Drug Development and Trials - Bezuclastinib is a highly selective tyrosine kinase inhibitor targeting the KIT D816V mutation, primarily responsible for Systemic Mastocytosis (SM) and advanced gastrointestinal stromal tumors (GIST) [49]. - The median survival for patients with Advanced Systemic Mastocytosis (AdvSM) is less than 3.5 years, highlighting the urgent need for new treatment options [52]. - The SUMMIT trial for Non-AdvSM has enrolled 54 patients in Part 1, with Part 2 expected to include 159 patients and top-line results anticipated by the end of 2025 [53]. - In the SUMMIT Part 1b, 100% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL at week 12, compared to 0% in the placebo group [53]. - The APEX trial for AdvSM reported an objective response rate (ORR) of 52%, with a 56% ORR for TKI-treatment-naïve patients [54]. - The PEAK trial for GIST patients demonstrated a median progression-free survival (mPFS) of 19.4 months in second-line patients previously treated with imatinib [56]. - Bezuclastinib has received orphan drug designation from the FDA and EMA for both SM and GIST treatments [56]. - The company is advancing CGT4859, a reversible, selective FGFR2 inhibitor, with plans to initiate a clinical trial by the end of 2024 [59]. - CGT4255, a novel ErbB2 mutant program, demonstrated low nM potency against ErbB2 mutations with over 100-fold selectivity over wild-type EGFR, and IND-enabling studies are set to begin in mid-2024 [60]. - The company is developing CGT4824, a PI3Kα inhibitor targeting the H1047R mutation, which affects over 30,000 cancer patients annually, showing over 95% inhibition of pAKT in preclinical models [61]. Financial Performance and Projections - The company reported a net loss of $117.3 million for the six months ended June 30, 2024, compared to a net loss of $82.7 million for the same period in 2023, resulting in an accumulated deficit of $720.9 million as of June 30, 2024 [62]. - The company expects to incur significant expenses and operating losses for at least the next several years, particularly as it initiates and increases enrollment for clinical trials and continues to develop additional product candidates [62]. - As of June 30, 2024, the company had cash, cash equivalents, and marketable securities totaling $389.9 million, which is expected to fund operations into 2027 [63]. - The company has not generated any revenue from product sales and will need substantial additional funding to support ongoing operations and growth strategy [62]. - General and administrative expenses are anticipated to increase due to the expansion of operations to support ongoing discovery and clinical activities [66]. - Total operating expenses for the three months ended June 30, 2024, were $64.4 million, an increase of $17.3 million (36.7%) compared to $47.1 million for the same period in 2023 [68]. - Research and development expenses increased by $15.4 million (39.6%) to $54.3 million for the three months ended June 30, 2024, driven by higher costs associated with bezuclastinib and increased personnel costs [70]. - General and administrative expenses rose to $10.1 million, up $1.9 million (23.1%) from $8.2 million for the same period in 2023, primarily due to higher personnel costs [71]. - Net loss for the three months ended June 30, 2024, was $58.9 million, compared to a net loss of $44.1 million for the same period in 2023, reflecting an increase of $14.9 million (33.8%) [68]. - For the six months ended June 30, 2024, total operating expenses were $126.8 million, an increase of $36.5 million (40.4%) from $90.3 million in the same period in 2023 [74]. - Research and development expenses for the six months ended June 30, 2024, totaled $107.0 million, up $32.1 million (42.8%) from $74.9 million in 2023, driven by costs related to bezuclastinib and ongoing trials [76]. - The company completed a public offering in June 2023, raising approximately $161.8 million in net proceeds [81]. - For the six months ended June 30, 2024, cash used in operating activities was $95.2 million, compared to $71.6 million for the same period in 2023, reflecting an increase of approximately 33% [83]. - The net cash used in investing activities for the six months ended June 30, 2024, was $83.6 million, significantly higher than $17.8 million in the same period of 2023, indicating a 370% increase [84]. - Net cash provided by financing activities was $213.8 million for the six months ended June 30, 2024, up from $162.5 million in 2023, representing a 31.6% increase [85]. - The company anticipates increased expenses related to ongoing clinical development and research activities, which may impact future cash flow requirements [86]. - The company has no off-balance sheet arrangements as of the reporting period [89]. - The company may require additional funding to support ongoing research and development programs, which could lead to dilution of existing ownership interests [87]. - The company is subject to various risks that could affect its ability to raise additional funds when needed, including adverse regulatory decisions and clinical trial delays [87]. Safety Profile - The majority of treatment-emergent adverse events in clinical trials were low-grade and reversible, indicating a favorable safety profile for bezuclastinib [56]. Tax and Accounting - The company has recorded a full valuation allowance against its net deferred tax assets, with U.S. federal and state net operating loss carryforwards of $195.7 million and $110.6 million, respectively [67]. - There have been no material changes in critical accounting estimates during the three months ended June 30, 2024 [88]. - There have been no material changes to market risks as described in the previous annual report [92].

Financial Performance - As of June 30, 2024, cash, cash equivalents, and marketable securities totaled $389.9 million, down from $435.7 million as of March 31, 2024, sufficient to fund operations into 2027[9] - General and administrative expenses for Q2 2024 were $10.1 million, up from $8.2 million in Q2 2023, indicating a 23% increase due to organizational growth[11] - The net loss for Q2 2024 was $59.0 million, compared to a net loss of $44.1 million for the same period in 2023, representing a 34% increase in losses[11] Research and Development - Research and development expenses for Q2 2024 were $54.3 million, compared to $38.9 million in Q2 2023, reflecting an increase of 39% primarily due to accelerated enrollment in clinical trials[10] - The company expects to complete enrollment in the global Phase 3 PEAK trial in Q3 2024 and report top-line results by the end of 2025[13] - The company anticipates completing enrollment in the registration-directed APEX Phase 2 trial by the end of 2024 and reporting top-line results by mid-2025[13] Clinical Trial Results - The median progression-free survival (mPFS) for patients treated with bezuclastinib and sunitinib was 10.2 months, with a mPFS of 19.4 months observed in a subset of patients with second-line gastrointestinal stromal tumors[4] - The objective response rate (ORR) for all patients treated with bezuclastinib and sunitinib was 27.5%, while the ORR for the subset of second-line patients was 33.3%[5] Corporate Developments - The company appointed Cole Pinnow as Chief Commercial Officer, bringing extensive experience from Pfizer, where he led a $5 billion cancer portfolio[6] - The company initiated IND-enabling studies for the ErbB2 program, demonstrating 80% brain penetrance in mice and well-tolerated at high concentrations[7]

Core Insights - The SUMMIT study is a global, multicenter, double-blind, placebo-controlled phase II trial aimed at evaluating the safety and efficacy of bezuclastinib in patients with nonadvanced systemic mastocytosis (Non-AdvSM) [1][4] - Bezuclastinib is a selective tyrosine kinase inhibitor targeting the KIT D816V mutation and other mutations in KIT exon 17 [2] - The company has reached alignment with the FDA on the use of the Mastocytosis Symptom Severity Daily Diary (MS2D2) for measuring patient-reported outcomes in the SUMMIT study [11] Study Details - The SUMMIT study includes a part 1 that has completed enrollment and a part 2 that is currently enrolling 159 patients, expected to complete by Q2 2025 [12][14] - In part 1, patients treated with 100 mg of bezuclastinib showed significant reductions in severe symptoms and mast cell reactions, with improvements in skin lesions correlating with symptomatic relief [4] - The MS2D2 questionnaire assesses symptom changes throughout the trial, focusing on the 11 most frequent and severe symptoms to determine the primary endpoint [3] Future Developments - Cogent is on track to complete enrollment in the APEX study for advanced systemic mastocytosis by the end of 2024, with top-line results expected by mid-2025 [5][14] - The PEAK study, which evaluates bezuclastinib in combination with sunitinib for gastrointestinal stromal tumors (GIST), is ongoing with an expected completion of enrollment by Q3 2024 and top-line results by the end of 2025 [6][15] Financial Position - As of March 31, 2024, Cogent reported cash, cash equivalents, and marketable securities totaling $435.7 million, sufficient to fund operations and clinical trials through 2027 [17] - The company's shares have increased by 43.7% year-to-date, contrasting with a 5.9% decline in the industry [16] Company Overview - Cogent is developing a portfolio of targeted therapies aimed at serious, genetically driven diseases, initially focusing on mutations in FGFR2, ErbB2, and PI3Kα [7] - Currently, Cogent holds a Zacks Rank of 3 (Hold) [18]

Core Insights - Bezuclastinib demonstrates substantial efficacy in reducing severe symptoms and mast cell reactions in patients with nonadvanced systemic mastocytosis, addressing significant unmet medical needs [1][4][9] - The ongoing SUMMIT clinical trial is focused on evaluating bezuclastinib's effectiveness and safety, with promising results presented at the 2024 European Hematology Association Congress [2][10] Clinical Trial Details - The SUMMIT trial is a randomized, double-blind, placebo-controlled Phase 2 clinical trial designed to assess the recommended dose of bezuclastinib and its effects on symptoms of nonadvanced systemic mastocytosis [10] - As of December 18, 2023, patients treated with the recommended dose of 100 mg showed over 90% reductions in markers of mast cell burden and clinically meaningful improvements in symptom severity [10][4] Safety and Tolerability - The 100 mg dose of bezuclastinib has a favorable safety and tolerability profile, with no reported serious adverse events or cognitive impairment [4][11] - The trial results indicate significant reductions in individual symptoms measured by the Mastocytosis Symptom Severity Daily Diary (MS2D2) [4][9] Future Developments - Cogent Biosciences is on track to complete enrollment in the registration-directed SUMMIT Part 2 study by the second quarter of 2025, with topline results expected by the end of 2025 [9][11] - The company is also progressing with the APEX study for advanced systemic mastocytosis, aiming for completion by the end of 2024 [11]

Core Insights - Cogent Biosciences announced promising data from the SUMMIT clinical trial for bezuclastinib, a selective KIT D816V inhibitor, showing significant reductions in symptoms for patients with nonadvanced systemic mastocytosis [5][16] - The trial demonstrated over 90% reductions in mast cell burden and clinically meaningful improvements in various symptoms, including skin lesions and overall disease severity [6][12][16] Company Overview - Cogent Biosciences is focused on developing precision therapies for genetically defined diseases, with bezuclastinib being the most advanced program targeting systemic mastocytosis and gastrointestinal stromal tumors [4][5] - The company is based in Waltham, MA, and Boulder, CO, and is actively engaged in clinical trials to expand its portfolio of targeted therapies [4] Clinical Trial Details - The SUMMIT trial is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of bezuclastinib in patients with nonadvanced systemic mastocytosis [6][16] - As of December 18, 2023, the recommended dose of 100 mg showed a favorable safety profile, with no serious adverse events reported [13][16] - Enrollment for the registration-directed SUMMIT Part 2 study is expected to be completed in the second quarter of 2025, with topline results anticipated by year-end 2025 [14][16]

"We are thrilled to welcome Cole to our leadership team, as we begin preparations for commercializing bezuclastinib, a product we believe has clear potential to become a standard of care treatment for patients with systemic mastocytosis and advanced GIST," said Andrew Robbins, the Company's President and Chief Executive Officer. "Cole's broad commercial knowledge and leadership experience will be invaluable in helping Cogent expand from a research and development company to a fully-integrated commercial org ...

Core Insights - Cogent Biosciences, Inc. has appointed Cole Pinnow as Chief Commercial Officer to lead the commercialization efforts for bezuclastinib, targeting systemic mastocytosis and gastrointestinal stromal tumors [1][2] - Pinnow brings 25 years of commercial experience in the biopharmaceutical industry, including significant roles at Pfizer, where he managed a $5 billion cancer portfolio [2][3] - The company is focused on transitioning from a research and development entity to a fully integrated commercial organization [2] Company Overview - Cogent Biosciences specializes in developing precision therapies for genetically defined diseases, with bezuclastinib being the most advanced clinical program [5] - Bezuclastinib is a selective tyrosine kinase inhibitor aimed at treating systemic mastocytosis and advanced gastrointestinal stromal tumors, driven by the KIT D816V mutation [5] - The company is also developing a portfolio of targeted therapies addressing mutations in FGFR2, ErbB2, and PI3Kα [5] Leadership and Strategy - Cole Pinnow's role will involve building a commercial team responsible for sales, marketing, access, and operations, with a focus on the potential launch of bezuclastinib [1][2] - The company aims to establish bezuclastinib as a standard of care treatment for its target patient populations [2] - Pinnow expressed enthusiasm for the company's progress and the opportunity to contribute to its first potential product launch [2] Inducement Equity Award - As part of Pinnow's appointment, Cogent is granting him inducement equity awards, including options to purchase 525,000 shares and up to 214,000 performance-based restricted stock units [4] - The options have a 10-year term with a four-year vesting schedule, while the performance-based units are contingent on achieving specific stock price and R&D milestones [4]

Item 6. Exhibits. 3.2 10.2(1) 32.1*† Certification of Principal Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 104* The cover page for the Company's Quarterly Report on Form 10-Q has been formatted in Inline XBRL and contained in Exhibit 101 SIGNATURES Date: May 7, 2024 By: /s/ John Green John Green Chief Financial Officer (Principal Accounting and Financial Officer) PART II—OTHER INFORMATION Item 1. Legal Proceedings. We are not cu ...

Financial Performance - As of March 31, 2024, cash, cash equivalents, and marketable securities totaled $435.7 million, up from $273.2 million as of December 31, 2023, providing a cash runway into 2027[8] - The net loss for Q1 2024 was $58.3 million, compared to a net loss of $38.6 million for Q1 2023, with a net loss per share of $0.62[22][25] - The total operating expenses for Q1 2024 were $62.4 million, compared to $43.2 million for Q1 2023[25] - The company completed an oversubscribed private placement, resulting in net proceeds of $213.4 million, extending its cash runway into 2027[4] Research and Development - Research and development expenses for Q1 2024 were $52.7 million, compared to $36.0 million in Q1 2023, reflecting increased costs associated with clinical trials[21] - The company is developing a portfolio of novel targeted therapies, including a preclinical ErbB2 candidate showing promising results in early studies[18] Clinical Trials - The company expects to complete enrollment in the APEX trial by the end of 2024 and report top-line results in mid-2025[19] - Enrollment in the PEAK trial is on track to be completed by the end of 2024, with top-line results expected by the end of 2025[5][12] - The SUMMIT trial's Part 2 enrollment is anticipated to be completed in Q2 2025, with top-line results also expected by the end of 2025[7][12] - A 49% mean improvement in quality-of-life was observed at week 12 in the ongoing trials, with no significant safety concerns reported[4][26]

Product Development and Clinical Trials - The company is highly dependent on the success of its bezuclastinib program and the ability to discover and develop additional product candidates [209]. - Bezuclastinib is currently undergoing clinical trials (APEX, SUMMIT, and PEAK) targeting SM and GIST, with no guarantee of success [209]. - The company is working to build a pipeline of other product candidates, which will require substantial additional funding and is subject to inherent risks of failure [210]. - The updated formulation of bezuclastinib aims to reduce the number of daily tablets for GIST patients, but its success in clinical trials is unproven [228]. - The commercial success of bezuclastinib will depend on market acceptance by physicians, patients, and payors, influenced by safety, efficacy, and cost compared to alternatives [229]. - The company is conducting clinical trials for its lead product candidate, bezuclastinib, in patients with GIST, AdvSM, and Non-AdvSM, but may face challenges in obtaining regulatory approval [246]. - The company is dependent on developing companion diagnostic tests for its drug candidates, which may face scientific, technical, regulatory, and logistical challenges [255]. Regulatory and Market Risks - The incidence and prevalence of target patient populations for the drug candidates are not precisely established, which may adversely affect revenue potential [218]. - The company plans to seek regulatory approval for its product candidates internationally, which may expose it to additional risks and regulatory requirements [230]. - The company may choose to suspend or terminate discovery programs or product candidates if deemed not viable, potentially resulting in wasted resources [223]. - The ability to file INDs or CTAs for additional clinical trials may be delayed, and regulatory authorities may not permit further trials [226]. - The company faces potential delays in the clinical development and regulatory approval process, which could increase product development costs [242]. - The company is exposed to risks related to healthcare legislation and pricing practices, which could adversely affect its business model and revenue prospects [250]. Competition and Market Position - The company faces significant competition from larger pharmaceutical and biotechnology companies with greater resources and expertise [215]. - Difficulties in patient enrollment for clinical trials could delay development activities and increase costs [216]. Manufacturing and Supply Chain - The company relies on third parties for clinical trials and manufacturing, increasing the risk of delays in obtaining regulatory approval and commercializing its product candidates [232]. - The company does not own any manufacturing facilities and relies on third-party manufacturers, which could lead to supply issues and impact development efforts [235]. - The company currently has no long-term supply agreements with contract manufacturers, increasing the risk of not obtaining sufficient quantities of drug candidates [236]. - The company intends to identify and qualify additional manufacturers for its drug candidates to ensure a reliable supply chain [240]. - The company may need to establish redundant supply sources for its drug candidates to mitigate risks associated with single-source suppliers [239]. Financial Position and Funding - The company has incurred net losses since its inception in March 2014 and anticipates continuing to incur losses in the future, with no products approved for commercial sale and no revenue generated from product sales to date [276]. - The company requires substantial additional funding for the development and commercialization of its product candidates, including significant amounts for launching products if approved [274]. - The company has approximately $69.7 million in federal net operating losses and $4.0 million in state net operating losses, subject to annual limitations due to ownership changes [277]. - The trading price of the company's common stock is expected to remain highly volatile, influenced by various market factors [278]. - The company may need to raise additional capital through sales of common stock or other equity securities, which could dilute existing stockholders' ownership [281]. Human Resources and Management - The company has increased its headcount from 77 to 164 full-time employees over the past two years to support its growth in research, development, and manufacturing [269]. - The company is highly dependent on key personnel, and the loss of any executive officers could result in delays in product development [267]. - The company faces intense competition for skilled personnel, which may limit its ability to hire and retain qualified employees [268]. Technology and Cybersecurity - The company is increasingly reliant on its information technology systems, which are vulnerable to security breaches and system failures that could disrupt operations [272]. - The company maintains cyber insurance, but there is no assurance that it will be sufficient to cover all claims related to security breaches [273]. Miscellaneous - As of June 30, 2023, the company is classified as a large accelerated filer with a market value exceeding $700 million, subjecting it to additional disclosure requirements [270]. - The company does not use interest rate derivative instruments to manage exposure to interest rate changes, focusing on preserving invested principal funds [390]. - Inflation has not materially impacted the company's business or results of operations, although significant adverse changes could negatively affect future results [391]. - The company has not performed a Section 382 analysis since December 2020, which may affect the utilization of net operating loss carryforwards [277]. - Executive officers, directors, and stockholders owning 5% or more of the company beneficially owned approximately 65.1% of the outstanding common stock as of December 31, 2023, allowing them to exert significant influence over corporate matters [279].