Xilio Therapeutics : Corporate Update Call

Xilio Therapeutics Corporate Update Call

March 28, 2024

Forward-Looking Statements and Disclaimers

This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, timing and expectations related to: completing the Phase 1 combination dose escalation and selection of a recommended Phase 2 dose for XTX101 in combination with atezolizumab; initiating a Phase 2 trial to evaluate XTX101 in combination with atezolizumab in patients with MSS CRC; additional plans and anticipated milestones for XTX101, XTX202, XTX301 and Xilio's developmental candidates; Xilio's anticipated use of proceeds from the potential financing; the amount and use of proceeds expected from the transactions with Gilead Sciences, Inc. (Gilead); the timing and certainty of completion of the transactions with Gilead; expectations related to the cost, savings and timing of the strategic portfolio reprioritization and restructuring; the potential impact of the strategic portfolio reprioritization and restructuring on Xilio's operations and development timelines; Xilio's intent and ability to explore strategic opportunities to develop XTX202 in combination with other agents; the potential benefits of any of Xilio's current or future product candidates in treating patients as a monotherapy or combination therapy; the period in which Xilio expects to have cash to fund its operations; the potential for Xilio to leverage its research platform to develop bispecific and cell engager molecules; 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 presentation 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 presentation, including, without limitation, 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 advancement of multiple early-stage programs; interim or preliminary preclinical or clinical data or results, which 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, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of Xilio's 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 ability to obtain and maintain sufficient cash resources to fund its operations into the second quarter of 2025; the impact of international trade policies on Xilio's business, including U.S. and China trade policies; and Xilio's ability to maintain its clinical trial collaboration with Roche to develop XTX101 in combination with atezolizumab.

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 presentation 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.

Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Xilio's own internal estimates and research. While Xilio believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, Xilio has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of Xilio's internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.

This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. TECENTRIQ is a registered trademark of Genentech USA Inc., a member of the Roche Group.

Presenting On The Call Today

René Russo, Pharm. D.

PRESIDENT AND CHIEF EXECUTIVE OFFICER

Chris Frankenfield

CHIEF OPERATING OFFICER

Uli Bialucha, Ph.D.

CHIEF SCIENTIFIC OFFICER

Agenda

OPENING REMARKS

René Russo, Pharm. D.

XTX301 (IL-12) AND GILEAD PARTNERSHIP

Chris Frankenfield

XTX101 (ANTI-CTLA-4) OPPORTUNITY AND DEVELOPMENT PLAN

René Russo, Pharm. D.

XTX202 (IL-2) PHASE 2 DATA

Uli Bialucha, Ph.D.

NEW RESEARCH PROGRAMS

Uli Bialucha, Ph.D.

CLOSING REMARKS AND Q&A

René Russo, Pharm. D.

Immuno-Oncology Therapy has Curative Potential

Treatment potential for some of

the most promising immuno-

oncology (IO) targets has been

impeded by dose-limiting

systemic toxicity

Patient Portrayal

Xilio (ex-il-ee-oh) believes the next revolution in IO cancer therapies will trick tumors into activating their own treatments, while simultaneously sparing healthy tissues and cells, by leveraging dysregulated matrix metalloproteases (MMPs)

Xilio is Advancing a Portfolio of Tumor-Activated Molecules Designed to Unleash the Full Potential of Immuno-Oncology Therapies

Prioritizing Clinical Development for XTX301 (IL-12) and XTX101 (anti-CTLA-4) with Focused Investments in Research Platform for Bispecific and Cell Engager Molecules

• 1. Evaluating XTX101 in combination with atezolizumab (Tecentriq®) in Phase 1 combination dose escalation trial and planned Phase 2 combination trial in MSS CRC.

• 2. Evaluating XTX301 in Phase 1 monotherapy dose escalation for the treatment of advanced solid tumors.

• 3. Plan to discontinue further investment in XTX202 as a monotherapy

MSS CRC: metastatic colorectal cancer; RCC: renal cell cancer

XTX301 (IL-12) and Gilead Partnership

Chris Frankenfield

Chief Operating Officer

XTX301: Designed to Overcome Limitations of Systemically Active IL-12

• • Built using Xilio's validated masking platform and optimized for IL-12 mechanism

• • Half-life extended in masked state, releases short half-life IL-12 once activated

XTX301:

Tumor-activated IL-12

Efficient activation by human tumors demonstrated ex vivo

Tumor Type	Confirmed High Activation Efficiency XTX301 (IL-12)
Colon
Head & Neck
Prostate
RCC
Lung
Melanoma
Plasma

Dose-dependent anti-tumor activity

Tumor volume, mm3

(mean + SEM)

2000 1500 1000 500

TGI (D11) 60%

TGI (D11) 91%

TGI (D11) 92%

****

Vehicle mXTX301 0.039 mg/kg mXTX301 0.13 mg/kg mXTX301 0.39 mg/kg

**** 0

0

5

10

15

Days Post Dose

Tumor-selective increase in CD8 T cells

Spleen

Tumor

CD45+CD3+CD8+ (%of CD3+)

60

40

20

ns

*

0

CD45+CD3+CD8+ (%of CD3+)

60

*

***

40

20

0

Vehicle

0.13

0.39

Vehicle

0.13

0.39

mXTX301

mXTX301

Robust anti-tumor activity and tumor-selective PD in vivo in preclinical model

Second panel from left: Activation of XTX301 assessed in human tumor samples ex vivo. Third panel from left - Top: MC38 model; single IV dose of mXTX301 or vehicle on Day 0. Tumor growth data shown as mean±SEM. Tumor volume data was assessed by a two-way Analysis of Variance (ANOVA) followed by Bonferroni post hoc test on Day 11 compared to vehicle treated animals. **** p<0.0001 for all mXTX301 treatment groups. Third panel from left - Bottom: MC38 model; single IV dose of mXTX301 or vehicle on Day 0. On day 4 post treatment percent CD8 positive T cells (out of CD45+/CD3+ gate) from spleens or tumors was assessed by flow cytometry. The results were analyzed by One-way ANOVA followed by Dunnett's multiple comparisons test (*P<0.05; **P<0.005) compared to vehicle (PBS) treated animals. Right panel: XTX301 exposures in NHP at the 2 mg/kg dose (HNSTD) over one week plotted over exposures of mXTX301 in mice at doses enabling tumor regression and tumor growth inhibition with 6x adjustment to account for potency difference between human XTX301 and mouse surrogate mXTX301. HNSTD: highest non-severely toxic dose; NHP: non-human primate; PD: pharmacodynamic; Q1W: once every week; TI: therapeutic index; TGI: tumor growth inhibition.

10000

Tolerated Exposure in NHP (HNSTD)

Drug Exposure: AUC 0-168h

1000

(hr*ug/ml)

100

TherapeuticIndex

10

1

0

24

48 72 96 120 Timepoint (hours)

144

168

• • Exposure in mice adjusted for 6x potency relative to human XTX301

Potential for broad therapeutic index supported by robust preclinical data

Complete regressions in miceTumor growth inhibition in mice

Entered Into Transformational Partnership with Gilead, Designed to Explore Broad Potential of IL-12 Across Solid Tumors

$43.5M total upfront payments

($30M cash payment +	Gilead received an exclusive global license to
$13.5M initial equity investment at a premium ($1.97/share)
develop and commercialize Xilio's tumor-activated
IL-12 program, including XTX301
Up to $604M

additional contingent payments:

• • Includes up to $29M prior to transition fee for up to $11.5M in additional equity investments (1) and a development milestone

• • $75M transition fee

• • Up to $500M for additional development, regulatory and sales-based milestones after transition fee

• • Xilio responsible for clinical development of XTX301 in ongoing Phase 1 trial through initial planned Phase 2 trial

• • Following delivery by Xilio of specified clinical data package for XTX301, Gilead can elect to pay transition fee and transition development and commercialization to Gilead (2)

Tiered royalties: high single-digits to mid-teens

• 1. Subject to 19.9% ownership cap.

• 2. If Gilead elects not to transition responsibilities for development and commercialization, the agreement will automatically terminate.

XTX301 Monotherapy Phase 1 Dose Escalation:

No DLTs Observed Into DL3 (45 μg/kg, ~100x MTD for rhIL-12)

XTX301 Phase 1 Trial Design

Phase 1A

Monotherapy Dose Escalation

• ▪ Advanced solid tumors

• ▪ 3+3 design with optional dose expansion (up to 10 patients per cohort)

XTX301 Phase 1 Dose Escalation Plan

• • XTX301 is administered in the outpatient setting

• • DL3 (45 ug/kg) equivalent to ~100x MTD for rhIL-12

• • Generally well-tolerated into DL3

• • No DLTs reported through data cutoff date

10

Data cutoff date: January 5, 2024, 9 patients

DL1: dose level 1; DL2: dose level 2; DL3: dose level 3; DLT: dose limiting toxicity; MTD: maximum tolerated dose; PK: pharmacokinetic; rHIL: recombinant human Interleukin 12