Core Viewpoint - Actuate Therapeutics has initiated a Phase 1b clinical trial to evaluate the combination of elraglusib, retifanlimab, and modified FOLFIRINOX as a frontline therapy for advanced pancreatic adenocarcinoma, aiming to address unmet medical needs in this challenging cancer type [1][4]. Group 1: Clinical Trial Details - The Phase 1b trial, named RiLEY (NCT06896188), will enroll up to 12 patients initially, with plans for expansion based on interim efficacy results [2]. - The primary objective is to determine the recommended phase 2 dose (RP2D) for the combination regimen, while secondary objectives include evaluating overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and safety [2]. Group 2: Mechanism and Previous Results - The combination therapy is expected to provide a synergistic immune-modulatory approach, enhancing anti-tumor responses by targeting multiple immune checkpoints [3]. - Previous studies indicated that elraglusib combined with gemcitabine/nab-paclitaxel resulted in a significant increase in median overall survival, a 37% reduction in the risk of death, and a doubling of the 12-month survival rate in patients with metastatic pancreatic adenocarcinoma [3]. Group 3: Company Strategy and Future Plans - The collaboration with UPMC Hillman Cancer Center and Incyte aims to explore new synergistic opportunities for patients who have not yet received systemic therapy, enhancing both efficacy and durability of response [4]. - Actuate is also conducting a separate Phase 2 trial (NCT05077800) studying elraglusib in combination with FOLFIRINOX and losartan, with initial data showing promising results in patients with extensive liver metastases [4].

Incyte (INCY) Update Summary Company Overview - **Company**: Incyte Corporation - **Event**: Investor Event at ESMO 2024 - **Date**: September 14, 2024 Key Points Industry and Company Focus - Incyte is focusing on oncology, specifically targeting gynecological cancers and squamous cell anal cancer with their drug candidates, including retifanlimab and a new CDK2 inhibitor [2][3][4][5][6][9][31][41]. Core Programs and Data Updates - **Retifanlimab**: - Positive pivotal data presented for squamous cell anal cancer, showing a median progression-free survival (PFS) of 9.3 months compared to 7.4 months for placebo, with a hazard ratio of 0.63 [24][30]. - The study design included a combination of retifanlimab with chemotherapy for patients with advanced disease [21][22]. - **CDK2 Inhibitor**: - Focused on ovarian and endometrial cancers, with plans to initiate pivotal trials in 2025 [10][43][60]. - The drug targets cyclin E overexpression, which is prevalent in HRD negative ovarian cancer patients [35][44][63]. - Early data shows a response rate of 31% in heavily pretreated ovarian cancer patients, with a disease control rate of 75% [56][60]. Pipeline and Milestones - Incyte has several near-term milestones, including: - Approval of axatilamab for chronic graft versus host disease [5][71]. - Submission for pediatric atopic dermatitis for OPSILURA [71]. - Potential approval of retifanlimab in new indications, including anal cancer and non-small cell lung cancer [71][72]. - Ongoing discussions for regulatory strategies for the CDK2 inhibitor in platinum-resistant ovarian cancer [66][69]. Market Dynamics and Competitive Landscape - The incidence of anal cancer is increasing by approximately 3% annually, largely due to HPV [14][15]. - Current treatment options for advanced anal cancer are limited, with chemotherapy being the standard of care [18][19]. - In ovarian cancer, there is a significant unmet need for effective treatments, especially in HRD negative patients, where current therapies have limited efficacy [32][34][63]. Safety and Efficacy - Safety data from the CDK2 inhibitor trials indicate manageable adverse events, primarily hematological toxicities, with few discontinuations due to treatment-related issues [50][51]. - The combination of retifanlimab with chemotherapy has shown promising results without compromising the delivery of chemotherapy [30][60]. Future Directions - Incyte aims to position the CDK2 inhibitor as a new standard of care in ovarian cancer, particularly in combination with existing therapies like bevacizumab [38][41][60]. - The company is also exploring the potential of retifanlimab in other cancer types and is preparing for commercial launches in 2025 [71][80]. Additional Insights - The company is leveraging its existing infrastructure from previous drug launches to facilitate the introduction of new therapies [78][80]. - There is a focus on developing companion diagnostics to identify patients who would benefit most from the CDK2 inhibitor [84][86]. This summary encapsulates the critical insights and developments from Incyte's recent investor event, highlighting the company's strategic focus on oncology and the promising data emerging from its clinical trials.