SYDNEY, November 13, 2026 — Kazia Therapeutics will host a virtual event on December 2 to present its preclinical candidate NDL2, a nuclear PD-L1 protein degrader designed to tackle immunotherapy resistance in advanced solid tumors. The company announced the program on November 12, describing it as a potentially first-in-class approach with an initial focus on metastatic breast and colorectal cancer.
Why Nuclear PD-L1 Matters
PD-L1 is a protein that normally helps regulate the immune system by acting as a brake on T cells. Many cancers exploit this pathway, using PD-L1 on their surface to hide from immune attack. Checkpoint inhibitor drugs that block this interaction have transformed care for some patients, but resistance remains a significant problem. Early findings suggest that PD-L1 also migrates to the cell nucleus, where it can drive tumor growth and immune evasion through mechanisms that surface-blocking antibodies cannot reach.
How Targeted Protein Degradation Differs
Conventional inhibitors typically bind to a protein to block its function. Targeted protein degradation (TPD) works differently. It recruits the cell’s own waste-disposal system — the ubiquitin-proteasome machinery — to tag the disease-associated protein for destruction. By removing the protein entirely rather than just blocking its active site, TPD can address functions that inhibitors miss, including the non-canonical roles of nuclear PD-L1. Kazia describes NDL2 as an optimized bicyclic peptide designed to selectively degrade this nuclear pool of PD-L1, with the goal of restoring the body’s natural anti-tumor immune response.
First-in-Class Potential
According to the company, there are no known nuclear PD-L1 protein degraders currently in clinical development. If NDL2 advances, it would represent a new mechanistic class within the TPD field. The program is still in the pre-IND stage, meaning it has not yet entered human trials. The December 2 virtual event is expected to cover the scientific discovery process, molecular optimization, and the path toward IND-enabling studies.
Focus on Metastatic Breast and Colorectal Cancer
The initial development focus for NDL2 is metastatic breast cancer and colorectal cancer. These are settings where immunotherapy resistance is common and new mechanistic approaches are needed. Kazia’s lead asset, paxalisib, is also being studied in advanced breast cancer and colorectal cancer, as well as primary and metastatic brain tumors. Paxalisib has received U.S. FDA Fast Track and Orphan Drug designations for glioblastoma, Fast Track designation for PI3K-altered brain metastases with radiation, and Rare Pediatric Disease and Orphan Drug designations for select pediatric brain tumors.
Recent Recognition and Next Steps
On November 5, Kazia was named Drug Discovery Company of the Year in the 2026 BioTech Breakthrough Awards. Two abstracts on paxalisib preclinical research were accepted for poster presentation at the December 2026 San Antonio Breast Cancer Symposium. The virtual event on December 2 at 4:00 PM ET will provide the first detailed public overview of the NDL2 program. Patients should talk to their doctor or oncologist about current treatment options and whether clinical trial participation may be appropriate in the future.
Sources
- Paul A. Hopper
- Kazia Therapeutics to Host Virtual Event on December 2, 2026: Advancing a New Frontier in Oncology with a First-in-Class Nuclear PD-L1 Protein Degrader
- Weekly Recap: Paxalisib posters accepted and Kazia wins award
- Kazia Therapeutics to Host Virtual Event on December 2, 2026: Advancing a New Frontier in Oncology with a First-in-Class Nuclear PD-L1 Protein Degrader – AOL
- Kazia Therapeutics to Host Virtual Event on December 2, 2026: Advancing a New Frontier in Oncology with a First-in-Class Nuclear PD-L1 Protein Degrader
Photo: Belikov Maxim (CC BY 4.0)
