section&id=Pociredir%20for%20SCD) Pociredir is an oral small molecule designed to treat Sickle Cell Disease (SCD) by inducing fetal hemoglobin (HbF) production - Pociredir aims to treat the root cause of SCD by inducing HbF, which is known to mitigate clinical manifestations of the disease[73](index=73&type=chunk)[74](index=74&type=chunk) - Interim Phase 1b data from the 6 mg cohort showed up to **9.5% absolute HbF increases**, and data from the 12 mg cohort (prior to the hold) showed up to **10.0% absolute HbF increases** from baseline after 42 days[81](index=81&type=chunk)[82](index=82&type=chunk) - The FDA placed a full clinical hold on the pociredir IND in February 2023, citing hematological malignancies observed in toxicology studies, similar to other PRC2 inhibitors; the hold was lifted in August 2023[77](index=77&type=chunk)[78](index=78&type=chunk)[79](index=79&type=chunk) - The Phase 1b trial is being re-initiated with amended inclusion/exclusion criteria to target patients with higher disease severity, enrolling approximately 10 patients at the 12 mg dose and another 10 at the 20 mg dose[79](index=79&type=chunk)[85](index=85&type=chunk) [License Agreements and Collaborations](index=26&type=section&id=License%20Agreements%20and%20Collaborations) Fulcrum maintains several key strategic agreements for its pipeline, including in-licensing losmapimod and collaborating on new targets - Fulcrum in-licensed losmapimod from GSK, gaining exclusive worldwide rights, with the agreement including up to **$37.5 million** in development/regulatory milestones and up to **$60.0 million** in sales milestones, plus tiered royalties[99](index=99&type=chunk)[101](index=101&type=chunk) - The collaboration with MyoKardia (BMS) focuses on identifying targets for cardiomyopathies, for which Fulcrum received a **$10.0 million** upfront payment and is eligible for up to **$298.5 million** in milestones per target, plus tiered royalties[105](index=105&type=chunk)[108](index=108&type=chunk) - In July 2023, Fulcrum entered into an exclusive worldwide license agreement with CAMP4 for its Diamond Blackfan Anemia (DBA) program, with potential milestones totaling up to **$70.0 million**, plus royalties[110](index=110&type=chunk)[111](index=111&type=chunk) [Competition](index=30&type=section&id=Competition) The company faces competition from major pharmaceutical and biotechnology firms across its FSHD and SCD programs - For FSHD, there are no approved treatments, and key competitors in clinical development include **Roche**, **Avidity**, and **Arrowhead Pharmaceutical**[131](index=131&type=chunk)[132](index=132&type=chunk) - For SCD, pociredir competes with approved oral therapies (hydroxyurea, voxelotor, crizanlizumab, L-glutamine) and two recently approved gene therapies (**lovo-cel** and **exa-cel**)[133](index=133&type=chunk)[134](index=134&type=chunk) - Other SCD therapies in development include small molecules from **Novo Nordisk** (nDec) and **Agios** (mitapivat), and an HbS polymerization inhibitor from **Pfizer** (GBT-601)[137](index=137&type=chunk) [Government Regulation and Product Approvals](index=32&type=section&id=Government%20Regulation%20and%20Product%20Approvals) The company's operations are subject to extensive regulation by government authorities in the U.S. and other countries - The drug development and approval process in the U.S. requires successful completion of preclinical studies and three phases of human clinical trials before an NDA can be submitted to the FDA[141](index=141&type=chunk)[155](index=155&type=chunk) - The FDA has granted losmapimod **Orphan Drug** and **Fast Track** designations for FSHD, while pociredir has received **Orphan Drug** and **Fast Track** designations for SCD[39](index=39&type=chunk)[77](index=77&type=chunk) - In the EU, the approval process is managed by the EMA through a centralized procedure for rare diseases, leading to a single marketing authorization valid across the EU[216](index=216&type=chunk)[217](index=217&type=chunk)[215](index=215&type=chunk) - The company is subject to healthcare laws including the Anti-Kickback Statute, False Claims Act, and pricing regulations like the Inflation Reduction Act of 2022 (IRA), which could impact product pricing and reimbursement[200](index=200&type=chunk)[208](index=208&type=chunk) [Human Capital Management](index=56&type=section&id=Human%20Capital%20Management) The company emphasizes a patient-focused culture and is committed to diversity, equity, and inclusion to attract and retain talent - As of February 20, 2024, the company had **76 full-time employees**, with 26 holding M.D. or Ph.D. degrees and 47 engaged in R&D[248](index=248&type=chunk) - The company reports a diverse workforce, with women comprising approximately **55%** of full-time employees and non-white employees making up about **29%** of the U.S. workforce[251](index=251&type=chunk) [Risk Factors](index=58&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks related to its financial condition, clinical development, third-party reliance, and intellectual property - The company has a history of significant losses (**$97.3 million in 2023**) and an accumulated deficit of **$509.7 million** as of December 31, 2023, and expects to incur losses for several more years[255](index=255&type=chunk) - **Substantial additional funding** is required to continue clinical trials and development programs, and failure to raise capital could force delays or elimination of programs[258](index=258&type=chunk) - Clinical drug development is uncertain, as highlighted by the FDA's clinical hold on pociredir from February to August 2023, which underscores the risk of delays and unforeseen challenges[288](index=288&type=chunk)[293](index=293&type=chunk) - The company relies on third-party contract manufacturing organizations (CMOs) for its product candidates, which poses risks related to supply, quality, and regulatory compliance[329](index=329&type=chunk) - The company's ability to protect its intellectual property is critical, as the composition of matter patents for losmapimod licensed from GSK have expired, increasing reliance on method-of-use patents[367](index=367&type=chunk)[373](index=373&type=chunk) [Unresolved Staff Comments](index=114&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) The company reports no unresolved staff comments from the SEC - There are no unresolved staff comments[490](index=490&type=chunk) [Cybersecurity](index=114&type=section&id=Item%201C.%20Cybersecurity) The company has implemented a cybersecurity risk management process integrated into its enterprise risk management framework - The company's cybersecurity risk management is integrated into its overall enterprise risk management process and utilizes third-party security providers for testing and assessments[491](index=491&type=chunk)[492](index=492&type=chunk) - The audit committee has oversight responsibility for cybersecurity risks, with the Executive Director, IT & Operations leading the program[495](index=495&type=chunk)[497](index=497&type=chunk) [Properties](index=114&type=section&id=Item%202.%20Properties) The company's principal facility is leased office and laboratory space in Cambridge, Massachusetts - The company leases approximately **28,731 square feet** of office and lab space in Cambridge, MA, with the lease expiring in June 2028[499](index=499&type=chunk) [Legal Proceedings](index=114&type=section&id=Item%203.%20Legal%20Proceedings) The company is facing a class action lawsuit alleging violations of the Securities Exchange Act - A class action lawsuit was filed against the company and its officers related to the clinical hold on pociredir, alleging misleading statements about the drug's development[500](index=500&type=chunk) - The company filed a motion to dismiss the lawsuit in November 2023 and plans to defend against the litigation vigorously[500](index=500&type=chunk) [Mine Safety Disclosures](index=116&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's operations - This item is not applicable[501](index=501&type=chunk) Part II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=117&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock is traded on the Nasdaq Global Market, and it does not anticipate paying cash dividends - Common stock trades on the Nasdaq Global Market under the symbol **"FULC"**[503](index=503&type=chunk) - The company has never declared or paid cash dividends and does not intend to in the foreseeable future[505](index=505&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=118&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company's net loss decreased in 2023, and its cash position is expected to fund operations into 2026 Results of Operations (2023 vs. 2022) | (in thousands) | 2023 | 2022 | Change ($) | | :--- | :--- | :--- | :--- | | Collaboration revenue | $2,805 | $6,342 | $(3,537) | | Research and development | $71,801 | $76,782 | $(4,981) | | General and administrative | $41,668 | $41,694 | $(26) | | **Total operating expenses** | **$113,469** | **$118,903** | **$(5,434)** | | Loss from operations | $(110,664) | $(112,561) | $1,897 | | Other income, net | $13,329 | $2,690 | $10,639 | | **Net loss** | **$(97,335)** | **$(109,871)** | **$12,536** | - The decrease in R&D expenses was primarily driven by lower external costs for pociredir due to the clinical hold and a $5.0 million milestone payment to GSK in 2022 that did not recur, partially offset by higher costs for the advancing REACH trial[540](index=540&type=chunk) - As of December 31, 2023, the company had **$236.2 million** in cash, cash equivalents, and marketable securities, with a projected cash runway to fund operations into **2026**[517](index=517&type=chunk) - In January 2023, the company raised net proceeds of **$117.3 million** from a public offering of its common stock[513](index=513&type=chunk)[544](index=544&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=131&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity related to its investment portfolio - The main market risk is interest rate sensitivity on its **$236.2 million** portfolio of cash, cash equivalents, and marketable securities[576](index=576&type=chunk) - The company has some exposure to foreign currency fluctuations from contracts with non-U.S. vendors but does not currently use hedging instruments[577](index=577&type=chunk) [Financial Statements and Supplementary Data](index=131&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section contains the company's audited consolidated financial statements for fiscal years 2023 and 2022 Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $25,563 | $35,098 | | Marketable securities | $210,658 | $167,823 | | **Total Assets** | **$257,694** | **$226,685** | | **Liabilities & Equity** | | | | Total current liabilities | $13,675 | $16,725 | | **Total Liabilities** | **$22,501** | **$27,743** | | **Total Stockholders' Equity** | **$235,193** | **$198,942** | Consolidated Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | | :--- | :--- | :--- | | Collaboration revenue | $2,805 | $6,342 | | Total operating expenses | $113,469 | $118,903 | | Loss from operations | $(110,664) | $(112,561) | | **Net loss** | **$(97,335)** | **$(109,871)** | | Net loss per share | $(1.59) | $(2.44) | [Changes in and Disagreements With Accountants on Accounting and Financial Disclosure](index=131&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20With%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) The company reports no changes in or disagreements with its accountants - There were no disagreements with accountants on accounting and financial disclosure[580](index=580&type=chunk) [Controls and Procedures](index=133&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and internal control over financial reporting were effective - Management concluded that the company's disclosure controls and procedures were **effective** as of December 31, 2023[582](index=582&type=chunk) - Management concluded that internal control over financial reporting was **effective** as of December 31, 2023[585](index=585&type=chunk) - The company is exempt from providing an auditor's attestation report on internal controls due to its status as an **emerging growth company**[586](index=586&type=chunk) [Other Information](index=134&type=section&id=Item%209B.%20Other%20Information) The company terminated its at-the-market (ATM) equity distribution agreement - The company terminated its May 2022 at-the-market (ATM) offering program, which had an aggregate offering price of up to **$50.0 million**, and no shares were sold under this agreement[589](index=589&type=chunk) Part III [Directors, Executive Officers and Corporate Governance](index=135&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) This information will be provided in the company's 2024 Definitive Proxy Statement - Information regarding directors, executive officers, and corporate governance is incorporated by reference from the forthcoming 2024 Proxy Statement[593](index=593&type=chunk) [Executive Compensation](index=135&type=section&id=Item%2011.%20Executive%20Compensation) This information will be provided in the company's 2024 Definitive Proxy Statement - Information regarding executive compensation is incorporated by reference from the forthcoming 2024 Proxy Statement[595](index=595&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=135&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) This information will be provided in the company's 2024 Definitive Proxy Statement - Information regarding security ownership is incorporated by reference from the forthcoming 2024 Proxy Statement[596](index=596&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=135&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) This information will be provided in the company's 2024 Definitive Proxy Statement - Information regarding related transactions and director independence is incorporated by reference from the forthcoming 2024 Proxy Statement[597](index=597&type=chunk) [Principal Accountant Fees and Services](index=135&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services) This information will be provided in the company's 2024 Definitive Proxy Statement - Information regarding principal accountant fees and services is incorporated by reference from the forthcoming 2024 Proxy Statement[598](index=598&type=chunk) Part IV [Exhibits and Financial Statement Schedules](index=136&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists the consolidated financial statements and exhibits filed with the report - This item lists the financial statements and exhibits filed with the Form 10-K[600](index=600&type=chunk)[603](index=603&type=chunk) [Form 10-K Summary](index=136&type=section&id=Item%2016.%20Form%2010-K%20Summary) No Form 10-K summary is provided - This item is not applicable[604](index=604&type=chunk)

Exhibit 99.1 Fulcrum Therapeutics Announces Recent Business Highlights and Financial Results for Fourth Quarter and Full Year 2023 ― On track to report topline data for Phase 3 REACH trial of losmapimod in facioscapulohumeral muscular dystrophy (FSHD) in the fourth quarter of 2024 ― ― Restart of the Phase 1b PIONEER trial of pociredir in sickle cell disease (SCD) underway ― ― Conference call and webcast scheduled for 8:00 a.m. ET today ― CAMBRIDGE, Mass., – February 27, 2024 – Fulcrum Therapeutics, Inc. ® ( ...

[Preliminary Information](index=2&type=section&id=Preliminary%20Information) [Cautionary Note Regarding Forward-Looking Statements](index=2&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) This section cautions against undue reliance on forward-looking statements regarding operations, financial performance, and product development due to inherent risks - Forward-looking statements cover ongoing clinical trials (**losmapimod**, **pociredir**), impact of organizational streamlining, initiation/timing of **R&D programs**, **commercialization plans**, **funding expectations**, potential advantages of **product candidates**, **market acceptance**, **intellectual property**, and **collaborations**[6](index=6&type=chunk)[7](index=7&type=chunk) - Readers are cautioned not to place undue reliance on forward-looking statements, as **actual results may differ materially** due to various **risks and uncertainties**, particularly those detailed in the 'Risk Factors' and 'Management's Discussion and Analysis of Results of Operations' sections[8](index=8&type=chunk)[9](index=9&type=chunk) [Summary Risk Factors](index=3&type=section&id=SUMMARY%20RISK%20FACTORS) This section summarizes principal risks including accumulated losses, funding needs, early development stage, lengthy drug development, adverse events, competition, and third-party reliance Key Financial Risks | Metric | Amount (as of Sep 30, 2023) | Previous (as of Dec 31, 2022) | | :----- | :-------------------------- | :----------------------------- | | Net Loss (9 months) | $72.6 million | $109.9 million (FY2022) | | Accumulated Deficit | $484.9 million | $412.3 million (FY2022) | - The company expects to incur **losses** for several years and will require **substantial additional funding** to support product development programs (**losmapimod**, **pociredir**) and **commercialization efforts**[11](index=11&type=chunk) - Key operational risks include the **early stage of development** with only **two clinical candidates**, the **lengthy and uncertain nature** of clinical drug development (e.g., recent **clinical hold on pociredir**), potential for **serious adverse events**, and **reliance on contract manufacturing organizations (CMOs)** and **third parties for clinical trials**[11](index=11&type=chunk)[12](index=12&type=chunk) - Other risks include **substantial competition**, challenges in **intellectual property protection**, **adverse developments in the financial services industry**, and potential impacts from **pandemics or geopolitical events**[11](index=11&type=chunk)[12](index=12&type=chunk) [PART I. FINANCIAL INFORMATION](index=5&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) This section presents unaudited consolidated financial statements for Q3 2023 and 2022, covering balance sheets, operations, equity, cash flows, and detailed accounting notes [Consolidated Balance Sheets](index=6&type=section&id=Consolidated%20Balance%20Sheets%20as%20of%20September%2030%2C%202023%20and%20December%2031%2C%202022) Consolidated balance sheets show total assets increased to **$278.9 million** (Sep 30, 2023) from **$226.7 million** (Dec 31, 2022), driven by marketable securities and paid-in capital Consolidated Balance Sheet Highlights (in thousands) | Item | Sep 30, 2023 | Dec 31, 2022 | Change ($) | Change (%) | | :-------------------------------- | :----------- | :----------- | :--------- | :--------- | | Total Assets | $278,879 | $226,685 | $52,194 | 23.0% | | Cash and cash equivalents | $30,080 | $35,098 | $(5,018) | -14.3% | | Marketable securities | $227,011 | $167,823 | $59,188 | 35.3% | | Total Liabilities | $23,417 | $27,743 | $(4,326) | -15.6% | | Total Stockholders' Equity | $255,462 | $198,942 | $56,520 | 28.4% | | Accumulated Deficit | $(484,917) | $(412,338) | $(72,579) | 17.6% | - The increase in **total assets** is primarily due to a significant rise in **marketable securities**, while **cash and cash equivalents** saw a decrease[15](index=15&type=chunk) - **Stockholders' equity increased substantially**, mainly driven by **additional paid-in capital** from **common stock issuances**, despite an increase in **accumulated deficit**[15](index=15&type=chunk) [Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss%20for%20the%20three%20and%20nine%20months%20ended%20September%2030%2C%202023%20and%202022) Consolidated statements show a net loss of **$24.0 million** (Q3 2023) and **$72.6 million** (YTD Sep 2023), with nine-month loss decreasing despite lower collaboration revenue and R&D expenses Consolidated Statements of Operations Highlights (in thousands) | Item | 3 Months Ended Sep 30, 2023 | 3 Months Ended Sep 30, 2022 | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | | Collaboration revenue | $759 | $1,183 | $1,934 | $5,657 | | Research and development | $18,238 | $15,366 | $52,802 | $58,216 | | General and administrative | $9,961 | $9,707 | $31,804 | $31,564 | | Total operating expenses | $28,199 | $25,538 | $84,606 | $90,245 | | Loss from operations | $(27,440) | $(24,355) | $(82,672) | $(84,588) | | Other income, net | $3,423 | $617 | $10,093 | $852 | | Net loss | $(24,017) | $(23,738) | $(72,579) | $(83,736) | | Net loss per share (basic & diluted) | $(0.39) | $(0.51) | $(1.19) | $(1.97) | - Collaboration revenue decreased by **35.8%** for the three months and **65.8%** for the nine months ended September 30, 2023, primarily due to the **termination of the Acceleron collaboration agreement**[17](index=17&type=chunk) - Research and development expenses increased by **18.7%** for the three months but decreased by **9.3%** for the nine months ended September 30, 2023, reflecting **shifts in clinical trial activities**[17](index=17&type=chunk) - **Other income, net, significantly increased** for both periods, driven by **higher returns** on **cash, cash equivalents, and marketable securities**[17](index=17&type=chunk) [Consolidated Statements of Stockholders' Equity](index=8&type=section&id=Consolidated%20Statements%20of%20Stockholders%27%20Equity%20for%20the%20three%20and%20nine%20months%20ended%20September%2030%2C%202023%20and%202022) Stockholders' equity increased from **$198.9 million** (Dec 31, 2022) to **$255.5 million** (Sep 30, 2023), driven by common stock offerings and stock-based compensation, despite accumulated losses Stockholders' Equity Changes (in thousands) | Item | Dec 31, 2022 | Sep 30, 2023 | Change ($) | | :-------------------------- | :----------- | :----------- | :--------- | | Common Stock (Amount) | $52 | $62 | $10 | | Additional Paid-In Capital | $612,025 | $741,203 | $129,178 | | Accumulated Deficit | $(412,338) | $(484,917) | $(72,579) | | Total Stockholders' Equity | $198,942 | $255,462 | $56,520 | - The increase in **additional paid-in capital** is largely attributable to **$117.3 million** in net proceeds from a **public offering of common stock** in January 2023[20](index=20&type=chunk) - **Stock-based compensation expense** contributed **$11.4 million** to **additional paid-in capital** for the nine months ended September 30, 2023[20](index=20&type=chunk) [Consolidated Statements of Cash Flows](index=9&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows%20for%20the%20nine%20months%20ended%20September%2030%2C%202023%20and%202022) Cash flows show a net decrease of **$5.0 million** (YTD Sep 2023), a shift from a **$55.5 million** increase (prior year), primarily due to increased net cash used in investing activities Consolidated Cash Flow Highlights (in thousands) | Activity | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :------------------------------------------ | :-------------------------- | :-------------------------- | | Net cash used in operating activities | $(67,807) | $(77,354) | | Net cash (used in) provided by investing activities | $(55,046) | $48,775 | | Net cash provided by financing activities | $117,835 | $84,105 | | Net (decrease) increase in cash, cash equivalents, and restricted cash | $(5,018) | $55,526 | | Cash, cash equivalents, and restricted cash, end of period | $31,172 | $92,030 | - **Net cash used in operating activities decreased by $9.6 million**, mainly due to a **lower net loss** and **increased interest income**[23](index=23&type=chunk) - **Net cash used in investing activities increased by $103.8 million**, primarily driven by **net purchases of marketable securities** in 2023 compared to net maturities in 2022[23](index=23&type=chunk) - **Net cash provided by financing activities increased by $33.7 million**, largely from **$117.3 million** in net proceeds from a January 2023 **public offering of common stock**[23](index=23&type=chunk) [Notes to Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) These notes detail business nature, accounting policies, fair value, cash, marketable securities, property, equity, stock compensation, collaborations, leases, commitments, contingencies, and net loss per share [1. Nature of the Business and Basis of Presentation](index=10&type=section&id=1.%20Nature%20of%20the%20Business%20and%20Basis%20of%20Presentation) Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on rare diseases, with **$484.9 million** accumulated deficit and ongoing need for additional funding - Fulcrum Therapeutics, Inc. was incorporated in Delaware on August 18, 2015, and focuses on developing **small molecules** for **genetically-defined rare diseases**[25](index=25&type=chunk) - The company has incurred **recurring losses** and **negative cash flows** from operations since inception, with an **accumulated deficit of $484.9 million** as of September 30, 2023[31](index=31&type=chunk) - In January 2023, the company completed a **public offering**, issuing **9,615,384 shares** of common stock at **$13.00 per share**, generating net proceeds of **$117.3 million**[29](index=29&type=chunk) - Management expects existing cash, cash equivalents, and marketable securities to fund operations for at least **12 months** from the financial statement issuance date, but acknowledges the need for **future financing** through **equity, debt, or collaborations**[32](index=32&type=chunk) [2. Summary of Significant Accounting Policies](index=11&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines significant accounting policies, including consolidation, estimates, and off-balance sheet risk, and details the adoption of new accounting pronouncements with no material impact - The **consolidated financial statements** include Fulcrum Therapeutics, Inc. and its **wholly-owned subsidiary**, Fulcrum Therapeutics Securities Corp., with all **intercompany transactions eliminated**[33](index=33&type=chunk) - Key estimates in financial statement preparation include **revenue recognition**, **accrued expenses**, **stock-based compensation**, and **income taxes**[35](index=35&type=chunk) - The company adopted **ASU No. 2016-13 (Credit Losses)** and **ASU No. 2019-12 (Income Taxes)** effective **January 1, 2023**, with **no material impact** on its financial position or results of operations[37](index=37&type=chunk)[38](index=38&type=chunk) - The company has **no significant off-balance sheet risk** and manages credit risk primarily through **diversified investments** in **cash, cash equivalents, and marketable securities** held at large financial institutions[36](index=36&type=chunk) [3. Fair Value Measurements](index=12&type=section&id=3.%20Fair%20Value%20Measurements) This note details fair value measurements of financial assets, primarily cash equivalents and marketable securities, totaling **$257.1 million** (Sep 30, 2023), mostly classified as Level 2 Fair Value Measurements at September 30, 2023 (in thousands) | Item | Total | Level 1 | Level 2 | Level 3 | | :---------------------- | :------ | :------ | :------ | :------ | | Cash equivalents: | | | | | | Money market funds | $17,336 | $17,336 | — | — | | U.S. Treasury securities | $1,991 | — | $1,991 | — | | Commercial paper | $10,753 | — | $10,753 | — | | Marketable securities: | | | | | | U.S. Treasury securities | $19,516 | — | $19,516 | — | | Government agency securities | $69,690 | — | $69,690 | — | | Commercial paper | $32,552 | — | $32,552 | — | | Corporate bonds | $105,253 | — | $105,253 | — | | **Total** | **$257,091** | **$17,336** | **$239,755** | **—** | - The majority of marketable securities and a portion of cash equivalents are classified as **Level 2**, indicating fair value derived from **observable inputs** other than quoted prices[39](index=39&type=chunk) - There were **no transfers** between fair value levels during the three and nine months ended September 30, 2023[39](index=39&type=chunk) [4. Cash Equivalents and Marketable Securities](index=13&type=section&id=4.%20Cash%20Equivalents%20and%20Marketable%20Securities) This note details cash equivalents and marketable securities, with a total fair value of **$257.1 million** (Sep 30, 2023) and a net accumulated other comprehensive loss of **$886 thousand** from unrealized losses Cash Equivalents and Marketable Securities (in thousands) | Item | Amortized Cost (Sep 30, 2023) | Fair Value (Sep 30, 2023) | Gross Unrealized Losses (Sep 30, 2023) | | :-------------------------- | :---------------------------- | :------------------------ | :------------------------------------- | | Total cash equivalents | $30,084 | $30,080 | $(4) | | Total marketable securities | $227,893 | $227,011 | $(882) | | **Total** | **$257,977** | **$257,091** | **$(886)** | - As of September 30, 2023, the company held **83 debt securities** in an unrealized loss position for less than **12 months** (**$216.6 million** fair value) and **5 debt securities** for greater than **12 months** (**$10.4 million** fair value)[40](index=40&type=chunk) - The company has the **intent and ability to hold** its debt securities until recovery and did not record any **credit-related impairment charges**[41](index=41&type=chunk) [5. Property and Equipment, Net](index=14&type=section&id=5.%20Property%20and%20Equipment%2C%20Net) Property and equipment, net, decreased to **$5.6 million** (Sep 30, 2023) from **$6.9 million** (Dec 31, 2022), primarily due to accumulated depreciation Property and Equipment, Net (in thousands) | Item | Sep 30, 2023 | Dec 31, 2022 | | :-------------------------- | :----------- | :----------- | | Total property and equipment | $17,973 | $17,568 | | Less: accumulated depreciation | $(12,327) | $(10,662) | | **Property and equipment, net** | **$5,646** | **$6,906** | - Depreciation expense was **$0.5 million** for the three months and **$1.7 million** for the nine months ended September 30, 2023[42](index=42&type=chunk) [6. Additional Balance Sheet Detail](index=14&type=section&id=6.%20Additional%20Balance%20Sheet%20Detail) This note details prepaid expenses and other current assets, increasing to **$4.8 million**, and accrued expenses and other current liabilities, decreasing to **$7.8 million** (Sep 30, 2023) Prepaid Expenses and Other Current Assets (in thousands) | Item | Sep 30, 2023 | Dec 31, 2022 | | :-------------------------------- | :----------- | :----------- | | Prepaid expenses | $3,466 | $3,425 | | Prepaid sign-on bonuses subject to vesting provisions | $254 | $92 | | Interest income receivable | $1,099 | $852 | | **Total** | **$4,819** | **$4,369** | Accrued Expenses and Other Current Liabilities (in thousands) | Item | Sep 30, 2023 | Dec 31, 2022 | | :-------------------------- | :----------- | :----------- | | External research and development | $3,107 | $4,700 | | Payroll and benefits | $4,023 | $4,211 | | Professional services | $422 | $535 | | Other | $265 | $105 | | **Total** | **$7,817** | **$9,551** | [7. Preferred Stock](index=14&type=section&id=7.%20Preferred%20Stock) The company authorized **5,000,000** preferred shares, but none were issued or outstanding as of September 30, 2023, and no dividends have been declared since inception - **5,000,000 shares** of preferred stock were authorized, but **none were issued or outstanding** as of September 30, 2023, and December 31, 2022[44](index=44&type=chunk) - **No dividends** have been declared on preferred stock since inception[45](index=45&type=chunk) [8. Common Stock](index=14&type=section&id=8.%20Common%20Stock) This note details common stock, with **200,000,000** shares authorized and **61,822,554** outstanding (Sep 30, 2023), plus shares reserved for employee benefit plans - **200,000,000 shares** of common stock, **$0.001 par value**, were authorized[46](index=46&type=chunk) Common Shares Issued and Outstanding | Date | Shares Issued and Outstanding | | :---------------- | :---------------------------- | | Sep 30, 2023 | 61,822,554 | | Dec 31, 2022 | 52,099,211 | - Common stockholders are not entitled to receive dividends unless declared by the board of directors, and **no dividends** have been declared or paid since inception[47](index=47&type=chunk) Shares Reserved for Future Issuance | Item | Sep 30, 2023 | Dec 31, 2022 | | :------------------------------------------ | :----------- | :----------- | | Shares reserved for exercises of outstanding stock options | 10,108,766 | 6,504,080 | | Shares reserved for vesting of restricted stock units | 78,142 | 76,718 | | Shares reserved for future issuance under the 2019 Stock Incentive Plan | 2,896,782 | 1,941,054 | | Shares reserved for future issuance under the 2019 Employee Stock Purchase Plan | 1,438,938 | 1,061,279 | | Shares reserved for future issuance under the 2022 Inducement Stock Incentive Plan | 1,003,472 | 329,880 | | **Total** | **15,526,100** | **9,913,011** | [9. Stock-based Compensation Expense](index=15&type=section&id=9.%20Stock-based%20Compensation%20Expense) This note details stock-based compensation plans, summarizing stock option and restricted stock unit activity, and total stock-based compensation expense recognized - The **2019 Stock Incentive Plan** and **2022 Inducement Stock Incentive Plan** have seen **increases in shares reserved** for issuance, with **2,896,782** and **1,003,472 shares** available, respectively, as of September 30, 2023[50](index=50&type=chunk)[52](index=52&type=chunk) Stock Option Activity (9 months ended Sep 30, 2023) | Item | Number of Shares | Weighted Average Exercise Price | | :-------------------------- | :--------------- | :------------------------------ | | Outstanding at Dec 31, 2022 | 6,504,080 | $11.99 | | Granted | 5,790,673 | $5.92 | | Exercised | (38,903) | $8.96 | | Cancelled | (2,147,084) | $11.96 | | Outstanding at Sep 30, 2023 | 10,108,766 | $8.53 | | Exercisable at Sep 30, 2023 | 2,890,946 | $12.74 | Stock-based Compensation Expense (in thousands) | Category | 3 Months Ended Sep 30, 2023 | 3 Months Ended Sep 30, 2022 | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | | General and administrative | $2,734 | $2,597 | $8,533 | $7,138 | | Research and development | $1,003 | $756 | $2,820 | $2,941 | | **Total** | **$3,737** | **$3,353** | **$11,353** | **$10,079** | - As of September 30, 2023, the company had **$35.2 million** of unrecognized stock-based compensation expense, to be recognized over a weighted average period of **3.07 years**[58](index=58&type=chunk) [10. Collaboration Agreements](index=17&type=section&id=10.%20Collaboration%20Agreements) This note details collaboration agreements with Acceleron (terminated Oct 2022) and MyoKardia, the latter involving an exclusive worldwide license for cardiomyopathies with upfront, research, milestone, and royalty payments - The **Acceleron Collaboration Agreement**, focused on pulmonary disease targets, terminated effective **October 1, 2022**, resulting in **no collaboration revenue** from this agreement in 2023[61](index=61&type=chunk)[62](index=62&type=chunk) - The **MyoKardia Collaboration Agreement** grants an **exclusive worldwide license** for **genetically defined cardiomyopathies**, including assay screening and research services[64](index=64&type=chunk)[65](index=65&type=chunk) - Under the MyoKardia agreement, the company received a **$10.0 million upfront payment** and **$2.5 million in prepaid research funding**, with potential for up to **$298.5 million** in aggregate **milestone payments** per target and **tiered royalties**[67](index=67&type=chunk) MyoKardia Collaboration Revenue (in thousands) | Period | Collaboration Revenue | | :-------------------------- | :-------------------- | | 3 Months Ended Sep 30, 2023 | $759 | | 3 Months Ended Sep 30, 2022 | $1,183 | | 9 Months Ended Sep 30, 2023 | $1,934 | | 9 Months Ended Sep 30, 2022 | $4,700 | - As of September 30, 2023, deferred revenue from MyoKardia was **$0.3 million**, and unbilled accounts receivable was **$0.6 million**[79](index=79&type=chunk) [11. License Agreements](index=20&type=section&id=11.%20License%20Agreements) This note describes key license agreements: GSK for **losmapimod** (FSHD) and CAMP4 for the **Diamond Blackfan Anemia (DBA)** program, both granting exclusive worldwide rights - Under the **GSK Agreement**, the company has an **exclusive worldwide license** to develop and commercialize **losmapimod**, with potential milestone payments up to **$37.5 million** (including **$7.5 million** achieved) and **tiered royalties** on net sales[80](index=80&type=chunk)[81](index=81&type=chunk) - The **CAMP4 Agreement**, entered in **July 2023**, grants an **exclusive worldwide license** for the **Diamond Blackfan Anemia (DBA) program**, including small molecule compounds and patent rights[84](index=84&type=chunk) - The CAMP4 Agreement includes an undisclosed upfront payment and potential development, regulatory, and sales milestone payments of up to **$35.0 million each**, plus **tiered royalties** on worldwide net sales[85](index=85&type=chunk) [12. Leases](index=22&type=section&id=12.%20Leases) This note details operating lease agreements for corporate headquarters at **26 Landsdowne Street** and office space at **125 Sidney Street**, outlining terms, commitments, and expenses - The lease for **26 Landsdowne Street** (**28,731 sq ft**) commenced **December 2017** and ends **June 30, 2028**, with a total commitment of **$25.1 million** over ten years[89](index=89&type=chunk) Future Minimum Lease Payments (26 Landsdowne Street, in thousands) | Year | Amount | | :--- | :----- | | 2023 | $633 | | 2024 | $2,572 | | 2025 | $2,649 | | 2026 | $2,729 | | 2027 | $2,811 | | Thereafter | $1,426 | | **Total minimum lease payments** | **$12,820** | - Operating lease expense for **26 Landsdowne Street** was approximately **$0.5 million** for the three months and **$1.3 million** for the nine months ended September 30, 2023[89](index=89&type=chunk) - An additional lease for **125 Sidney Street** (**12,196 sq ft**) commenced **November 2021** and ends **March 31, 2024**, with a total commitment of **$1.7 million** over the initial term[91](index=91&type=chunk) [13. Commitments and Contingencies](index=23&type=section&id=13.%20Commitments%20and%20Contingencies) This note addresses commitments and contingencies, including indemnification agreements and a securities class action lawsuit related to a clinical hold on **pociredir** - The company provides **indemnification** to vendors, lessors, business partners, directors, and senior management, with potential **unlimited future payments**, but has **not incurred material costs** to date[93](index=93&type=chunk) - A **class action complaint** (Celano v. Fulcrum Therapeutics, Inc., et al.) was filed on **April 28, 2023**, alleging violations of **Section 10(b)** and **20(a)** of the Exchange Act related to a clinical hold on **pociredir**[94](index=94&type=chunk) - The lawsuit seeks **compensatory damages** for an allegedly inflated stock price between **March 3, 2022**, and **March 8, 2023**, and attorneys' fees and costs. The company intends to **vigorously defend** against this litigation[94](index=94&type=chunk) [14. Defined Contribution Plan](index=23&type=section&id=14.%20Defined%20Contribution%20Plan) This note describes the company's **401(k) defined contribution savings plan**, with contributions of **$0.2 million** (Q3) and **$0.6 million** (YTD Sep) for both 2023 and 2022 - The company has a **401(k) defined contribution savings plan** for eligible employees[96](index=96&type=chunk) 401(k) Plan Contributions (in millions) | Period | 2023 | 2022 | | :-------------------------- | :--- | :--- | | 3 Months Ended Sep 30 | $0.2 | $0.2 | | 9 Months Ended Sep 30 | $0.6 | $0.6 | [15. Net Loss per Share](index=23&type=section&id=15.%20Net%20Loss%20per%20Share) This note provides the calculation of basic and diluted net loss per share, listing anti-dilutive common stock equivalents excluded from the diluted calculation Net Loss Per Share (Basic and Diluted) | Period | 2023 | 2022 | | :-------------------------- | :----- | :----- | | 3 Months Ended Sep 30 | $(0.39) | $(0.51) | | 9 Months Ended Sep 30 | $(1.19) | $(1.97) | Anti-Dilutive Common Stock Equivalents Excluded (in thousands) | Item | 3 Months Ended Sep 30, 2023 | 3 Months Ended Sep 30, 2022 | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | :-------------------------- | | Outstanding stock options | 10,108,766 | 5,929,065 | 10,108,766 | 5,929,065 | | Unvested restricted stock units | 78,142 | 95,174 | 78,142 | 95,174 | | **Total** | **10,186,908** | **6,024,239** | **10,186,908** | **6,024,239** | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=24&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section discusses financial condition and results, focusing on clinical-stage candidates, operating losses, funding needs, revenue, expenses, and cash flow changes, emphasizing drug development risks [Overview](index=24&type=section&id=Overview) Fulcrum is a clinical-stage biopharmaceutical company developing small molecules for rare diseases, with lead candidates **losmapimod** (FSHD) and **pociredir** (SCD), facing significant losses and requiring additional funding - Fulcrum is a **clinical-stage biopharmaceutical company** focused on genetically defined rare diseases[99](index=99&type=chunk) - **Losmapimod** (FSHD) is in a **Phase 3 clinical trial (REACH)**, with enrollment completed in **September 2023** and topline data expected in **Q4 2024**[99](index=99&type=chunk) - **Pociredir** (SCD) is in a **Phase 1b clinical trial**; a clinical hold was placed in **February 2023** and lifted in **August 2023**. The trial is re-initiating at **12 mg** and **20 mg dose levels**, targeting patients with higher disease severity[100](index=100&type=chunk) - The company has incurred net losses of **$24.0 million** (Q3 2023) and **$72.6 million** (YTD Sep 2023), with an accumulated deficit of **$484.9 million**[103](index=103&type=chunk) - Existing cash, cash equivalents, and marketable securities of **$257.1 million** are expected to fund operations into **2026**, but substantial additional funding will be needed for ongoing R&D and potential commercialization[105](index=105&type=chunk)[107](index=107&type=chunk) [Components of Results of Operations](index=25&type=section&id=Components%20of%20Results%20of%20Operations) This section breaks down revenue and operating expenses, with collaboration revenue from MyoKardia, fluctuating R&D expenses, general and administrative costs, and other income from investments [Revenue](index=25&type=section&id=