Material Event (Form 8-K)

Xilio Therapeutics Announces Initiation of Phase 2 Trial for Efarindodekin Alfa (XTX301), a Tumor-Activated IL-12, and Achievement of $17.5 Million Development Milestone Under Exclusive License Agreement with Gilead

Phase 1 data for efarindodekin alfa (XTX301) demonstrate promising anti-tumor activity in patients with advanced solid tumors

Achievement of milestone extends anticipated cash runway into first quarter of 2027

WALTHAM, Mass., September 9, 2025 -- Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced the initiation of patient dosing in Phase 2 of an ongoing Phase 1/2 clinical trial evaluating efarindodekin alfa (XTX301), a tumor-activated IL-12, as a monotherapy in patients with certain advanced solid tumors. In addition, today Xilio announced the achievement of a $17.5 million development milestone under Xilio's license agreement with Gilead Sciences, Inc. (Gilead) and updated data from the ongoing Phase 1 trial for efarindodekin alfa.

"We are pleased to announce the initiation of the Phase 2 clinical trial for efarindodekin alfa (XTX301), a tumor-activated IL-12, in patients with advanced solid tumors," said René Russo, Pharm.D., president and chief executive officer of Xilio. "The achievement of this important milestone highlights the promising Phase 1 data demonstrated for efarindodekin alfa to date, including two partial responses in late-line patients with advanced solid tumors and a generally well-tolerated safety profile. These data also provide further clinical validation for our proprietary masking technology and approach, which we believe is best-in-class and has potential across a wide range of therapies and modalities."

"We are encouraged by the totality of data observed to date for efarindodekin alfa (XTX301) as a monotherapy in patients with advanced solid tumors, and we are excited for the potential that IL-12 has to treat a broad range of tumor types," said Bernard Fine, vice president, oncology early development at Gilead. "We look forward to advancing the efarindodekin alfa (XTX301) program in the Phase 2 trial in partnership with Xilio."

Efarindodekin alfa (XTX301): tumor-activated IL-12

Efarindodekin alfa (XTX301) is an investigational 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. In March 2024, Xilio entered into an exclusive license agreement with Gilead related to Xilio's tumor-activated IL-12 program, including efarindodekin alfa. Xilio is evaluating efarindodekin alfa as a monotherapy in an ongoing Phase 1/2 clinical trial in patients with advanced solid tumors.

In connection with the initiation of Phase 2, Xilio achieved a development milestone of $17.5 million.

Efarindodekin alfa has not been approved by any regulatory agency and its efficacy and safety have not been established.

Financial Guidance

As of June 30, 2025, Xilio had cash and cash equivalents of $121.6 million. Based on its current operating plans, Xilio anticipates that its cash and cash equivalents as of June 30, 2025, together with the $17.5 million development milestone achieved under the license agreement with Gilead, will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2027. Xilio expects to receive payment of the $17.5 million development milestone by the fourth quarter of 2025.

About the Gilead License Agreement

In March 2024, Xilio entered into an exclusive global license agreement with Gilead to develop and commercialize efarindodekin alfa (XTX301), a tumor-activated IL-12, and specified other molecules directed to IL-12.

Xilio is responsible for conducting clinical development for efarindodekin alfa through the initial Phase 2 portion of the ongoing Phase 1/2 clinical trial. Following the delivery by Xilio of a specified clinical data package for efarindodekin alfa related to the Phase 1/2 clinical trial, Gilead can elect to transition responsibilities for the development and commercialization of efarindodekin alfa to Gilead, subject to the terms of the license agreement and payment by Gilead of a $75.0 million transition fee.

If Gilead exercises its option for efarindodekin alfa, Xilio will be eligible to receive up to $500.0 million in specified development, regulatory and sales-based milestones and will be eligible to receive tiered royalties ranging from high single digits to mid-teens on annual global net product sales.

About Efarindodekin Alfa (XTX301) and the Phase 1/2 Clinical Trial

Efarindodekin alfa (XTX301) is an investigational masked 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. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio's tumor-activated IL-12 program, including efarindodekin alfa. Xilio is currently evaluating the safety and tolerability of efarindodekin alfa as a monotherapy in patients with advanced solid tumors in the Phase 1 portion of a first-in-human, multi-center, open-label Phase 1/2 clinical trial and the safety and efficacy of efarindodekin alfa as a monotherapy in the Phase 2 portion in patients with advanced solid tumors. The Phase 2 portion of the trial is anticipated to enroll approximately 40 patients in specific tumor types at multiple sites in the United States. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

About Xilio Therapeutics

Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated, or masked, immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people

living with cancer without the systemic side effects of current I-O treatments. The company is leveraging its proprietary platform to advance a pipeline of novel, tumor-activated I-O molecules that are designed to optimize the therapeutic index by localizing anti-tumor activity within the tumor microenvironment. Learn more by visiting www.xiliotx.com and follow us on LinkedIn (Xilio Therapeutics, Inc.).