Data demonstrated that XTX101, a tumor-selective anti-CTLA-4 antibody, and anti-PD-1 combination increased tumor growth inhibition without an increase in toxicity in vivo
Company anticipates submitting IND application for XTX101 in the second quarter of 2021
WALTHAM, MA, USA I May 12, 2021 I Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, announced today 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. The findings will be reported today in a poster presentation at The New York Academy of Sciences’ Frontiers in Cancer Immunotherapy 2021 Virtual Symposium.
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.
About Xilio Therapeutics
Xilio Therapeutics is a privately-held biotechnology company that uses its proprietary technology to engineer potent cancer immunotherapies that have the potential to unleash the power of the immune system selectively at the site of the tumor. Xilio has designed its investigational therapies with the goal of maximizing efficacy and overcoming the significant toxicities associated with certain clinically validated immuno-oncology therapies, positioning them as potential treatments for a significant number of patients. The company’s proprietary pipeline includes XTX202, a tumor-selective modified form of IL-2, and XTX101, a tumor-selective anti-CTLA-4 monoclonal antibody (mAb), as well as tumor-selective IL-12 and IL-15 research programs. Xilio was founded in 2016 and is headquartered in Waltham, Mass. For more information, please visit www.xiliotx.com.
SOURCE: Xilio Therapeutics
Post Views: 81
Data demonstrated that XTX101, a tumor-selective anti-CTLA-4 antibody, and anti-PD-1 combination increased tumor growth inhibition without an increase in toxicity in vivo
Company anticipates submitting IND application for XTX101 in the second quarter of 2021
WALTHAM, MA, USA I May 12, 2021 I Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, announced today 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. The findings will be reported today in a poster presentation at The New York Academy of Sciences’ Frontiers in Cancer Immunotherapy 2021 Virtual Symposium.
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.
About Xilio Therapeutics
Xilio Therapeutics is a privately-held biotechnology company that uses its proprietary technology to engineer potent cancer immunotherapies that have the potential to unleash the power of the immune system selectively at the site of the tumor. Xilio has designed its investigational therapies with the goal of maximizing efficacy and overcoming the significant toxicities associated with certain clinically validated immuno-oncology therapies, positioning them as potential treatments for a significant number of patients. The company’s proprietary pipeline includes XTX202, a tumor-selective modified form of IL-2, and XTX101, a tumor-selective anti-CTLA-4 monoclonal antibody (mAb), as well as tumor-selective IL-12 and IL-15 research programs. Xilio was founded in 2016 and is headquartered in Waltham, Mass. For more information, please visit www.xiliotx.com.
SOURCE: Xilio Therapeutics
Post Views: 81