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].

Financial Performance - Cogent Biosciences reported a net loss of $54.4 million for Q4 2023 and $192.4 million for the full year, compared to a net loss of $39.6 million and $140.2 million in the same periods of 2022, respectively[18]. - Net loss for Q4 2023 was $54,365 thousand, up from a net loss of $39,618 thousand in Q4 2022, reflecting a 37.4% increase in losses[22]. - Net loss per share attributable to common stockholders was $(0.63) in Q4 2023, compared to $(0.56) in Q4 2022[22]. Research and Development - Research and development expenses increased to $48.7 million for Q4 2023 and $173.8 million for the full year, up from $36.7 million and $121.6 million in 2022, driven by progress in clinical trials[16]. - Research and development expenses increased to $48,719 thousand in Q4 2023 from $36,742 thousand in Q4 2022, representing a 32.5% increase[22]. - The company is actively enrolling three registration-directed clinical trials of bezuclastinib, with topline results expected by the end of 2025 for SUMMIT and PEAK trials, and mid-2025 for the APEX trial[3][12]. - Bezuclastinib demonstrated a 56% overall response rate in TKI-naïve patients, with 86% achieving a pure pathological response[6]. - The APEX trial for advanced systemic mastocytosis is on track to complete enrollment by the end of 2024[7]. - The PEAK Phase 3 trial for second-line GIST patients is also expected to complete enrollment by the end of 2024[12]. - Cogent plans to initiate a Phase 1 trial for its FGFR2 inhibitor in the second half of 2024, targeting best-in-class potential[13]. - The company reported a 51% mean improvement in total symptom score for bezuclastinib at week 12, with 70% of patients achieving at least a 50% improvement in symptom severity[8]. Financial Position - As of December 31, 2023, Cogent had cash, cash equivalents, and marketable securities totaling $273.2 million, which, along with the $225 million from a recent PIPE financing, is expected to fund operations into 2027[15]. - Cash, cash equivalents, and marketable securities totaled $273,170 thousand as of December 31, 2023, up from $259,276 thousand a year earlier, indicating a 5.5% increase[23]. - Total assets increased to $313,437 thousand as of December 31, 2023, compared to $300,810 thousand as of December 31, 2022, representing a 4.2% growth[23]. - Total liabilities rose to $55,635 thousand as of December 31, 2023, up from $45,075 thousand in the previous year, reflecting a 23.4% increase[23]. - Total stockholders' equity slightly increased to $257,802 thousand as of December 31, 2023, compared to $255,735 thousand a year earlier, showing a 0.8% growth[23]. Capital Financing - The company closed a $225 million oversubscribed PIPE financing, selling approximately 17 million shares at $7.50 per share, a 37% premium to the closing price prior to the offering[5].

Pro-forma cash, cash equivalents and marketable securities expected to fund the Company into 2027 and through clinical readouts from ongoing SUMMIT, PEAK and APEX registration-directed trials Cogent to host investor webcast at 8:00 a.m. ET on February 23 to review the SUMMIT Part 1b data with bezuclastinib at AAAAI annual meeting WALTHAM, Mass. and BOULDER, Colo., Feb. 14, 2024 (GLOBE NEWSWIRE) --  Cogent Biosciences, Inc. (NASDAQ:COGT), a biotechnology company focused on developing precision therapies for ...

Financial Performance - The company reported a net loss of $138.0 million for the nine months ended September 30, 2023, compared to a net loss of $100.6 million for the same period in 2022[120]. - Total operating expenses for the nine months ended September 30, 2023, were $149.9 million, an increase of $45.8 million compared to $104.1 million for the same period in 2022[129]. - Research and development expenses rose by $40.2 million to $125.0 million for the nine months ended September 30, 2023, driven by higher external costs related to clinical trials and increased personnel costs[130]. - General and administrative expenses increased to $24.9 million for the nine months ended September 30, 2023, up from $19.2 million in the same period of 2022, primarily due to higher personnel costs[131]. - Interest income for the nine months ended September 30, 2023, was $9.2 million, a significant increase from $1.9 million for the same period in 2022, attributed to higher average interest rates[132]. - Net cash used in investing activities was $108.3 million for the nine months ended September 30, 2023, compared to $153.1 million for the same period in 2022[136]. - Net cash provided by financing activities was $163.5 million for the nine months ended September 30, 2023, slightly up from $163.2 million in the same period in 2022[137]. - The company expects expenses to increase as it advances clinical development and research activities, with existing cash and equivalents of $312.8 million projected to fund operations into 2026[138]. Research and Development - Bezuclastinib's research and development expenses for Q3 2023 were $27.965 million, an increase of $15.141 million compared to $12.824 million in Q3 2022[125]. - Total research and development expenses for Q3 2023 reached $50.127 million, up from $29.936 million in Q3 2022, reflecting a change of $20.191 million[125]. - The APEX trial for bezuclastinib is on track to complete enrollment by the end of 2024, with updated clinical results from Part 1 to be presented at the 2023 ASH Annual Meeting[117]. - SUMMIT Part 1 completed enrollment in Q3 2023 with over 54 patients, and initial clinical data will be presented at the 2023 ASH Annual Meeting[117]. - The Phase 3 portion of the PEAK study is on track to complete enrollment by the end of 2024, with a 55% Disease Control Rate observed in heavily pre-treated GIST patients[118]. - The company has achieved a clinical milestone payment of $2.5 million to Plexxikon in June 2022 due to the progression of the PEAK study[118]. - The company has filed a provisional patent application for its optimized formulation of bezuclastinib, potentially providing exclusivity through at least 2043[118]. Operational Outlook - The company anticipates an increase in general and administrative expenses due to the expansion of operations to support ongoing discovery and clinical activities[122]. - The company has no off-balance sheet arrangements as defined by SEC regulations[139]. - The company anticipates becoming a "large accelerated filer" by December 31, 2023, which will require compliance with new accounting standards[141]. - There are no material legal proceedings currently affecting the company, although it may face ordinary course claims[164].

Common Stock, $0.001 Par Value COGT The Nasdaq Global Select Market (Mark One) OR | --- | --- | --- | |------------------------------------------------------------|------------------------------------------------------------------------------------|-----------------------------------------------------| | Delaware | Cogent Biosciences, Inc. (Exact name of registrant as specified in its charter) \n | 46-5308248 | | (State or other incorporation or | jurisdiction of (I.R.S. organization) Identification | Emplo ...

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=5&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Cogent Biosciences reported an increased net loss for Q1 2023 driven by higher R&D expenses, with a decrease in cash and total assets from year-end 2022 [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2023, total assets and liabilities decreased, primarily due to reduced marketable securities and CVR liability settlement | Balance Sheet Items (in thousands) | March 31, 2023 | December 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $160,698 | $139,886 | | Marketable securities | $59,566 | $119,390 | | Total current assets | $226,270 | $264,966 | | Total assets | $263,198 | $300,810 | | **Liabilities & Equity** | | | | Total current liabilities | $21,120 | $26,849 | | Total liabilities | $39,635 | $45,075 | | Total stockholders' equity | $223,563 | $255,735 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For Q1 2023, net loss increased to $38.6 million, primarily driven by a significant rise in research and development expenses | Statement of Operations (in thousands) | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :--- | :--- | :--- | | Research and development | $36,038 | $25,470 | | General and administrative | $7,199 | $5,948 | | Total operating expenses | $43,237 | $31,418 | | Loss from operations | ($43,237) | ($31,418) | | Total other income, net | $4,650 | $784 | | **Net loss** | **($38,587)** | **($30,634)** | | **Net loss per share** | **($0.55)** | **($0.68)** | [Condensed Consolidated Statements of Cash Flows](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased in Q1 2023, offset by significant cash provided by investing activities, resulting in a net increase in cash | Cash Flow Items (in thousands) | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | ($39,517) | ($28,334) | | Net cash (used in) provided by investing activities | $59,884 | ($441) | | Net cash provided by financing activities | $445 | $138 | | **Net (decrease) increase in cash** | **$20,812** | **($28,637)** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=9&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Notes detail the company's lead program bezuclastinib, expected cash runway, CVR liability reduction, and stock-based compensation expenses - The company's most advanced program is **bezuclastinib**, a selective tyrosine kinase inhibitor for genetically defined diseases like Systemic Mastocytosis (SM) and gastrointestinal stromal tumors (GIST)[26](index=26&type=chunk) - The fair value of the CVR liability was reduced by **$1.7 million** to zero during the first quarter of 2023, as the probability of milestone payments occurring before the CVR's expiration is now considered remote[41](index=41&type=chunk)[42](index=42&type=chunk) Stock-Based Compensation (in thousands) | Stock-Based Compensation (in thousands) | Q1 2023 | Q1 2022 | | :--- | :--- | :--- | | Research and development | $2,956 | $1,924 | | General and administrative | $2,894 | $2,251 | | **Total** | **$5,850** | **$4,175** | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=17&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses progress of lead candidate bezuclastinib, pipeline development, increased net loss due to R&D, and the company's liquidity position [Overview and Pipeline](index=17&type=section&id=Overview%20and%20Pipeline) Cogent focuses on bezuclastinib for SM and GIST across three trials, while advancing FGFR2 and ErbB2 inhibitor programs towards 2024 clinical trials - The company's lead program, **bezuclastinib**, is being evaluated in three clinical trials: APEX (Advanced Systemic Mastocytosis), SUMMIT (Non-Advanced Systemic Mastocytosis), and PEAK (Gastrointestinal Stromal Tumors)[71](index=71&type=chunk)[75](index=75&type=chunk)[76](index=76&type=chunk)[78](index=78&type=chunk) - Initial clinical data for the SUMMIT trial in patients with Non-AdvSM is expected in the **second half of 2023**[76](index=76&type=chunk) - The research team is developing novel inhibitors for **FGFR2** and **ErbB2** mutations, with plans to initiate clinical trials for both programs in **2024**[83](index=83&type=chunk)[85](index=85&type=chunk)[86](index=86&type=chunk) [Results of Operations](index=22&type=section&id=Results%20of%20Operations) Total operating expenses increased in Q1 2023, driven by a significant rise in research and development costs for clinical trials and pipeline development Operating Results (in thousands) | Operating Results (in thousands) | Q1 2023 | Q1 2022 | Change | | :--- | :--- | :--- | :--- | | Research and development | $36,038 | $25,470 | $10,568 | | General and administrative | $7,199 | $5,948 | $1,251 | | **Total operating expenses** | **$43,237** | **$31,418** | **$11,819** | | **Net loss** | **($38,587)** | **($30,634)** | **($7,953)** | - The **$10.6 million** increase in R&D expense was driven by manufacturing and development costs for bezuclastinib, costs for the APEX, SUMMIT, and PEAK trials, and development of the research pipeline[106](index=106&type=chunk) - The increase in G&A expenses was primarily due to higher personnel costs from increased headcount, including a **$0.6 million** increase in stock-based compensation[107](index=107&type=chunk) [Liquidity and Capital Resources](index=23&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2023, the company held **$220.3 million** in cash and equivalents, expected to fund operations into 2025, supplemented by prior public offerings - As of March 31, 2023, the company had cash, cash equivalents and marketable securities of **$220.3 million**[92](index=92&type=chunk)[117](index=117&type=chunk) - The current cash position is expected to fund operating expenses and capital expenditure requirements into **2025**[92](index=92&type=chunk)[117](index=117&type=chunk)[125](index=125&type=chunk) - In June 2022, the company completed an underwritten public offering, raising net proceeds of approximately **$161.9 million**[114](index=114&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=27&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Cogent Biosciences is exempt from providing market risk disclosures - As a smaller reporting company, Cogent Biosciences is not required to provide quantitative and qualitative disclosures about market risk[133](index=133&type=chunk) [Item 4. Controls and Procedures](index=27&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2023, with no material changes to internal control over financial reporting - Based on an evaluation as of March 31, 2023, the CEO and CFO concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level[135](index=135&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that materially affected, or are reasonably likely to materially affect, these controls[136](index=136&type=chunk) PART II—OTHER INFORMATION [Item 1. Legal Proceedings](index=28&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - The company reports that it is not currently a party to any material legal proceedings[139](index=139&type=chunk) [Item 1A. Risk Factors](index=28&type=section&id=Item%201A.%20Risk%20Factors) No material changes have occurred to the risk factors previously disclosed in the company's 2022 Annual Report on Form 10-K - No material changes have occurred to the risk factors described in the company's 2022 Annual Report on Form 10-K[140](index=140&type=chunk) [Other Part II Items](index=28&type=section&id=Other%20Part%20II%20Items) The company reported no recent sales of unregistered securities, no defaults, no mine safety disclosures, and no other material information for Items 2-5 - Item 2: No recent sales of unregistered securities were reported[141](index=141&type=chunk) - Items 3, 4, and 5 were noted as 'Not applicable' or 'None'[142](index=142&type=chunk)[143](index=143&type=chunk)[144](index=144&type=chunk)

Part I [Item 1. Business](index=7&type=section&id=Item%201.%20Business) Cogent Biosciences develops precision therapies, with lead candidate bezuclastinib for SM and GIST, and other pipeline programs under regulatory oversight [Bezuclastinib Program](index=8&type=section&id=Bezuclastinib%20Program) Bezuclastinib, a selective KIT inhibitor with a best-in-class profile, is being evaluated in three active clinical trials for SM and GIST - Bezuclastinib is designed as a selective Type I inhibitor targeting KIT receptor tyrosine kinase mutations, demonstrating potency comparable to FDA-approved inhibitors but with greater selectivity and limited blood-brain-barrier penetration in preclinical studies[32](index=32&type=chunk) - The company has initiated three clinical trials—APEX (AdvSM), SUMMIT (Non-AdvSM), and PEAK (GIST)—to evaluate the safety and efficacy of bezuclastinib, all of which are actively recruiting patients[14](index=14&type=chunk) Bezuclastinib Selectivity Profile | Compound | PDGFRa | PDGFRB | CSF1R | FLT3 | KDR | |---|---|---|---|---|---| | Bezuclastinib | >10,000 | >10,000 | >10,000 | >1000 | >1000 | | Avapritinib | 53 | 10 | 249 | 305 | >1000 | [Research Programs](index=15&type=section&id=Research%20Programs) The research team is expanding the pipeline with novel small molecule inhibitors for FGFR2 and ErbB2 mutations, with clinical trials expected in 2024 - The research team is developing a next-generation FGFR2 inhibitor designed to retain potency against resistance mutations while sparing FGFR1, potentially avoiding common toxicities like hyperphosphatemia[62](index=62&type=chunk) - A novel ErbB2 mutant program is also underway, focusing on providing broad mutant coverage in various solid tumors while sparing wild-type EGFR engagement[114](index=114&type=chunk) - Cogent anticipates initiating clinical trials for both the FGFR2 and ErbB2 programs in 2024[88](index=88&type=chunk) [Intellectual Property](index=16&type=section&id=Intellectual%20Property) Cogent protects its technology through in-licensed patents for bezuclastinib, with exclusivity extending to 2033-2034, potentially to 2043 with new formulations - The company's intellectual property strategy relies on in-licensed patents from Plexxikon, know-how, and trade secrets[89](index=89&type=chunk) - Issued U.S. patents covering bezuclastinib and its therapeutic uses are expected to expire in 2033 and 2034. A provisional patent application for a new formulation filed in 2022 could provide exclusivity through at least 2043[116](index=116&type=chunk) [Competition](index=17&type=section&id=Competition) Cogent faces intense competition in SM and GIST from larger pharmaceutical companies with greater resources and established therapies - In the AdvSM market, Cogent competes with approved drugs like avapritinib (Blueprint) and midostaurin (Novartis). For Non-AdvSM, there are no currently approved drugs, but Blueprint's avapritinib is under FDA review[97](index=97&type=chunk) - In GIST, the competitive landscape includes established therapies such as imatinib, sunitinib, regorafenib, and ripretinib, as well as drug candidates from companies like Celldex, Deciphera, and Theseus Pharmaceuticals[126](index=126&type=chunk) - Many competitors have significantly greater financial resources and expertise in R&D, manufacturing, clinical trials, and marketing[123](index=123&type=chunk) [Government Regulation](index=18&type=section&id=Government%20Regulation) Operations are extensively regulated by U.S. and EU authorities, requiring lengthy approval processes and ongoing compliance with strict post-market requirements - Drug development in the U.S. requires a multi-step process including preclinical studies, an Investigational New Drug (IND) application, and three phases of human clinical trials before submitting a New Drug Application (NDA) to the FDA[101](index=101&type=chunk) - In the European Union, marketing authorization can be obtained through centralized or decentralized procedures, with the EMA's CHMP playing a key role. The new Clinical Trials Regulation (CTR) aims to streamline the trial application process via a centralized EU portal[203](index=203&type=chunk)[178](index=178&type=chunk) - Both U.S. and EU regulations impose strict post-approval requirements, including adherence to Good Manufacturing Practices (cGMP), pharmacovigilance, and restrictions on off-label promotion[141](index=141&type=chunk)[214](index=214&type=chunk)[246](index=246&type=chunk) - The company's primary focus is on developing **bezuclastinib**, a selective tyrosine kinase inhibitor, to treat genetically defined diseases like Systemic Mastocytosis (SM) and Gastrointestinal Stromal Tumors (GIST) by targeting KIT mutations[396](index=396&type=chunk) - Cogent's strategy includes exploring bezuclastinib's utility in Advanced SM (AdvSM), Non-Advanced SM (Non-AdvSM), and GIST, while preparing for potential commercialization and advancing its preclinical programs for FGFR2 and ErbB2[30](index=30&type=chunk) [Item 1A. Risk Factors](index=39&type=section&id=Item%201A.%20Risk%20Factors) The company faces substantial risks including bezuclastinib program failure, intense competition, reliance on third parties, regulatory hurdles, IP protection, and significant funding needs [Risks Related to Discovery and Development of Our Drug Candidates](index=39&type=section&id=Risks%20Related%20to%20the%20Discovery%20and%20Development%20of%20Our%20Drug%20Candidates) Success hinges on bezuclastinib, facing risks of clinical trial failure, adverse side effects, intense competition, and challenges in patient enrollment - The business is highly dependent on the success of the bezuclastinib program, which may not succeed in its ongoing APEX, SUMMIT, and PEAK clinical trials or obtain regulatory approval[299](index=299&type=chunk)[275](index=275&type=chunk) - The company faces significant competition from well-established biotechnology and pharmaceutical companies with greater financial resources and expertise[277](index=277&type=chunk)[303](index=303&type=chunk) - Unacceptable side effects identified during development could lead to the abandonment or limitation of drug candidates[276](index=276&type=chunk)[301](index=301&type=chunk) [Risks Related to Our Reliance on Third Parties](index=43&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) Extensive reliance on third-party CROs and single-source CMOs for bezuclastinib manufacturing poses significant risks to development and supply - The company depends on third-party CROs and medical institutions to conduct clinical trials, giving it less direct control over timing and execution[320](index=320&type=chunk)[337](index=337&type=chunk) - Cogent relies on third-party CMOs for manufacturing and does not own its own facilities, increasing the risk of supply shortages, cost issues, and quality control problems[323](index=323&type=chunk)[339](index=339&type=chunk) - The API and drug product for bezuclastinib are supplied by single-source suppliers, and the loss of any of these could significantly harm the business[342](index=342&type=chunk)[326](index=326&type=chunk) [Risks Related to Our Intellectual Property](index=47&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) IP protection, largely in-licensed for bezuclastinib, faces risks of challenge, invalidation, infringement claims, and license termination - The company's efforts to protect its proprietary technology may not be adequate, potentially allowing competitors to erode its market position[38](index=38&type=chunk)[173](index=173&type=chunk) - Cogent is dependent on its license agreement with Plexxikon for bezuclastinib; termination of this agreement would cause the loss of significant rights and harm the business[42](index=42&type=chunk)[43](index=43&type=chunk) - The company may face third-party claims of intellectual property infringement, which could prevent or delay product development and lead to substantial damages or royalty payments[46](index=46&type=chunk) [Risks Related to Our Financial Position and Need for Additional Capital](index=51&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has a history of net losses, requires substantial additional funding, and faces limitations on using NOLs due to prior ownership changes - The company has incurred net losses every year since inception and expects to continue incurring losses, consuming substantial cash for R&D and clinical development[346](index=346&type=chunk)[353](index=353&type=chunk) - Substantial additional funding is required to complete development and commercialization. Failure to raise capital may force the company to delay or scale back operations[152](index=152&type=chunk)[345](index=345&type=chunk) - The company's ability to use its net operating loss (NOL) carryforwards is subject to an annual limitation under Section 382 due to a prior ownership change, which resulted in the write-off of some deferred tax assets[348](index=348&type=chunk)[355](index=355&type=chunk) [Item 2. Properties](index=53&type=section&id=Item%202.%20Properties) Cogent Biosciences leases corporate headquarters in Waltham, a research facility in Boulder, and a partially subleased former headquarters in Cambridge - The company subleases approximately **17,749 square feet** of office space in Waltham, Massachusetts for its corporate headquarters, with the lease expiring in September 2026[402](index=402&type=chunk) - A **44,657 square feet** office and laboratory space is leased in Boulder, Colorado, housing research and administrative personnel under a 12-year lease term[674](index=674&type=chunk) - The former headquarters in Cambridge, Massachusetts, approximately **33,500 square feet**, is under a lease expiring in April 2023, with about **70%** of the space being subleased[675](index=675&type=chunk) [Item 3. Legal Proceedings](index=53&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings, though it may face ordinary course claims - The company is not currently a party to any material legal proceedings[268](index=268&type=chunk)[683](index=683&type=chunk) Part II [Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=55&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) Cogent's common stock trades on Nasdaq under "COGT"; the company has never paid dividends and retains earnings for operations - The company's common stock trades on the Nasdaq Global Select Market under the symbol "**COGT**"[405](index=405&type=chunk) - Cogent has never paid cash dividends and does not anticipate paying any in the foreseeable future, intending to retain all available funds for business operations[406](index=406&type=chunk) [Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=55&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Net loss increased to $140.2 million in 2022 due to higher R&D and G&A expenses, with $259.3 million in cash expected to fund operations into 2025 [Results of Operations](index=60&type=section&id=Results%20of%20Operations) Net loss increased to $140.2 million in 2022, driven by a $72.3 million rise in operating expenses, primarily R&D and G&A Results of Operations (2022 vs 2021) (in thousands) | | Year Ended Dec 31, 2022 | Year Ended Dec 31, 2021 | Change | |---|---|---|---| | Research and development | $121,627 | $55,913 | $65,714 | | General and administrative | $26,212 | $19,638 | $6,574 | | **Total operating expenses** | **$147,839** | **$75,551** | **$72,288** | | Loss from operations | $(147,839) | $(75,551) | $(72,288) | | Total other income, net | $7,598 | $3,278 | $4,320 | | **Net loss** | **$(140,241)** | **$(72,273)** | **$(67,968)** | - R&D expenses increased by **$65.7 million** in 2022, driven by higher external costs for the manufacturing and development of bezuclastinib for the APEX, SUMMIT, and PEAK trials, as well as increased personnel costs and lab supplies for the research team[601](index=601&type=chunk) - G&A expenses increased by **$6.6 million** in 2022, primarily due to higher personnel costs from increased headcount, including a **$2.6 million** increase in stock-based compensation[602](index=602&type=chunk) [Liquidity and Capital Resources](index=62&type=section&id=Liquidity%20and%20Capital%20Resources) Cogent held $259.3 million in cash as of Dec 2022, sufficient into 2025, after raising $161.9 million from an offering, but requires more funding - The company had **$259.3 million** in cash, cash equivalents, and marketable securities as of December 31, 2022, which is expected to fund operations into **2025**[448](index=448&type=chunk)[438](index=438&type=chunk) - In June 2022, the company completed an underwritten public offering, raising net proceeds of approximately **$161.9 million**[578](index=578&type=chunk)[569](index=569&type=chunk) Cash Flow Summary (in thousands) | | Year Ended Dec 31, 2022 | Year Ended Dec 31, 2021 | |---|---|---| | Net cash used in operating activities | $(118,638) | $(58,763) | | Net cash used in investing activities | $(124,718) | $(1,719) | | Net cash provided by financing activities | $163,558 | $37,976 | [Item 8. Financial Statements and Supplementary Data](index=67&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section presents the independent auditor's report and consolidated financial statements for 2022 and 2021, including balance sheets, income statements, equity, cash flows, and notes [Consolidated Financial Statements](index=69&type=section&id=Consolidated%20Financial%20Statements) The consolidated financial statements show total assets of $300.8 million, liabilities of $45.1 million, and a net loss of $140.2 million in 2022 Consolidated Balance Sheet Highlights (in thousands) | | Dec 31, 2022 | Dec 31, 2021 | |---|---|---| | Cash, cash equivalents & marketable securities | $259,276 | $219,684 | | Total Assets | $300,810 | $232,092 | | Total Liabilities | $45,075 | $17,908 | | Total Stockholders' Equity | $255,735 | $214,184 | Consolidated Statement of Operations Highlights (in thousands) | | Year Ended Dec 31, 2022 | Year Ended Dec 31, 2021 | |---|---|---| | Total operating expenses | $147,839 | $75,551 | | Net loss | $(140,241) | $(72,273) | | Net loss per share | $(2.39) | $(1.87) | [Notes to Consolidated Financial Statements](index=74&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) Notes detail accounting policies, including expensing R&D, valuation allowance for deferred tax assets, NOL carryforwards, and operating lease commitments - Research and development costs, including upfront and milestone payments for licensed technology, are expensed as incurred[504](index=504&type=chunk)[505](index=505&type=chunk) - The company has federal and state net operating loss (NOL) carryforwards of **$151.9 million** and **$65.1 million**, respectively, as of Dec 31, 2022. However, a full valuation allowance has been established against deferred tax assets due to uncertainty of realization[608](index=608&type=chunk)[610](index=610&type=chunk) - Under its license agreement with Plexxikon, the company is obligated to pay up to **$7.5 million** in clinical milestones and **$25.0 million** in regulatory milestones, plus tiered royalties on net sales. A **$2.5 million** clinical milestone was paid in June 2022[617](index=617&type=chunk) [Item 9A. Controls and Procedures](index=91&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2022, with no material changes - The CEO and CFO concluded that the company's disclosure controls and procedures were effective as of December 31, 2022[622](index=622&type=chunk) - Management assessed internal control over financial reporting based on the COSO framework and concluded it was effective as of December 31, 2022[624](index=624&type=chunk) - The company is an emerging growth company and is therefore exempt from the auditor attestation requirement regarding internal control over financial reporting[728](index=728&type=chunk) Part III [Items 10-14](index=93&type=section&id=Items%2010-14) Information for Items 10-14, covering governance, compensation, and ownership, is incorporated by reference from the 2023 proxy statement - The information for Items 10, 11, 12, 13, and 14 is incorporated by reference from the definitive proxy statement for the 2023 Annual Meeting of Stockholders[365](index=365&type=chunk)[645](index=645&type=chunk) Part IV [Item 15. Exhibits, Financial Statement Schedules](index=94&type=section&id=Item%2015.%20Exhibits%2C%20Financial%20Statement%20Schedules) This section lists financial statements, schedules, and exhibits, including key agreements and certifications, filed as part of the Form 10-K - This item contains the index of financial statements and a list of all exhibits filed with the annual report[632](index=632&type=chunk) - Key exhibits include the License Agreement with Plexxikon Inc. (10.8), the Underwriting Agreement from the June 2022 offering (10.11), and various employment and compensation plan documents[660](index=660&type=chunk)[661](index=661&type=chunk)

Summary of Cogent Biosciences Conference Call Company Overview - **Company**: Cogent Biosciences - **Lead Product**: Bezuclasinib, a drug targeting KIT mutations, particularly D816V, associated with systemic mastocytosis and gastrointestinal stromal tumors (GIST) [4][6] Key Points and Arguments Product Development and Pipeline - **Bezuclasinib** is in development for two subgroups of mastocytosis and in a global Phase III trial for GIST [4][6] - The company has a strong cash position, expected to last until 2025, allowing for continued development of its pipeline [6][40] - The company is running three clinical studies: APeX, SUMMIT, and PEEK, which could serve as the basis for registration if successful [6][14] Competitive Landscape - In GIST, the current standard of care is **Sunitinib**, which has limitations against certain mutations [10][12] - Bezuclasinib is positioned to cover all secondary resistance mutations, potentially leading to better outcomes in combination with Sunitinib [12][30] - In systemic mastocytosis, Bezuclasinib competes with **Avapritinib** and **BLU-263**, with a focus on a better tolerability profile [13][61] Market Potential - The total available market in the U.S. for the targeted indications is estimated at **$2.5 billion**, with a global potential of **$3.5 billion** [14][65] - The systemic mastocytosis market is projected to be around **$300 million** in the U.S. and **$500 million** globally [65] Clinical Data and Efficacy - The APeX study has shown an objective response rate of **73%**, increasing to **89%** in treatment-naive patients [19][20] - The safety profile of Bezuclasinib is favorable, with no significant cognitive effects or bleeding events reported [21][22] - The company plans to initiate investigations of Bezuclasinib in combination with other therapies to enhance its market position [24] Future Catalysts - Upcoming milestones include updates from the APeX study, results from the Phase III PEEK study, and progress on early-stage programs targeting FGFR2 and ErbB2 [38][39][40] Important but Overlooked Content - The company emphasizes the unmet need for effective therapies in systemic mastocytosis, particularly for the indolent form of the disease, where current options are limited [15][17] - The potential for Bezuclasinib to be used alongside other hematologic therapies could unlock significant market opportunities that competitors may not address effectively [65] Conclusion Cogent Biosciences is strategically positioned in the precision medicine space with its lead product, Bezuclasinib, targeting rare diseases driven by genetic mutations. The company is focused on demonstrating clinical efficacy and safety to capture a significant share of the market, while navigating a competitive landscape with limited alternatives for patients.