On May 12, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, reported the presentation of data from preclinical studies of XTX101, its tumor-selective anti-CTLA-4 antibody, demonstrating combination potential with anti-PD-1 therapy, as well as enhanced preclinical activity and improved tolerability compared to ipilimumab, an anti-CTLA-4 antibody therapeutic approved by the U.S. Food and Drug Administration (Press release, Xilio Therapeutics, MAY 12, 2021, View Source [SID1234579820]). The findings will be reported today in a poster presentation at The New York Academy of Sciences’ Frontiers in Cancer Immunotherapy 2021 Virtual Symposium.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment and have the potential to result in localized clinical activity without dose-limiting toxicities. XTX101 is specifically designed to target the anti-CTLA-4 effect geographically within the tumor and to minimize off-tumor peripheral effects. XTX101 is activated in a protease-dependent manner with high binding affinity to CTLA-4, potentially enabling it to overcome CTLA-4 inhibition of T cell activation and freeing T cells to attack cancer.
"The broad clinical benefit of CTLA-4 blockade, as with ipilimumab, for the treatment of cancer is well-established; however, challenging toxicities arising from systemic immune activation have limited use of these agents as both monotherapy and in combination, including with anti-PD-1 agents," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "XTX101 has been engineered to overcome the tolerability and potency limitations associated with other anti-CTLA-4 antibodies by applying our proprietary masking technology to the antibody and engineering enhanced binding to target receptors. We believe these data validate our approach, and we observed that XTX101 induces tumor-selective biological activity and robust tumor growth inhibition, with favorable tolerability, in preclinical studies. We look forward to advancing XTX101 into a planned Phase 1 clinical trial in the second half of 2021."
Data reported in a poster entitled, "Tumor-Activated Anti-CTLA-4 Monoclonal Antibody, XTX101, Demonstrates Monotherapy and Anti-PD-1 Combination Benefit in Preclinical Models," include:
In a colon cancer model, the combination of XTX101 with an anti-PD-1 antibody showed robust tumor growth inhibition, including two complete responses (CRs) (n=8), where treatment with XTX101 or the anti-PD-1 agent as a monotherapy achieved only modest tumor growth inhibition and no CRs.
No significant body weight loss was observed in animals treated with either XTX101 or anti-PD-1 as a monotherapy or the combination regimen, suggesting that XTX101 can be effectively combined with anti-PD-1 without enhanced toxicity.
In a bladder cancer model, XTX101 monotherapy demonstrated tumor growth inhibition superior to ipilimumab, while a dose of 3 mg/kg of ipilimumab was required to achieve similar activity of XTX101 at 0.3 mg/kg, suggesting XTX101 has 10-fold higher potency than ipilimumab.
XTX101 as a monotherapy induced an increase in CD8+ T cells within the tumor, and a decrease in T regulatory cells in the tumor compared to ipilimumab. In addition, XTX101 achieved CRs without increasing CD4+ T cells in the blood.