On April 17, 2026 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing masked immuno-oncology therapies for people living with cancer, reported new preclinical data for XTX601, a masked T cell engager targeting claudin 18.2 (CLDN18.2), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place from April 17–22, 2026 at the San Diego Convention Center in San Diego, California.

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"The data to be presented at AACR (Free AACR Whitepaper) underscore the significant potential of our clinically-validated masking technology to address the central challenge that has limited the advancement of T cell engagers in solid tumors – namely, the inability to achieve meaningful anti-tumor activity without inducing severe systemic toxicities," said Uli Bialucha, Ph.D., chief scientific officer of Xilio Therapeutics. "XTX601 has demonstrated a promising preclinical profile, including potent tumor cell killing across multiple CLDN18.2-expressing tumor models and a favorable tolerability profile in non-human primates, supporting its potential to achieve a wide therapeutic index. Importantly, our modular architecture for masked T cell engagers provides flexibility to rapidly evaluate multiple designs in parallel, including masking of the CLDN18.2 binding domain and/or the addition of a co-stimulatory domain, which enables us to seek to optimize the molecule for the best possible clinical profile."

Masked T Cell Engager Design

XTX601 is a potentially first-in-class masked T cell engager designed to selectively target CLDN18.2, a tumor-associated antigen expressed in gastric, pancreatic and esophageal cancers. XTX601 incorporates Xilio’s clinically-validated masking technology and advanced tumor-activated cell engager (ATACR) format, which consists of a T cell engager with a masked CD3 targeting domain, with the goal of minimizing systemic T cell engagement in healthy tissue and overcoming the significant systemic toxicities that have limited non-masked T cell engagers targeting CLDN18.2. In addition, XTX601 is designed with a conditional half-life modulation element for antibody-like pharmacokinetics in its masked state and a short half-life upon activation in the tumor microenvironment to further limit peripheral exposure.

Preclinical Data Highlights Presented at AACR (Free AACR Whitepaper)

In preclinical studies, XTX601 demonstrated the potential to achieve a wide therapeutic index.

XTX601 demonstrated protease-dependent activation and tumor cell killing in high- and low-expression settings for CLDN18.2, with effective masking of the anti-CD3 domain.
XTX601 exhibited robust, dose-dependent anti-tumor activity in multiple murine cell line-derived xenograft models, including GSU gastric carcinoma and OE19 esophageal adenocarcinoma models engrafted with human T cells.
Consistent with its masked design, XTX601 was well tolerated in non-human primates (NHP) with no evidence of cytokine release syndrome and no changes in liver enzymes.
Integration of drug exposure data from murine tumor models and NHP studies indicated a favorable, positive therapeutic index for XTX601 and supports the potential for XTX601 to achieve meaningful anti-tumor activity at doses that are well-tolerated systemically.

Xilio plans to advance its masked T cell engager program targeting CLDN18.2 into investigational new drug (IND)-enabling studies and submit an IND application for this program in 2027.

Presentation Details

Xilio’s poster presentation at AACR (Free AACR Whitepaper) is listed below, and a copy of the presentation will be available under the "Our Approach—Presentations & Publications" section of the company’s website at www.xiliotx.com.

Title: Discovery and Optimization of XTX601, a Masked Claudin 18.2-Targeting T Cell Engager
Session Category: Immunology
Session Title: T Cell Engagers 1
Session Date and Time: Monday, Apr. 20, 2026, from 9:00 a.m. to 12:00 p.m. PST
Location: Poster Section 10, Poster Board 11
Abstract Number: 1619

(Press release, Xilio Therapeutics, APR 17, 2026, View Source [SID1234664510])