Ikena’s IK-412 is a highly active and stable engineered human kynurenine-degrading enzyme that may be able to overcome resistance to immune modulating agents.
IK-412 is a highly active and stable engineered human kynurenine-degrading enzyme.
Kynurenine is a metabolite of the tryptophan degradation pathway and has long been recognized as an important contributor to immunosuppression. Recent clinical data suggests that increased kynurenine is an adaptive resistance mechanism to anti-PD1 therapy in multiple cancers. Kynurenine is produced by the enzymes indoleamine-pyrrole 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO2). Increased kynurenine production has been linked to tumor growth and therapeutic resistance. Since IDO1 and TDO2 are often expressed together, Ikena believes that inhibition of either IDO1 or TDO2 alone may be insufficient to disrupt the immunosuppressive effect of kynurenine.
Ikena is advancing IK-412 (formerly known as KYN-412 or “Kynase”), an engineered human kynurenine degrading enzyme. Direct catalytic degradation of kynurenine itself, rather than merely inhibiting IDO or TDO, is a superior way of modulating the immunosuppressive tumor microenvironment and may achieve a more powerful antitumor response. This approach, therefore, has the potential to result in improved outcomes for patients with tumors that express IDO1 or TDO2 or both.
IK-412 is currently undergoing IND-enabling studies and Ikena expects to file an IND in the second half of 2020. The first-in-human clinical trial will be focused on patients with cancers that express high IDO1/TDO2, reflecting our biomarker-based, rational drug development approach.
In January 2019, Ikena entered into an exclusive global strategic collaboration with Celgene Corporation, now Bristol-Myers Squibb, for the development of IK-175 and IK-412. Ikena is responsible for research and development activities for IK-412 through Phase 1b. Bristol-Myers Squibb is then eligible to assume a global license to IK-412 and would be responsible for further development and commercialization.
For more information, please see the press release announcing the Ikena-Bristol-Myers Squibb partnership.
IK-412 has met the target development candidate profile:
- Highly active and stable
- Non-immunogenic in preclinical species
- Can be dosed weekly
Preclinically, IK-412 has shown
- Durable and significant depletion of kynurenine after a single dose
- Superior to IDO1 selective inhibition in both kynurenine depletion and immune stimulation
- Antitumor activity as a single agent and in combination with other therapies in preclinical models of cancer