Cogent Biosciences Announces Positive Top-line Results of APEX Trial of Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM)

Rhea-AI Summary

Cogent Biosciences (NASDAQ: COGT) reported positive top-line results from the APEX Part 2 trial of bezuclastinib in advanced systemic mastocytosis (AdvSM) on Dec 8, 2025. Key outcomes: 57% ORR per mIWG criteria and 80% ORR per PPR; 89% of patients achieved ≥50% reductions in bone marrow mast cells and in serum tryptase; 91% achieved ≥50% reduction in KIT D816V VAF (n=43). Median time to response was 2.0 months; median duration of response is not yet mature. Safety: no discontinuations due to treatment-related adverse events and 14.8% required dose reductions. Cogent expects an NDA submission in 1H 2026 and will present detailed data in 1H 2026.

Positive

• 57% ORR per mIWG primary endpoint
• 80% ORR per PPR key secondary endpoint
• 89% achieved ≥50% reduction in bone marrow mast cells
• 89% achieved ≥50% reduction in serum tryptase
• Median time to response 2.0 months
• No patients discontinued due to treatment-related adverse events

Negative

• Neutropenia occurred in 29.6% of patients
• Hair color change occurred in 30.9% of patients
• ALT/AST elevations occurred in 20.9% of patients
• Median duration of response not yet mature

News Market Reaction – COGT

+3.95%

13 alerts

+3.95% News Effect

+7.1% Peak Tracked

-7.1% Trough Tracked

+$236M Valuation Impact

$6.22B Market Cap

0.1x Rel. Volume

On the day this news was published, COGT gained 3.95%, reflecting a moderate positive market reaction. Argus tracked a peak move of +7.1% during that session. Argus tracked a trough of -7.1% from its starting point during tracking. Our momentum scanner triggered 13 alerts that day, indicating notable trading interest and price volatility. This price movement added approximately $236M to the company's valuation, bringing the market cap to $6.22B at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

ORR (mIWG criteria): 57% ORR (PPR criteria): 80% Patients treated: 81 patients +5 more

8 metrics

ORR (mIWG criteria) 57% AdvSM APEX Part 2; CR+CRh+PR+CI per mIWG-MRT-ECNM

ORR (PPR criteria) 80% AdvSM APEX Part 2; CR+CRh+PR per pure pathological response

Patients treated 81 patients AdvSM APEX Part 2 at 150 mg bezuclastinib

Serum tryptase reduction 89% Proportion with ≥50% reduction; n=80 in APEX Part 2

Bone marrow mast cell reduction 89% ≥50% reduction or clearance of aggregates; n=80

KIT D816V VAF reduction 91% Proportion with ≥50% reduction in variant allele frequency; n=43

Dose reductions 14.8% APEX Part 2 patients requiring bezuclastinib dose reduction

TRAEs leading to discontinuation 0 patients No discontinuations due to treatment-related adverse events in APEX Part 2

Market Reality Check

Price: $37.34 Vol: Volume 1,837,763 vs 20-da...

low vol

$37.34 Last Close

Volume Volume 1,837,763 vs 20-day average 4,743,340 (0.39x average turnover). low

Technical Shares at $38.77, trading above 200-day MA of $12.14 and 6.1% below 52-week high of $41.27.

Peers on Argus

Peers showed mixed moves, with DYN appearing on momentum scanners, up 10.95% wit...

1 Up

Peers showed mixed moves, with DYN appearing on momentum scanners, up 10.95% without tagged news in the scanner. Other high-affinity biotech peers (CLDX, AUPH, IMCR, MESO) had small single‑stock moves, suggesting APEX results were primarily company‑specific rather than sector‑wide.

Common Catalyst Both COGT and peer DYN reported positive topline clinical trial results, pointing to trial-readout driven, stock-specific moves rather than a broad biotech rotation.

Historical Context

5 past events · Latest: Nov 14 (Neutral)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Nov 14	Conference participation	Neutral	-0.9%	Jefferies healthcare conference appearance with webcast and replay details.
Nov 11	Financing transactions	Neutral	+3.0%	Priced equity and 1.625% 2031 convertible note offerings with stated use of proceeds.
Nov 10	Proposed offerings	Neutral	+119.0%	Announced proposed common stock and convertible note offerings for funding and debt repayment.
Nov 10	Clinical trial results	Positive	+119.0%	Positive PEAK Phase 3 GIST top-line data with improved mPFS and ORR for bezuclastinib combo.
Nov 03	Earnings and pipeline	Neutral	-4.9%	Q3 financials plus updates on SUMMIT, PEAK, APEX timelines and cash runway into 2027.

Pattern Detected

The prior major positive clinical trial (PEAK Phase 3) aligned with a very large positive price reaction, suggesting investors have rewarded pivotal bezuclastinib data releases.

Recent Company History

Over the last few months, Cogent has advanced bezuclastinib through multiple pivotal milestones. On Nov 3, 2025, Q3 results highlighted upcoming PEAK and APEX readouts and a planned NDA for NonAdvSM by year-end 2025. On Nov 10, 2025, positive PEAK Phase 3 GIST data drove a strong stock move, followed by concurrent equity and convertible note offerings on Nov 10–13, 2025 that bolstered funding for development and anticipated commercial launches. Today’s APEX AdvSM results build directly on that pivotal dataset momentum.

Market Pulse Summary

This announcement adds a third pivotal success for bezuclastinib in 2025, with the APEX AdvSM trial ...

Analysis

This announcement adds a third pivotal success for bezuclastinib in 2025, with the APEX AdvSM trial showing up to 80% ORR and high rates of ≥50% reductions in mast cell and biomarker measures. It follows earlier positive SUMMIT and PEAK readouts and recent financings that strengthened the balance sheet for launch preparation. Investors may watch for the planned AdvSM NDA submission in 1H 2026, detailed APEX data presentations, and progress toward multiple commercial launches in the second half of 2026.

Key Terms

objective response rate, advanced systemic mastocytosis, variant allele frequency, new drug application, +2 more

6 terms

objective response rate medical

"resulting in an objective response rate (CR+CRh+PR+CI) of 57% per mIWG"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

advanced systemic mastocytosis medical

"clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM)"

Advanced systemic mastocytosis is a rare, aggressive disease in which certain immune cells called mast cells grow uncontrollably and build up in organs such as the bone marrow, liver, spleen or skin, causing organ damage and severe symptoms. For investors, it matters because the condition represents a high unmet medical need with clear clinical endpoints, potentially sizable but specialized treatment markets, and distinct regulatory and trial pathways that can make successful therapies commercially and strategically important for biotech and pharmaceutical companies.

variant allele frequency medical

"≥50% reduction in KIT D816V variant allele frequency (n=43) | 91%"

Variant allele frequency is the proportion of DNA molecules in a sample that carry a specific genetic change, usually measured by sequencing and expressed as a percentage. Think of it as the share of colored marbles in a jar: a higher share means the mutation is more common in the measured tissue or virus. For investors, VAF matters because it helps assess how strongly a mutation drives disease, how likely a targeted therapy will work, and whether resistance or diagnostic tests will be commercially relevant.

new drug application regulatory

"expects to submit a new drug application (NDA) to the U.S. Food and Drug"

A new drug application is a formal request submitted to government regulators seeking approval to market a new medicine. It is like a detailed proposal that shows the drug has been tested for safety and effectiveness. For investors, receiving approval signals that the drug may soon become available for sale, potentially leading to revenue growth and impacting the company's value.

restricted stock units financial

"purchase 294,600 shares of Cogent common stock and (ii) 34,000 restricted stock units (RSUs)"

Restricted stock units are a type of company reward where employees are promised shares of stock, but they only fully own these shares after meeting certain conditions, like staying with the company for a set time. They matter because they can become valuable assets and are often used to motivate employees to help the company succeed.

nonqualified options financial

"the aggregate, (i) nonqualified options to purchase 294,600 shares of Cogent"

Nonqualified options are employee stock options that give a holder the right to buy company shares at a set price for a limited period, like a coupon letting you buy a product later at today’s price. They matter to investors because when exercised the difference between market price and the set price is taxed as regular income (affecting the holder’s tax bill) and can dilute existing shares and create a tax deduction for the company.

AI-generated analysis. Not financial advice.

-- Bezuclastinib demonstrated rapid and deep clinical benefit in AdvSM patients resulting in an objective response rate (CR+CRh+PR+CI) of 57% per mIWG criteria and 80% per PPR criteria --

-- Bezuclastinib demonstrated a powerful effect on mast cell burden with 89% of patients achieving ≥50% reduction in bone marrow mast cells or clearance of aggregates –

-- Bezuclastinib was very well tolerated with only 14.8% of patients requiring dose reduction and no patients requiring discontinuation due to treatment related adverse events --

-- APEX NDA submission expected in 1H 2026 –

-- Cogent to host investor conference call and webcast today at 8:00 a.m. ET --

WALTHAM, Mass. and BOULDER, Colo., Dec. 08, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (NASDAQ: COGT) today announced positive top-line results from the registration-directed APEX Part 2 clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) demonstrating clinically meaningful results as measured by consensus criteria used to assess patient response. This is the third positive pivotal trial result for bezuclastinib in 2025, following positive announcements from the SUMMIT trial in NonAdvSM patients and the PEAK trial in GIST patients earlier this year. Based on these top-line data, Cogent expects to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in AdvSM during the first half of 2026. In addition, Cogent plans to present detailed data from the APEX trial at an upcoming scientific meeting in the first half of 2026.

“We are excited to announce the third positive pivotal trial for bezuclastinib this year. The results from the APEX trial demonstrate the clear benefit that a highly selective, highly potent KIT mutant inhibitor is capable of providing to patients with AdvSM,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “Coupling rapid, deep, durable responses with the safety and tolerability profile demonstrated by bezuclastinib provides these patients with a new choice to fight their disease without compromising their quality of life. With positive results from APEX, taken together with data from SUMMIT and PEAK, Cogent is preparing for multiple commercial launches in the second half of 2026.”

In Part 2 of the APEX trial, 81 AdvSM patients were treated with 150 mg of bezuclastinib, including 57 patients with SM-AHN, 11 patients with ASM and 13 patients with MCL. 68 of these patients were mIWG-MRT-ECNM evaluable for assessment on the primary endpoint. Clinical activity analyzed from these patients showed:

• Primary endpoint: 57% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM (mIWG) criteria
  • 49% ORR (CR+CRh+PR) per mIWG
  • At the time of data cut-off, multiple additional patients had achieved unconfirmed response criteria and remain on study awaiting follow-up assessment
    
    
• Key secondary endpoint: 80% ORR (CR+CRh+PR) per pure pathological response (PPR) criteria
  
  
• Median time to achieve response was 2.0 months and median duration of response is not yet mature.
  
  
• Bezuclastinib achieved clear and clinically significant reductions in objective disease markers for these AdvSM patients:

Outcome measure	Bezuclastinib
Proportion with ≥50% reduction in serum tryptase (n=80)	89%
Proportion with ≥50% reduction in bone marrow mast cells or clearance of aggregates (n=80)	89%
Proportion with ≥50% reduction in KIT D816V variant allele frequency (n=43)	91%

“Bezuclastinib demonstrated the rapid, deep clinical activity we were expecting given its earlier clinical results,” 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. “What is most exciting about these data is the impressive safety and tolerability results with no discontinuations due to treatment-related adverse events (TRAEs) and only infrequent dose modifications. With this profile, bezuclastinib will become an important treatment option for this patient population.”

APEX Part 2 Safety and Tolerability

The most frequent TRAEs reported on bezuclastinib treatment were hair color change (30.9%), neutropenia (29.6%), altered taste (28.4%), thrombocytopenia (24.7%) and ALT/AST elevations (20.9%). Only 14.8% of patients required dose reduction, and no patients discontinued due to TRAEs. The majority of transaminase elevations were of low grade, asymptomatic and reversible. Only one patient experienced Gr 3 transaminase elevation which fully resolved with dose reduction and the patient continues on therapy.

Complete analysis of the full APEX Part 2 data are ongoing, and Cogent plans to present detailed results at an upcoming major medical conference in the first half of 2026.

Webcast Details
Cogent will host a live webcast today, Monday, December 8, at 8:00 a.m. ET to discuss the full data from SUMMIT in NonAdvSM shared at the American Society of Hematology (ASH) Annual Meeting as well as today’s APEX top-line 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.

Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)
Cogent also announced today that, on December 1, 2025 and December 5, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to thirteen new employees under the company’s 2020 Inducement Plan with grant dates of December 2, 2025 and December 8, 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, (i) nonqualified options to purchase 294,600 shares of Cogent common stock and (ii) 34,000 restricted stock units (RSUs). 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. The RSUs vest annually over 4 years from the grant date, provided such employee remains employed through each such vesting date.

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. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2/3 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in ErbB2, PI3Kα, KRAS and JAK2. 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 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 plans to submit an NDA to the FDA for bezuclastinib in AdvSM during the first half of 2026; plans to present detailed results from the APEX trial at an upcoming scientific meeting in the first half of 2026; the expectation that bezuclastinib will provide AdvSM patients with a new choice to fight their disease without compromising their quality of life; the expectation that Cogent will have multiple commercial launches in the second half of 2026 and the expectation that bezuclastinib will become an important treatment option for AdvSM 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 Waarich 
Senior Director, Investor Relations 
christi.waarich@cogentbio.com
617-830-1653 

FAQ

What were the APEX trial top-line ORR results for COGT bezuclastinib on Dec 8, 2025?

APEX Part 2 reported a 57% ORR per mIWG criteria and 80% ORR per PPR.

When does Cogent (COGT) expect to submit an NDA for bezuclastinib in AdvSM?

Cogent expects to submit an NDA in 1H 2026 for bezuclastinib in AdvSM.

How quickly did patients respond to bezuclastinib in the APEX trial (COGT)?

Median time to achieve response was 2.0 months.

What safety issues were reported for bezuclastinib in APEX Part 2 (COGT)?

Most frequent TRAEs: hair color change 30.9%, neutropenia 29.6%, altered taste 28.4%.

Did any patients discontinue bezuclastinib due to treatment-related adverse events in APEX?

No patients discontinued due to treatment-related adverse events.

What biomarker reductions did bezuclastinib achieve in the APEX trial (COGT)?

Proportions with ≥50% reductions: serum tryptase 89%, bone marrow mast cells 89%, KIT D816V VAF 91% (n=43).

Will Cogent (COGT) present detailed APEX data to investors and when?

Cogent will present detailed APEX data at a major medical conference in 1H 2026 and hosted a webcast on Dec 8, 2025.