Solid Tumor Spotlight: TGFβR2xPD-1 Bi-specific Antibody and KRAS G12D Inhibitor ESMO 2025 October 19, 2025 Forward looking statements Except for the historical information set forth herein, the matters set forth in this release contain predictions, estimates and other forward-looking statements, including any discussion of the potential and opportunities presented by INCA33890 and INCB161734 and plans for further development of the same. These forward-looking statements are based on Incyte's current expecta ...

Core Insights - Verastem Oncology announced positive updated efficacy and safety data from GenFleet Therapeutics' Phase 1/2 monotherapy study of GFH375, an oral KRAS G12D inhibitor for advanced pancreatic ductal adenocarcinoma [1] Company Summary - Verastem Oncology is focused on developing new medicines for patients with RAS/MAPK-pathway-driven cancers [1] - GFH375, also known as VS-7375 outside of China, targets KRAS G12D mutations in advanced pancreatic ductal adenocarcinoma [1] Study Details - The study involved 59 heavily pre-treated patients, indicating a significant patient population for evaluating the drug's efficacy and safety [1]

Summary of Conference Call Company and Industry Overview - The conference call primarily discusses Verastem Oncology and its focus on developing treatments for cancers with high unmet needs, particularly pancreatic cancer and KRAS-driven cancers [1][2][51]. Key Points and Arguments Product Pipeline and Innovations - Verastem has several investigational drugs, including: - **Vutametinib**: A RAFmAbK inhibitor. - **Defactinib**: A FAC inhibitor. - **G12D inhibitor**: A drug developed in collaboration with Genfleet Therapeutics [2][24]. - The recently approved drug, **Avmapke Faxingia Copac**, was approved on May 8, two months ahead of schedule [2]. Clinical Data and Efficacy - In a study of low-grade serous ovarian cancer, there was a **44% overall response rate** with unprecedented durability [3]. - The **Ramp 205 study** focused on untreated, pathologically proven metastatic pancreatic cancer, showing an **83% radiographic response rate** at the first dose level tested, significantly higher than the typical 30% response rate for standard treatments [12][13]. - The study also reported a **92% control rate** for disease progression after four cycles of therapy, which is notably higher than historical comparators [13]. Treatment Landscape for Pancreatic Cancer - Pancreatic cancer has a **5-year survival rate of only 13.3%**, with adenocarcinoma survival rates dropping below 8% [6][7]. - The majority of pancreatic cancer patients have **KRAS mutations**, with G12D being the most common [7]. - Current treatment regimens lack consensus on effectiveness, and many patients experience recurrence [9]. Mechanism of Action - The drugs discussed aim to block the **RasRaf pathway** and the **FAC pathway**, with a focus on the duality and synergy of these treatments [10][11]. - The combination of vutametinib and defactinib, along with chemotherapy, has shown promising preclinical synergy [11]. Future Development Plans - Verastem plans to expand the **Ramp 205 trial** to include additional patients and is preparing for a randomized trial set to initiate in 2026 [52]. - The company is also exploring combinations with other therapies, particularly for newly diagnosed and borderline resectable pancreatic cancer patients [53]. Market Potential - There are approximately **61,000 patients annually** in the U.S. diagnosed with KRAS G12D mutations across various cancers, indicating a significant market opportunity [36][46]. Important but Overlooked Content - The discussion highlighted the importance of managing **GI toxicities** associated with treatments, which are common in oncology but manageable [66][72]. - The pharmacokinetics (PK) of the drugs are crucial, with a focus on ensuring effective dosing schedules that patients can tolerate [40][41]. - The potential for **brain metastases** in lung cancer patients treated with KRAS inhibitors was raised, emphasizing the need for further studies in this area [48]. This summary encapsulates the key points from the conference call, focusing on Verastem Oncology's advancements in cancer treatment, particularly for pancreatic cancer, and the promising data from their clinical studies.