XTX101 is a tumor-selective anti-CTLA-4 monoclonal antibody designed to improve upon the safety of current therapies in the same class.
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Xilio Therapeutics is celebrating a first this morning as the Waltham, MA-based biotech announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug Application (NDA) to evaluate checkpoint inhibitor, XTX101, for the treatment of patients with solid tumors.
XTX101 is a tumor-selective anti-CTLA-4 monoclonal antibody designed to improve upon the safety of current therapies in the same class.
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) acts as an immune checkpoint to downregulate immune responses. CTLA-4 plays an important role in the immune system, preventing T cells from attacking healthy cells. Unfortunately, it can also prevent T cells from identifying and killing cancer cells.
Anti-CTLA-4 antibodies strengthen the immune system by promoting the function and growth of these T cells, but they have their own limitations, and that is where therapies like XTX101 are trying to make their mark.
Activated in the tumor microenvironment, XTX101 has the potential to inspire localized clinical activity without dose-limiting toxicities.
“It is well known that checkpoint inhibitors hold significant clinical potential; however, treatment with anti-CTLA-4 therapies has been limited because of challenging autoimmune toxicities. Using our geographically precise solutions (GPS) platform, we have engineered XTX101 with the goal of enhancing the desirable features of an anti-CTLA-4 antibody while limiting the known liabilities,” said Xilio chief medical officer, Marty Huber, M.D. “We look forward to beginning Phase I development to evaluate the potential that XTX101 may offer as both a monotherapy and combination agent for patients in need.”
With its aptly named proprietary GPS platform, Xilio is creating immunotherapies that preferentially bind their targets in tumors while minimizing activity in healthy tissues.
In pre-clinical studies, XTX101 demonstrated tumor-selective biological activity and robust tumor growth inhibition and resulted in complete responses in murine cancer models. The experimental therapy also showed improved tolerability compared to fellow anti-CTLA-4 monoclonal antibody, ipilimumab.
Xilio, which has three other programs in development including XTX202, a tumor-selective IL-2 agonist, is just on the cusp of taking its work to the next level.
“This first IND acceptance for Xilio represents a significant milestone for us as we transition to a clinical-stage organization,” said Huber.
The company will waste no time getting into the clinic, as it plans to initiate a Phase I trial during the second half of 2021 to study XTX101 both as a monotherapy and in combination with Merck’s blockbuster anti-PD-1 (programmed death receptor-1) drug, KEYTRUDA®, in solid tumors.
Soon after presenting data in early May that showed optimistic combination potential with an anti-PD-1 therapy, Xilio established a clinical trial collaboration with Merck to evaluate the two drugs together.
“XTX101 is designed to be tumor-selective and based on data observed in preclinical studies, we believe it could be an ideal CTLA-4-targeting candidate to combine with checkpoint inhibitors like KEYTRUDA,” Huber said at the time.
Today’s announcement caps what has been a significant first half of 2021 for Xilio, which raised $95 million in a Series C round in February. The funds will be used to advance both XTX101 and XTX202 into the clinic.
