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Kazia Therapeutics Limited, a clinical-stage oncology company advancing therapies to reprogramme cancer biology and overcome treatment resistance, announces the in-licensing of a first-in-class SETDB1-targeted epigenetic drug development platform from QIMR Berghofer.
The platform includes use of an AI-integrated epigenetic drug discovery engine, enabling rapid, precise, and scalable candidate generation. The lead drug candidate, MSETC, was discovered and optimized 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 signalling in tumours that have become resistant to immunotherapy, including checkpoint inhibitors.
“SETDB1 represents a compelling emerging target in oncology,” said Dr. John Friend, CEO of Kazia Therapeutics. “With this acquisition, we are extending our strategy to target how cancer controls its own behaviour by addressing immune resistance at the chromatin level, one of the earliest layers of tumour immune regulation, alongside transcriptional reprogramming with paxalisib and targeted protein degradation with our PD-L1 platform. Together, these programmes position Kazia’s pipeline to address cancer therapy across multiple layers of tumour biology.”
SETDB1 A High-Value Target in Immune Resistance SETDB1 is increasingly recognized as a key epigenetic regulator of tumour immune evasion and has been associated with aggressive disease and poorer clinical outcomes in several tumour types. Preclinical studies suggest that inhibition of SETDB1 can restore interferon signalling, enhance antigen presentation, and increase tumour 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 programme is supported by extensive peptide screening and optimization, 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 behaviour underpins resistance to many current therapies, including immunotherapy.
Kazia’s pipeline now spans three complementary layers of cancer control:
• Chromatin-level regulation (SETDB1) restoring immune visibility by reactivating suppressed signalling pathways
• Transcriptional reprogramming (paxalisib) altering gene expression programs that drive tumour growth and immune suppression
• Protein-level control (PD-L1 degrader platform, NDL2) eliminating intracellular PD-L1 and overcoming resistance mechanisms beyond antibody-based therapies
This integrated approach is designed to address tumour resistance at its source and create new opportunities for combination therapies across multiple cancer types.
Epigenetic therapies represent a validated and expanding segment of oncology, with multiple approved agents demonstrating clinical impact. Earlier approaches helped establish the importance of epigenetic regulation in cancer but were often limited by broad, non-specific activity and modest clinical impact, particularly in solid tumours.
Advances in the understanding of tumour biology and immune resistance now enable more precise, mechanism-driven approaches. These next-generation strategies are designed to target specific drivers of tumour adaptation and immune evasion, with the potential for broader applicability and improved outcomes, particularly in combination with immunotherapy.
The global epigenetic therapeutics market is estimated to be in the range of $15–20 billion annually and is expected to grow meaningfully over the next decade, driven by next-generation approaches targeting immune resistance and tumour plasticity.
By targeting SETDB1, Kazia is addressing a major unmet need in aggressive, treatment refractory cancers that account for a significant proportion of cancer-related mortality. The approach is designed to restore immune responsiveness across multiple tumour types, particularly in advanced and metastatic disease settings where treatment options remain limited.
The SETDB1 programme is currently in preclinical development with a defined path toward IND enabling studies. Kazia plans to generate translational data to support biomarker-driven development and combination strategies with immunotherapies and targeted agents.
Given its broad applicability across tumour types, and its role in immune resistance, the company believes the programme represents a compelling opportunity for early strategic partnerships.
Kazia intends to advance the SETDB1 programme in parallel with its PD-L1 degrader platform through IND-enabling studies. By leveraging shared CRO resources, coordinated study design, and established scientific collaborations, the company expects to achieve meaningful execution efficiencies.
The combined cost to advance both programmes to IND readiness is expected to be approximately $6 million over 18 months, with a substantial portion of eligible expenditure expected to qualify for the Australian R&D tax incentive. This approach enables Kazia to expand its pipeline while maintaining capital discipline and preserving focus on ongoing clinical programmes.
Under the terms of the agreement, Kazia has acquired global rights to the SETDB1 platform, including the lead candidate MSETC. Financial terms include an upfront payment of approximately $1.39 million and a tiered revenue-sharing structure aligned with development progress, with no clinical or regulatory milestone obligations.
Kazia Therapeutics Limited is an oncology-focused drug development company, based in Sydney, Australia. Its lead programme is paxalisib, an investigational brain penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in this disease.
QIMR Berghofer is a world-leading, translational medical research institute based in Brisbane, Australia. Established in 1945, the Institute is home to almost 1,000 scientists, clinician scientists, support staff, and students working across four key research programmes of Cancer Research, Infection and Inflammation, Population Health, and Brain and Mental Health.
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