Don Tracy, Associate Editor

Deal aims to commercialize XTX301 for treating advanced solid tumors by leveraging Xilio’s tumor-activated immuno-oncology therapies.
Gilead Sciences and Xilio Therapeutics announced that they have agreed to terms on a licensing agreement regarding XTX301, Xilio’s Phase I tumor-activated IL-12. According to Gilead, the partnership aims to expand the company’s focus in immuno-oncology, leveraging Xilio's novel tumor-activation platform to improve its therapeutic nature and build a consistent pipeline of tumor-activated molecules. As per the deal, Xilio will receive an upfront payment of $43.5 million, with $30 million in cash and an equity investment of $13.5 million provided by Gilead in common stock. Overall, Xilio will have the opportunity to earn up to $604 million based on specified development, regulatory, and sales-based milestones.1
“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, SVP, oncology clinical development, Gilead Sciences, in a press release. “We believe IL-12 has the potential to treat a broad range of tumor types and are excited to partner with Xilio to advance XTX301, a tumor-activated IL-12, as a monotherapy and a combination therapy across a variety of solid tumors.”
In November 2021, Xilio announced promising data for XTX301 at the Society for Immunotherapy in Cancer’s 36th Annual Meeting. Results show that the therapy produced up to 90% tumor growth inhibition in mouse models, with little peripheral immune activation. Additionally, it showed equal in vitro potency compared to the non-masked control.2
“The presentations at SITC exemplify the progress we’ve made at Xilio in 2021 with our pipeline of clinical and preclinical-stage tumor selective antibody and cytokine product candidates,” said Martin Huber, MD, president, R&D, chief medical officer, Xilio, in a press release. “IL-12 has the potential to be a meaningful treatment for patients with cancer, but current therapies are encumbered with severe toxicities due to their peripheral activity, leading to sub-optimal dosing and limited efficacy. Using our GPS platform, we have engineered XTX301 to achieve systemic delivery of tumor-selective IL-12, while avoiding the known side effect challenges. These preclinical data showcase our engineering efforts to activate XTX301 only when it is within the tumor microenvironment, resulting in the potential to achieve an optimized therapeutic index and enhanced anti-tumor activity…”
Xilio will continue to focus on development of XTX301 during Phase I of the clinical trial process until dose expansion. Moving forward, Gilead will have the choice to take over development upon a $75 million transition fee. Xilio will also have the potential to earn $29 million in additional equity investments.1
“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 René Russo, PharmD, president, CEO, Xilio, in the press release. “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.”