Xilio Therapeutics Announces Pipeline and Business Updates and Fourth Quarter and Full Year 2024 Financial Results Additional Phase 2 data for vilastobart, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with

Xilio Therapeutics Announces Pipeline and Business Updates and Fourth Quarter and Full Year 2024 Financial Results

Additional Phase 2 data for vilastobart, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab in patients with MSS CRC anticipated in the middle of 2025

Advancing masked T cell engager programs in novel ATACR and SEECR formats for PSMA, CLDN18.2 and STEAP1

Announced collaboration with AbbVie in the first quarter of 2025 to develop novel tumor-activated, antibody-based immunotherapies, including

masked T cell engagers

WALTHAM, Mass., March 11, 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 pipeline progress and business updates and reported financial results for the fourth quarter and full year ended

We started 2025 with multiple promising updates across our pipeline, including encouraging initial Phase 2 combination data

for vilastobart, our tumor-activated anti-CTLA-4, in patients with late-line MSS CRC, a difficult to treat, immunologically cold tumor type that is increasing in incidence, particularly in younger

people, said Ren Russo, Pharm.D., president and chief executive officer of Xilio. These data included a preliminary 27% objective response rate in patients without liver metastases and continue to support a differentiated safety

profile, including a low incidence of immune-related adverse events and only 5% of patients reporting colitis. We look forward to reporting additional data from the ongoing Phase 2 trial in the middle of this year.

Dr. Russo added, In addition, we are excited to be advancing multiple novel masked T cell engager programs internally and as part of our recently

announced collaboration with AbbVie. Each of these programs leverages our clinically-validated, tumor-activation technology, which we believe has great potential to enhance the activity and tolerability of T cell engagers and open up promising new

targets within this class of immunotherapies.

Pipeline and Business Updates

Vilastobart: tumor-activated, Fc-enhanced, high affinity binding

Vilastobart is an investigational tumor-activated,

Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when

activated in the tumor microenvironment (TME).

XTX301: tumor-activated IL-12

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the

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. (Gilead) related to Xilio s tumor-activated IL-12 program, including XTX301.

masked PD-1/IL-2 bispecific

XTX501 is a novel, tumor-activated

bispecific PD-1/IL-2 designed to selectively stimulate PD-1 positive, antigen-experienced T cells and enhance their function.

XTX501 incorporates masking designed to overcome IL-2 receptor-mediated clearance and peripheral activity. In preclinical studies, XTX501 demonstrated robust monotherapy activity (including in settings

insensitive to PD-1) and tumor-selective pharmacodynamics consistent with its intended mechanism of action. Xilio is currently advancing XTX501 in investigational new drug (IND) application enabling studies

and plans to submit an IND application for XTX501 in the middle of 2026.

Masked T Cell Engager Programs

Xilio is leveraging its proprietary, clinically-validated tumor-activation platform to advance multiple preclinical programs for masked T cell engagers,

including wholly-owned programs targeting the tumor-associated antigens for PSMA, CLDN18.2 and STEAP1 and an additional program in collaboration with AbbVie.

Xilio s masked T cell engager programs include bispecific molecules designed using its advanced tumor-activated cell engager (ATACR) format, which

consists of a T cell engager with a masked CD3 targeting domain, and tri-specific molecules designed using its selective effector-enhanced cell engager (SEECR) format. The SEECR format builds upon the ATACR

format by adding co-stimulatory signaling designed to further enhance potency and T cell activation.

Year-End and Fourth Quarter 2024 Financial Results

Based on its current operating plans,

Xilio anticipates that its cash and cash equivalents as of December 31, 2024, together with the $52.0 million in upfront payments received in the first quarter of 2025 in connection with the collaboration agreement with AbbVie, will be

sufficient to enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2026.

About Vilastobart and the

Phase 1/2 Combination Clinical Trial

Vilastobart is an investigational tumor-activated, Fc-enhanced, high

affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023,

Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq ) in a

multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the safety and efficacy of the combination in Phase 2 in patients

with metastatic microsatellite stable colorectal cancer with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

About XTX301 and the Phase 1 Clinical Trial

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 XTX301. 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 1 clinical

trial. 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

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including,

without limitation, statements regarding plans, expectations, development timelines and anticipated milestones for Xilio s programs; the receipt of future contingent payments under Xilio s collaboration or partnership agreements with

Roche, Gilead and AbbVie; the potential benefits of any of Xilio s current or future product candidates in any indication; the sufficiency of, and the period in which Xilio expects to have, cash to fund its operations, capital expenditure

requirements, and development plans and milestones; and Xilio s strategy, goals and anticipated financial performance, milestones, business plans and focus. The words aim, may, will, could,

would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential,

continue, seek, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in

this press release are based on management s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual events or results to differ materially from those expressed or

implied by any forward-looking statements contained in this press release, including, without limitation, risks related to general market conditions and geopolitical uncertainties; risks and uncertainties related to ongoing and planned research and

development activities, including initiating, conducting or completing preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned preclinical studies or

clinical trials or the development of Xilio s current or future product candidates; Xilio s ability to obtain and maintain sufficient preclinical and clinical supply of current or future product candidates; Xilio s ability to advance

multiple early-stage masked T cell engager programs; initial, preliminary or interim preclinical or clinical data or results may not be replicated in or predictive of future preclinical or clinical data or results; Xilio s ability to

successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; results from preclinical studies or clinical trials for Xilio s product candidates may not

support further development of such product candidates; actions of regulatory agencies may affect the initiation, timing and progress of current or future clinical trials; Xilio s ability to obtain, maintain and enforce patent and other

intellectual property protection for current or future product candidates; Xilio s need to obtain additional cash resources to fund its operations beyond the first quarter of 2026, including to advance its pipeline of tumor-activated I-O molecules; the impact of international trade policies on Xilio s business, including U.S. and China trade policies; and Xilio s ability to maintain its collaboration or partnership agreements with

Roche, Gilead and AbbVie. These and other risks and uncertainties are described in greater detail in the sections entitled Risk Factor Summary and Risk Factors in Xilio s filings with the U.S. Securities and Exchange

Commission ( SEC ), including Xilio s most recent Quarterly Report on Form 10-Q and any other filings that Xilio has made or may make with the SEC in the future. Any forward-looking statements

contained in this press release represent Xilio s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Xilio explicitly disclaims any obligation to update

any forward-looking statements.

This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press

TECENTRIQ is a registered trademark of Genentech USA, Inc., a member of the Roche Group.

Investor and Media Contact

Vice President, Investor Relations and Corporate

XILIO THERAPEUTICS, INC.

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