A novel cancer therapy developed at QIMR Berghofer is set to enter clinical development following a new collaboration and in-licensing agreement with Kazia Therapeutics, an oncology-focused drug development company. The therapy, known as NDL2, is a first-in-class PD-L1 protein degrader and represents a new frontier in cancer immunotherapy.
Under the agreement, Kazia Therapeutics has secured exclusive rights to develop and commercialise the program, which was discovered and developed by Professor Sudha Rao and her team at QIMR Berghofer. NDL2 is currently the most advanced PD-L1 degrader in development globally.
PD-L1 is a protein that cancer cells use to evade immune attack. When PD-L1 on a tumour cell binds to PD-1 on a T cell, the immune response is suppressed. Existing therapies, such as pembrolizumab (Keytruda®) and nivolumab (Opdivo®), use monoclonal antibodies to block this interaction on the cell surface.
However, research has shown that PD-L1 also exists in post-translationally modified forms inside the cell, particularly in patients who fail or relapse on checkpoint inhibitor therapy. These modified proteins contribute to resistance and tumour progression.
NDL2 takes a fundamentally different approach. This bicyclic peptide degrader is designed to specifically recognise and break down these resistant forms of PD-L1 across all cellular compartments—including the surface, cytoplasm and nucleus. By recruiting the cell’s natural protein disposal machinery, NDL2 eliminates PD-L1 pools that antibody therapies cannot reach.
Kazia Therapeutics CEO John Friend and QIMR Berghofer Director and CEO Professor Fabienne Mackay
Professor Sudha Rao, Principal Investigator at QIMR Berghofer and inventor of the PD-L1 degrader program, said:
“NDL2 has the potential to redefine immunotherapy by targeting all functional pools of PD-L1 protein, not just the surface expression blocked by current antibodies. By eliminating PD-L1 throughout the cell, we can address resistance and other pathways that drive aggressive cancers like triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). We are thrilled to partner with Kazia to potentially translate this novel science into a transformative therapy for patients.”
In preclinical models of TNBC, NDL2 has demonstrated significant tumour growth reduction, both as a monotherapy and in combination with anti-PD-1 therapies. Treated tumours showed reduced T-cell exhaustion and enhanced immune activity, consistent with the compound’s dual mechanism of action. No toxicity has been observed in preclinical studies to date, suggesting the molecule may offer a safe and effective approach.
Working with world-leading oncology peptide manufacturers, QIMR Berghofer researchers have optimised the stability, potency, pharmacokinetics and pharmacodynamics of the NDL2 formulation.
The program will initially target advanced TNBC and NSCLC - two cancers where PD-1/PD-L1 therapies are widely used but resistance remains common. Investigative new drug enabling studies are expected to begin within six months, with first-in-human trials anticipated in approximately 15 months.
Kazia Therapeutics also plan to explore combination opportunities with its existing pipeline assets, including paxalisib (a pan-PI3K/mTOR inhibitor) and EVT801 (a selective VEGFR3 inhibitor), which offer complementary mechanisms of action in modulating
the tumour microenvironment.
Dr John Friend, Chief Executive Officer of Kazia Therapeutics, said: “This agreement positions Kazia at the forefront of next-generation immuno-oncology. NDL2 is a truly first-in-class asset, representing the furthest advanced PD-L1 degrader globally and we believe one of the most exciting innovations in targeted protein degradation. This program complements our existing pipeline, with clear opportunities for synergy with other immunotherapies as well as Paxalisib and EVT801, and we are positioned to rapidly advance it toward the clinic.”
The licensing agreement was formally signed by Dr John Friend and QIMR Berghofer Director and CEO, Professor Fabienne Mackay, marking the beginning of a collaboration that could have widespread positive implications for people living with cancer.