Gilead Sciences will develop and commercialize Xilio’s Phase I tumor-activated IL-12 program. Xilio’s lead candidate, XTX301, is a tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic “cold” tumors towards an inflamed or “hot” state and thus more sensitive to immunotherapy. IL-12 is a cytokine and “a master orchestrator of initiating inflammation,” according to Xilio.
“What we have been missing in cancer immunotherapy is how to bring it to more patients,” René Russo Xilio president and CEO told Inside Precision Medicine. Only about 20% of patients respond to current immunotherapies (IO). Tumors that are “cold,” and not inflamed, are thought to be the most resistant. Making them “hotter” could make them more responsive to IO. Russo added that,”One of the reasons we are so excited about IL-12 it has broad downstream effects on the inflammatory response.”
Gilead will pay $43.5 million in upfront payments and Xilio will be eligible to receive up to $604.0 million in contingent payments.
“Xilio’s novel tumor-activation platform naturally complements Gilead’s clinical development program in difficult-to-treat cancers and expands our focus in immuno-oncology,” said Bill Grossman, MD, PhD, senior vice president, oncology clinical development at Gilead.
Xilio is using its proprietary tumor-activation platform to build a pipeline of novel, tumor-activated molecules, including antibodies, cytokines, bispecifics, and cell engagers, which are designed to optimize the therapeutic index and localize anti-tumor activity within the tumor microenvironment. Because the drugs hone in on the tumor microenvironment, they may have less side effects too.
“Gilead’s confidence in our tumor-activated technology, combined with their deep expertise in developing and commercializing novel immuno-oncology products, will enable us to accelerate and expand the development of XTX301, our tumor-activated IL-12,” said Russo.
She added that, “We look forward to collaborating with Gilead as we seek to deliver on the potential for XTX301 to provide a meaningful benefit for a range of tumor types, including immunologically cold tumors, while overcoming the severe toxicities historically associated with IL-12.”
Xilio will be responsible for conducting clinical development of XTX301 in the ongoing Phase I clinical trial through dose expansion. Following the delivery by Xilio of a specified clinical data package for XTX301, Gilead can elect to transition responsibilities for the development and commercialization of XTX301 to Gilead.
Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase I clinical trial (NCT05684965).
The startup is using its proprietary platform to build a pipeline of novel, tumor-activated molecules, including antibodies, cytokines, bispecifics and cell engagers, which are designed to optimize the therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as leveraging its differentiated research platform to advance tumor-activated bispecific and cell engager molecules in preclinical development.
Xilio is focusing on a variety of solid tumors and does not believe, at this point, that they need a test to guide patient selection.
