Xilio Therapeutics is advancing its pipeline of tumor-activated immunotherapies with key clinical milestones anticipated in the coming months, according to the company's latest pipeline and business updates.
XTX101 Advances to Phase 2 in Colorectal Cancer
Xilio plans to initiate the Phase 2 portion of its clinical trial evaluating XTX101 in combination with atezolizumab in patients with microsatellite stable colorectal cancer (MSS CRC) in the third quarter of 2024. XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, is designed to block CTLA-4 and deplete regulatory T cells specifically when activated in the tumor microenvironment.
The company expects to report initial Phase 2 data from approximately 20 patients with MSS CRC in the fourth quarter of 2024, with additional data from approximately 20 more patients anticipated in the first quarter of 2025. This trial is being conducted under a co-funded clinical collaboration with Roche that was established in the third quarter of 2023.
"In the first quarter, our team remained hard at work advancing our differentiated pipeline of clinical-stage tumor-activated I-O therapies, and we believe we are well-positioned to execute on several anticipated near-term clinical milestones and potential value-drivers in the coming year," said René Russo, Pharm.D., president and chief executive officer of Xilio.
Strategic Partnership with Gilead for XTX301
In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences for its tumor-activated IL-12 program, including XTX301. Under the terms of the agreement, Xilio received $43.5 million in upfront payments, comprising a $30 million cash payment and an initial equity investment by Gilead of approximately $13.5 million in Xilio common stock.
The company is eligible to receive up to a total of $592.5 million in contingent payments, including a $75 million transition fee and specified development, regulatory, and sales-based milestones. Additionally, Xilio stands to receive tiered royalties ranging from high single digits to mid-teens on annual global net product sales.
XTX301 is currently being evaluated in a Phase 1 monotherapy dose escalation study in patients with advanced solid tumors. The company plans to report Phase 1 safety, pharmacokinetic, and pharmacodynamic data for XTX301 in the fourth quarter of 2024.
Research Pipeline Expansion
Xilio's research-stage development efforts are focused on advancing a pipeline of tumor-activated bispecifics and immune cell engagers, including tumor-activated cell engagers and tumor-activated effector-enhanced cell engagers.
In April 2024, the company presented preclinical data from its first bispecific program, XTX501, a tumor-activated PD-1/IL-2 bispecific development candidate, at the American Association for Cancer Research Annual Meeting. The preclinical data suggest that XTX501 has the potential to improve upon the anti-tumor activity of existing PD-1/PD-L1 immunotherapies while maintaining a favorable therapeutic index.
Strategic Portfolio Prioritization
In March 2024, Xilio implemented a strategic portfolio prioritization designed to focus its resources on rapidly advancing clinical development for XTX301 and XTX101 while leveraging the company's research platform to advance differentiated tumor-activated bispecific and immune cell engager molecules.
As part of this reprioritization, Xilio announced plans to discontinue further investment in XTX202, its tumor-activated IL-2, as a monotherapy. The company continues to explore strategic opportunities to develop XTX202 in combination with other agents. Data from the Phase 1/2 trial for XTX202 in advanced solid tumors will be presented at the 2024 American Society of Clinical Oncology Annual Meeting in Chicago from May 31 to June 4, 2024.
Financial Position
Xilio reported cash and cash equivalents of $34.0 million as of March 31, 2024, compared to $44.7 million as of December 31, 2023. In April 2024, the company received approximately $44.6 million in gross proceeds related to the upfront payment under the license agreement with Gilead and private placements with certain existing investors and Gilead.
Research and development expenses were $10.4 million for the quarter ended March 31, 2024, compared to $16.1 million for the same period in 2023. General and administrative expenses were $6.1 million, down from $7.4 million in the prior-year period. Net loss was $17.2 million for the first quarter of 2024, compared to $22.6 million for the first quarter of 2023.
Based on its current operating plans, Xilio anticipates that its existing cash and cash equivalents, together with the recent payments and proceeds, will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2025.
Tumor-Activated Immunotherapy Approach
Xilio Therapeutics is developing tumor-activated immuno-oncology therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current immunotherapy treatments. The company's proprietary platform is designed to optimize the therapeutic index by localizing anti-tumor activity within the tumor microenvironment.
This approach includes tumor-activated cytokines and antibodies (including bispecifics) and immune cell engagers that are designed to remain masked until they reach the tumor microenvironment, potentially reducing systemic toxicity while maintaining potent anti-tumor activity.
