Cogent Biosciences announces initial positive clinical data from the ongoing phase 2 APEX study evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM)

Cogent Biosciences, Inc.

All patients treated with bezuclastinib achieved ≥50% reduction in serum tryptase, with an average reduction of 89%, regardless of previous treatment with KIT D816V inhibitor

All patients evaluated by bone marrow biopsy achieved ≥50% reduction in bone marrow mast cells and decreased fraction of KIT D816V variant allele in blood (VAF)

Bezuclastinib demonstrates an initial favorable safety and tolerability profile, with no reports of periorbital or peripheral edema, cognitive effects, or intracranial bleeding events.

Cogent to hold investor conference call and webcast today at 8 am ET

CAMBRIDGE, Massachusetts and BOULDER, Colorado, June 10, 2022 (GLOBE NEWSWIRE) — Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced positive initial data from its ongoing phase 2 APEX clinical trial evaluating the KIT D816V selective inhibitor bezuclastinib in patients with advanced systemic mastocytosis. (AdvSM). The data is being presented today in a poster presentation at the European Hematology Association (EHA) Congress 2022 in Vienna, Austria.

“Advanced systemic mastocytosis is a serious and debilitating hematologic disorder and clinicians and patients remain in search of more effective and better tolerated treatment options to combat this disease,” said Daniel DeAngelo, MD, Ph.D., Division Chief of Leukemia from the Dana-Farber Cancer Institute and APEX clinical trial investigator. “I am very impressed with the initial and encouraging results presented today from the APEX study. If results like these can be shown in a larger pool of patients with AdvSM, I believe that bezuclastinib has the potential to help us take a big step forward in treating patients with systemic mastocytosis.”

“We are very excited to present initial clinical data from the APEX study of bezuclastinib in advanced systemic mastocytosis,” said Andrew Robbins, CEO of Cogent Biosciences. “These results support the hypothesis that a potent and selective KIT D816V inhibitor with limited penetration into the CNS has the potential to provide significant clinical activity to all patients with systemic mastocytosis, without the tolerability challenges seen with other available treatment options. Based on these results, we expect to accelerate our timelines and investments and look forward to providing another clinical update of APEX by the end of 2022 and presenting SUMMIT clinical data in patients with non-advanced systemic mastocytosis (NonAdvSM) in the first half of 2023.”

Data from the ongoing APEX Phase 2 Clinical Trial
APEX is a global, open-label, multicenter, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetics and pharmacodynamics profiles of bezuclastinib. At the data cut-off date of May 24, 2022, 11 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). The mean age of patients at baseline was 70 years (ranging from 48 to 87 years). Patients were enrolled with the following subtypes: two patients with aggressive systemic mastocytosis (ASM), eight patients with systemic mastocytosis with associated hematologic malignancy (SM-AHN), and one patient with mast cell leukemia (MCL). Two patients had received previous treatment with avapritinib and midostaurin.

Initial security data
At the cut-off date, May 24, 2022, bezuclastinib was generally well tolerated at all doses. The majority of adverse events were Grade 1/2 and observed in no more than one patient with a serious adverse event and no Grade 4 events reported. Grade 3 events reported as at least possibly related were anemia (1 patient), neutropenia (1 patient), and mediator hypersensitivity/burst (1 patient). There have been no reported cases of periorbital/peripheral oedema, cognitive effects, or intracranial bleeding events that have been associated with other KIT inhibitors. At the cut-off date, all patients remained in the study. Subsequently, an SM-AHN patient with chronic myelomonocytic leukemia (CMML) turned to acute myeloid leukemia (AML) and discontinued participation in the study.

Initial clinical activity data
At the data cut-off date of May 24, 2022, all 11 treated patients were evaluated for signs of clinical activity. Eight of the 11 patients were treated for at least two cycles, had bone marrow biopsy data available, and were evaluated for additional evaluable Cycle 3 Day 1 (C3D1) parameters.

  • 11/11 patients achieved ≥50% reduction in serum tryptase levels by central assessment

  • 8/8 patients (assessed by C3D1) achieved ≥50% reduction in bone marrow mast cells by central review

  • 8/8 patients (evaluable C3D1) demonstrated decreases in the fraction of the KIT D816V variant allele (VAF) by digital droplet polymerase chain reaction (ddPCR)

  • All patients remained on treatment with treatment durations ranging from 0.5 to 4.8 months.

Two enrolled patients had previously received and discontinued avapritinib for reasons of toxicity (intracranial hemorrhage, thrombocytopenia). Both patients demonstrated clinical results consistent with avapritinib-naïve patients, including similar magnitude reductions in serum tryptase.

Clinical Development of Bezuclastinib
Based on the favorable initial safety and tolerability profile and observed clinical activity to date in the Phase 2 APEX clinical trial of bezuclastinib for AdvSM, Cogent will continue to enroll patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the study. A pre-planned interim review is scheduled once approximately 28 patients have received at least two cycles of study treatment in Part 1. Cogent plans to submit additional APEX data through the end of 2022. In addition, Cogent continues to enroll patients actively in SUMMIT, a Phase 2 clinical trial of bezuclastinib for NonAdvSM, and PEAK, a global, randomized, open-label, enrolled Phase 3 clinical trial in patients with imatinib-resistant Gastrointestinal Stromal Tumors (GIST). Cogent plans to present initial data from SUMMIT and initial data from PEAK in the first half of 2023.

EHA conference call information and poster
Cogent will host a webcast today at 8:00 am ET to discuss today’s APEX results. The webcast will be accessible through the Investors and Media section of the Cogent website at https://investors.cogentbio.com/events. After the live webcast, an archived replay will also be available.

dial number
US/Canada dial number: 844-686-3753
International Dial Number: 704-753-0395
Conference ID: 2951969

The APEX poster to be presented at the EHA is available to registered conference attendees as well as on the Cogent Biosciences website in the posters and publications section of 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 designed to potently inhibit the KIT D816V mutation, as well as other mutations in exon 17 KIT. of mast cells. Mutations in exon 17 are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer heavily dependent on KIT oncogenic signaling. In addition to bezuclastinib, Cogent’s research team is developing a portfolio of new targeted therapies to help patients battling severe disease and genetically targeted initially to FGFR2 and ErbB2. Cogent Biosciences is headquartered in Cambridge, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. 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.

Forecast 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 about the potential for bezuclastinib to provide significant clinical activity to patients with systemic mastocytosis without the challenges of tolerability observed with other available treatment options, the expectation to accelerate timeframes and investments and provide another clinical update of APEX by the end of 2022, the expectation to present SUMMIT clinical data in non-AdvSM patients in the first half of 2023, the expectation to present PEAK clinical data on GIST patients in the first half of 2023, and the plan to continue enrolling patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the study. The use of words such as, but not limited to, “anticipate”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “may”, “could”, “plan, ” “potential”, “anticipate”, “project”, “should”, “target”, “will” or “would” and similar word expressions are intended to identify forward-looking statements. Forward-looking statements are not historical facts or guarantees of future performance. Rather, they are based on our current beliefs, expectations and assumptions about the future of our business, future plans and strategies, our clinical outcomes, the enrollment rate for our clinical trials and other future conditions. New risks and uncertainties may arise from time to time, and it is not possible to predict all risks and uncertainties. No representation or warranty (express or implied) is made as to the accuracy of such forward-looking statements. We may not 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 in the caption “Risk Factors” in Cogent’s most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of risks potential, uncertainties and other important factors in our subsequent filings with the SEC. Any forward-looking statement speaks only as of the date it was made. Neither we, nor our affiliates, consultants or representatives undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be construed as representing our views at any later date than the date hereof.

Contact:

Christchurch Waarich
Senior Director, Investor Relations
617-830-1653
christi.waarich@cogentbio.com

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