On May 9, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the first quarter ended March 31, 2023 (Press release, Xilio Therapeutics, MAY 9, 2023, View Source [SID1234631302]).

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"In the first quarter, we continued to progress multiple clinical programs, notably with the recent initiation of our first Phase 2 clinical trial," said René Russo, Pharm.D., chief executive officer of Xilio. "The Phase 2 trial will assess the safety and efficacy of XTX202, our tumor-activated IL-2, in patients with advanced renal cell carcinoma and melanoma. To date, we have administered XTX202 in the outpatient setting at high dose levels and have not observed any of the severe systemic side effects commonly associated with recombinant IL-2. In addition, we plan to report preliminary data later this quarter from our Phase 1 clinical trial for XTX101, our tumor-activated, Fc-enhanced anti-CTLA-4."

Pipeline and Business Updates

XTX202: tumor-activated, engineered, beta-gamma biased IL-2

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). XTX202 is currently being evaluated in an ongoing Phase 1/2 clinical trial in patients with advanced solid tumors.

● Xilio recently initiated patient dosing at an initial dose of 1.4 mg/kg in a Phase 2 clinical trial evaluating XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment.
● In addition, Xilio recently cleared the 1.4 mg/kg dose level (dose level five) in monotherapy dose-escalation (Part 1A) for the Phase 1 clinical trial and is currently dosing patients at the 2.8 mg/kg dose level (dose level six).
● A maximum tolerated dose has not yet been determined, and enrollment in Part 1A and Part 1B of the Phase 1 clinical trial is ongoing.
● Xilio anticipates reporting preliminary anti-tumor activity, safety, pharmacokinetic (PK) and pharmacodynamic (PD) data from the Phase 1/2 clinical trial in the third quarter of 2023. The company anticipates the reported data will include approximately 15-20 evaluable 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 has 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.
● 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, Fc-enhanced anti-CTLA-4

XTX101, an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, is currently being evaluated in monotherapy dose-expansion (Part 1B) of an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● Xilio reported the acceptance of an abstract highlighting preliminary Phase 1 data at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Xilio plans to report additional preliminary Phase 1 safety, PK, PD, and anti-tumor activity data by the end of 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 and Accepted Abstracts

Xilio reported the acceptance of the following two abstracts at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.

Xilio will present a trials-in-progress poster highlighting details of the Phase 1 clinical trial for XTX301:

● Presentation title: A first-in-human study of XTX301, a masked, tumor-activated interleukin-12 (IL-12), in patients with advanced solid tumors.
● Session date and time: June 3, 2023, 9:00 am to 12:00 pm EDT
● Abstract number: TPS2672
The following abstract highlighting preliminary safety, PK, and anti-tumor activity data from the Phase 1 clinical trial for XTX101 was accepted for inclusion in the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting Proceedings, Journal of Clinical Oncology supplement:

● Presentation Title: Phase 1/2 study of XTX101, a masked, tumor-selective Fc-modified anti-CTLA-4, in patients with advanced solid tumors.
● Abstract number: e14685
First Quarter 2023 Financial Results

● Cash Position: Cash and cash equivalents were $93.3 million as of March 31, 2023, compared to $120.4 million as of December 31, 2022.
● Research & Development (R&D) Expenses: R&D expenses were $16.1 million for the quarter ended March 31, 2023, compared to $14.9 million for the quarter ended March 31, 2022. The increase was primarily driven by increased clinical development activities for XTX202, increased clinical development and manufacturing activities for XTX301, increased personnel-related costs, and increased costs related to the company’s earlier-stage programs. These increases were partially
offset by decreases in manufacturing activities for XTX202, preclinical development activities for XTX301 and clinical development activities for XTX101.
● General & Administrative (G&A) Expenses: G&A expenses were $7.4 million for the quarter ended March 31, 2023, compared to $6.3 million for the quarter ended and March 31, 2022. The increase was primarily driven by increased personnel-related costs and an increase in professional and consulting fees.
● Net Loss: Net loss was $22.6 million for the quarter ended March 31, 2023, compared to $21.4 million for the quarter ended March 31, 2022.
Financial Guidance

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

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

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to 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. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.