Unleashing the full potential of immuno-oncology therapies
Current immuno-oncology (I-O) therapies have curative potential for patients with cancer; however, their potential is significantly curtailed by systemic toxicity that results from activity of the therapeutic molecule outside the tumor microenvironment (TME). Our focus is to improve upon two of the foundational mechanisms of IO – cytokines and checkpoint inhibitors – with the goal of overcoming the limitations of current I-O therapies to develop products with an improved efficacy-to-toxicity ratio, or therapeutic index.
We are leveraging our geographically precise solutions (GPS) platform to rapidly engineer novel molecules, including cytokines and other biologics, that are designed to optimize their therapeutic index by geographically localizing their activity inside tumors.
Our GPS Platform
Our geographically precise solutions (GPS) platform enables us to engineer a broad range of immune-modulatory molecules, including cytokines and antibodies, that contain masking domains that minimize the activity of these molecules outside of the tumor microenvironment (TME). The molecules are then designed to be turned on selectively in the TME where they are activated by the unique conditions in the TME, including the preferential activity of matrix metalloproteases (MMPs), which are enzymes that are essential for tumor growth. Specifically, MMPs cleave a linker that connects the masking protein domain to the active agent. This separates the mask from the active agent, enabling the unmasked agent to promote an anti-tumor response within the TME. This approach is intended to bring the benefits of I-O therapy to patients by minimizing toxicity while enhancing anti-tumor activity.
Lung Cancer Example
Xilio Tumor Selective
Lung Cancer Example
We have shown preclinical validation of the ability of our GPS platform to develop tumor-selective antibodies and cytokines, as evidenced by our tumor-selective anti-CTLA-4 antibody, XTX101, and our tumor-selective IL-2, XTX202. In preclinical studies, each of these product candidates has exhibited tumor-selective biological activity, tumor growth inhibition and minimal to no toxicity outside of the TME. In addition, the reproducibility of these data, as evidenced by tumor-selective activity observed in preclinical studies with our engineered IL-12 cytokine, XTX301, highlights the potential breadth of application of our GPS platform to multiple structurally diverse cytokines or antibodies.
Leveraging our GPS platform, we intend to develop a number of additional product candidates using a range of tumor targeting approaches, with the goal of achieving a clinically meaningful improvement in their therapeutic index. We also plan to evaluate opportunities for better tolerated and more efficacious combination therapies, using product candidates from across our portfolio with other cancer therapies, to increase the potential for curative regimens in oncology. Beyond oncology, we also plan to apply our GPS platform to other disease areas in which the immune system is dysregulated, such as in autoimmune and inflammatory diseases.
Presentations and Publications
XTX301 Poster Presentation at the New York Academy of Sciences’ Frontiers in Cancer Immunotherapy 2022 Conference A half-life extended, tumor selective IL-12 activated tumor infiltrating immune cells and demonstrated anti-tumor activity in the MC38 syngeneic mouse model
XTX301 Poster Presentation at the Society for Immunotherapy in Cancer’s 36th Annual Meeting (SITC)
XTX301, A Protein-engineered IL-12, Exhibits Tumor-selective Activity In Mice Without Peripheral Toxicities And Is Well Tolerated In Non-Human Primates
Presentation at the Next-Gen Cytokine Therapeutics Summit
Tumor selective cytokines for cancer therapy
XTX202 (IL-2) Poster Presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting
XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates
XTX101 (CTLA-4) Poster Presentation at The New York Academy of Sciences’ Frontiers in Cancer Immunotherapy 2021 Virtual Symposium
Tumor-Activated Anti-CTLA-4 Monoclonal Antibody, XTX101, Demonstrates Monotherapy and Anti-PD-1 Combination Benefit in Preclinical Models
XTX101 (CTLA-4) Poster Presentation at 35th Annual Meeting of The Society for Immunotherapy of Cancer
Tumor-activated Fc-engineered Anti-CTLA-4 Monoclonal Antibody, XTX101, Demonstrates Tumor-selective PD and Efficacy in Preclinical Models
XTX201 (IL-2) Poster Presentation at 35th Annual Meeting of The Society for Immunotherapy of Cancer
XTX201, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates