SCAI-003

SUMMIT and APEX clinical presentations planned for 2023 ASH Annual Meeting; SUMMIT NonAdvSM data selected for oral presentation SUMMIT Part I completed upsized enrollment during Q3; SUMMIT Part 2 expected to begin in 1H 2024 at over 50 sites globally 33% ORR and >14 months median duration of treatment for 2nd-line GIST patients from updated PEAK lead-in data presented at 2023 CTOS Annual Meeting Ended Q3 2023 with $312.8 million, providing cash runway into 2026 WALTHAM, Mass. and BOULDER, Colo., Nov. 02, 2023 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported recent business highlights and financial results for the third quarter ended September 30, 2023. “This quarter was marked by meaningful progress as we furthered our efforts developing bezuclastinib for the AdvSM, NonAdvSM and GIST patient populations,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We look forward to the opportunity to present clinical data from both SUMMIT, selected for an oral presentation, and APEX clinical trials at the 2023 American Society of Hematology (ASH) annual meeting in December, and are pleased with the updated PEAK lead-in data we are sharing at the 2023 Connective Tissue Oncology Society (CTOS) annual meeting this weekend. With these important advances coupled with our cash runway into 2026, we believe we are well positioned to further build on our momentum to bring best-in-class therapies to patients with genetically defined diseases.” Business Highlights & Milestones Oral presentation of initial clinical data from SUMMIT Part 1a at the ASH annual meeting on Saturday, December 9, 2023. SUMMIT is a randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). Cogent will host an investor webcast to review the results on Monday, December 11, 2023 at 8:00 a.m. ET. Details will be provided closer to the event. Presentation will include safety, tolerability, pharmacokinetics, biomarker and symptomatic improvement results from the 20 patients enrolled in SUMMIT Part 1a. Measures of symptomatic improvement will include clinical data collected from multiple patient reported outcome measures including MAS, MCQoL, PGIS and PGIC. SUMMIT Part 1 enrollment completed in Q3 2023, including over-enrollment at 54 patients across Part 1a and Part 1b. Clinical results from the entire Part 1 patient population are planned for presentation at a scientific conference in Q1 2024. SUMMIT Part 2, a registration-directed, global, randomized placebo-controlled trial is on track for initiation in 1H 2024, ahead of schedule. Updated clinical data from the lead-in portion of the ongoing PEAK Phase 3 study to be shared in an oral presentation at the 2023 CTOS annual meeting on November 4, 2023. PEAK is an ongoing, multi-part Phase 3 randomized, global, multicenter trial evaluating bezuclastinib in combination with sunitinib in patients with imatinib-resistant gastrointestinal stromal tumors (GIST). Safety and tolerability data from 42 patients enrolled in Part 1a and Part 1b are consistent with results shared at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, demonstrating the combination of bezuclastinib and sunitinib was well tolerated and the adverse event pro similar to sunitinib monotherapy. Updated clinical activity from a subset of 2nd-line GIST patients demonstrates a 33% confirmed overall response rate (ORR) with ongoing median duration of therapy greater than 14 months. Together with clinical data previously reported from a Phase 1/2 trial, 4 of 10 evaluable 2nd-line GIST patients treated with the combination have reached confirmed partial response status. Phase 3 portion of the PEAK study remains on track to complete enrollment by the end of 2024, with over 100 active sites globally. Updated clinical results from Part 1 of the ongoing APEX study to be presented at the 2023 ASH annual meeting on Monday, December 11, 2023. APEX is a global, multi-part Phase 2 trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). Presentation will include safety, tolerability, pharmacokinetics, biomarker and response assessments from 33 patients enrolled in APEX Part 1. APEX Part 2 is on track to complete enrollment by the end of 2024. An additional APEX cohort was initiated in Q3 and is designed to allow concomitant administration of bezuclastinib with azacitadine in patients with systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Presented preclinical data at the 2023 ENA annual meeting on the Company’s next-generation, reversible, non-covalent fibroblast growth factor receptor 2 (FGFR2) program, which exhibited low nanomolar potency on WT FGFR2 and FGFR2 mutations and is selective against the kinome and a panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in a mutant-driven mouse model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at 5 mg/kg PO and was well-tolerated. Cogent anticipates filing an Investigational New Drug (IND) Application and beginning a clinical trial in 2024. Upcoming Scientific Presentations 2023 ASH - Oral Presentation Title: Initial Results from Summit: An Ongoing, 3-Part, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of Bezuclastinib in Adult Patients with NonAdvanced Systemic Mastocytosis (NonAdvSM) Date: Saturday, December 9, 2023 Session Time: 9:30 a.m. – 11:00 a.m. PT/12:30 p.m. – 2:00 p.m. ET Presenter: Dr. Prithviraj Bose, MD Anderson Cancer Center, Houston, Texas 2023 CTOS – Oral Presentation Title: Peak Study: A Phase 3, Randomized, Open-Label, Multicenter Clinical Study of Bezuclastinib (CGT9486) and Sunitinib Combination Versus Sunitinib in Patients with Gastrointestinal Stromal Tumors (GIST) Date: November 4, 2023 Session Time: 9:00 a.m. – 10:00 a.m. GMT/5:00 a.m. – 6:00 a.m. ET Presenter: Dr. Neeta Somaiah, MD Anderson Cancer Center, Houston, Texas 2023 ASH – Poster Presentation Title: Safety and Efficacy of Bezuclastinib (CGT9486), a Novel, Highly Selective, Potent KIT D816V Tyrosine Kinase Inhibitor, in Patients with Advanced Systemic Mastocytosis (AdvSM): Results From Part 1 of the Phase 2 Apex Trial Date: Monday, December 11, 2023 Session Time: 6:00 p.m. – 8:00 p.m. PT/9:00 p.m. – 11:00 p.m. ET Presenter: Dr. Pankit Vachhani, University of Alabama, Birmingham Upcoming Investor Conferences A live webcast of the following events 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 events and will be archived for up to 30 days. Jefferies London Healthcare Conference on Wednesday, November 15, 2023 at 12:00 p.m. GMT (7:00 a.m. ET). Piper Sandler 35th Annual Healthcare Conference on Tuesday, November 28, 2023 at 2:30 p.m. ET. Third Quarter 2023 Financial Results Cash Position: As of September 30, 2023, cash, cash equivalents and marketable securities were $312.8 million, as compared to $350.9 million as of June 30, 2023. The company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2026. R&D Expenses: Research and development expenses were $50.1 million for the third quarter of 2023 as compared to $29.9 million for the third quarter of 2022. R&D expenses include non-cash stock compensation expense of $4.0 million for the third quarter of 2023 compared to $2.1 million for the third quarter of 2022. In the quarter, $6.6 million in non-recurring charges were incurred for third party CDMOs to prepare for bezuclastinib pre-commercialization and to support sunitinib clinical supply for the PEAK study. Additional increases resulted from costs associated with the acceleration of APEX, SUMMIT and PEAK clinical trials and the continued development of our research pipeline. G&A Expenses: General and administrative expenses were $9.5 million for the third quarter of 2023 as compared to $6.9 million for the third quarter of 2022. G&A expenses include non-cash stock compensation expense of $4.8 million for the third quarter of 2023 compared to $2.6 million for the third quarter of 2022. Net Loss: Net loss was $55.4 million for the third quarter of 2023 as compared to a net loss of $35.1 million for the same period of 2022. About Cogent Biosciences, Inc. Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting FGFR2 and ErbB2. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at . Follow Cogent Biosciences on social media: Twitter and LinkedIn. Information that may be important to investors will be routinely posted on our website and Twitter. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: planned SUMMIT and APEX clinical presentations at the 2023 ASH annual meeting, the upcoming presentation of PEAK clinical data at the 2023 CTOS annual meeting, the expected initiation of SUMMIT Part 2 in 1H 2024, the company’s anticipated cash runway into 2026, the company’s mission of bringing best-in-class therapies to patients with genetically defined diseases, plans to present clinical results from all of SUMMIT Part 1 at a scientific conference in Q1 2024, the expectation that enrollment in both PEAK and APEX Part 2 will be completed by the end of 2024, and plans to IND and initiate a clinical trial for the company’s FGFR2 program in 2024. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. COGENT BIOSCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except share and per share amounts) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Operating expenses: Research and development $ 50,127 $ 29,936 $ 125,036 $ 84,885 General and administrative 9,453 6,885 24,866 19,209 Total operating expenses 59,580 36,821 149,902 104,094 Loss from operations (59,580 ) (36,821 ) (149,902 ) (104,094 ) Other income: Interest income 4,198 1,500 9,207 1,879 Other income, net — 259 950 1,592 Change in fair value of CVR liability — — 1,700 — Total other income, net 4,198 1,759 11,857 3,471 Net loss $ (55,382 ) $ (35,062 ) $ (138,045 ) $ (100,623 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.64 ) $ (0.50 ) $ (1.79 ) $ (1.84 ) Weighted average common shares outstanding, basic and diluted 86,165,951 69,576,359 $ 77,274,580 54,780,041 COGENT BIOSCIENCES, INC. SELECTED CONDENSED CONSOLIDATED BALANCE SHEET DATA (in thousands) (unaudited) September 30, 2023 December 31, 2022 Cash, cash equivalents and marketable securities $ 312,835 $ 259,276 Working capital $ 251,234 $ 238,117 Total assets $ 355,446 $ 300,810 Total liabilities $ 52,548 $ 45,075 Total stockholders’ equity $ 302,898 $ 255,735 Contact: Christi Waarich Senior Director, Investor Relations christi.waarich@cogentbio.com 617-830-1653

IDRX-42, a highly potent, oral, multi-mutant-selective KIT inhibitor, demonstrated promising early evidence of antitumor activity and a favorable safety pro a monotherapy in heavily pre-treated patients with advanced metastatic gastrointestinal stromal tumors (GIST) Tumor shrinkage and confirmed partial responses were observed across all clinically relevant KIT mutations, including both primary drivers and secondary resistance mutations PLYMOUTH, Mass.--(BUSINESS WIRE)-- IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced preliminary clinical data from the dose escalation portion of the company’s ongoing Phase 1 StrateGIST study of IDRX-42 in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) who have previously received one or more prior lines of tyrosine kinase inhibitor (TKI) therapy. IDRX-42 is a highly potent, multi-mutation-selective inhibitor of KIT targeting all major classes of primary drivers and resistance mutations in patients with KIT-mutant GIST (including mutations in exons 9, 11, 13 and 17). These early data, which demonstrate promising antitumor activity and a favorable safety pro IDRX-42 in a heavily pre-treated group of patients with advanced GIST after failure of imatinib and other lines of TKI therapies, will be presented by Professor Patrick Schöffski, MD, MPH, head of the Department of General Medical Oncology at the University Hospitals Leuven, in a poster at the Connective Tissue Oncology Society (CTOS) 2023 Annual Meeting, being held November 1‑4, in Dublin, Ireland. “Advanced GIST generally carries a poor prognosis after failure of imatinib and new therapies such as IDRX-42, that target key primary activating drivers as well as secondary resistance mutations in KIT, are urgently needed,” said Prof. Schöffski. “These preliminary data demonstrate exciting and clinically meaningful antitumor activity in a highly refractory and difficult to treat GIST patient population and warrant the investigation of IDRX-42 in earlier lines of therapy.” “We are highly encouraged by these initial data of IDRX-42, supporting a potentially best-in-class pro improve the outcomes of patients with GIST in all lines of therapy, which we believe remains one of targeted oncology’s great unmet medical needs,” said Ben Auspitz, co-founder and chief executive officer of IDRx. “Importantly, these preliminary data will help guide our discussions with physicians regarding development strategies for IDRX-42 in patients with GIST in early lines of therapy to prevent the emergence of genomically-driven resistance mutations. Early suppression of such resistance mutations in KIT is likely to benefit patients with GIST, versus trying to treat clinically heterogeneous disease in any individual with multiple resistant clones.” Presentation Highlights: Initial data (October 5, 2023 cut-off date) from the dose escalation portion of the ongoing Phase 1 StrateGIST study include 33 patients (all with KIT-mutant GIST) who received IDRX-42 across doses ranging from 120 mg once daily (QD) to 400 mg twice daily (BID). Patients were heavily pretreated, with a median of 4 prior lines of therapy. 28 patients are evaluable for objective response. Median duration on treatment was 16 weeks and continuing, with 70% (23/33) of patients remaining on treatment at time of data cutoff. Maximum tolerated dose (MTD) has not yet been reached. Confirmed partial responses (PRs) by modified RECIST have been demonstrated to date in four patients (at 120 mg QD, 400 mg QD, and 600 mg QD [n=2]). Although an MTD has not yet been reached, a 68% (19/28 patients) clinical benefit rate (confirmed complete response/PR or stable disease ≥16 weeks) was observed across the initial doses studied to date. 4/28 patients are on study for <16 weeks and continuing on study drug. Tumor shrinkage and confirmed partial responses were observed across all major classes of KIT mutational variants, including both primary driver mutations in exons 9 and 11, and secondary resistance mutations in exons 13 and 17. Additionally, notable reductions in mutant allele fraction were observed in circulating tumor DNA across these classes of KIT variants. Preliminary pharmacokinetic analyses demonstrate dose-dependent increases in exposure, with a long half-life (approximately 125 hours), and a 5 to 8-fold accumulation between single-dose and steady-state at Cycle 2 (Day 28). IDRX-42 exhibited a favorable safety and tolerability pro most adverse events being mild (Grade 1) in severity. Treatment related adverse events included diarrhea (70%), nausea (52%), and vomiting (27%). No safety-related treatment discontinuations have been observed to date. Two events coded as dose-limiting toxicities were reported (Grade 3 syncope at 600 mg QD, and Grade 3 vomiting at 400 mg BID); both patients chose to continue on study with dose reduction and are continuing on treatment for 5 months and 2 months, respectively. Four dose levels (120, 240, 400 and 600 mg QD) have been cleared to date, and dose escalation continues with accrual to the 800 mg (400 mg BID) cohort ongoing. Presentation Details: Title: Phase 1 Study of IDRX-42 in Patients with Advanced Gastrointestinal Stromal Tumors Resistant to Prior Systemic Therapy: Early Results Presenter: Patrick Schöffski, MD, MPH Abstract Number: P 26 Presentation Type: Poster Session: CTOS Poster Reception 5:30-6:30 p.m. GMT, Thursday, November 2nd Location: The Convention Center, Dublin, Ireland About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the StrateGIST Study StrateGIST1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany, and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy. About IDRX-42 IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is current being evaluated in a first-in-human Phase 1/1b study. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s pipeline programs include small molecule tyrosine kinase inhibitors, IDRX-42 and IDRX-73, designed to inhibit key genetic drivers and drug-resistant mutations of gastrointestinal stromal tumor (GIST). Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved drugs. To learn more, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts 1AB Katie Engleman katie@1abmedia.com Source: IDRx, Inc. View this news release online at: