TEAD Inhibitor Program

IK-930, a TEAD inhibitor targeting a key tumor suppressor axis with tumor cell intrinsic dependence and immunomodulatory mechanisms of action known as the Hippo pathway, is in IND-enabling studies.

TEAD Program

IK-930 is a TEAD inhibitor targeting a key tumor suppressor axis with tumor cell intrinsic dependence and immunomodulatory mechanisms of action known as the Hippo pathway.

IK-930

The Hippo pathway is a critical signal transduction pathway that regulates cell fate, polarity, proliferation, and survival, as well as organ size and tissue homeostasis. Numerous non-canonical oncogenes and tumor suppressors, including KRAS, NRAS, p53, PTEN, PIK3CA, EGFR, and β-catenin, can affect Hippo signaling in multiple cancer types. Key nodes in the pathway, such as NF2 and LATS1/2, are also highly dysregulated in cancer. Activated Hippo signaling correlates with poor patient outcomes in a number of cancers. Moreover, the Hippo pathway has been shown to promote immune evasion via multiple mechanisms.

When the Hippo pathway is inactivated, the transcriptional coactivators YAP and TAZ are stabilized, translocate into the cell nucleus and bind to the TEAD transcription factor to drive transcription of multiple genes involved in tumor initiation and progression, cancer metastasis, and therapeutic resistance. It has been demonstrated that acquired Tyrosine Kinase Inhibitor (TKI) resistance is dependent upon increased YAP/TAZ-TEAD transcription via direct activation to bypass BRAF. Inhibition of TEAD can lead to restored TKI sensitivity.

The internally developed IK-930 TEAD inhibitor product candidate is currently in IND-enabling studies. Ikena plans to file an IND in the second half of 2021 and to initiate a Phase 1 clinical trial evaluating single-agent IK-930 in biomarker-enriched patient populations, such as those with Hippo pathway-altered tumors.

Ikena believes that their TEAD inhibitors have the potential to be active both as single-agent therapy and in combination with other standard of care oncology agents to overcome therapeutic resistance. In addition, translational studies are ongoing to identify additional tumor types likely to be Hippo pathway-driven and dependent on TEAD function.

Our pipeline includes patient-directed programs targeting tumor cells and modulating the immune system.