Kazia Therapeutics has announced the in-licensing of a first-in-class SETDB1-targeted epigenetic drug development platform from QIMR Berghofer.

The platform includes use of an Artificial Intelligence (AI)-integrated epigenetic drug discovery engine, enabling rapid, precise, and scalable candidate generation. The lead drug candidate, MSETC, was discovered and optimised using this AI-integrated epigenetic drug discovery engine. MSETC is a highly selective bicyclic peptide designed to target a novel, disease-associated nuclear SETDB1 complex. By targeting SETDB1, the program is intended to restore immune signaling in tumors that have become resistant to immunotherapy, including checkpoint inhibitors.

"SETDB1 represents a compelling emerging target in oncology," said Dr. John Friend, CEO, Kazia Therapeutics. "With this acquisition, we are extending our strategy to target how cancer controls its own behavior by addressing immune resistance at the chromatin level, one of the earliest layers of tumor immune regulation, alongside transcriptional reprogramming with paxalisib and targeted protein degradation with our PD-L1 platform. Together, these programs position Kazia's pipeline to address cancer therapy across multiple layers of tumor biology."

SETDB1 is increasingly recognised as a key epigenetic regulator of tumor immune evasion and has been associated with aggressive disease and poorer clinical outcomes in several tumor types. Preclinical studies suggest that inhibition of SETDB1 can restore interferon signaling, enhance antigen presentation, and increase tumor immune recognition.

Internal translational research has also identified a novel SETDB1-associated nuclear complex observed in resistant and metastatic disease settings, supporting continued development of Kazia's first-in-class therapeutic approach targeting this biology.

The SETDB1 program is supported by extensive peptide screening and optimisation, generating a pipeline of candidates with strong selectivity and intracellular targeting capability.

Cancer cells can evade treatment through genetic mutations, but also by dynamically reprogramming how genes and immune signals are regulated. This adaptive behavior underpins resistance to many current therapies, including immunotherapy.