Xilio Therapeutics

Xilio designs monoclonal antibodies and cytokines with proprietary peptide masks that block the molecule's functional domain until tumor-associated proteases cleave the mask in the tumor microenvironment. The goal is to limit systemic immune activation — and therefore the dose-limiting toxicities that have constrained CTLA-4, IL-12, and IL-2 therapies historically — while maintaining anti-tumor activity where it matters. The approach is a protein-engineering solution to the therapeutic-index problem in immuno-oncology, distinct from antibody-drug conjugates or systemic half-life extension strategies.

Vilastobart (XTX101), a masked anti-CTLA-4 monoclonal antibody, is the lead program and has completed Phase 1 monotherapy dose escalation in advanced solid tumors. The company is also evaluating vilastobart in combination with atezolizumab. XTX301, a masked IL-12, entered Phase 1 in 2023 under an IND cleared by the FDA and is now partnered with Gilead Sciences. Earlier masked cytokine programs targeting IL-2 and IL-15 remain preclinical or earlier-stage assets that were deprioritized in the 2023 restructuring.

Xilio went public via IPO in October 2021, raising approximately $118 million. In early 2023, the company restructured to extend its cash runway into 2025, cutting preclinical work and headcount. The Gilead partnership for XTX301, signed in early 2024, injected $43.5 million upfront plus an equity investment, further extending the anticipated cash runway. The company remains pre-revenue and dependent on clinical data milestones and partnership economics to fund future development.

Founder and CEO Rene Russo, Pharm.D., previously led development at Avila Therapeutics and has focused exclusively on proximity-activated biologics. Martin Huber, M.D., serves as President of R&D and Chief Medical Officer; his background includes senior clinical roles at Schering-Plough and Merrimack Pharmaceuticals, where he worked on tumor-targeted delivery systems. The deep bench familiar with both biologics engineering and clinical immunology informs the transition from a preclinical concept to a partnered clinical-stage pipeline.

In early 2024, Xilio granted Gilead an exclusive global license to develop and commercialize XTX301, the masked IL-12 program. Gilead paid Xilio $43.5 million upfront, purchased equity in the company, and agreed to fund future development, with Xilio remaining responsible for ongoing Phase 1 activities through a specified transition period. Xilio retains rights to its masked CTLA-4 program and other internal pipeline assets not covered by the agreement.

No. Xilio explicitly focuses on tumor-activated biologics — primarily masked monoclonal antibodies and masked cytokines — rather than ADCs, bispecific T cell engagers, or cell therapy platforms. All disclosed programs target the soluble or cellular immune components of the tumor microenvironment using conditional activation, not payload delivery or cell engineering.

The critical data events center on vilastobart (XTX101) in solid-tumor indications and the initial dose-escalation readouts from XTX301. For vilastobart, the field is watching to see whether masked CTLA-4 blockade produces response rates competitive with ipilimumab but with meaningfully lower Grade 3/4 immune-related adverse events, which has been the historical barrier. For XTX301, the priority is establishing that IL-12 can be safely dosed even at low levels without provoking the cytokine-release syndromes that have derailed prior IL-12 approaches.