Cogent Biosciences Announces Positive Initial Clinical Data from Ongoing APEX Phase 2 Trial Evaluating Bezuclastinib in Patients With Advanced Systemic Mastocytosis (AdvSM)

Cogent Biosciences, Inc.

All patients treated with bezuclastinib achieved ≥50% reduction in serum tryptase, with a median reduction of 89%, regardless of prior treatment with KIT D816V inhibitor

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

Bezuclastinib has a favorable baseline safety and tolerability profile, with no reported periorbital or peripheral edema, cognitive effects, or intracranial bleeding events

Cogent will host a conference call and webcast for investors today at 8:00 a.m. ET

CAMBRIDGE, Mass. and BOULDER, Colo., June 10, 2022 (GLOBE NEWSWIRE) — Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company specializing in the development of precision therapies for genetically defined diseases, today announced positive early data from its ongoing APEX Phase 2 clinical trial evaluating the selective KIT inhibitor D816V bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). The data is 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 hematological disorder and physicians and patients continue to seek more effective and better tolerated treatment options to combat this disease,” said Daniel DeAngelo, MD, Ph.D. , chief of the leukemia division at the Dana-Farber Cancer Institute and the APEX clinical trial investigator. “I am very impressed with the encouraging initial results presented today from the APEX study. If results like these can be demonstrated in more patients with AdvSM, I believe bezuclastinib has the potential to help us take a big step forward in the treatment of patients with systemic mastocytosis. »

“We are pleased 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 CNS penetration has the potential to provide significant clinical activity to all patients with systemic mastocytosis, without the tolerability issues seen with d other treatment options available. Based on these results, we plan to accelerate our timelines and investments and look forward to delivering another APEX clinical update by the end of 2022 and presenting clinical data from SUMMIT in patients with nonadvanced 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. As of the data cutoff date of May 24, 2022, 11 patients had been treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID, or 400 mg QD). The median age of patients at study entry was 70 years (range 48 to 87). Patients were recruited with the following subtypes: two patients with aggressive systemic mastocytosis (ASM), eight patients with systemic mastocytosis with associated haematological neoplasm (SM-AHN), and one patient with mast cell leukemia (MCL). Two patients had previously received 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 were observed in only one patient with a serious adverse event and no grade 4 events were reported. Grade 3 events reported as at least possibly related were anemia (1 patient), neutropenia (1 patient), and mediating hypersensitivity/flare (1 patient). No cases of periorbital/peripheral edema, cognitive effects, or intracranial bleeding events have been reported, which have been associated with other KIT inhibitors. At the cut-off date, all patients remained in the study. Subsequently, one SM-AHN patient with chronic myelomonocytic leukemia (CMML) progressed to acute myeloid leukemia (AML) and discontinued participation in the trial.

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

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

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

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

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

Two patients included had previously received and stopped avapritinib for reasons of toxicity (intracranial haemorrhage, thrombocytopenia). Both patients demonstrated clinical outcomes consistent with avapritinib-naïve patients, including reductions of similar magnitude in serum tryptase.

Clinical development of bezuclastinib
Based on the initial favorable safety and tolerability profile and clinical activity seen to date in the APEX Phase 2 clinical trial with bezuclastinib for AdvSM, Cogent will continue to enroll patients in Part 1 of the ‘APEX to determine a recommended dose for use in Part 2 of the trial. A pre-planned interim analysis is planned once approximately 28 patients have received at least two cycles of study treatment in Part 1. Cogent expects to present additional data from APEX by the end of 2022. Additionally, Cogent continues to actively enroll patients in SUMMIT, a Phase 2 clinical trial with bezuclastinib for the treatment of NonAdvSM, and PEAK, an international, randomized, open-label, Phase 3 clinical trial in patients with gastrointestinal stromal tumors. -intestinal (GIST) resistant to imatinib. Cogent expects to present initial data from SUMMIT and preliminary data from PEAK in the first half of 2023.

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

Call number
Phone number in the United States and Canada: 844-686-3753
International dial-in number: 704-753-0395
Conference ID: 2951969

The APEX poster to be presented at EHA is available to registered conference attendees as well as on the Cogent Biosciences website in the Posters and Publications section of

About Cogent Biosciences, Inc.
Cogent Biosciences is a biotechnology company specializing in the development of 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 KIT exon 17 mutations. KIT D816V is responsible for systemic mastocytosis, a serious disease caused by uncontrolled proliferation. of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer highly dependent on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent research team is developing a portfolio of novel targeted therapies to help patients combat serious genetic diseases initially targeting FGFR2 and ErbB2. Cogent Biosciences is based in Cambridge, MA and Boulder, CO. Visit our website for more information at Follow Cogent Biosciences on social networks: Twitter and LinkedIn. Information that may be important to investors will be regularly posted on our website and on 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 the potential of bezuclastinib to provide significant clinical activity in patients with systemic mastocytosis without the tolerability issues seen with other available treatment options, the expectation to accelerate timelines and investments and provide another APEX clinical update by the end of 2022, the expectation to present the SUMMIT clinical data in NonAdvSM patients in the first half of 2023, the expectation to present PEAK clinical data in GIST patients in the first half of 2023, and the plan to continue to enroll patients in APEX Part 1 for determine a recommended dose to use in Part 2 of the trial. The use of words such as, but not limited to, “anticipate”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “may”, “could”, “plan”, “potential”, “predict”, “project”, “should”, “target”, “shall” or “would” and similar expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor guarantees of future performance. Instead, they are based on our current beliefs, expectations and assumptions about the future of our business, our future plans and strategies, our clinical results, our clinical trial enrollment rate and other future conditions. New risks and uncertainties may arise from time to time and it is not possible to foresee all risks and uncertainties. No representation or warranty (express or implied) is made as to the accuracy of these forward-looking statements. We may not achieve any forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. These forward-looking statements are subject to a number of important risks and uncertainties, including, but not limited to, those set forth under the heading “Risk Factors” in Cogent’s most recently filed Annual Report on Form 10-K. with the SEC, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings 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 a result of new information, future events or otherwise, except as required by law. requires it. These forward-looking statements should not be taken to represent our views as of any date subsequent to the date hereof.


Christi Waarich
Senior Director, Investor Relations

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