PART I: FINANCIAL INFORMATION This section presents the company's unaudited condensed consolidated financial statements and management's discussion and analysis of financial condition and results of operations [Item 1. Financial Statements (Unaudited)](index=10&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements for Bicara Therapeutics Inc., including balance sheets, statements of operations, stockholders' equity, and cash flows, along with detailed notes explaining the company's business, significant accounting policies, and specific financial line items [Condensed Consolidated Balance Sheets](index=10&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section provides a snapshot of the company's financial position at specific points in time, detailing assets, liabilities, and stockholders' equity | Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :-------------------------------- | :----------------------------- | :------------------------------- | | Cash and cash equivalents | $436,606 | $489,711 | | Total current assets | $444,391 | $502,533 | | Total assets | $453,587 | $509,996 | | Total current liabilities | $17,227 | $17,990 | | Total liabilities | $18,391 | $18,121 | | Total stockholders' equity | $435,196 | $491,875 | | Accumulated deficit | $(285,250) | $(221,016) | - Cash and cash equivalents decreased from **$489.7 million** at December 31, 2024, to **$436.6 million** at June 30, 2025. Total assets also decreased from **$509.9 million** to **$453.5 million** during the same period. The accumulated deficit increased significantly from **$(221.0) million** to **$(285.2) million**[24](index=24&type=chunk) [Condensed Consolidated Statements of Operations](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) This section details the company's revenues, expenses, and net loss over specific periods, reflecting operational performance | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Total operating expenses | $32,018 | $19,750 | $73,806 | $35,124 | | Loss from operations | $(32,018) | $(19,750) | $(73,806) | $(35,124) | | Interest income | $4,682 | $2,701 | $9,696 | $5,568 | | Net loss | $(27,388) | $(17,049) | $(64,234) | $(29,557) | | Net Loss per share, basic and diluted | $(0.50) | $(19.01) | $(1.18) | $(38.19) | - Net loss increased significantly year-over-year for both the three-month and six-month periods ended June 30, 2025, primarily due to higher operating expenses. Net loss per share (basic and diluted) for the three months ended June 30, 2025, was **$(0.50)** compared to **$(19.01)** in the prior year, and for the six months, it was **$(1.18)** compared to **$(38.19)**, reflecting a substantial increase in weighted-average shares outstanding[27](index=27&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=13&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section outlines changes in the company's equity accounts, including common stock, additional paid-in capital, and accumulated deficit | Metric (in thousands) | December 31, 2024 | March 31, 2025 | June 30, 2025 | | :-------------------- | :---------------- | :------------- | :------------ | | Total Stockholders' Equity | $491,875 | $458,957 | $435,196 | | Accumulated Deficit | $(221,016) | $(257,862) | $(285,250) | | Additional Paid-in Capital | $712,884 | $716,812 | $720,439 | - Total stockholders' equity decreased from **$491.8 million** at December 31, 2024, to **$435.1 million** at June 30, 2025, driven by net losses of **$(36.8) million** and **$(27.3) million** in Q1 and Q2 2025, respectively. Additional paid-in capital increased due to stock-based compensation and option exercises[34](index=34&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=14&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section summarizes the cash inflows and outflows from operating, investing, and financing activities over specific periods | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(53,700) | $(27,495) | | Net cash provided by investing activities | $0 | $39 | | Net cash provided by financing activities | $595 | $871 | | Net decrease in cash and cash equivalents | $(53,105) | $(26,585) | | Cash and cash equivalents at end of period | $436,606 | $203,855 | - Net cash used in operating activities increased to **$53.7 million** for the six months ended June 30, 2025, from **$27.5 million** in the prior year, primarily due to increased net loss. Cash and cash equivalents decreased by **$53.1 million** in the first half of 2025, ending at **$436.6 million**[37](index=37&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=15&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations and disclosures supporting the condensed consolidated financial statements [1. Description of Business, Organization, and Liquidity](index=15&type=section&id=1.%20Description%20of%20Business,%20Organization,%20and%20Liquidity) This section describes the company's core business, organizational structure, and its current liquidity position and future funding needs - Bicara Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing bifunctional therapies for solid tumors, with its lead program, ficerafusp alfa, targeting EGFR and TGF-β[38](index=38&type=chunk) - The company has incurred significant operating losses since inception, with an accumulated deficit of **$285.3 million** as of June 30, 2025. It expects its **$436.6 million** cash and cash equivalents to fund operations for at least one year from the issuance date of the financial statements[44](index=44&type=chunk)[45](index=45&type=chunk) - In September 2024, the company completed a **9.2435-to-1** reverse stock split and an IPO, issuing **20,125,000** shares of common stock for net proceeds of **$332.4 million**[40](index=40&type=chunk)[41](index=41&type=chunk) [2. Summary of Significant Accounting Policies](index=16&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This section outlines the key accounting principles and methods used in preparing the financial statements, including revenue recognition and R&D expenses - The financial statements are prepared in conformity with U.S. GAAP on a going concern basis, including the accounts of Bicara and its wholly-owned subsidiary[46](index=46&type=chunk)[47](index=47&type=chunk) - Bicara is an 'emerging growth company' and has elected to use the extended transition period for complying with new or revised accounting standards, which may make its financial statements not comparable to other public companies[49](index=49&type=chunk)[150](index=150&type=chunk) - Research and development costs are expensed as incurred. R&D expenses were **$24.8 million** and **$15.8 million** for the three months ended June 30, 2025 and 2024, respectively, and **$59.1 million** and **$27.9 million** for the six months ended June 30, 2025 and 2024, respectively[52](index=52&type=chunk)[54](index=54&type=chunk) - Stock-based compensation is recognized using a fair-value based method, with fair value of options determined by the Black-Scholes model. Total stock-based compensation expense was **$3.5 million** and **$1.0 million** for the three months ended June 30, 2025 and 2024, respectively, and **$6.9 million** and **$2.2 million** for the six months ended June 30, 2025 and 2024, respectively[56](index=56&type=chunk)[84](index=84&type=chunk) [3. Fair Value Measurements](index=

Investment Highlights - Bicara Therapeutics is advancing ficerafusp alfa (FICERA), a bifunctional EGFR-directed antibody x TGF-β ligand trap, designed to enable tumor penetration by breaking barriers in the tumor microenvironment to drive deep and durable responses[8, 125] - FICERA + pembro offers a potential new 1L therapy for HPV-negative R/M HNSCC, with the FORTIFI-HN01 Ph 2/3 trial ongoing and enrolling[8, 125] - The company has a robust financial position with approximately $437 million in cash and equivalents[8, 125] Clinical Trial & Market Opportunity - There is a significant market opportunity with approximately 23,000 cases of R/M HNSCC annually in the U S, and a significant unmet need for better treatment options (13% 5yr survival)[8, 33, 125] - In a Ph 1b trial of FICERA + Pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC, the confirmed ORR was 54% (15/28)[60, 75] - The same trial showed a median PFS of 9 9 months and a median OS of 21 3 months, with a 2-year OS rate of 46%[66, 72, 75] - The median DOR was 21 7 months, with DOR rates of 79% at 6 months, 65% at 12 months, and 57% at 18 months[69, 75] Expansion Opportunities - The company is expanding into other squamous cell carcinomas and solid tumors, with encouraging clinical activity observed in Ph 1b expansion cohorts to date[8, 125] - In 2L+ cutaneous squamous cell carcinoma (cSCC), FICERA monotherapy showed an ORR of 30% (7/23) and a mPFS of 7 0 months in PD-1-refractory patients[114] - In 2L+ squamous cancer of the anal canal (SCAC), FICERA + pembro showed a 25% ORR (7/28) and a 12-month PFS rate of 40 7%[118]

[Company Overview & Q2 2025 Highlights](index=1&type=section&id=Company%20Overview%20%26%20Q2%202025%20Highlights) Bicara Therapeutics reported Q2 2025 financial results and business updates, showcasing positive Phase 1/1b trial data for ficerafusp alfa and a strong financial position [Key Highlights](index=1&type=section&id=Key%20Highlights) Bicara Therapeutics reported Q2 2025 results, highlighting updated Phase 1/1b ficerafusp alfa data and a strong $437 million cash position - Updated data from Phase 1/1b trial of ficerafusp alfa presented at 2025 ASCO Annual Meeting showed **deep and durable responses** in 1L HPV-negative R/M HNSCC[1](index=1&type=chunk) - Data from additional Phase 1/1b expansion cohorts evaluating alternate dose regimens in HPV-negative patients are expected by **Q1 2026**[1](index=1&type=chunk) Cash Position | Metric | Value (million USD) | | :-------------------------------- | :------------------- | | Cash and Cash Equivalents (June 30, 2025) | $437 | | Expected Funding Runway | Into the first half of 2029 | [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Claire Mazumdar highlighted ficerafusp alfa's progress, with ASCO 2025 data supporting its differentiated mechanism and pivotal trial design - CEO highlighted excellent progress with ficerafusp alfa development, noting updated Phase 1/1b data presented at ASCO 2025[2](index=2&type=chunk) - The data from the 1500mg weekly cohort demonstrated ficerafusp alfa's ability to remodel tumor stroma and drive tumor penetration, resulting in **deep, durable anti-tumor responses** in HPV-negative R/M HNSCC patients[2](index=2&type=chunk) - The ASCO data provides a strong foundation for the pivotal Phase 2/3 FORTIFI-HN01 trial and reinforces confidence in its design, with additional Phase 1/1b expansion cohort data expected to further characterize the safety and efficacy profile[2](index=2&type=chunk) [Business Update: Pipeline Highlights](index=1&type=section&id=Business%20Update%3A%20Pipeline%20Highlights) This section details the development of ficerafusp alfa, including its mechanism, pivotal trial progress, and data from Phase 1/1b studies [Ficerafusp Alfa Overview](index=1&type=section&id=Ficerafusp%20Alfa%20Overview) Ficerafusp alfa is a first-in-class, dual-action bifunctional antibody targeting EGFR and TGF-β, designed to enhance tumor penetration - Ficerafusp alfa is a **first-in-class, dual-action bifunctional epidermal growth factor receptor (EGFR)/transforming growth factor beta (TGF-β) antibody**[3](index=3&type=chunk) - It is designed to enhance tumor penetration by breaking barriers in the tumor microenvironment that have challenged the treatment of multiple solid tumor cancers[3](index=3&type=chunk) [FORTIFI-HN01: Pivotal Phase 2/3 Clinical Trial](index=1&type=section&id=FORTIFI-HN01%3A%20Pivotal%20Phase%202/3%20Clinical%20Trial) Enrollment is ongoing for FORTIFI-HN01, a pivotal Phase 2/3 trial evaluating ficerafusp alfa plus pembrolizumab in 1L R/M HNSCC (HPV-negative) - Enrollment is ongoing in FORTIFI-HN01, a global, randomized, double-blind, placebo-controlled, **pivotal Phase 2/3 trial**[4](index=4&type=chunk) - The trial evaluates ficerafusp alfa in combination with pembrolizumab in **first-line (1L) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)**[4](index=4&type=chunk) - Patients with oropharyngeal squamous cell carcinoma associated with human papillomavirus infection (HPV-positive) are excluded[4](index=4&type=chunk) [Phase 1/1b Clinical Trial Data in 1L R/M HNSCC](index=2&type=section&id=Phase%201/1b%20Clinical%20Trial%20Data%20in%201L%20R/M%20HNSCC) Updated Phase 1/1b trial data for ficerafusp alfa in 1L R/M HNSCC (HPV-negative) showed promising efficacy and safety, with further data expected [1500mg Weekly Cohort (ASCO 2025 Data)](index=2&type=section&id=1500mg%20Weekly%20Cohort%20(ASCO%202025%20Data)) ASCO 2025 data for the 1500mg weekly ficerafusp alfa cohort in 1L R/M HNSCC (HPV-negative) demonstrated significant efficacy and a manageable safety profile - Updated data with extended follow-up from a Phase 1/1b trial evaluating 1500mg ficerafusp alfa weekly in patients with 1L R/M HNSCC was highlighted at the 2025 ASCO Annual Meeting[8](index=8&type=chunk) Efficacy in HPV-negative population (n=28) | Metric | Value | | :-------------------------------- | :------------------- | | Median Duration of Response (DOR) | **21.7 months** (among responders, n=15) | | Median Overall Survival (OS) | **21.3 months** | | 2-year OS rate | **46%** | | Confirmed Objective Response Rate (ORR) | **54%** (15/28) | | Total ORR (including unconfirmed) | **64%** (18/28) | | Complete Response Rate (CRR) | **21%** (6/28) | | Responders achieving deep response (≥80% tumor shrinkage) | **80%** (12/15) | | Disease Control Rate (DCR) | **89%** (25/28) | | Median Progression-Free Survival (PFS) | **9.9 months** | | Safety Profile | Manageable, consistent with previously reported adverse events | [Additional Phase 1b Expansion Cohorts](index=2&type=section&id=Additional%20Phase%201b%20Expansion%20Cohorts) Data from additional Phase 1b expansion cohorts evaluating alternate ficerafusp alfa dose regimens and patient populations are anticipated in late 2025 and 2026 - Data from a cohort evaluating 750mg of ficerafusp alfa weekly in combination with pembrolizumab in HPV-negative patients are expected to be presented at a medical meeting in **Q4 2025 or Q1 2026**[8](index=8&type=chunk) - Data from a cohort evaluating 2000mg of ficerafusp alfa every other week in combination with pembrolizumab in HPV-negative patients are expected to be presented at a medical meeting in **Q1 2026**[8](index=8&type=chunk) - A cohort evaluating 1500mg weekly of ficerafusp alfa in combination with pembrolizumab in HPV-negative patients with combined positive scores (CPS) of 0 continues to enroll, with data expected in **2026**[8](index=8&type=chunk) [Development Across Other Solid Tumor Types](index=2&type=section&id=Development%20Across%20Other%20Solid%20Tumor%20Types) Bicara is expanding ficerafusp alfa's development into other solid tumor types, including an ongoing Phase 1b expansion cohort in metastatic colorectal cancer - A Phase 1b expansion cohort evaluating ficerafusp alfa as monotherapy and in combination with pembrolizumab in patients with **3L+ metastatic colorectal cancer (RAS/BRAF wild type)** is currently enrolling[6](index=6&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) This section details Bicara's Q2 2025 financial performance, including cash position, operating expenses, and net loss [Financial Highlights](index=2&type=section&id=Financial%20Highlights) Bicara Therapeutics reported decreased cash, increased R&D and G&A expenses, and a higher net loss for Q2 2025 year-over-year Cash Position | Date | Cash and Cash Equivalents (million USD) | | :---------------- | :------------------------ | | June 30, 2025 | $436.6 | | December 31, 2024 | $489.7 | * **Change:** Decrease of **$53.1 million** (-10.8%) QoQ * **Funding Runway:** Expected to fund operations into the first half of 2029 Research and Development Expenses (Q2 YoY) | Period | Amount (million USD) | | :---------------- | :------------------- | | Q2 2025 | $24.8 | | Q2 2024 | $15.8 | * **Change:** Increase of **$9.0 million** (+57.0%) YoY * **Primary Reason:** Additional costs for FORTIFI-HN01 initiation, ongoing Phase 1/1b trials, and increased personnel costs General and Administrative Expenses (Q2 YoY) | Period | Amount (million USD) | | :---------------- | :------------------- | | Q2 2025 | $7.2 | | Q2 2024 | $3.9 | * **Change:** Increase of **$3.3 million** (+84.6%) YoY * **Primary Reason:** Additional personnel costs and professional fees to support clinical trials and public company operations Net Loss (Q2 YoY) | Period | Amount (million USD) | | :---------------- | :------------------- | | Q2 2025 | $27.4 | | Q2 2024 | $17.0 | * **Change:** Increase of **$10.4 million** (+61.2%) YoY [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The statements of operations show increased operating expenses and net loss for Q2 and H1 2025, driven by higher R&D and G&A costs Condensed Consolidated Statements of Operations (in thousands USD) | | Three Months Ended June 30, | | Six Months Ended June 30, | | :------------------------------------------------- | :--- | :--- | :--- | :--- | | | **2025** | **2024** | **2025** | **2024** | | Operating expenses | | | | | | Research and development - related party | $ 2,932 | $ 1,510 | $ 9,507 | $ 5,091 | | Research and development | 21,866 | 14,331 | 49,624 | 22,782 | | General and administrative | 7,220 | 3,909 | 14,675 | 7,251 | | **Total operating expenses** | **32,018** | **19,750** | **73,806** | **35,124** | | Loss from operations | (32,018) | (19,750) | (73,806) | (35,124) | | Other income | | | | | | Interest income | 4,682 | 2,701 | 9,696 | 5,568 | | Total other income | 4,682 | 2,701 | 9,696 | 5,568 | | Net loss before income taxes | (27,336) | (17,049) | (64,110) | (29,556) | | Income tax expense | (52) | – | (124) | (1) | | **Net loss** | **$ (27,388)** | **$ (46,606)** | **$ (64,234)** | **$ (29,557)** | | Net Loss per share, basic and diluted | $ (0.50) | $ (19.01) | $ (1.18) | $ (38.19) | | Weighted-average number common shares outstanding, basic and diluted | 54,539,230 | 896,744 | 54,496,862 | 774,012 | | Expenses include the following non-cash stock-based compensation expense | | | | | | Research & Development | $ 1,159 | $ 251 | $ 2,300 | $ 481 | | General and administrative | 2,333 | 787 | 4,643 | 1,704 | | **Total stock-based compensation expense** | **$ 3,492** | **$ 1,038** | **$ 6,943** | **$ 2,185** | [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Bicara's balance sheet as of June 30, 2025, reflects decreased cash and total assets, stable liabilities, and reduced stockholders' equity Condensed Consolidated Balance Sheets (in thousands USD) | | June 30, 2025 | December 31, 2024 | | :------------------------------------ | :------------ | :---------------- | | **Assets** | | | | Cash and cash equivalents | $ 436,606 | $ 489,711 | | Prepaid expenses and other assets | 7,785 | 12,822 | | Total current assets | 444,391 | 502,533 | | Property and equipment, net | 117 | 155 | | Right of use asset – operating lease | 2,237 | 690 | | Other assets | 6,842 | 6,618 | | **Total assets** | **$ 453,587** | **$ 509,996** | | **Liabilities and stockholders' equity** | | | | Accounts payable | $ 2,041 | $ 3,893 | | Accounts payable – related party | 870 | 615 | | Accrued expenses and other current liabilities | 12,000 | 12,875 | | Accrued expenses and other current liabilities – related party | 1,242 | — | | Operating lease liability – current portion | 1,074 | 607 | | Total current liabilities | 17,227 | 17,990 | | Operating lease liability – net of current portion | 1,164 | 131 | | **Total liabilities** | **18,391** | **18,121** | | **Total stockholders' equity** | **435,196** | **491,875** | | **Total liabilities and stockholders' equity** | **$ 453,587** | **$ 509,996** | [About Bicara Therapeutics](index=3&type=section&id=About%20Bicara%20Therapeutics) Bicara Therapeutics is a clinical-stage biopharmaceutical company developing transformative bifunctional therapies for solid tumors, with ficerafusp alfa as its lead program - Bicara Therapeutics is a **clinical-stage biopharmaceutical company** committed to bringing transformative bifunctional therapies to patients with solid tumors[10](index=10&type=chunk) - Ficerafusp alfa, the lead program, is a **first-in-class bifunctional antibody** designed to drive tumor penetration by breaking barriers in the tumor microenvironment[10](index=10&type=chunk) - It combines two clinically validated targets: an epidermal growth factor receptor (EGFR) directed monoclonal antibody with a domain that binds to human transforming growth factor beta (TGF-β), reversing the fibrotic and immune-excluded tumor microenvironment[10](index=10&type=chunk) [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) This section outlines standard forward-looking statements regarding Bicara's strategy, clinical development, and financial outlook, subject to inherent risks and uncertainties - The press release contains forward-looking statements regarding Bicara's strategy, business plans, clinical development of ficerafusp alfa (including enrollment, progress, and anticipated data readouts), expected therapeutic potential, and cash runway[11](index=11&type=chunk) - These statements are based on management's current expectations and beliefs and are subject to risks and uncertainties, including those related to product candidate development, clinical trial results, regulatory developments, and sufficiency of cash resources[11](index=11&type=chunk) - Bicara explicitly disclaims any obligation to update forward-looking statements and advises against relying on them as representing views as of any subsequent date[11](index=11&type=chunk) [Investor Relations](index=4&type=section&id=Investor%20Relations) Bicara Therapeutics uses its Investor Relations website as a primary channel for disclosing material nonpublic information and fulfilling Regulation FD obligations - Bicara intends to use its Investor Relations website for disclosing **material nonpublic information** and complying with Regulation FD[12](index=12&type=chunk) - Investors should monitor the Company's Investor Relations website in addition to press releases, SEC filings, public conference calls, presentations, and webcasts[12](index=12&type=chunk) [Contacts](index=7&type=section&id=Contacts) This section provides essential contact information for investor and media inquiries - Contact information for investors (Rachel Frank, IR@bicara.com) and media (Amanda Lazaro, 1AB, Amanda@1abmedia.com) is provided[17](index=17&type=chunk)

Core Insights - Bicara Therapeutics Inc. has presented updated data from its Phase 1/1b trial at the 2025 ASCO Annual Meeting, showing significant anti-tumor responses in patients with HPV-negative recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [1][2] - The company maintains a strong financial position with approximately $437 million in cash and cash equivalents, expected to fund operations into the first half of 2029 [1][11] Clinical Development - Ficerafusp alfa, a first-in-class bifunctional antibody, is being developed to enhance tumor penetration by addressing barriers in the tumor microenvironment [3][8] - The ongoing pivotal Phase 2/3 FORTIFI-HN01 trial is evaluating ficerafusp alfa in combination with pembrolizumab for first-line treatment in recurrent/metastatic HNSCC [4][8] - Updated Phase 1/1b trial data indicates a median duration of response of 21.7 months and a median overall survival of 21.3 months in the HPV-negative population [5] Efficacy Data - In the efficacy evaluable HPV-negative population (n=28), the confirmed objective response rate (ORR) was 54%, with a complete response rate of 21% [5] - The disease control rate was reported at 89%, and 80% of responders achieved a deep response (≥80% tumor shrinkage) [5] Financial Performance - For the second quarter of 2025, research and development expenses increased to $24.8 million from $15.8 million in the same quarter of 2024, primarily due to costs associated with the FORTIFI-HN01 trial [11] - General and administrative expenses rose to $7.2 million from $3.9 million year-over-year, reflecting increased personnel costs and professional fees [11] - The net loss for the second quarter of 2025 was $27.4 million, compared to $17.0 million in the same quarter of 2024 [11]

Group 1 - May 23 marked a significant day for patients, oncologists, and investors in the treatment of head and neck cancer, with key presentations scheduled at the American Society of Clinical Oncology (ASCO) [1] - Bicara Therapeutics Inc. is involved in the development of treatments for head and neck cancer, indicating potential investment opportunities in this sector [1]

Financial Data and Key Metrics Changes - The company reported an overall survival (OS) of 21 months for patients treated with Fisera, which is significantly higher than the 9 months seen with pembrolizumab monotherapy in HPV negative head and neck cancer [4][17][50] - The depth of response was notable, with 50% of responders achieving a median duration of response (DOR) beyond 21 months and an 80% depth of response rate [5][4] Business Line Data and Key Metrics Changes - The lead program, Fisera, is focused on solid tumors, particularly HPV negative head and neck cancers, where it aims to improve response rates and overall survival compared to existing therapies [3][4] - The company is conducting a Phase III/II study comparing Fisera plus pembrolizumab to pembrolizumab plus placebo, with an interim analysis planned for accelerated approval [10][56] Market Data and Key Metrics Changes - The company is targeting the HPV negative population, which has a higher unmet medical need and higher levels of EGFR and TGF beta, leading to a refined patient selection strategy [25][28] - The competitive landscape includes other therapies like cetuximab and pitocentamab, with the company positioning Fisera as having a best-in-disease profile in terms of durability and overall survival [32][34] Company Strategy and Development Direction - The company aims to leverage the unique mechanism of action of Fisera, combining EGFR targeting with TGF beta inhibition to remodel the tumor microenvironment and enhance immune response [14][22] - The strategic focus is on demonstrating deep and durable responses in difficult-to-treat populations, particularly in the HPV negative cohort [34][50] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the data presented at ASCO, highlighting the importance of long-term durability data as predictive of overall survival in pivotal studies [50][53] - The management acknowledged the challenges posed by short-term landmark analyses and emphasized the need for mature data to support their claims [49][50] Other Important Information - The company has seen encouraging early signs of activity in other subsets of head and neck cancers, including HPV positive smokers and CPS low recurrent metastatic settings [11][12] - The ongoing studies are designed to provide insights into the efficacy of Fisera across various patient populations, with plans to disclose additional data in the coming year [12][54] Q&A Session Summary Question: What is the significance of the 21 months OS reported? - The 21 months OS is unprecedented in the HPV negative head and neck cancer population, significantly higher than the 9 months seen with pembrolizumab monotherapy, indicating a potential breakthrough in treatment [4][50] Question: How does Fisera compare to existing therapies? - Fisera has shown a best-in-disease profile in terms of durability and overall survival, with deeper responses compared to cetuximab and other therapies [32][34] Question: What is the strategy for patient selection in upcoming trials? - The company is focusing on the HPV negative population due to higher levels of EGFR and TGF beta, which are expected to yield better outcomes [25][28] Question: How does management view the competitive landscape? - Management believes that the unique mechanism of action of Fisera positions it favorably against competitors, particularly in terms of durability and patient quality of life [34][50] Question: What are the next steps for the clinical trials? - The company plans to continue its Phase III/II study with interim analyses for accelerated approval, aiming to demonstrate the efficacy and safety of Fisera in a larger patient population [56][58]

Core Insights - Bicara Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing bifunctional therapies for patients with solid tumors [3] - The company will participate in the Goldman Sachs 46th Annual Global Healthcare Conference on June 10, 2025 [1] Company Overview - Bicara Therapeutics is dedicated to creating transformative bifunctional therapies, with its lead program being ficerafusp alfa, a first-in-class bifunctional antibody [3] - Ficerafusp alfa targets the tumor microenvironment by combining an epidermal growth factor receptor (EGFR) directed monoclonal antibody with a domain that binds to human transforming growth factor beta (TGF-β) [3] - The therapy aims to reverse the fibrotic and immune-excluded tumor microenvironment, facilitating deeper tumor penetration and promoting durable responses [3] - Ficerafusp alfa is currently being developed for head and neck squamous cell carcinoma and other solid tumor types, addressing significant unmet medical needs [3]

Summary of Bicara Therapeutics (BCAX) Update / Briefing June 01, 2025 Company and Industry Overview - **Company**: Bicara Therapeutics - **Industry**: Oncology, specifically focusing on head and neck cancer treatment Key Points and Arguments 1. **Treatment Efficacy**: Updated data shows deep and durable responses with Fiserafusp alfa (Fysera) plus pembrolizumab in patients with HPV negative head and neck cancer, addressing a significant unmet medical need in this patient population [1][3][79] 2. **Current Standard of Care**: The current standard of care, pembrolizumab, has a low response rate of only 19% in HPV negative head and neck cancer patients, highlighting the need for more effective therapies [3][11] 3. **Mechanism of Action**: Fysera is designed to inhibit TGF beta directly at the tumor site, which helps to remodel the tumor microenvironment (TME) and allows immune cells to penetrate the tumor, leading to improved treatment outcomes [4][5][85] 4. **Clinical Data**: In a phase 1b study, the combination of Fysera and pembrolizumab demonstrated a 54% confirmed response rate and an 89% disease control rate among HPV negative patients, with 80% of responders achieving at least 80% tumor shrinkage [19][21] 5. **Survival Metrics**: The median overall survival for HPV negative patients treated with Fysera plus pembrolizumab is reported at 21.3 months, significantly better than the typical 9-12 months seen with standard treatments [21][94] 6. **Durability of Response**: The median duration of response (DOR) is 21.7 months, indicating that the treatment not only provides a response but also maintains it over time [20][23] 7. **Patient Demographics**: The study population included patients with a high burden of disease, with 47% presenting with bulky tumors and a significant proportion having low CPS scores, which are typically associated with poorer outcomes [16][17][90] 8. **Safety Profile**: The combination therapy has a manageable safety profile, with adverse events primarily related to EGFR and TGF beta, which are generally mild and resolve quickly [18][19] 9. **Future Trials**: Bicara is advancing to a pivotal phase 2/3 trial (FORTIFY HN01) focusing on HPV negative patients, designed to demonstrate improved overall survival compared to pembrolizumab alone [28][30] 10. **Commercial Opportunity**: The company views the potential approval of Fysera as a significant commercial opportunity in a market with high unmet needs for effective treatments in HPV negative head and neck cancer [33][34] Additional Important Insights - **Unmet Medical Need**: There is a critical need for therapies that not only extend survival but also improve the quality of life for patients suffering from head and neck cancer [11][90] - **Distinct Disease Biology**: HPV negative and HPV positive head and neck cancers are recognized as distinct diseases, each requiring tailored treatment approaches [12][92] - **Regulatory Strategy**: The trial design and patient selection are informed by historical data and FDA feedback, aiming to ensure a robust demonstration of efficacy and safety [30][39] This summary encapsulates the critical findings and strategic direction of Bicara Therapeutics as presented in the June 2025 briefing, emphasizing the innovative approach to treating HPV negative head and neck cancer.

Core Insights - Bicara Therapeutics presented updated data from its Phase 1/1b clinical trial of ficerafusp alfa combined with pembrolizumab for treating first-line recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), showing promising efficacy and overall survival rates [1][2][4] Efficacy Data - The median duration of response (DOR) was reported at 21.7 months, with 80% of responders achieving a deep response defined as ≥80% tumor shrinkage [1][4] - The median overall survival (OS) was 21.3 months, with a 2-year OS rate of 46% in HPV-negative patients [2][4] - The objective response rate (ORR) was 54% (15 out of 28 patients), with a complete response rate of 21% (6 out of 28 patients) [4] Clinical Significance - The results indicate a significant improvement over historical controls for HPV-negative recurrent/metastatic HNSCC, addressing a critical unmet need in this patient population [3][4] - The combination therapy demonstrated a median progression-free survival of 9.9 months and a disease control rate of 89% [4] Mechanism of Action - Ficerafusp alfa is a first-in-class bifunctional antibody designed to enhance tumor penetration by targeting both the epidermal growth factor receptor (EGFR) and human transforming growth factor beta (TGF-β), which helps remodel the tumor microenvironment [8][10] Company Overview - Bicara Therapeutics is a clinical-stage biopharmaceutical company focused on developing transformative bifunctional therapies for solid tumors, with ficerafusp alfa being its lead program [10]

Group 1 - Bicara Therapeutics Inc. (NASDAQ: BCAX) released updated interim data from its phase 1/1b study using its bifunctional EGFR/TGF-beta in combination with KEYTRUDA (pembrolizumab) for the treatment of patients with 1st-line recurrent/metastatic head and neck squamous cell carcinoma [2] - The Biotech Analysis Central service offers a deep-dive analysis of many pharmaceutical companies, including a library of over 600 biotech investing articles and a model portfolio of 10+ small and mid-cap stocks [2] - The service is available for $49 per month, with a yearly plan offering a 33.50% discount, bringing the price to $399 per year [1]