On February 25, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and announced financial results for the fourth quarter and full year of 2024 (Press release, Cogent Biosciences, FEB 25, 2025, View Source [SID1234650522]).
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"Cogent is preparing to report data from three bezuclastinib pivotal clinical trials this year," said Andrew Robbins, the company’s President and Chief Executive Officer. "Given our strong cash balance, and emerging pipeline of potential best-in-class targeted therapies, we are poised for a transformational year culminating with the planned submission of Cogent’s first NDA for bezuclastinib by the end of 2025."
Q4 2024 and Recent Business Highlights
In December 2024, announced updated clinical results from SUMMIT, showcasing dramatic symptomatic improvement in nonadvanced systemic mastocytosis (NonAdvSM) patients and positive updated data from the APEX trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting. In both trials, bezuclastinib continued to demonstrate an encouraging safety and tolerability profile. Highlights include:
In SUMMIT, a registration-directed, global, randomized, placebo-controlled trial in patients with NonAdvSM, treatment with 100 mg bezuclastinib demonstrated:
56% mean improvement in Total Symptom Score (TSS) at 24 weeks with 76% of patients achieving at least a >50% reduction from baseline in TSS
89% of patients had >50% decrease in serum tryptase levels by four weeks of treatment
In APEX, a registration-directed, global, open-label trial in patients with AdvSM, treatment with various doses of bezuclastinib demonstrated:
52% ORR per mIWG criteria, including 83% ORR for patients receiving 100 mg BID
88% ORR per PPR criteria, including 100% ORR for patients receiving 100 mg BID
2.2 months median time-to-response with median duration-of-response and median PFS not yet reached with at least 20 months follow-up
In October 2024, announced the addition of a potent and selective KRAS inhibitor to Cogent’s pipeline at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) International Symposium on Molecular Targets and Cancer Therapeutics.
Cogent’s internally-developed pan-KRAS(ON) inhibitor demonstrated picomolar (pM) activity across KRAS mutations with selectivity over H/NRAS leading to potential advantages versus other molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. Lead optimization of the program is ongoing.
In October 2024, shared progress on Cogent’s clinical candidate CGT6297, a potent allosteric inhibitor of PI3Kα, with 25-fold selectivity over PI3Kα WT. In a poster at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) International Symposium on Molecular Targets and Cancer Therapeutics, CGT6297 showed high oral bioavailability and low clearance across species, providing robust inhibition of downstream signaling and efficacy in animal models. Importantly, when compared to a clinically relevant dose of a currently approved therapy in a mouse tumor model, CGT6297 demonstrated superior efficacy with no increase in insulin.
Projected Near-Term Milestones
Bezuclastinib – Systemic Mastocytosis (SM)
Poster presentation focused on symptomatic performance of patients from SUMMIT Part 1 who have received 100 mg bezuclastinib for at least 48 weeks at the 2025 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI).
Report top-line results in July 2025 from the SUMMIT trial.
Report top-line results during the second half of 2025 from the APEX trial.
Submit the first bezuclastinib New Drug Application (NDA) by the end of 2025.
Bezuclastinib – Gastrointestinal Stromal Tumors (GIST)
Report top-line results by the end of 2025 from the pivotal Phase 3 PEAK trial. PEAK is a global, blinded, randomized clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant gastrointestinal stromal tumors (GIST).
Bezuclastinib – Expanded Access Program
In Q1, initiate Expanded Access Programs (EAP) in the U.S. for SM and GIST patients to receive investigational bezuclastinib after meeting certain eligibility criteria.
CGT4859 (FGFR2 inhibitor)
Enroll patients in the ongoing Phase 1 trial with CGT4859, a reversible, selective FGFR2 inhibitor in patients with documented FGFR mutations, including advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well-tolerated dose for further clinical investigation.
Preclinical Pipeline
Submit an IND application in 2025 for CGT4255, a potent, selective ErbB2 inhibitor, highlighted by potential best-in-class brain-penetrant properties.
Submit an IND application in 2025 for CGT6297, a potent allosteric inhibitor of PI3Kα, with 25-fold selectivity over PI3Kα WT.
Upcoming Investor Conference
Leerink Healthcare Conference on Wednesday, March 12 at 10:00 a.m. ET.
A live webcast can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days.
Fourth Quarter and Full Year 2024 Financial Results
Cash and Cash Equivalents: As of December 31, 2024, Cogent had cash, cash equivalents and marketable securities of $287.1 million. Cogent believes this year-end balance, together with the $25.0 million gross proceeds from shares sold under the Company’s at-the-market (ATM) stock offering in February 2025, will be sufficient to fund its operating expenses and capital expenditure requirements into late 2026, including through clinical readouts from the ongoing SUMMIT, PEAK and APEX registration-directed trials.
R&D Expenses: Research and development expenses were $62.0 million for the fourth quarter of 2024 and $232.7 million for the year ended December 31, 2024, as compared to $48.7 million for the fourth quarter of 2023 and $173.8 million for the year ended December 31, 2023. The increase was driven by the development of bezuclastinib, including costs associated with the accelerated completion of enrollment of the SUMMIT and PEAK trials and ongoing cost of the APEX trial, and the continued progression of our research pipeline. R&D expenses include non-cash stock compensation expense of $5.0 million for the fourth quarter of 2024 and $19.0 million for the year ended December 31, 2024, as compared to $4.1 million for the fourth quarter of 2023 and $14.6 million for the year ended December 31, 2023.
G&A Expenses: General and administrative expenses were $11.7 million for the fourth quarter of 2024 and $43.3 million for the year ended December 31, 2024, as compared to $9.5 million for the fourth quarter of 2023 and $34.4 million for the year ended December 31, 2023. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.0 million for the fourth quarter of 2024 and $20.8 million for the year ended December 31, 2024, as compared to $4.8 million for the fourth quarter of 2023 and $16.0 million for the year ended December 31, 2023.
Net Loss: Net loss was $67.9 million for the fourth quarter of 2024 and $255.9 million for the year ended December 31, 2024, as compared to a net loss of $54.4 million for the fourth quarter of 2023 and $192.4 million for the year ended December 31, 2023.
Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)
Cogent also announced today that, on February 12, 2025 and February 24, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of "inducement" equity awards to five new employees under the company’s 2020 Inducement Plan with grant dates of February 12, 2025, February 19, 2025 and February 24, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 78,500 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date.