Xilio raises $95M to take twists on Yervoy and IL-2 into clinic 

cancer newspaper
Xilio plans to file INDs for its two lead candidates this year. (PDPics/Pixabay)

Xilio Therapeutics has raised $95 million to take IL-2 and CTLA-4 immunotherapies into clinical trials. The series C positions Xilio to provide early clinical validation of anti-cancer agents that are designed to remain inactive until they reach tumors. 

Immuno-oncology drugs are typically given systemically, causing them to trigger immune responses that affect healthy and cancerous tissues alike. The resulting adverse events are unpleasant and can prevent physicians from administering the most efficacious dose. Patients suffer from both the side effects and worse outcomes due to the use of suboptimal doses.

Xilio, formerly known as Akrevia Therapeutics, is built on a platform designed to minimize the effect of cancer drugs on healthy tissues. The potential of the platform has attracted a who’s who of VCs.

Rock Springs Capital led the series C round with support from new backers including Bain Capital Life Sciences, Deerfield Management and RA Capital Management. Existing Xilio investors including Atlas Venture, SV Health Investors and Takeda Ventures also contributed to the financing.

Xilio will use the money to take two drugs, XTX202 and XTX101, into clinical development. XTX202 is a formulation of IL-2, a cytokine that is hamstrung by limitations such as a short half-life and immune effects that necessitate the administration of high doses. XTX101 is a monoclonal antibody against CTLA-4, the immune checkpoint receptor targeted by Bristol Myers Squibb’s Yervoy. INDs for both candidates are planned for this year.

Working with technology licensed from City of Hope and Thomas Jefferson University, Xilio links the drugs to peptides designed to mask the molecules until they reach the tumor microenvironment. The linker is cleaved by proteases found near to tumors, causing the targeted unmasking of the drug.

The approach holds particular promise for potentially highly efficacious molecules that must be given at reduced doses due for safety and tolerability reasons. Xilio thinks IL-2 and CTLA-4 fit the bill. 

“While high dose rhIL-2 has the potential for durable complete responses, it is only given to a small number of patients due to its life-threatening toxicity. Similarly, approved aCTLA4 therapy produces severe autoimmune toxicity, limiting potential benefit by preventing patients from receiving highly therapeutic doses or completing full courses of treatment,” Martin Huber, M.D., Xilio chief medical officer, said in a statement.