Kazia Therapeutics Secures Collaboration and In-Licensing for First-in-Class PD-L1 Protein Degrader Program
Thursday, October 09, 2025
Kazia Therapeutics Limited, an oncology-focused drug development company, has entered an exclusive collaboration and in-licensing agreement with QIMR Berghofer for a first-in-class PD-L1 degrader programme. The lead compound, NDL2, is an advanced PD-L1 protein degrader representing a novel approach in cancer immunotherapy.
PD-L1 is commonly expressed by cancer cells to evade immune attack by inactivating T cells. Traditional checkpoint inhibitors, such as pembrolizumab and nivolumab, block PD-L1 on the cell surface to restore T-cell activity. However, PD-L1 can also exist in modified forms within the cytoplasm and nucleus, contributing to treatment resistance and tumour progression.
NDL2 is a bicyclic peptide degrader designed to selectively target these resistant forms of PD-L1. By binding PD-L1 and recruiting the cell’s natural protein disposal system, NDL2 promotes degradation of PD-L1 across all cellular compartments. This strategy may overcome resistance to conventional antibody therapies and restore durable immune activity against tumours.
Preclinical studies in aggressive triple-negative breast cancer models showed that NDL2, both as monotherapy and in combination with anti-PD-1 therapies, significantly reduced tumour growth while reducing T-cell exhaustion and enhancing immune response. No toxicity has been observed in preclinical testing. The programme is being optimised for stability, potency, and pharmacokinetic properties in collaboration with leading oncology peptide manufacturers.
The initial focus of the programme will be on advanced breast cancer and non-small cell lung cancer, where PD-1/PD-L1 immunotherapies are commonly used but resistance remains a challenge. IND-enabling studies are expected to begin within six months, with first-in-human studies targeted within approximately 15 months. Kazia also plans to explore combining NDL2 with existing pipeline assets, including paxalisib and EVT801, to leverage complementary mechanisms in modulating the tumour microenvironment.
NDL2 represents a first-in-class approach in targeted protein degradation, aiming to address all functional PD-L1 pools within tumour cells and potentially overcome resistance to current immunotherapies.
Source: prnewswire.com
