XTX301, a tumor-activated IL-12
Xilio is focused on developing cytokines with exemplary clinical activity and tolerability. We are developing XTX301, a tumor-activated, engineered IL-12, for the treatment of advanced solid tumors.
About IL-12
IL-12, or Interleukin-12, has emerged as one of the most potent cytokine mediators of antitumor activity because of its multiple effects on different immune cells in the tumor microenvironment (TME). IL-12 has the ability to activate and bridge both innate (natural killer or NK cell) and adaptive (cytotoxic CD8+ T and CD4+ T cells) immunity for tumor cell killing while further coordinating additional anti-cancer defenses such as regulatory T-cell suppression and anti-angiogenic effects. Despite research across the field suggesting that IL-12 can significantly benefit patients in fighting cancer, there are currently no approved IL-12 agents due to severe systemic toxicity with unmodified IL-12.
XTX301, a tumor-activated IL-12
XTX301 is a highly potent, extended half-life, tumor-activated IL-12, that has the potential to deliver a therapeutic dose with low systemic toxicity and achieve a broad therapeutic index.
The design of our masked IL-12 cytokine molecule is closely related to that of our masked IL-2 cytokine molecule, which illustrates the flexibility and robustness of our cytokine engineering approach. The masking domain is designed to prevent binding to cell-surface expressed high affinity IL-12 receptor, unless the linker containing the protease site is cleaved by proteases preferentially active in the TME. The half-life extension domain is designed to overcome the short circulating half-life of the native cytokine and the overall molecule is designed to enhance the efficiency of manufacturing.
XTX301: Pre-Clinical Studies
In pre-clinical studies, we observed that XTX301 was activated in a protease-dependent manner and was clinically active and well-tolerated.
A murine version of XTX301 (mXTX301) potently inhibited tumor growth in MC38 (hot) and B16F10 (cold) syngeneic tumor mouse models without toxicity. Furthermore, XTX301 was well-tolerated in non-human primates with repeated dosing.
XTX301 demonstrated robust activation in human tumor samples but was minimally activated in vitro in human patient plasma, indicating tumor-selective activation.
XTX301 is designed to achieve potent anti-tumor activity while widening the potential therapeutic index of IL-12 treatment.
XTX301 Presentations and Publications
05/10/2022
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
11/12/2021
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