On March 2, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Xilio Therapeutics, MAR 2, 2023, View Source [SID1234628075]).

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"In 2022, we made significant progress against our goals, advancing the clinical development of all three of our novel tumor-activated immuno-oncology programs. Importantly, we observed promising early clinical evidence of our platform in the first two on-treatment tumor samples from patients treated with XTX202, where both the pharmacodynamics in the tumor and in the patients’ peripheral blood were consistent with our expectations for how our tumor-activated molecules are designed to perform," said René Russo, Pharm.D., chief executive officer of Xilio. "In addition, we look forward to several anticipated milestones in 2023, including reporting clinical data from our trials for XTX101, XTX202 and XTX301."

Pipeline and Business Updates

XTX202: tumor-activated, engineered IL-2

XTX202 is an investigational tumor-activated beta-gamma biased (non-alpha), 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). XTX202 is currently being evaluated in an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● Xilio recently completed dosing patients at the 1 mg/kg dose level (dose level four) and is currently dosing patients at the 1.4 mg/kg dose level (dose level five) in monotherapy dose-escalation (Part 1A) for the Phase 1 clinical trial.
● As of March 1, 2023, a total of 16 patients have been treated with XTX202 in the outpatient setting at five dose levels ranging from 0.27 mg/kg to 1.4 mg/kg once every three weeks (Q3W) in Part 1A for the Phase 1 clinical trial, and monotherapy dose expansion (Part 1B) is open for enrollment.
● No signs of vascular leak syndrome (VLS), including hypotension or decreases in albumin (an early sign of VLS) or hemodynamic compromise, have been observed in patients to date.
● Xilio recently reported preliminary intra-tumoral pharmacokinetics (PK) and pharmacodynamic (PD) data for two patients treated with XTX202, each of whom had an optional on-treatment tumor biopsy and are the only two patients from whom a tumor sample analysis is available to date. For each patient, the tumor sample featured increased numbers of stromal tumor infiltrating

lymphocytes (TILs) and increased frequency of CD8+ effector T cells among these TILs. At the time of the tumor sample, these changes occurred in each patient in the absence of peripheral changes to CD8+ effector T cells demonstrating preliminary evidence of tumor-selective activation.
● A maximum tolerated dose has not yet been determined, and enrollment in Part 1A and Part 1B of the clinical trial is ongoing.

Xilio anticipates multiple milestones for XTX202 through the end of 2023:

● Initiate patient enrollment in a Phase 2 clinical trial evaluating XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma in April 2023.
● Report preliminary anti-tumor activity, safety, PK and PD data from the Phase 1/2 clinical trial in the third quarter of 2023. Xilio anticipates the reported data will include approximately 15-20 patients across a range of solid tumors treated at the 1 mg/kg dose or higher across all cohorts in the Phase 1/2 clinical trial.

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 recently opened clinical trial sites and is actively screening patients for enrollment at a starting dose of 5.0 ug/kg (0.005 mg/kg) in monotherapy dose-escalation for its Phase 1 clinical trial evaluating the safety and tolerability of XTX301 in patients with advanced solid tumors.
● In addition, Xilio anticipates reporting preliminary safety data from the Phase 1 clinical trial into at least the third dose level in the fourth quarter of 2023.

XTX101: tumor-activated anti-CTLA-4

XTX101, an investigational Fc-enhanced, tumor-activated anti-CTLA-4, is currently being evaluated in an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● As of March 1, 2023, 24 patients have been treated with XTX101 in the Phase 1 clinical trial. Enrollment in monotherapy dose-escalation (Part 1A) has been completed, and enrollment in monotherapy dose-expansion (Part 1B) is ongoing.
● Xilio has determined a recommended Phase 2 dose (RP2D) of 150 mg once every six weeks (Q6W).
● Xilio anticipates reporting preliminary safety, PK, PD and anti-tumor activity data from the Phase 1 clinical trial in the second quarter of 2023.
● In addition, as previously announced, Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 trial.

Upcoming Presentations

Xilio reported the acceptance of the following two abstracts for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida.

Xilio will present a poster highlighting preclinical data demonstrating anti-tumor activity of XTX301 in preclinical mouse models with improved tolerability compared to a systemically active IL-12 molecule.

● Presentation title: A half-life extended, tumor-activated IL-12 increased the infiltration of effector immune cells into the tumor microenvironment and demonstrated anti-tumor activity in syngeneic mouse models.
● Session date and time: Sunday, April 16, 2023, at 1:30 pm to 5:00 pm E.T.
● Abstract number: 587
● Poster Board Number: 21

Xilio will present a poster highlighting preclinical data for a discovery-stage, tumor-activated multi-functional molecule.

● Presentation title: Tumor-activated PD1-directed IL-2 increased antigen specific T cells in tumors and demonstrated anti-tumor activity in mice.
● Session date and time: Sunday, April 16, 2023, at 1:30 pm to 5:00 pm E.T.
● Abstract number: 572
● Poster Board Number: 6

Year-End and Fourth Quarter 2022 Financial Results

● Cash Position: Cash and cash equivalents were $120.4 million as of December 31, 2022, compared to $198.1 million as of December 31, 2021.
● Research & Development (R&D) Expenses: R&D expenses were $15.0 million for the quarter ended December 31, 2022, compared to $11.4 million for the quarter ended December 31, 2021. R&D expenses were $59.2 million for the year ended December 31, 2022, compared to $51.2 million for the year ended December 31, 2021. The year-over-year increase was primarily driven by increased manufacturing, preclinical and clinical development activities for XTX301, increased clinical development activities for XTX202, increased personnel-related costs and increased costs related to the company’s earlier-stage programs. These increases were partially offset by a decrease in manufacturing and preclinical expenses for XTX202 as the program advanced further into clinical development in 2022.
● General & Administrative (G&A) Expenses: G&A expenses were $8.2 million for the quarters ended December 31, 2022 and December 31, 2021, respectively. G&A expenses were $29.9 million for the year ended December 31, 2022, compared to $23.9 million for the year ended December 31, 2021. The year-over-year increase was primarily driven by increased personnel-related costs and an increase in expenses associated with operating as a public company.
● Net Loss: Net loss was $22.5 million for the quarter ended December 31, 2022, compared to $19.7 million for the quarter ended December 31, 2021. Net loss was $88.2 million for the year ended December 31, 2022, compared to $75.8 million for the year ended December 31, 2021.
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 second quarter of 2024.

About XTX202 (IL-2) and the Phase 1/2 Clinical Trial

XTX202 is an investigational tumor-activated beta-gamma biased (non-alpha), 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. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

The planned Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and anti-tumor activity of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma at the recommended Phase 2 dose. 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. In November 2022, the U.S. Food and Drug Administration cleared Xilio’s investigational new drug application for the evaluation of XTX301 as a potential treatment for patients with advanced solid tumors.

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 XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial

XTX101 is an investigational Fc-enhanced, tumor-activated anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the 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. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.