Avapritinib

56% mean improvement in Total Symptom Score (TSS) at 24 weeks with 76% of patients achieving at least a 50% reduction in TSS 89% of patients had >50% decrease in serum tryptase by four weeks of treatment and 95% of patients with elevated baseline tryptase achieved serum tryptase levels <20 ng/ml by week 24 SUMMIT Part 2 enrollment completed early; surpassing original enrollment target with 179 patients enrolled, top-line results now expected in July 2025 Cogent to host investor webcast today, Monday, December 9 at 8:00 a.m. ET WALTHAM, Mass. and BOULDER, Colo., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced updated clinical results from the Open Label Extension (OLE) portion of SUMMIT, a clinical trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). The OLE data are being presented at the 66th American Society of Hematology (ASH 2024) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, CA. “The rapid, deep, and sustained symptomatic improvement reported by SUMMIT patients receiving bezuclastinib is very impressive,” said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. “Coupled with its favorable tolerability profile, bezuclastinib has clear potential to establish itself as the best-in-class KIT inhibitor for systemic mastocytosis patients.” “The SUMMIT data reported today are encouraging to thousands of NonAdvSM patients around the world who are waiting for a novel treatment that can rapidly and meaningfully improve a wide variety of symptoms that impact their daily lives,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We set out earlier this year to enroll our registration-directed SUMMIT Part 2 trial, and I’m excited to announce that based on the overwhelming demand from investigators and patients around the world, we’ve completed enrollment in the study with 179 patients more than six months ahead of schedule. Top-line results are now expected in July 2025, meaning we have dramatically accelerated our timeline as we aim to make bezuclastinib available to all NonAdvSM patients.” Patient DemographicsSUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with NonAdvSM. In SUMMIT Part 1, patients received bezuclastinib or placebo for a 12-week period to determine the recommended dose for use in the pivotal portion of the trial, SUMMIT Part 2. Earlier this year, Cogent announced that the recommended go-forward dose was selected at once-daily 100 mg. After the initial 12-week period, all patients were given the opportunity to receive bezuclastinib in the SUMMIT Open Label Extension (OLE). The clinical results presented today focus on 27 patients in the OLE who were treated with the once-daily 100 mg dose of bezuclastinib. The median age of patients at study entry was 52 years (ranging from 36-76 years). One patient had received prior avapritinib. Patient Reported Outcomes (PRO) DataSUMMIT patients were evaluated for signs of clinical activity over 24 weeks using multiple PRO measures, including the Mastocytosis Symptom Severity Daily Diary (MS2D2) and the Mastocytosis Quality-of-Life (MC-QoL) scale. Updated clinical data presented today show: 56% mean improvement in Total Symptom Score (TSS) at 24 weeks76% of patients demonstrated >50% reduction from baseline in MS2D2 Total Symptom Score (TSS) with 88% of patients exceeding 30% reduction from baseline after 24 weeks49% mean improvement in MC-QoL Total Score at 24 weeks At 24 weeks of treatment, 31% of patients have already reduced or discontinued best supportive care (BSC) medications. Pharmacodynamic DataBezuclastinib showed rapid, deep, and sustained reductions in serum tryptase over the course of 24 weeks of treatment including: 89% of patients had >50% decrease in serum tryptase levels by four weeks of treatment95% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL by week 2484% of patients with baseline serum tryptase >11.4ng/ml achieved <11.4ng/mL by week 24 Safety DataAs of the data cutoff, August 29, 2024, the median duration of bezuclastinib treatment was 56 weeks for patients in the active arm and 40 weeks for placebo patients who crossed over to the OLE. The majority of treatment emergent adverse events were low grade and reversible with no treatment-related bleeding or cognitive impairment events reported. The most common treatment related adverse events were hair discoloration and transaminase elevations. All patients experiencing elevated transaminases were asymptomatic and reversible: five patients resolved without any dose modifications and remain on study; two patients resolved with dose reduction and remain on study, one of whom re-escalated to original dose; and two patients resolved following discontinuation, one of whom was presented previously at ASH 2023. There were no other discontinuations due to adverse events. SUMMIT Enrollment UpdateCogent also announced today that enrollment in the registration-directed SUMMIT Part 2 study is now complete. In the nine months between February and October 2024, 265 NonAdvSM patients were screened for SUMMIT Part 2 at 70 clinical sites, concentrated predominantly in the U.S. and Western Europe. More than 90% of these patients were naïve to KIT inhibitor therapy. A total of 179 patients were enrolled and top-line results from the trial are expected in July 2025. Webcast Information and ASH PosterCogent will host a webcast today, Monday, December 9, 2024, at 8:00 a.m. ET to discuss these updated SUMMIT clinical results. The live event will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days. The ASH poster is available to registered conference attendees and is also in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research. 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 mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis 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: the company’s expectation to present top-line results from SUMMIT Part 2 in July 2025; the potential for bezuclastinib to establish itself as the best-in-class KIT inhibitor for systemic mastocytosis patients; and the company’s goal of making bezuclastinib available to all NonAdvSM patients. 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. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

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 Median time to response 2.2 months with median duration of response and median PFS not yet reached Top-line data from APEX Part 2 on-track for mid-2025 Cogent to host investor webcast on Monday, December 9 at 8:00 a.m. ET WALTHAM, Mass. and BOULDER, Colo., Dec. 08, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported positive updated data from Part 1 of the Company’s ongoing Phase 2 APEX clinical trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the 66th American Society of Hematology (ASH 2024) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, CA. “Bezuclastinib has the potential to transform the treatment landscape for people living with advanced systemic mastocytosis,” said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. “The impressive clinical data presented today from APEX Part 1 demonstrates a combination of rapid and deep clinical responses, with a safety profile that avoids several of the most concerning side effects for AdvSM patients today.” “We are excited to share today the updated clinical data from APEX Part 1 studying bezuclastinib in patients with advanced systemic mastocytosis,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “These results show the enormous promise that a highly potent, highly selective, non-brain penetrant KIT inhibitor may provide to this patient population. We look forward to completing enrollment in APEX Part 2 and sharing the results from that study in mid-2025.” Patient DemographicsAPEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. Thirty-two patients were treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). Earlier this year, Cogent announced APEX Part 2 would be conducted at the optimized 150mg QD dose, which closely matches the exposure from 100 mg BID dose in APEX Part 1. The median age of patients at study entry was 68 years (ranging from 33-87 years). Patients were enrolled with the following sub-types: seven patients with aggressive systemic mastocytosis (ASM), 23 patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and two patients with mast cell leukemia (MCL). Five patients had received prior avapritinib and 10 patients had received prior midostaurin treatment. Clinical Activity DataAs of the data cutoff date of October 11, 2024, 32 patients enrolled were evaluated for signs of clinical activity, 27 of whom were mIWG-MRT-ECNM evaluable. Clinical activity analyzed across dose levels and focused on 100 mg BID cohort showed: 52% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM criteria, including 61% ORR for TKI-treatment-naïve patients 83% ORR for patients treated at 100 mg BID dose cohort 88% ORR (CR+PR) per pure pathological response (PPR) criteria 100% ORR for patients treated at 100 mg BID dose cohort Median time to achieve response was 2.2 months and median duration of response has not yet been reached Median PFS was not yet reached at median follow-up of 20 months; PFS rate at 24 months was 82% Pharmacodynamic DataNearly all patients demonstrated a significant improvement in biomarkers associated with disease burden. Patients without post baseline biomarker data were excluded from relevant analyses. 94% of patients achieved ≥50% reduction in serum tryptase levels 100% of patients receiving ≥2 cycles achieved ≥50% reduction66% of patients achieved reduction of serum tryptase below 20 ng/mL 93% of KITD816V-positive patients achieved ≥50% reduction in KIT D816V variant allele fraction (VAF)100% of evaluable patients achieved a ≥50% reduction in bone marrow mast cell burden 83% achieved complete clearance of mast cell aggregates by central review Safety DataAs of the data cutoff date of October 11, 2024, bezuclastinib continues to demonstrate a differentiated safety and tolerability profile across doses. The majority of hematological adverse events were low grade and reversible. There have been no new treatment related serious adverse events or discontinuations reported since ASH 2023. Due to confounding medical issues, one patient previously reported with DILI has been reassessed and reported as a Grade 4 gamma-glutamyl transferase (GGT) elevation case. Twelve patients required dose reduction, eight of whom were treated at a 400 mg daily dose. Bezuclastinib in Systemic Mastocytosis Cogent is actively enrolling patients into APEX Part 2 which is anticipated to complete enrollment in Q1 2025 with top-line results expected in mid-2025. Cogent will present 24-week follow-up data from patients who participated in the Open Label Extension portion of the ongoing SUMMIT trial on Monday, December 9, 2024 at ASH. SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter Phase 2 trial evaluating bezuclastinib in patients with Nonadvanced Systemic Mastocytosis (NonAdvSM). Webcast Information and ASH PostersCogent will host a webcast on Monday, December 9, 2024 at 8:00 a.m. ET to discuss updated clinical results from both the APEX and SUMMIT ASH presentations. The live event will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days. The ASH posters will be available to registered conference attendees and will also be in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research. 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 mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis 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: the expectation for the company to complete enrollment for APEX Part 2 in Q1 2025 and to have top-line data in mid-2025; the potential for bezuclastinib to transform the treatment landscape for people living with AdvSM; and the potential benefit that a highly potent, highly selective, non-brain penetrant KIT inhibitor may provide to patients with AdvSM. 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. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653