Summary of the Conference Call Company Overview - **Company**: 加科思 (Jia Ke Si) - **Industry**: Biopharmaceuticals, specifically focusing on oncology treatments Key Projects and Developments 1. **Pan KRAS Inhibitor (JAB-23,173)** - Global leader in the pan KRAS inhibitor market, expected to release dosage data by the end of 2025 and full clinical results in the first half of 2026 - Safety profile shows only 10% skin toxicity, all grade 1, with significant market potential estimated at $20 billion peak sales [2][3][17] 2. **SHIP2 Inhibitor (加该雷赛)** - Approved in China for second-line non-small cell lung cancer (NSCLC) - Rights partially transferred to艾力斯 (Ailis) for 900 million RMB, with initial payment of 200 million RMB and milestone payment of 50 million RMB - Gastrointestinal toxicity below 10%, outperforming similar products [2][5][6] 3. **CDK2 Inhibitor Combined with 克莱雷赛** - Entered phase III registration clinical trials for first-line NSCLC treatment - Objective response rate (ORR) of 77% and progression-free survival (PFS) of 12 months, making it the first oral combination therapy to reach this stage globally [2][5][21] 4. **TADC Platform** - First project EX600 has shown preliminary success, with ongoing development of competitive antibody-drug conjugates (ADCs) focusing on KRAS and STING pathways to enhance efficacy and safety [2][4][19] Safety and Efficacy - **克莱雷赛 (KRAS G12C Inhibitor)** - Notable safety advantage with gastrointestinal toxicity at 5%-8%, significantly lower than competitors like Amgen and BMS at 40% - Approved for second-line NSCLC in China, triggering a milestone payment of 50 million RMB [6][21] - **Clinical Data** - No observed dose-limiting toxicity (DLT) or severe organ toxicity in clinical trials, with skin toxicity at 10% [17] Future Development Focus - Continue advancing the four core projects while exploring innovative therapies - Plans to disclose complete clinical results for pan KRAS in the first half of 2026 and further research on CDK2 and 克莱雷赛 combinations [7][32] Financial Management - R&D expenses for the first half of 2025 were approximately 93 million RMB - Cash flow remains stable with over 60 million RMB from various financing channels and a total of 1.5 billion RMB in cash reserves [31] Market Potential and Competitive Landscape - The pan KRAS inhibitor market is projected to address 25% of cancer cases, with annual new cases exceeding 2.7 million, similar to the PD-1 monoclonal antibody market - Peak sales potential estimated at $20 billion annually [14][15] Challenges and Innovations - Addressing the cold tumor problem with new mechanisms to convert cold tumors into hot tumors using STING agonists - Ongoing research to ensure the stability of STING agonists in plasma to avoid cytokine storms during treatment [9][40][42] Conclusion 加科思 is positioned as a leader in the oncology sector with a robust pipeline of innovative therapies, strong safety profiles, and significant market potential. The company is focused on advancing its core projects while exploring new therapeutic avenues to maintain its competitive edge in the biopharmaceutical industry.