Bezuclastinib

SUMMIT, PEAK and APEX registration-directed clinical trial enrollment remains on track; topline results expected from all three studies in 2025 Ended 2Q 2024 with $390 million, sufficient to fund operations into 2027 WALTHAM, Mass. and BOULDER, Colo., Aug. 06, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported financial results for the second quarter ended June 30, 2024. “Cogent has made tremendous progress in the first half of 2024 and we look forward to continuing to execute on our key priorities across the portfolio,” said Andrew Robbins, the Company’s President and Chief Executive Officer. “All three of our bezuclastinib registration-directed trials remain on track and we expect to complete enrollment in our PEAK global Phase 3 trial this quarter, with topline data expected from all three trials in 2025. In parallel, our Research team continues to make excellent progress as we develop next-generation programs to build out our pipeline.” Recent Business Highlights Announced alignment with the U.S. Food and Drug Administration (FDA) on the Company’s novel patient reported outcome measure, Mastocytosis Symptom Severity Daily Diary (MS2D2), for use in Part 2 of the registration-directed SUMMIT trial evaluating bezuclastinib in Nonadvanced Systemic Mastocytosis (NonAdvSM) patients.Announced additional clinical data from SUMMIT Part 1 at the 2024 European Hematology Association (EHA) Congress. As of the cutoff date, December 18, 2023, patients in Part 1 treated at the recommended dose of 100 mg bezuclastinib demonstrated >90% reductions across all markers of mast cell burden. Additional data also showed meaningful reduction in symptom severity and objective measures of disease, including: Substantial reduction in mast cell reactions (>50%) and patients’ most severe symptoms as measured by MS2D2.Clinically meaningful reduction in all individual MS2D2 TSS symptoms and domains, as well as additional symptoms including dizziness, diarrhea severity, and brain fog. Clinically meaningful improvement in skin symptoms as well as objective reduction in skin lesions. Consistent with results previously reported, the recommended dose of 100 mg demonstrates a favorable safety and tolerability profile. Presented positive lead-in data from the ongoing Phase 3 PEAK trial at the 2024 ASCO annual meeting. As of the cutoff date, April 1, 2024, 42 patients in Part 1 had been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of patients with second-line gastrointestinal stromal tumors (GIST) with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months. In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only.The combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (“TEAEs”) were low-grade and reversible and discontinuations due to TEAEs remain limited. Announced a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. The open label, single-arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. Appointed Cole Pinnow Chief Commercial Officer. Mr. Pinnow joined Cogent from Pfizer, where he held increasing roles of responsibility, including President and Managing Director of Pfizer Canada and most recently as Global Franchise Lead, Genitourinary and Breast Cancer Business where he led a global commercial team accountable for the growth of a $5B innovative cancer portfolio in prostate, kidney, bladder and breast therapies. Prior to Pfizer, he held several leadership roles with Hospira and founded the company’s commercial development organization. Mr. Pinnow began his pharmaceutical career as a scientist at Abbott Laboratories. Initiated IND-enabling studies for the potent, selective CNS-penetrant ErbB2 program following presentation of new preclinical data at the American Association for Cancer Research (AACR) 2024 Annual Meeting. The poster described CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species.In addition, CGT4255 demonstrated 80% brain penetrance in mice and was well-tolerated at 10 fold maximally efficacious concentration, resulting in mouse tumor regression, suggesting potential best-in class performance. Anticipated Upcoming Milestones Complete enrollment in the global, Phase 3 PEAK trial in patients with GIST in Q3 2024.Provide additional safety, tolerability, and patient-reported outcomes data from the open label extension portion of SUMMIT Part 1 by the end of 2024.Complete enrollment in the registration-directed APEX Phase 2 trial in patients with Advanced Systemic Mastocytosis (AdvSM) by the end of 2024 and report top-line results by mid-2025.Complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and deliver top-line results by the end of 2025.Initiate a Phase 1 trial of the first Cogent-discovered pipeline program, designed as a potent, selective, reversible FGFR2 inhibitor with best-in-class potential in the second half of 2024.Select lead candidate and initiate IND-enabling studies from ongoing PI3Kα program, designed to potently and selectively target the H1047R driver mutation, which affects >30,000 cancer patients each year. Second Quarter 2024 Financial Results Cash Position: As of June 30, 2024, cash, cash equivalents and marketable securities were $389.9 million, as compared to $435.7 million as of March 31, 2024. The company expects its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2027 and through clinical readouts from ongoing SUMMIT, PEAK, and APEX registration-directed trials. R&D Expenses: Research and development expenses were $54.3 million for the second quarter of 2024 as compared to $38.9 million for the second quarter of 2023. The increase was primarily due to costs associated with accelerating enrollment in both SUMMIT and PEAK clinical trials, on-going APEX costs and costs related to development of the research pipeline. R&D expenses include non-cash stock compensation expense of $4.7 million for the second quarter of 2024 as compared to $3.5 million for the second quarter of 2023. In the quarter, an additional $4.5 million was incurred to support sunitinib clinical supply for the PEAK trial due to faster than expected enrollment. G&A Expenses: General and administrative expenses were $10.1 million for the second quarter of 2024 as compared to $8.2 million for the second quarter of 2023. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.3 million for the second quarter of 2024 as compared to $3.6 million for the second quarter of 2023. Net Loss: Net loss was $59.0 million for the second quarter of 2024 as compared to a net loss of $44.1 million for the same period of 2023. 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 and PI3Kα. 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 anticipated cash runway into 2027, the expectation to complete enrollment in the global Phase 3 PEAK trial in the third quarter of 2024 and to report top-line results by the end of 2025, the expectation to complete enrollment in the SUMMIT Part 2 trial in the second quarter of 2025 and to report top-line results by the end of 2025, the expectation to complete enrollment in the registration-directed APEX Phase 2 trial by the end of 2024 and to report top-line results mid-2025, the expectation to provide additional safety, tolerability and patient-reported outcomes data from the open label extension portion of SUMMIT Part 1 by the end of 2024, the expectation to initiate a Phase 1 trial of the company’s FGFR2 inhibitor with best-in-class potential in the second half of 2024, the expectation to select a lead candidate and initiate IND-enabling studies from the company’s ongoing PI3Kα program. 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. COGENT BIOSCIENCES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share amounts)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development$54,294 $38,871 $106,999 $74,909 General and administrative 10,093 8,214 19,792 15,413 Total operating expenses 64,387 47,085 126,791 90,322 Loss from operations (64,387) (47,085) (126,791) (90,322)Other income: Interest income 5,393 2,741 9,450 5,009 Other income, net 44 268 43 950 Change in fair value of CVR liability — — — 1,700 Total other income, net 5,437 3,009 9,493 7,659 Net loss$(58,950) $(44,076) $(117,298) $(82,663)Net loss per share attributable to common stockholders, basic and diluted$(0.59) $(0.59) $(1.21) $(1.14)Weighted average common shares outstanding, basic and diluted 99,240,030 74,753,269 $97,022,345 72,755,210 COGENT BIOSCIENCES, INC.SELECTED CONDENSED CONSOLIDATED BALANCE SHEET DATA(in thousands)(unaudited) June 30, December 31, 2024 2023 Cash, cash equivalents and marketable securities $389,904 $273,170 Working capital $329,968 $232,603 Total assets $429,935 $313,437 Total liabilities $56,712 $55,635 Total stockholders’ equity $373,223 $257,802 Contact:Christi WaarichSr. Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

01 c-Kit激酶 c-Kit激酶是人体中众多酪氨酸激酶中的一种，其本质是一种跨膜蛋白。c-Kit蛋白通过激活各种信号通路，对细胞的增值，分化，存活，以及迁移起着重要的作用。 c-Kit蛋白由胞外区，跨膜区和胞内区三部分组成。其中,胞外区由5个免疫球蛋白样结构域组成，跨膜区为一次跨膜α螺旋，胞内区为受体催化域，具体分为近膜（juxtamembrane (JM)域，酪氨酸激酶1域，酪氨酸激酶插入域，酪氨酸激酶2域。在正常的状态下，失活时c-Kit以单体形式存在；一旦与配体干细胞因子结合，c-Kit就会二聚化。二聚化的单体相互在Y568，Y570和（或）Y823发生自身磷酸化，从而激活下游信号通路，引起细胞生长和分化。一些含有SH2和蛋白酪氨酸结合域的蛋白，如蛋白酪氨酸磷酸酶 SHP-1，细胞因子抑制剂6（suppressor of cytokine signaling 6 ，SOCS6）等，是c-Kit活性的负调控蛋白。 已有研究表明，c-Kit的丧失功能突变会导致耳聋，便秘等疾病；而获得功能的突变则与胃肠基质瘤（GIST），肥大细胞白血病（MCL），急性髓系白血病（AML）等疾病有关。临床上针对酪氨酸激酶的小分子抑制剂用来治疗各种癌症，并且，对于不同的癌症病人都已经有了很多可选择的治疗方案，这些特异的对激酶信号通路的抑制能够导致肿瘤的生长大小，生长速度，延缓病情恶化。 02 c-Kit在研格局 根据新药情报库所披露信息 ，目前c-kit靶点共有在研药物112个，包含的适应症有557种，在研机构211家，涉及相关的临床试验4892件，专利多达21701件…… 多款特异性c-KIT抑制剂已进入临床研究阶段，如Bezuclastinib（PLX-9486）、KTN-0158、JSP-191、BLU-263、CDX-0159，等十几项临床研究在海外进行中，其中除Bezuclastinib、BLU-263 进展较快已进入Ⅲ期阶段外，大多为I期临床研究。 6月12日，Celldex Therapeutics在Clinicaltrials.gov网站上注册了Barzolvolimab治疗慢性自发性荨麻疹（CSU）的三期临床试验。Barzolvolimab为一款KIT抗体，是Celldex的首发管线，正在探索多种自免适应症，此前的二期临床在表现出优异的疗效。 国内来看，聚焦自免的荃信生物，今年2月申报了一款针对c-kit靶点的人源化IgG1单克隆抗体QX013N，今年5月获批临床，拟开发用于治疗慢性自发性荨麻疹（CSU）。 03 展望 过去十年，KIT抑制剂在GIST等肿瘤领域的应用为患者治疗带来新的选择和方向。然而,仍有相当部分患者初始治疗无效, 或出现继发耐药。临床实践中, 可以考虑与其它治疗策略进行联用, 包括化疗、放疗、各种分子靶向药物、免疫抑制剂、细胞因子抑制剂、病毒疗法及肿瘤疫苗等。相信随着恶性肿瘤的治疗及耐药机制探索的不断深入, 未来越来越多的患者将会从治疗中获益。 吉满生物特色产品 为满足c-Kit相关药物研发需求，吉满生物分别开发出高质量的稳定过表达细胞株和抗体，可用于抗体筛选、表征、一致性评价, 充分满足药物研发的需求，助力抗体药物临床申报。除此之外，吉满生物还可提供高活性c-Kit重组蛋白，可满足客户在动物免疫、抗体筛选以及表位鉴定等不同场景中的需求，所有产品均已通过严格的质量监测。(咨询吉满客服联系同微信:18916119826）。 产品列表 数据展示（部分）： GM-C36580 H_c-Kit(CD117) GNNK(-) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证 GM-C36717 H_c-Kit(CD117) GNNK(+) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证结果 GM-C36581 Cynomolgus_c-Kit(CD117) GNNK(-) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证结果 蛋白数据展示 GM-87117RP   Human c-Kit(CD117) Protein His Tag SDS-PAGE On SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★ His Tag ELISA验证  His Tag (Catalog # GM-87117RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Human SCF Protein; mFc Tag (Catalog # GM-87653RP) were added. ★  His Tag ELISA验证 His Tag (Catalog # GM-87117RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab) (Catalog # GM-86542AB) were added. ★ GM-87120RP   Cynomolgus c-Kit(CD117) Protein  His Tag SDS-PAGE On SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★ His Tag ELISA验证 Cynomolgus c-Kit(CD117) Protein; His Tag (Catalog # GM-87120RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab) (Catalog # GM-86542AB) were added. ★ GM-87119RP   Human c-Kit(CD117) Protein hFc Tag SDS-PAGE On SDS-PAGE under nun-reducing (NR) condition and reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★  hFc Tag ELISA验证 Human SCF Protein; His Tag (Catalog # GM-87651RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Human c-Kit(CD117) Protein; hFc Tag (Catalog # GM-87119RP) were added. 联系我们 吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域，截止当前已布局近300个热门靶向药靶点，1000余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。 扫码咨询 扫码找现货