Core Insights - Xilio Therapeutics, Inc. presented new data at the Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting, showcasing the potential of its masked T cell engager programs and tumor-activated therapies, including efarindodekin alfa and vilastobart [1][2] Group 1: Masked T Cell Engager Programs - Xilio is advancing multiple preclinical programs for masked T cell engagers targeting tumor-associated antigens such as PSMA, CLDN18.2, and STEAP1, with a collaboration with AbbVie [3] - The company's masked T cell engager programs utilize advanced formats like ATACR and SEECR, designed to enhance T cell activation and durability [4] - Preclinical data indicate that Xilio's masking technology can significantly expand the therapeutic window for T cell engagers, demonstrating potent anti-tumor activity and reduced systemic toxicity in murine models [5] Group 2: Efarindodekin Alfa - Efarindodekin alfa is an investigational tumor-activated IL-12 being evaluated in a Phase 1/2 clinical trial for patients with advanced solid tumors, with promising Phase 1 data showing a generally well-tolerated safety profile and encouraging anti-tumor activity [7][11] - As of September 2, 2025, 62 patients had been treated, with a median age of 66 years, and most patients had received multiple prior lines of therapy [7] - The treatment demonstrated partial responses in patients with advanced solid tumors, including a 33% decrease in target lesions for HPV-negative head and neck squamous cell carcinoma and a 55% decrease for uveal melanoma [11] Group 3: Vilastobart - Vilastobart is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody being evaluated in combination with atezolizumab for advanced solid tumors and MSS mCRC [9][19] - New data presented at SITC suggest that circulating tumor DNA (ctDNA) may serve as an early biomarker for response to vilastobart treatment, with significant reductions in ctDNA correlating with treatment response [10][18] - The combination therapy is currently in Phase 1C and Phase 2 trials, with ongoing evaluations of safety and efficacy [19] Group 4: Development Plans - Xilio plans to nominate development candidates for its CLDN18.2 and STEAP1 programs in late 2025 and early 2026, respectively, with expectations to advance at least two programs into IND enabling studies by 2027 [6] - The company has completed enrollment in the Phase 1A and Phase 1B portions of the clinical trial for efarindodekin alfa, with ongoing evaluations [8][13]