IL-2Rγ

Demonstrated initial clinical validation of tumor-selective activation technology for both XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4, and XTX202, a tumor-activated, beta-gamma IL-2 On track to activate trial sites for XTX101 dose escalation in combination with atezolizumab under clinical collaboration with Roche in the fourth quarter of 2023 Reported initial Phase 1/2 data for XTX202, including a 50% disease control rate at higher doses (≥2.8 mg/kg), and plans to evaluate XTX202 as monotherapy at 4.0 mg/kg in ongoing Phase 2 trial in patients with melanoma and renal cell carcinoma Anticipate reporting preliminary Phase 1 safety data for XTX301, a tumor-activated, engineered IL-12, in the fourth quarter of 2023 WALTHAM, Mass., Nov. 09, 2023 (GLOBE NEWSWIRE) -- 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 third quarter ended September 30, 2023. “Colorectal cancer is the third largest solid tumor cancer in terms of number of patients diagnosed annually and the second leading cause of cancer-related deaths globally,” said René Russo, Pharm.D., president and chief executive officer of Xilio. “Rates of MSS colorectal cancer are rising in younger people, particularly in men under 50 years old, and patients often present with advanced Stage 4 disease along with liver metastases. Despite these alarming trends, there are few treatment options and no approved immunotherapies for these patients today. We believe the unique tumor-selective mechanism of XTX101 combined with atezolizumab has the potential to treat MSS colorectal cancer, and we are focused on initiating the co-funded collaboration with Roche to study this combination in patients. We are also encouraged by the recent Phase 1/2 data reported at SITC for XTX202 demonstrating a 50% disease control rate at higher doses (≥2.8 mg/kg), including patients with cold tumors, and a generally well-tolerated safety profile across all dose levels. We look forward to evaluating the 4 mg/kg dose for XTX202 in Phase 2 for patients with melanoma and renal cell carcinoma.” Pipeline and Business Updates XTX101: tumor-activated, Fc-enhanced anti-CTLA-4 XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). XTX101 is currently being evaluated at the recommended Phase 2 dose and schedule of 150 mg once every six weeks in monotherapy dose expansion of an ongoing Phase 1 clinical trial in patients with advanced solid tumors. In the third quarter of 2023, Xilio reported updated data from the Phase 1 trial for XTX101, including an ongoing durable confirmed partial response through 36 weeks as of an August 3, 2023 data cutoff date in a patient with Stage 4 non-small cell lung cancer treated with XTX101 monotherapy, including resolution of liver metastases.Additionally, Xilio recently reported pharmacokinetic (PK) data showing activation of XTX101 in two on-treatment biopsies from patients in the Phase 1 trial, which included a primary melanoma tumor and a metastatic lesion in the liver from a patient with microsatellite stable colorectal cancer (MSS CRC). For both patients, XTX101 was more than 70% activated in the tumor while maintaining a peripheral activation level of 13%, consistent with the tumor-selective design for XTX101.In the third quarter of 2023, Xilio entered into a clinical trial collaboration with Roche to evaluate XTX101 in combination with atezolizumab in Phase 1 combination dose escalation in patients with advanced solid tumors and a planned Phase 2 trial in patients with MSS CRC. Xilio anticipates activating clinical trial sites for the Phase 1 combination dose escalation in the fourth quarter of 2023. In addition, subject to obtaining sufficient additional capital, Xilio plans to: Complete Phase 1 combination dose escalation and select a recommended Phase 2 dose for XTX101 in combination with atezolizumab in the second quarter of 2024.Subject to the results of Phase 1 combination dose escalation, initiate a Phase 2 trial for XTX101 in combination with atezolizumab in patients with MSS CRC in the third quarter of 2024.Report initial Phase 2 data for XTX101 in combination with atezolizumab in approximately 20 patients with MSS CRC in the fourth quarter of 2024 and in approximately 20 additional patients (40 patients total) in the first quarter of 2025. XTX202: tumor-activated, engineered, beta-gamma biased IL-2 XTX202 is an investigational tumor-activated, engineered, beta-gamma biased IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the TME. XTX202 is currently being evaluated in an ongoing Phase 1/2 clinical trial in patients with advanced solid tumors. In November 2023, Xilio announced initial Phase 1/2 monotherapy safety, PK, pharmacodynamic (PD) and anti-tumor activity data for XTX202 at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting. As of a data cutoff date of October 26, 2023, these data included: Initial evidence of a dose-dependent increase in disease control rate (DCR) for XTX202 across all dose levels in a range of solid tumors, including cold tumors, with a 50% DCR in response-evaluable patients at higher doses (≥2.8 mg/kg) and a 31% DCR in response-evaluable patients across all dose levels, including a patient with Stage 4 MSS CRC with ongoing stable disease at 57 weeks and resolution of three out of four non-target lesions. No signs or symptoms of vascular leak syndrome were reported by investigators through the 4.0 mg/kg dose. In addition, XTX202 was generally well-tolerated with treatment-related adverse events (TRAE) primarily Grade 1 or 2 and no treatment discontinuations due to TRAEs. Preliminary PK analysis demonstrated tumor-selective activation of XTX202, including an approximately 40-fold higher concentration of activated XTX202 in the tumor as compared to peripheral blood based on an analysis of an on-treatment biopsy from a patient at the 2.8 mg/kg dose level, which demonstrated approximately 15% activated XTX202 in the tumor compared to <1% activated XTX202 in plasma across patients at the 2.8 mg/kg dose level. Consistent with IL-2 beta-gamma biology, preliminary PD analysis of four available on-treatment tumor samples showed an average increase >200% of CD8+ effector T cells in the tumor as compared to pre-treatment biopsies.For more information, read the press release here. As previously announced, XTX202 recently cleared dose level seven (4.0 mg/kg) in Phase 1 monotherapy dose-escalation, and Xilio recently opened enrollment at a second dose level of 4.0 mg/kg in the ongoing Phase 2 monotherapy trial for XTX202. Based on the initial monotherapy data for XTX202, Xilio also plans to explore opportunities for strategic partnerships to evaluate XTX202 as a combination therapy.Subject to obtaining sufficient additional capital, Xilio plans to report Phase 2 monotherapy data for XTX202 in approximately 20 patients treated at the 4.0 mg/kg dose with metastatic renal cell carcinoma (RCC) or unresectable or metastatic melanoma in the second quarter of 2024. XTX301: tumor-activated, engineered IL-12 XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic “cold” tumors towards an inflamed or “hot” state. Xilio is currently dosing patients in monotherapy dose escalation of an ongoing Phase 1 clinical trial evaluating the safety and tolerability of XTX301 in patients with advanced solid tumors. As previously announced, Xilio anticipates reporting preliminary safety data from the Phase 1 clinical trial into the third dose level in the fourth quarter of 2023.Subject to obtaining sufficient additional capital, Xilio plans to report Phase 1 safety and PK/PD data for XTX301 in advanced solid tumors in the second half of 2024. Corporate Highlights In September 2023, Xilio announced the promotions of Katarina Luptakova, M.D., to Chief Medical Officer and Scott Coleman, Ph.D., to Chief Development Officer. Upcoming PresentationsXilio will present a poster for XTX101 with updated preliminary Phase 1 data and outlining the planned Phase 2 trial design at the European Society for Medical Oncology (ESMO) Immuno-Oncology Annual Congress on December 6-8, 2023. Title: Phase 1/2 study of XTX101, a masked, tumor-activated Fc-enhanced anti-CTLA-4 in patients with advanced solid tumorsPresentation Date and Time: Thursday, December 7, 2023, from 12:00 to 1:00 p.m. CETAbstract number: 490 Third Quarter 2023 Financial Results Cash Position: Cash and cash equivalents were $59.8 million as of September 30, 2023, compared to $120.4 million as of December 31, 2022. Research & Development (R&D) Expenses: R&D expenses were $11.1 million for the quarter ended September 30, 2023, compared to $13.0 million for the quarter ended September 30, 2022. The decrease was primarily driven by decreased manufacturing and preclinical activities for XTX301 and a reduction of XTX101 costs due to a cost-sharing payment earned under the clinical trial collaboration with Roche. These decreases were partially offset by increases in clinical activities for XTX202 and XTX301, preclinical activities for other early programs and indirect research and development expenses. General & Administrative (G&A) Expenses: G&A expenses were $6.3 million for the quarter ended September 30, 2023, compared to $7.2 million for the quarter ended September 30, 2022. The decrease was primarily driven by a decrease in professional and consulting fees.Net Loss: Net loss was $16.7 million for the quarter ended September 30, 2023, compared to $19.8 million for the quarter ended September 30, 2022. Financial Guidance Xilio continues to anticipate that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the end of the second quarter of 2024. About XTX101 (anti-CTLA-4) and the Phase 1 Monotherapy and Phase 1/2 Combination Clinical Trials XTX101 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 (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of adult patients with advanced solid tumors. Xilio has completed monotherapy dose escalation (Part 1A) and is currently enrolling patients at the recommended Phase 2 dose and schedule of 150 mg once every six weeks in monotherapy dose expansion (Part 1B). Please refer to NCT04896697 on www.clinicaltrials.gov for additional details. In addition, Xilio plans to evaluate the safety, tolerability and efficacy of XTX101 in combination with atezolizumab (Tecentriq®) in the Phase 1/2 clinical trial. The Phase 1 portion is designed to assess the safety and tolerability of XTX101 in combination with atezolizumab in dose escalation in patients with advanced solid tumors. The planned Phase 2 portion is designed to evaluate the safety and efficacy of the combination in patients with microsatellite stable colorectal cancer (MSS CRC). About XTX202 (IL-2) and the Phase 1/2 Clinical Trials XTX202 is an investigational tumor-activated beta-gamma biased, engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial for XTX202 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and efficacy of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details. About XTX301 (IL-12) and the Phase 1 Clinical Trial XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic “cold” tumors towards an inflamed or “hot” state. The Phase 1 clinical trial for XTX301 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. 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 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 using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including antibodies, cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on LinkedIn (Xilio Therapeutics, Inc.). 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 to activate clinical trial sites for the Phase 1 dose escalation portion of the clinical trial evaluating XTX101 in combination with atezolizumab; plans to report preliminary Phase 1 safety data for XTX301; additional plans and anticipated milestones for XTX101, XTX202 and XTX301, subject to obtaining sufficient additional capital; 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; 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 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 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 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 until and beyond the end of the second quarter of 2024; 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 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 release. TECENTRIQ is a registered trademark of Genentech USA, Inc., a member of the Roche Group. For Investor and Media Inquiries: Julissa VianaVice President, Head of Investor Relations and Corporate Communicationsinvestors@xiliotx.com Melissa ForstArgot Partnersxilio@argotpartners.com XILIO THERAPEUTICS, INC.Condensed Consolidated Balance Sheets(In thousands)(Unaudited) September 30, December 31, 2023 2022Assets Cash and cash equivalents$59,772 $120,385 Other assets 18,070 18,780 Total assets$77,842 $139,165 Liabilities and Stockholders’ Equity Liabilities$25,344 $33,518 Stockholders’ equity 52,498 105,647 Total liabilities and stockholders’ equity$77,842 $139,165 XILIO THERAPEUTICS, INC.Condensed Consolidated Statements of Operations and Comprehensive Loss(In thousands, except share and per share data)(Unaudited) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2023 2022 2023 2022Operating expenses (1) Research and development $11,051 $13,028 $40,400 $44,204 General and administrative 6,310 7,168 20,603 21,778 Total operating expenses 17,361 20,206 61,003 65,982 Loss from operations (17,361) (20,206) (61,003) (65,982)Other income, net Other income, net 613 416 2,254 226 Total other income, net 613 416 2,254 226 Net loss and comprehensive loss $(16,748) $(19,790) $(58,749) $(65,756)Net loss per share, basic and diluted $(0.61) $(0.72) $(2.14) $(2.40)Weighted average common shares outstanding, basic and diluted 27,523,821 27,399,906 27,475,579 27,384,085 _______________(1) Operating expenses include the following amounts of non-cash stock-based compensation expense: Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Research and development expense $548 $594 $1,670 $1,827 General and administrative expense 1,313 1,277 3,782 4,782 Total stock-based compensation expense $1,861 $1,871 $5,452 $6,609

Initial evidence of dose-dependent disease control rate with 50% disease control rate at higher doses (≥2.8 mg/kg) and 31% disease control rate across all dose levels in a range of solid tumor types, including cold tumors Treatment-related adverse events primarily Grade 1-2 at doses up to 4 mg/kg administered once every three weeksin outpatient setting, with no reported signs or symptoms of vascular leak syndrome Two patients continuing treatment for more than 1 year, demonstrating XTX202 was well-tolerated with repeated, long-term dosing Plan to evaluate XTX202 as a monotherapy in ongoing Phase 2 proof-of-concept trial at 4.0 mg/kg in patients with advanced melanoma and renal cell carcinoma Xilio Therapeutics to host investor conference call and webcast on Monday, November 6, 2023 at 8:00 a.m. ET WALTHAM, Mass., Nov. 03, 2023 (GLOBE NEWSWIRE) -- 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 initial safety, pharmacokinetic (PK), pharmacodynamic (PD) and anti-tumor activity data from its ongoing Phase 1/2 clinical trial evaluating XTX202, an investigational tumor-activated, engineered, beta-gamma IL-2, in late line patients with advanced solid tumors. The data were presented at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting in San Diego, CA being held on November 1-5, 2023. “The newly reported data from our Phase 1/2 clinical trial for XTX202 expands the evidence across our programs supporting clinical validation of our tumor-activated technology. We observed a disease control rate of 50% at higher doses (≥2.8 mg/kg) and 31% across all dose levels in a variety of advanced and IO refractory solid tumors, including cold tumors. Importantly, treatment-related adverse events were primarily Grade 1-2 with no evidence of vascular leak syndrome reported at any dose level, and two patients are continuing on treatment for more than one year, highlighting XTX202’s potential for long-term tolerability at high doses,” said Katarina Luptakova, M.D., chief medical officer of Xilio. “In addition, an analysis of an on-treatment biopsy from a patient receiving 2.8 mg/kg of XTX202 demonstrated evidence of activation in the tumor with minimal active drug in peripheral circulation and also suggests that monotherapy doses at or above 2.8 mg/kg are approaching the optimal range to engage CD8+ T effector cell and NK cell expansion while continuing to avoid stimulation of regulatory T cells. Overall, these encouraging data support continued evaluation of XTX202 at a dose of 4.0 mg/kg in our Phase 2 trial of patients with metastatic renal cell carcinoma and unresectable or metastatic melanoma and the exploration of opportunities for combination therapy.” Investigator Dr. Howard Kaufman, M.D., FACS of Massachusetts General Hospital commented, “As opposed to the trademark toxicities associated with recombinant IL-2, the preliminary data from the XTX202 Phase 1/2 clinical trial demonstrate a marked difference in tolerability and the potential for long-term treatment at high doses for XTX202 that has not been possible previously with systemically active IL-2 molecules. These data showcase the importance of concentrating potent IO molecules directly in the tumor microenvironment and offer an encouraging signal for continued investigation of XTX202 monotherapy at high doses along with its broad combination potential with other mechanisms of action where the stimulation of CD8+ T cells and NK cells without expansion of regulatory T cells would be synergistic.” Data from the Ongoing Phase 1/2 Clinical Trial for XTX202 As of a data cutoff date of October 26, 2023, 62 patients with advanced solid tumors had been administered XTX202 in an outpatient setting. Fifty-four (54) patients were treated in Phase 1 monotherapy dose-escalation and dose-expansion at seven dose levels ranging from 0.27 mg/kg to 4 mg/kg administered once every three weeks (Q3W). Eight (8) patients were treated in Phase 2 monotherapy at a dose level of 1.4 mg/kg Q3W. Patients enrolled in Phase 1 were heavily pre-treated, with 74% of patients previously treated with three or more lines of anti-cancer therapy and 69% of patients previously treated with an immunotherapy. All patients in Phase 2 had been previously treated with an immunotherapy. As of the data cutoff date, 20 patients were continuing treatment with XTX202 across the Phase 1/2 trial. Preliminary Safety Data Across all dose levels administered in the Phase 1/2 trial, 62 patients were evaluable for safety. No signs or symptoms of vascular leak syndrome were reported by investigators through the 4.0 mg/kg dose. XTX202 was generally well-tolerated. Treatment-related adverse events (TRAE) were primarily Grade 1 or 2, and no patients discontinued treatment due to a TRAE. Higher grade TRAEs were primarily asymptomatic laboratory abnormalities, and no Grade 5 TRAEs were reported by investigators. The most common TRAEs (≥10% incidence) of any grade reported by investigators across all dose levels were: fatigue (19%, no grade ≥3); pyrexia (18%, no grade ≥3); chills (16%, 2% grade 3); and lymphocyte count decreased (15%, 8% grade 3-4). Grade 3 TRAEs reported in one patient each (2%) were: diarrhea/colitis; myalgia; hypoxia; lymphopenia; and aspartate transferase (AST)/alanine transaminase (ALT) increased. Investigators reported two Grade 4 TRAEs of lymphocyte count decreased/lymphopenia, which were both transient (<3 days) and resolved without intervention, with both patients able to continue on treatment. Across all dose levels, only two patients (3%) had a dose reduction due to a TRAE, and only one dose-limiting toxicity was observed, which was a reversible and transient (<5 days) Grade 3 elevation of AST and ALT at the 1 mg/kg dose. Preliminary Anti-Tumor Activity Across all dose levels administered in the Phase 1/2 trial, 42 patients were evaluable for anti-tumor activity. Of these response-evaluable patients, 27 patients were treated at dose levels of 1.4 mg/kg or higher, including six patients treated at the 2.8 mg/kg dose level or higher. Data demonstrated evidence of a dose-dependent increase in disease control rate (DCR). Among the 42 response-evaluable patients treated across all dose levels, investigators reported stable disease (SD) of at least 9-weeks duration in 13 patients (31% DCR) across a range of solid tumors, including cold tumors: melanoma (n=3); renal cell carcinoma (RCC) (n=2); non-small cell lung cancer (n=2); colorectal cancer (n=2); and myoepithelial carcinoma, vaginal cancer, testicular cancer and squamous penile cancer (n=1 each). Among the six response-evaluable patients treated at the 2.8 mg/kg dose level or higher, investigators reported SD of at least 9-weeks duration in three patients (50% DCR). In addition, two patients were ongoing on treatment for more than one year as of the data cutoff date, including a treatment-refractory microsatellite stable colorectal cancer (MSS CRC) patient and an RCC patient, suggesting XTX202 was well-tolerated with repeated, long-term dosing in these patients. Preliminary PK and PD Data Preliminary PK analysis demonstrated limited XTX202 activation in peripheral circulation, including: Dose-proportional exposure for XTX202 with minimal levels of unmasked XTX202 detected in peripheral circulation that were consistent across dose levels. Approximately 15% activated XTX202 in the tumor based on an analysis of an on-treatment patient biopsy for a patient treated with XTX202 at the 2.8 mg/kg dose level as compared to <1% activated XTX202 in plasma across patients treated with XTX202 at the 2.8 mg/kg dose level for whom PK analysis was available. These data along with non-clinical pharmacology data suggest 2.8 mg/kg or higher monotherapy doses of XTX202 are approaching the optimal range to activate CD8+ effector T cells and natural killer (NK) cells in the tumor. Consistent with IL-2 beta-gamma biology, preliminary PD analysis of four available on-treatment tumor samples showed an average increase >200% of CD8+ effector T cells in the tumor as compared to pre-treatment biopsies. Poster Presentation A copy of Xilio’s data presentation from the SITC Annual Meeting for XTX202 is available in the “Our Approach—Publications and Presentations” section of the company’s website at . Clinical Development Plans for XTX202 XTX202 recently cleared dose level seven (4.0 mg/kg) in Phase 1 monotherapy dose-escalation, and Xilio recently opened enrollment at a second dose level of 4.0 mg/kg in the ongoing Phase 2 monotherapy trial for XTX202. Based on the initial monotherapy data for XTX202, Xilio also plans to explore opportunities for strategic partnerships to evaluate XTX202 as a combination therapy. Key Upcoming Milestones As previously reported, Xilio anticipates achieving the following milestones in 2023: Activate clinical trial sites for the Phase 1 dose escalation portion of the clinical trial evaluating XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab in the fourth quarter of 2023 Report preliminary Phase 1 safety data for XTX301, a tumor-activated, engineered IL-12, into the third dose level in the fourth quarter of 2023 In addition, subject to obtaining sufficient additional capital, Xilio today announced plans to: Complete Phase 1 combination dose escalation and select a recommended Phase 2 dose for XTX101 in combination with atezolizumab in the second quarter of 2024 Subject to the results of Phase 1 combination dose escalation, initiate a Phase 2 trial for XTX101 in combination with atezolizumab in patients with MSS CRC in the third quarter of 2024 Report initial Phase 2 data for XTX101 in combination with atezolizumab in approximately 20 patients with MSS CRC in the fourth quarter of 2024 and in approximately 20 additional patients (40 patients total) in the first quarter of 2025 Report Phase 2 monotherapy data for XTX202 in approximately 20 patients treated at the 4.0 mg/kg dose with metastatic RCC or unresectable or metastatic melanoma in the second quarter of 2024 Report Phase 1 safety and PK/PD data for XTX301 in advanced solid tumors in the second half of 2024 Conference Call Information As previously announced, Xilio Therapeutics will host a live conference call and webcast Monday, November 6, 2023 at 8:00 a.m. ET to review progress across its pipeline of tumor-activated molecules, including the Phase 1/2 clinical data presented for XTX202 at the SITC Annual Meeting. The webcast may be accessed by clicking here. The webcast of the conference call will also be available under “Events and Presentations” in the Investors & Media section of the Xilio Therapeutics website at . The archived webcast will become available on the Xilio Therapeutics website approximately two hours after the conference call and will be available for 30 days following the call. About XTX202 and the Phase 1/2 Clinical Trials XTX202 is an investigational tumor-activated beta-gamma biased, engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial for XTX202 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and efficacy of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment. Please refer to NCT05052268 on for additional details. About Xilio Therapeutics Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated 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 using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including antibodies, cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting and follow us on LinkedIn (Xilio Therapeutics, Inc.). 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 to activate clinical trial sites for the Phase 1 dose escalation portion of the clinical trial evaluating XTX101 in combination with atezolizumab; plans to report preliminary Phase 1 safety data for XTX301; additional plans and anticipated milestones for XTX101, XTX202 and XTX301, subject to obtaining sufficient additional capital; the potential benefits of any of Xilio’s current or future product candidates in treating patients; 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 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 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 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 beyond the end of the second quarter of 2024; 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 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 release. For Investor and Media Inquiries: Julissa Viana Vice President, Head of Investor Relations and Corporate Communications investors@xiliotx.com Melissa Forst Argot Partners Xilio@argotpartners.com

LA JOLLA, Calif.--(BUSINESS WIRE)-- Equillium Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced a presentation at the 18th Annual Peptide Therapeutics Symposium highlighting EQ302, a second generation orally deliverable multi-cytokine inhibitor in development to target IL-15 and IL-21. The symposium, bringing together leaders in peptide research from academia and industry to focus on advances in core technology pertinent to peptide-based drug discovery and therapeutic candidate development, is taking place October 16 and 17 at the Scripps Seaside Forum in San Diego, California. Title: Peptide Stapling for Better Stability & Oral Delivery Presenting Author: Adrian J. Giovannone, Ph.D., Associate Director, Translational Science & Early Development at Equillium Date and Time: Live for the entire conference beginning at 9:30 am PT on Monday, October 16 The presentation outlines the origins of EQ302 from its parent peptide, EQ102, which was originally modeled from the D-helix of the IL-2 family of cytokines and binds directly to CD132 to inhibit the signaling of IL-15 and IL-21. Stable peptide derivatives of EQ102, including EQ302, are being developed by adding hydrocarbon staples to confer proteolytic resistance and increase stability in the gastrointestinal (GI) tract while retaining cytokine inhibitory properties​, making it a potential candidate for clinical testing in a variety of GI diseases via oral administration. EQ302 was administered to mice via oral delivery in a pre-clinical formulation designed to enhance permeability of the intestine. Following oral administration to mice challenged with human IL-15, small intestinal tissue was harvested and shown to contain significant amounts of EQ302. To demonstrate the local efficacy of the peptide, IL-15-induced Interferon-gamma (IFNγ) levels within the intestinal tissue were measured and shown to be significantly decreased in EQ302-treated animals versus vehicle control animals. The data illustrates that: Adding hydrocarbon staples to a peptide can confer increased stability in the GI tract while retaining its cytokine inhibitory properties​. Utilizing a pre-clinical formulation for enhanced epithelial permeability, EQ302 achieved meaningful concentration levels for localized cytokine inhibition in the small intestine. EQ302 delivered to mice via oral gavage can inhibit IL-15-induced IFNγ transcription locally in the GI tract indicating potential utility for Celiac Disease and inflammatory bowel disease.​ The oral presentation is available on the Presentations page of Equillium’s website, under the Multi-Cytokine Inhibition tab. About Multi-Cytokine Platform and EQ101, EQ102 & EQ302 Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases. Current platform assets include EQ101, a first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery; EQ102, a first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for subcutaneous delivery; EQ302, in development as a first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets targeting immuno-inflammatory pathways. EQ101: a tri-specific cytokine inhibitor that selectively targets IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata. EQ102: a bi-specific cytokine inhibitor that selectively targets IL-15 and IL-21; currently under evaluation in a Phase 1 first-in-human clinical study to include healthy volunteers and celiac disease patients. EQ302, in development as a first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21; currently in pre-clinical development. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd. For the development and commercialization of itolizumab under an option and asset purchase agreement. For more information, visit . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical and pre-clinical studies; whether the results from clinical and pre-clinical studies will validate and support the safety and efficacy of Equillium’s product candidates. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Equillium's filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website at and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.