Summary of IO Biotech Conference Call Company Overview - **Company**: IO Biotech - **Key Personnel**: CEO Mai-Britt Zocca, CFO Amy Sullivan - **Event**: Piper Sandler Healthcare Conference Industry Context - **Focus**: Biotech industry, specifically cancer therapeutics - **Key Product**: IO102-IO103, a therapeutic cancer vaccine Core Points and Arguments 1. **Phase 3 Trial Results**: The phase 3 trial for IO102-IO103 in combination with Pembrolizumab for first-line metastatic melanoma showed a median progression-free survival (PFS) of 19.4 months compared to 11 months in the control arm, with a hazard ratio of 0.77, indicating a clinically meaningful outcome despite a narrow P-value [3][13][15] 2. **Safety Profile**: The drug demonstrated a clear safety profile, which is crucial for its acceptance in the market [3][16] 3. **Mechanism of Action**: The approach targets IDO-expressing cells and aims to modify the tumor microenvironment to enhance immune response, differentiating it from previous IDO inhibitors like Epacadostat [6][7][9] 4. **Regulatory Feedback**: The FDA recommended against submitting a Biologics License Application (BLA) based on the pivotal study data due to the missed P-value, despite the observed efficacy and safety [17][18] 5. **New Trial Design**: A proposed global adaptive phase 2-3 clinical trial will evaluate IO102-IO103 in combination with Opdualag, reflecting the changing standard of care in the US [19][21][23] 6. **European Market Engagement**: IO Biotech plans to engage with EU regulators for a potential Marketing Authorization Application (MAA) submission by 2026, with expectations for positive feedback based on different regulatory guidelines [24] 7. **Adjuvant and Neoadjuvant Studies**: Ongoing studies in the neoadjuvant and adjuvant settings aim to prolong time to recurrence in melanoma and head and neck cancers [25][26] 8. **Broader Applications**: The company is exploring the use of IO102-IO103 beyond melanoma, with promising data in other indications like non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN) [29] 9. **Pipeline Development**: IO Biotech is advancing other candidates like IO112 and IO170, targeting Arginase 1 and TGF- respectively, with positive early data and plans for clinical trials [32][34] 10. **Financial Position**: The company ended Q3 with approximately $31 million in cash, expected to last through Q1 2026, with plans to raise additional capital for upcoming trials [35][36] 11. **Market Perception**: There is a perceived disconnect between the company's valuation and investor understanding of the potential market impact of IO102-IO103 and its broader applications [37] Additional Important Insights - **KOL Feedback**: Key opinion leaders have expressed excitement about the data, noting the significance of a therapeutic cancer vaccine showing clear benefits in metastatic settings [16] - **Future Outlook**: The company is optimistic about 2026 being a pivotal year for its growth and product development [39][41]

Core Insights - IO Biotech announced new pre-clinical data for its cancer vaccine candidates IO112 and IO170 at the Society for Immunotherapy of Cancer's 40th Annual Meeting [1][6] - The company plans to file an Investigational New Drug Application for IO112 in 2026, indicating a commitment to advancing its cancer immunotherapy pipeline [2] Group 1: Vaccine Candidates - IO112, targeting arginase 1 (Arg1), shows robust expansion of Arg1-specific T cells that inhibit tumor growth by reprogramming immune suppressive myeloid cells [3][5] - IO170, targeting Transforming Growth Factor (TGF)-β, activates TGF-β-specific T cells to promote anti-tumor activities, demonstrating significant tumor growth inhibition and reduced lung metastasis [4][5] Group 2: Research and Development - The data presented highlight the unique approach of IO Biotech's T-win® platform, which targets both tumor cells and immune-suppressive cells in the tumor microenvironment [5][8] - The company is advancing its lead cancer vaccine candidate, Cylembio®, in clinical trials while developing additional candidates through preclinical stages [8]

Summary of IO Biotech FY Conference Call Company Overview - **Company**: IO Biotech (NasdaqGS: IOBT) - **Focus**: Development of SilentBio™, an immune modulatory cancer vaccine targeting advanced melanoma and other cancers Key Industry Insights - **Market Opportunity**: The market for first-line advanced melanoma is significant, with 15,000 new diagnoses annually in the US and a growth rate of 9% per year, representing a billion-dollar opportunity [4][11] - **Unmet Need**: 50% of patients treated with current standard care do not benefit, highlighting the need for better treatment options [4][11] Core Product Insights - **SilentBio™**: - Combination of IO102 and IO103, showing promising results in clinical trials - Demonstrated a median progression-free survival (PFS) of 19.4 months compared to 11.0 months for the control group [3][7] - Hazard ratio of 0.77 and a p-value of 0.056, indicating a near statistical significance [3][7] - Improved PFS observed across all pre-specified subgroups without added systemic toxicity [3][9] Clinical Trial Results - **Phase 3 Trial**: - Conducted in over 100 centers globally with 407 patients enrolled [6][7] - Notable results include: - Median PFS of 24.8 months for patients without prior anti-PD-1 exposure [8] - Dramatic PFS improvement in PD-L1 negative patients, with 16.6 months versus 3 months in the control group [8] - Overall survival (OS) trends favoring the combination arm, with a hazard ratio of 0.79 [9][10] Regulatory and Market Readiness - **FDA Engagement**: - Preparing for a Biologics License Application (BLA) submission by the end of 2025 [4][16] - Discussions with the FDA are ongoing, with a meeting scheduled for Q3 2025 [4][20] - **Manufacturing and Distribution**: - Secured supply chain and commercial-scale manufacturing in place [5][11] Future Pipeline and Expansion - **Additional Trials**: - Two Phase 2 trials for SilentBio™ in lung and head and neck cancers are underway [13] - Plans to expand into earlier clinical stages and other indications [16][17] - **New Targets**: - Development of IO112 (arginase) and IO170 (TGF-beta) for broader indications [15][17] Financial Position - **Cash Reserves**: - Cash balance of $28 million as of Q2 2025, sufficient to fund operations into Q1 2026 [20] Conclusion - IO Biotech is positioned to potentially set a new standard in the treatment of advanced melanoma with SilentBio™, backed by promising clinical data and a robust pipeline for future growth [11][12]

Cylembio (IO102-IO103) Development and Clinical Trials - Cylembio, in combination with pembrolizumab, has Breakthrough Therapy Designation for advanced melanoma[11, 12] - Phase 3 pivotal trial in advanced melanoma with PFS as the primary endpoint, readout expected in Q3 2025[12, 23, 27] - Phase 1/2 trial (MM1636) showed 80% ORR, 50% CRR, and 255 months mPFS in melanoma[13, 55] - Completed enrollment of 407 patients in the Phase 3 trial in December 2023[27, 55] - A Phase 2 neoadjuvant/adjuvant basket study is fully enrolled[57] Pipeline and Platform - T-win platform delivers investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccines[11, 35, 66] - The company has 3 pipeline programs, including IO170 targeting Melanoma, SCCHN, NSCLC, and other cancers[11, 35] - IO112, targeting Arginase 1, is a next pipeline candidate expected to enter clinical development, with an IND filing planned in 2025[35, 63, 64] Market and Financial Outlook - The global melanoma market is expected to reach >$13 billion by 2030[15] - The US melanoma market was approximately $45 billion in 2023, growing at 9%[32] - The global NSCLC market is expected to reach approximately $60 billion by 2030[36, 37] - The global SCCHN market is expected to reach approximately $5 billion by 2030[40]

Core Insights - IO Biotech presented new preclinical data for its dual-antigen and TGF-β-directed vaccines at the AACR Annual Meeting 2025, highlighting their potential to reshape the tumor microenvironment and enhance anti-tumor immunity [1][2] Company Overview - IO Biotech is a clinical-stage biopharmaceutical company focused on developing immune-modulatory, off-the-shelf therapeutic cancer vaccines using its T-win® platform, which aims to activate T cells against both tumor cells and immune-suppressive cells [4] - The company is advancing its lead investigational cancer vaccine candidate, Cylembio® (IO102-IO103), which has received Breakthrough Therapy Designation from the FDA for treating advanced melanoma in combination with Merck's KEYTRUDA® [4] Vaccine Candidates - IO102-IO103, a dual-antigen vaccine targeting IDO1+ and PD-L1+ cells, demonstrated strong T-cell responses and modulated the tumor microenvironment in mouse models, indicating a potentially synergistic mechanism compared to conventional PD-1 or PD-L1 inhibitors [7] - IO170, targeting TGF-β, showed significant tumor growth inhibition in breast and prostate cancer mouse models, leading to increased infiltration of vaccine-specific T cells and reshaping the tumor microenvironment to favor immune activation [7]