Group 1 - Xilio Therapeutics held a conference call to discuss key data updates presented at the Society for Immunotherapy of Cancer (SITC) conference [2][3] - The call featured participation from key executives including the CEO, Chief Medical Officer, and Chief Financial and Operating Officer, along with clinical investigators from the Vilastobart study [3] Group 2 - Details of the SITC presentation can be found in press releases on Xilio's Investor Relations section of their website [2]

Vilastobart Clinical Data and Opportunity - Vilastobart, in combination with atezolizumab, showed a 40% Overall Response Rate (ORR) in MSS mCRC patients without liver metastases and with high plasma TMB[30, 42] - 63% of plasma TMB-evaluable patients had high plasma TMB (≥10 mutations/Mb) in the Phase 2 trial, including all TMB-evaluable responders[32, 33, 42] - A statistically significant correlation (p=0.05) was observed between plasma TMB status and response to vilastobart plus atezolizumab[33, 42] - The combination of vilastobart and atezolizumab demonstrated a differentiated safety profile, with a low discontinuation rate of 5% and only 7% of patients experiencing colitis of any grade[35, 36, 42] Market and Competitive Landscape - Approximately 95% of mCRC patients are MSS, and standard of care in 3L+ provides minimal benefit (1-6% ORR)[23] - Real-world data indicates that approximately 55% of patients with MSS CRC have high plasma TMB, which is substantially higher than historically reported with tissue-based TMB assays[28, 42] - Next-generation anti-CTLA-4 agents in development show promising clinical efficacy in MSS mCRC, with ORRs ranging from 8-29% and discontinuation rates due to AEs up to ~30%[21] Technology and Pipeline - Xilio's clinically-validated platform technology is being applied across diverse mechanisms and architectures, including antibodies, cytokines, bispecifics, and T cell engagers[13, 14] - Efarindodekin Alfa (tumor-activated IL-12) demonstrated promising clinical efficacy with a generally well-tolerated safety profile in Phase 1 in patients with advanced solid tumors[44] - Masked T cell engager programs demonstrated potent anti-tumor activity with favorable tolerability across a diverse range of targets in preclinical models[50, 51, 52] Financial Outlook and Milestones - The company anticipates a cash runway into Q1 2027, including a $175 million development milestone received under the Gilead license in Q4 2025[53] - Anticipated milestones include reporting updated Phase 2 data for vilastobart in combination with atezolizumab in metastatic MSS mCRC in 1H 2026 and IND submissions for at least two masked T cell engager programs in 2027[53]

Pipeline and Programs - Vilastobart (tumor-activated anti-CTLA-4) reported a preliminary Objective Response Rate (ORR) of 26% in Phase 2 for heavily pre-treated patients with microsatellite stable colorectal cancer (MSS CRC) without liver metastases[35, 41] - XTX301 (tumor-activated IL-12) is advancing in partnership with Gilead, with a potential $75 million option fee at Phase 1/2 data package[67, 69] - XTX501 (tumor-activated PD-1/IL-2 bispecific) IND submission is anticipated in mid-2026[74] - The company plans to nominate development candidates for PSMA, CLDN182, and STEAP1 masked T cell engager programs in Q3 2025, Q4 2025, and 1H 2026, respectively[24, 101] Financials and Partnerships - The company had $89.1 million in cash and cash equivalents as of March 31, 2025[120] - The company received approximately $47.2 million in estimated net proceeds from equity financing in June 2025[120] - The company anticipates a cash runway through the end of Q3 2026[21, 120] - The company is eligible to receive up to $100 million in additional gross proceeds from equity financing by 2H 2026[21, 120] - The company has a collaboration, license, and option agreement with AbbVie for tumor-activated immunotherapies, including masked T cell engagers, with up to ~$2.1 billion in total contingent payments[20, 113] Technology and Approach - The company's platform exploits dysregulated matrix metalloprotease (MMP) activity in tumors to activate molecules[12] - The company's masked T cell engagers are designed to optimize the therapeutic index by maximizing tumor exposure and minimizing peripheral activity and off-tumor cytotoxicity[98]

Core Insights - Xilio Therapeutics, Inc. is set to present updated data from its Phase 2 clinical trial of vilastobart, an anti-CTLA-4 therapy, in combination with atezolizumab for metastatic microsatellite stable colorectal cancer at the 2025 ASCO Annual Meeting [1] - The presentation will take place on May 31, 2025, during a poster session focused on gastrointestinal cancer [2] Company Overview - Xilio Therapeutics is a clinical-stage biotechnology company focused on developing tumor-activated immuno-oncology therapies aimed at improving cancer treatment outcomes while minimizing systemic side effects [3] - The company utilizes a proprietary platform to create novel tumor-activated immuno-oncology molecules that enhance localized anti-tumor activity within the tumor microenvironment [3] Clinical Trial Details - Vilastobart is designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment [2] - In 2023, Xilio entered a collaboration with Roche to co-fund a clinical trial evaluating vilastobart in combination with atezolizumab in a multi-center, open-label Phase 1/2 trial [2] - The ongoing trials include a Phase 1C dose escalation for advanced solid tumors and a Phase 2 trial for metastatic microsatellite stable colorectal cancer, with and without liver metastases [2]