Kazia Therapeutics Limited, a Sydney-based oncology-focused drug development company, has entered into an exclusive collaboration and in-licensing agreement with QIMR Berghofer to advance a pioneering PD-L1 degrader programme. The lead compound, NDL2, represents a first-in-class, optimised PD-L1 protein degrader designed to overcome resistance in cancer immunotherapy.

Cancer cells often express PD-L1 proteins that help them evade immune system attacks. While current checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) block surface PD-L1 to reactivate immune response, they do not address post-translationally modified PD-L1 forms that contribute to resistance and disease progression.

NDL2, a novel bicyclic peptide degrader developed by Professor Sudha Rao, targets and destroys these resistant PD-L1 proteins across all cellular compartments by recruiting the cell’s natural protein disposal mechanisms. This approach offers the potential to overcome immunotherapy resistance and restore durable T-cell activity.

Preclinical studies in triple-negative breast cancer (TNBC) demonstrated that NDL2, both as monotherapy and in combination with anti-PD-1 therapies, significantly reduced tumour growth and reversed T-cell exhaustion, with no observed toxicity.

The programme will initially focus on advanced breast cancer and non-small cell lung cancer (NSCLC), with IND-enabling studies expected within six months and first-in-human trials planned in around 15 months.

Dr John Friend, CEO of Kazia Therapeutics, stated: “This agreement positions Kazia at the forefront of next-generation immuno-oncology. NDL2 is a truly first-in-class PD-L1 degrader and represents one of the most exciting innovations in targeted protein degradation. It complements our pipeline and creates clear synergy opportunities with paxalisib and EVT801.”

Under the agreement, Kazia will make a one-time payment of approximately USD 1.39 million within 15 business days of signing and will bear all development costs. The company will also share a percentage of future commercialisation revenues, including out-licensing income.