UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
| Item 5.07. | Submission of Matters to a Vote of Security Holders. |
On Tuesday, June 7, 2022, Cogent Biosciences, Inc. (the “Company”) held its 2022 Annual Meeting of Stockholders (the “2022 Annual Meeting”) at 9:00 a.m. Eastern Time. As of the close of business on April 19, 2022, the record date for the 2022 Annual Meeting, there were 45,819,266 shares of common stock entitled to vote at the meeting. At the 2022 Annual Meeting, each of the Company’s director nominees was elected and the other proposal voted on was approved. The proposals are described in the Company’s Definitive Proxy Statement on Schedule 14A filed with the Securities and Exchange Commission on April 26, 2022, and the final voting results are set forth below.
| Votes For |
Votes Withheld |
Broker Non-Votes |
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| Proposal 1. Election of Class I Directors |
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| • Karen Ferrante, M.D. |
22,072,688 | 15,019,426 | 4,252,852 | |||||||||||
| • Matthew E. Ros |
25,414,669 | 11,677,445 | 4,252,852 | |||||||||||
| Votes For |
Votes Against |
Abstentions | Broker Non-Votes |
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| Proposal 2. Ratification of PricewaterhouseCoopers LLP as Independent Registered Public Accounting Firm |
41,340,653 | 2,628 | 1,685 | 0 | ||||||||||||
| Item 8.01. | Other Events. |
On Friday, June 10, 2022, the Company issued a press release announcing positive initial data from its ongoing Phase 2 APEX clinical trial, which evaluates the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis. The Company will host a conference call today, Friday, June 10, 2022 at 8:00 a.m., Eastern Time, to discuss the data results.
A copy of the press release and the presentation which will be referenced during the conference call are furnished as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and are incorporated by reference herein.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press release dated June 10, 2022. | |
| 99.2 | Presentation dated June 10, 2022. | |
| 104 | The cover page from the Company’s Current Report on Form 8-K formatted in Inline XBRL. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: June 10, 2022 | COGENT BIOSCIENCES, INC. | |||||
| By: | /s/ Evan D. Kearns | |||||
| Evan D. Kearns | ||||||
| Chief Legal Officer | ||||||
Exhibit 99.1
Cogent Biosciences Announces Positive Initial Clinical Data from Ongoing Phase 2 APEX Trial Evaluating Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM)
All patients treated with bezuclastinib achieved ≥50% reduction in serum tryptase, with a median reduction of 89%, regardless of prior KIT D816V inhibitor treatment
All bone marrow biopsy-assessed patients achieved ≥50% bone marrow mast cell reduction and decreases in blood KIT D816V variant allele fraction (VAF)
Bezuclastinib demonstrates favorable initial safety and tolerability profile with no reported periorbital or peripheral edema, cognitive effects or intracranial bleeding events
Cogent to host investor conference call and webcast today at 8:00 a.m. ET
CAMBRIDGE, Mass. and BOULDER, Colo., June 10, 2022 – 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 selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). The data are being presented today in a poster presentation at the 2022 European Hematology Association (EHA) Congress in Vienna, Austria.
“Advanced systemic mastocytosis is a severe, debilitating hematologic disorder and physicians and patients remain in search of more effective and better tolerated treatment options to fight this disease,” said Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and APEX clinical trial investigator. “I am very impressed with the early, encouraging results presented today from the APEX study. If results like these can be shown in a larger set of patients with AdvSM, I believe bezuclastinib has the potential to help us take a big step forward in treating systemic mastocytosis patients.”
“We are very excited to present initial clinical data from the APEX study of bezuclastinib in advanced systemic mastocytosis,” said Andrew Robbins, Chief Executive Officer at Cogent Biosciences. “These results reinforce the hypothesis that a potent, selective KIT D816V inhibitor with limited CNS penetration has the potential to provide meaningful clinical activity to all systemic mastocytosis patients, without the tolerability challenges seen with other available treatment options. Based on these results, we expect to accelerate our timelines and investment and look forward to providing another APEX clinical update by the end of 2022, and to presenting SUMMIT clinical data in non-advanced systemic mastocytosis (NonAdvSM) patients in the first half of 2023.”
Data from Ongoing Phase 2 APEX Clinical Trial
APEX 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. 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 (ranging from 48-87 years). Patients were enrolled with the following sub-types: two patients with aggressive systemic mastocytosis (ASM), eight patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and one patient with mast cell leukemia (MCL). Two patients had received prior avapritinib and midostaurin treatment.
Initial Safety Data
As of the cutoff date, May 24, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and seen in no more than one patient with one 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 hypersensitivity/mediator flare (1 patient). There were no reported cases of periorbital/peripheral edema, cognitive effects or intracranial bleeding events, which have been associated with other KIT inhibitors. As of the cutoff date, all patients remained on study. Subsequently, one SM-AHN patient with chronic myelomonocytic leukemia (CMML) transformed to acute myeloid leukemia (AML) and discontinued participation in the trial.
Initial Clinical Activity Data
As of the data cutoff date of May 24, 2022, all 11 patients treated were evaluated for signs of clinical activity. Eight of 11 patients had been treated for at least two cycles, had available data from bone marrow biopsy, and were evaluated for additional endpoints Cycle 3 Day 1 (C3D1) evaluable.
| • | 11/11 patients achieved ≥50% reduction in serum tryptase levels by central assessment |
| • | 89% median reduction in serum tryptase |
| • | Six of these patients achieved reduction to <20 ng/mL |
| • | 8/8 patients (C3D1 evaluable) achieved ≥50% reduction in bone marrow mast cells by central review |
| • | Six of these patients achieved complete clearance of bone marrow mast cell aggregates |
| • | 8/8 patients (C3D1 evaluable) demonstrated decreases in KIT D816V variant allele fraction (VAF) by droplet digital polymerase chain reaction (ddPCR) |
| • | All |
Two patients enrolled had previously received and discontinued avapritinib for toxicity reasons (intracranial hemorrhage, thrombocytopenia). Both patients have demonstrated clinical outcomes consistent with the avapritinib-naïve patients, including similar magnitude reductions in serum tryptase.
Bezuclastinib Clinical Development
Based on the favorable initial safety and tolerability profile and clinical activity observed to date in the Phase 2 APEX clinical trial with bezuclastinib for AdvSM, Cogent will continue enrolling patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the trial. A pre-planned interim analysis is scheduled once approximately 28 patients have received at least two cycles of study treatment in Part 1. Cogent plans to present additional data from APEX by the end of 2022. In addition, Cogent continues to actively enroll patients in SUMMIT, a Phase 2 clinical trial with bezuclastinib for NonAdvSM, and PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with imatinib-resistant Gastrointestinal Stromal Tumors (GIST). Cogent plans to present initial data from SUMMIT and lead-in data from PEAK in the first half 2023.
Conference Call Information & EHA 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 Cogent’s website at https://investors.cogentbio.com/events. Following the live webcast, an archived replay will also be available.
Dial-in Number
U.S./Canada Dial-in Number: 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 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 FGFR2 and ErbB2. Cogent Biosciences is based 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.
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 for bezuclastinib to provide meaningful clinical activity to systemic mastocytosis patients without the tolerability challenges seen with other available treatment options, the expectation to accelerate timelines and investment and provide another APEX clinical update by the end of 2022, the expectation to present 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 enrolling patients in Part 1 of APEX to determine a recommended dose for 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,” “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 Annual Report on Form 10-K filed 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 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
617-830-1653
christi.waarich@cogentbio.com
Exhibit 99.2 Initial Data from APEX Phase 2 Study of Bezuclastinib in Advanced Systemic Mastocytosis Investor Webcast Presented at the European Hematology Association Congress June 10, 2022
Forward Looking Statement and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements regarding the potential for bezuclastinib to provide meaningful clinical activity to systemic mastocytosis patients without the tolerability challenges seen with other available treatment options, the expectation to accelerate timelines and investment and provide another APEX clinical update by the end of 2022, the expectation to present SUMMIT clinical data in NonAdvSM patients in 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 trial; any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical and pre-clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the potential impacts of raising additional capital, including dilution to our existing stockholders, restrictions on our operations or requirements that we relinquish rights to our technologies or product candidates; business interruptions resulting from the coronavirus disease outbreak or similar public health crises, which could cause a disruption to the development of our product candidates and adversely impact our business; our expected use of our existing cash and the net proceeds from this offering; the success, cost, and duration of our product development activities and clinical trials; the timing of our planned regulatory submissions to the FDA for our bezuclastinib product candidate, also known as CGT9486; our ability to obtain and maintain regulatory approval for our bezuclastinib product candidate and any other product candidates we may develop, and any related restrictions, limitations, and/or warnings in the label of an approved product candidate; the potential for our identified research priorities to advance our bezuclastinib product candidate or for our teams to discover and develop additional product candidates; the ability to license additional intellectual property rights relating to our bezuclastinib product candidate or future product candidates from third-parties and to comply with our existing or future license agreements and/or collaboration agreements; our ability to commercialize our bezuclastinib product candidate and future product candidates in light of the intellectual property rights of others; our ability to obtain funding for our operations, including funding necessary to complete further discovery, development and commercialization of our existing and future product candidates; the scalability and commercial viability of our manufacturing methods and processes; the commercialization of our product candidates, if approved; our ability to attract collaborators with development, regulatory, and commercialization expertise; future agreements with third parties in connection with the commercialization of our product candidates and any other approved product; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; the rate and degree of market acceptance of our product candidates; the pricing and reimbursement of our product candidates, if approved; regulatory developments in the United States and foreign countries; our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately; the development and success of competing therapies that are or may be under development in clinical trials or become available commercially; our ability to attract and retain key scientific and management personnel; the accuracy of our estimates regarding expenses, future revenue, capital requirements, and needs for additional financing; our use of the proceeds from the private placements, sales of our preferred stock and other public offerings of our common stock from time to time; and our expectations regarding our ability to obtain and maintain intellectual property protection for our bezuclastinib product candidate and future product candidates, among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our most recent Annual Report on Form 10-K and our subsequent periodic reports filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward-looking statements or to conform these statements to actual results or to changes in our expectations. All of Cogent Biosciences, Inc. (“Cogent”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Cogent has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. Any data pertaining to Cogent product candidates is interim data and may include investigator-reported interim data for which Cogent has not yet independently reviewed the source data. The interim data may not be representative of the final results that may be obtained in the corresponding trials and results from earlier trials may not be representative of results obtained in later trial or pivotal trials. 2
Webcast Agenda and Speakers Andrew Robbins Daniel J. DeAngelo, M.D., Ph.D. Jessica Sachs, M.D. President and Chief Executive Officer Chief of the Division of Leukemia Chief Medical Officer Dana-Farber Cancer Institute Introduction & Corporate Overview Andrew Robbins Review of Initial APEX Data with Bezuclastinib in Dr. Daniel DeAngelo Advanced Systemic Mastocytosis (ASM) patients Presentation Summary Andrew Robbins Andrew Robbins Q&A Dr. Jessica Sachs Dr. Daniel DeAngelo 3
Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases Demonstrating differentiated profile as potential best-in-class selective KIT mutant inhibitor Building exciting portfolio of next-generation potent, selective kinase inhibitors Cash runway into 2024; $191.0 million as of March 31, 2022 4
Significant Unmet Need Remains for Advanced Systemic Mastocytosis Patients Neurological Disease Overview: Aggressive and life-threatening form of Headache, brain fog, cognitive dysfunction, anxiety, depression systemic mastocytosis (SM) that is primarily driven by mutations in KIT D816V and leads to uncontrolled 1-5 proliferation of mast cells (MC) Systemic • Subtypes: aggressive SM (ASM); SM with associated Anaphylaxis hematologic neoplasm (SM-AHN); mast cell leukemia 6 (MCL) Cutaneous (skin) • Based on subtype, the median overall survival ranges Flushing of the face/neck/chest, hives, skin rashes, 4-7 from <6 months to 3-4 years itching with or without rash Significant Unmet Need Remains: Few approved therapies, Gastrointestinal which have associated dose-limiting toxicities Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD) • Reported toxicities for marketed therapies: nausea, vomiting, diarrhea, edema, intracranial bleeding, 10-12 cognitive effects Other Cardiovascular Skeletal Light-headedness, syncope (fainting), rapid Bone/muscle pain, heart rate, chest pain, low blood pressure, osteopenia, osteoporosis high blood pressure at reaction start, blood Gynecological pressure instability Uterine cramps, bleeding Ear/Nose/Throat/Respiratory Urinary Nasal itching and congestion, throat itching and swelling, wheezing, Bladder irritability, frequent voiding shortness of breath 5
Large, Yet Not Well Understood Population of SM Patients 16 Systemic Mastocytosis: Estimated prevalence in the U.S. is 20,000–30,000 patients NonAdvSM Significant unmet medical need Comprises upwards of for clinically active, well-tolerated 1 90% of all cases of SM treatment options for this patient population AdvSM 6
Bezuclastinib: Highly Selective and Potent KIT D816V Inhibitor • Oral, selective, and potent type I tyrosine kinase inhibitor (TKI) with potent activity against KIT D816V, an activation loop mutation • Preclinically, highly active with specificity for mutations in KIT exons 9, 11, 17, and 18, including D816V 13 • Spares closely related kinases, has minimal brain penetration, and favorable PK properties • Inhibition of closely related kinases have been linked to off-target toxicities, such as bleeding, edema and 14,15 pleural effusions Kinase Inhibition Profile of Clinical Stage and Approved KIT D816V Agents; Cell IC (nM) 50 KIT V560G/ Compound D816V (HMC 1.2) PDGFRα PDGFRβ CSF1R FLT3 KDR Bezuclastinib 14 >10,000 >10,000 >10,000 >1000 >1000 Avapritinib 13 53 10 249 305 >1000 BLU-263 6 21 6 161 345 >1000 7
Summary of mIWG-MRT-ECNM Response Thresholds Response duration Serum Tryptase Mast Cell Peripheral Blood C-Findings Improvement Improvement* Counts must be ≥12 weeks 9 • ANC ≥1×10 /L with Resolution of normal differential No presence of mast palpable CR • Platelet count <20 ng/mL hepatosplenomegaly cell aggregates 9 (complete remission) ≥100×10 /L and all C-findings • Hgb level ≥11 g/dL 9 • ANC ≥0.5×10 /L with Resolution of CRh normal differential No presence of mast palpable (CR with partial recovery • Platelet count <20 ng/mL cell aggregates hepatosplenomegaly 9 of peripheral blood ≥50×10 /L and all C-findings • Hgb level ≥8 g/dL counts) Resolution of at PR ≥50% reduction ≥ 50% reduction n/a least one C-finding (partial remission) 8 * Improvement in mast cells in bone marrow and/or other biopsied extracutaneous tissue
A Phase 2 Study of Bezuclastinib (CGT9486), A Novel, Highly Selective, Potent KIT D816V Inhibitor, in Adults with Advanced Systemic Mastocytosis (Apex): Methods, Baseline Data, and Early Insights ABSTRACT CODE: P1049 EHA2022 HYBRID CONGRESS | VIENNA, AUSTRIA 10 JUNE 2022
APEX: A Phase 2 Open-Label, Multicenter Clinical Study of Bezuclastinib in Patients with Advanced Systemic Mastocytosis PART 2: EXPANSION** KEY ENTRY CRITERIA PART 1: DOSE OPTIMIZATION* N=80 N=60 • Diagnosed with ASM, SM-AHN, or MCL per 50 mg BID AdvSM IWG evaluable (N=60) WHO 2016 100 mg BID Classification Selected R • Measurable disease per Dose 200 mg BID mIWG-MRT-ECNM AdvSM w/C-Findings not measurable 1:1:1:1 (IWG) confirmed by per IWG (N=20) 400 mg QD Eligibility Committee • No restrictions on prior therapy Primary Endpoint • Dose Optimization: Incidence of AEs/SAEs, laboratory changes, PK, biomarkers, ORR • Expansion: ORR (confirmed CR, CRh, PR and CI) per mIWG-MRT-ECNM and assessed by Central Response Review Committee Other Endpoints • Safety/Tolerability: Incidence of AEs leading to dose modification, changes in Patient Reported Outcomes (PROs) • Efficacy: DOR, TTR, PFS, OS, pure pathologic response • PK/PD: plasma concentration of bezuclastinib, serum tryptase, KIT D816V burden *Interim analysis (IA) when ~28 pts (~7pts/dose level) have completed Cycle 2 (C2) to enrich at promising dose levels 10 **Part 2 may be expanded based on Part 1 results and Regulatory Authority discussions
Demography and Baseline Characteristics Baseline Characteristics: 11 mIWG-evaluable patients enrolled as of 24-May-2022; median age 70 years (range: 48-87) 50mg BID 100mg BID 200mg BID 400mg QD Total Baseline Characteristics (N=3) (N=3) (N=3) (N=2) (N=11) Male, n (%) 2 (67) 3 (100) 2 (67) 2 (100) 9 (82) ECOG PS 0-1 2 (67) 3 (100) 3 (100) 1 (50) 9 (82) AdvSM Subtype per Central Eligibility Review, n (%) ASM 1 (33) 0 (0) 0 (0) 1 (50) 2 (18) SM-AHN 2 (67) 2 (67) 3 (100) 1 (50) 8 (73) MCL 0 (0) 1 (33) 0 (0) 0 (0) 1 (9) KIT D816V in Whole Blood, Positive, n (%) 3 (100) 3 (100) 2 (67) 2 (100) 10 (91) Treatment Naive, n (%) 3 (100) 2 (67) 2 (67) 2 (100) 9 (82) Prior Avapritinib, n (%) 0 (0) 1 (33) 1 (33) 0 (0) 2 (18) Prior Midostaurin, n (%) 0 (0) 1 (33) 1 (33) 0 (0) 2 (18) 60 70 10 55 30 Median Bone Marrow MC Burden, % (range) (30-70) (30-80) (7-30) (30-80) (7-80) 187 253 83 301 182 Median Serum Tryptase, ng/mL (range) (169-605) (144-1578) (67.9-111) (232-370) (67.9-1578) 11 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Summary of Safety and Tolerability • Majority of treatment emergent adverse events (TEAE) were of low-grade with one serious adverse event (SAE) and no Grade 4 events • No periorbital/peripheral edema, cognitive effects or intracranial bleeding reported • No treatment discontinuations; all patients remained on study* • Two patients dose reduced due to AEs; one re-escalated to randomized dose TEAE Occurring in >1 Patient and All Grade 3 Events TEAE Preferred Term, n (%) (N=11) Grade 1/2 Grade 3 Grade 4 Anemia 2 (18) 1 (9) 0 (0) Neutropenia 1 (9) 1 (9) 0 (0) Thrombocytopenia 2 (18) 0 (0) 0 (0) ‡ Diarrhea 0 (0) 1 (9) 0 (0) † Hypersensitivity 0 (0) 1 (9) 0 (0) ‡ Investigator assessed as not related to treatment † SAE of hypersensitivity (mediator flare); patient continued treatment and remains on study (See: Patient Summary; Case 2) * Subsequent to data cut-off, one SM-AHN patient with chronic myelomonocytic leukemia (CMML) transformed to acute myeloid leukemia (AML) and discontinued participation in the trial 12 Data as of: 24May2022 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Bezuclastinib Demonstrated Substantial Serum Tryptase Reductions Maximum Percent Change in Serum Tryptase from Baseline Summary of Clinical Activity • 11/11 patients experienced a ≥50% reduction in serum tryptase • 89% median reduction in serum tryptase • 6/11 patients achieved a serum tryptase level <20 ng/mL • Prior avapritinib patients achieved similar magnitude improvement as treatment naïve population <20 ng/mL serum tryptase A, prior avapritinib; M, prior midostaurin *Patient discontinued ava due to intracranial hemorrhage, **Patient discontinued ava due to thrombocytopenia Data as of: 24May2022 13 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Bezuclastinib Demonstrated Rapid Serum Tryptase Reductions Time to Serum Tryptase Reduction and Duration on Treatment Summary of Clinical Activity • 10/11 patients achieved ≥50% serum tryptase reduction within first week of treatment • 4 patients achieved <20 ng/mL serum tryptase level during first month of treatment • Serum tryptase reductions seen across all three patient sub-types >50% reduction in serum tryptase <20 ng/mL serum tryptase First response confirmation timepoint: C6D1 A, prior avapritinib; M, prior midostaurin *Patient discontinued ava due to intracranial hemorrhage, **Patient discontinued ava due to thrombocytopenia Data as of: 24May2022 14 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Bezuclastinib Demonstrated Impressive Bone Marrow MC Reductions Percent Change in Bone Marrow Mast Cell at C3D1 Summary of Clinical Activity • 8/8 patients with ≥2 cycles of treatment and available Cycle 3, Day 1 (C3D1) data achieved ≥50% reduction in bone marrow mast cells • 6/8 patients (C3D1) achieved complete clearance of mast cell aggregates by central review A, prior avapritinib; M, prior midostaurin **Patient discontinued avapritinib due to thrombocytopenia Data as of: 24May2022 15 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Bezuclastinib Demonstrated Impressive KIT D816V VAF Reductions Percent Change in KIT D816V VAF at C3D1 Summary of Clinical Activity • 8/8 patients (C3D1) demonstrated decreases in KIT D816V variant allele fraction (VAF) by ddPCR A, prior Avapritinib; M, prior midostaurin **Patient discontinued Avapritinib due to thrombocytopenia Data as of: 24May2022 16 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Case 1: Robust Clinical Activity in Avapritinib-Intolerant Patient Serum Bone Marrow KIT D816V Tryptase Mast Cell VAF • Background: Patient with SM-AHN, prior treatment with midostaurin (progression) and avapritinib (toxicity: Grade 3 thrombocytopenia and anemia) • Baseline labs: serum tryptase 1578 ng/mL, MC burden 80%, C-finding: platelets <75K/μL • Randomized to bezuclastinib 100 mg BID • Safety: Grade 3 anemia; patient remains on study treatment >2 months without treatment interruption or dose reduction • Clinical Activity: 93% reduction in serum tryptase (>50% by C1D8), 63% reduction in bone marrow MC, and a 63% reduction in KIT D816V VAF 100 mg BID Data as of: 24May2022 17 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Case 2: Rapid and Durable Clinical Activity for ASM Patient >4 months • Background: Patient with ASM, no prior TKI exposure • Baseline tryptase 370 ng/mL, baseline MC burden 80%, C-finding: spleen >5 cm below left coastal margin • Randomized to 400 mg QD • Safety: Hypersensitivity (mediator flare) on C1D2, dose reduced from 400 mg QD to 200 mg QD without interruption; symptoms resolved within 24 hours; patient remains on study treatment >4 months • Clinical Activity: 94% reduction in serum tryptase (>50% by C1D8), 50% reduction in bone marrow MC, and 72% reduction in KIT D816V VAF Patient Summary, Case 2 - (a, b) Prior to and (c, d) After 2 Cycles of Bezuclastinib Treatment Data as of: 24May2022 18 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
Bezuclastinib has Potential to Provide Meaningful Clinical Benefit • Bezuclastinib is a highly potent and selective tyrosine kinase inhibitor that targets the KIT D816V mutation, the primary driver of systemic mastocytosis • Bezuclastinib was generally well-tolerated across all dose levels o Majority of adverse events were Gr 1/2 and seen in no more than one patient, with one serious adverse event and no Grade 4 events reported o No reported periorbital/peripheral edema, cognitive effects or intracranial bleeding events o Hematological events are expected in this patient population with advanced hematologic disease, frequently presenting with baseline cytopenias related to underlying disease and/or prior therapy • Encouraging early signs of clinical activity demonstrated across all dose levels o Clinically meaningful reduction in serum tryptase levels, reductions in MC burden, and KIT D816V VAF in all evaluable patients across doses tested o With median 89%, all patients achieved ≥50% serum tryptase reduction; all C3D1 patients achieved ≥50% bone marrow MC reductions o Patients treated with prior KIT inhibitors, including avapritinib, demonstrated similar magnitude reductions across serum tryptase, MC burden, and KIT D816V VAF 19 DeAngelo D,. et al. European Hematology Association (EHA) 2022 Hybrid Congress; Vienna, Austria, 10 June 2022: Abstract Code: P1049
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Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases Demonstrating Demonstrating differentiated profile as differentiated profile as potential best-in-class potential best-in-class selective KIT mutant selective KIT mutant inhibitor inhibitor Building exciting portfolio Building exciting portfolio of next-generation potent, of next-generation potent, selective kinase inhibitors selective kinase inhibitors Cash runway into 2024; $191.0 million as of March 31, 2022 Additional APEX data by the end of 2022 Initial SUMMIT and PEAK lead-in data during 1H 2023 21
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References + Disclosures References: 1. Garcia-Montero AC, et al. Blood. 2006;108(7):2366-72 2. Jara-Acevedo M, et al. Mod Pathol. 2015;28(8):1138-49 3. Vaes M, et al. Front Med (Lausanne). 2017;4:110 4. Pardanani A. Am J Hematol. 2019;94(3):363-77 5. Gotlib J, et al. J Natl Compr Canc Netw. 2018;16(12):1500-37 6. NCCN: SM. J Natl Compr Canc Netw Version 2.2019:16, 2 7. Shomali W, Gotlib J. Hematology Am Soc Hematol Educ Program. 2018;2018(1):127-36 8. Jennings S, et al. J Allergy Clin Immunol Pract. 2014;2(1):70-6 9. Rossignol J, et al. F1000Res. 2019;8 10. Magliacane D, et al. Transl Med UniSa. 2014;8:65-74 11. RYDAPT [US Prescribing Information]. East Hanover, NJ: Novartis Pharmaceuticals; 2017 12. AVYAKIT [US Prescribing Information]. Cambridge, MA: Blueprint Medicines Corporation; 2021 13. Guarnieri et al, AACR Annual Meeting 2022; poster presentation:147 14. Das A, et al. Crit Rev Oncol Hematol. 2021 Jan;157:103186 15. Je Y, et al. Lancet Oncol. 2009 Oct;10(10):967-74 16. Coltoff A, Mascarenhas J., 2019. Disclosures: Miguel Piris Villaespesa: Research Funding: Novartis; Advisory Boards/Consulting/Honoraria: Novartis, Blueprint Medicines; Amanda Pilla, Ben Exter, Hina A. Jolin, Zamaneh Mikhak: Employees of Cogent Biosciences Funding: Study funded and managed by Cogent Biosciences 24