Kazia Therapeutics Unveils Collaboration on Innovative PD-L1 Protein Degrader Program

Kazia Therapeutics Limited (NASDAQ: KZIA), an eminent player in oncology drug development, recently disclosed an exclusive collaboration and in-licensing agreement with QIMR Berghofer to further a groundbreaking PD-L1 degrader program. The lead compound under this initiative, named NDL2, represents a pioneering approach in the domain of cancer immunotherapy, specifically designed to target and degrade the PD-L1 protein which many cancer cells exploit to shield themselves from immune responses.

Understanding PD-L1 Degradation and NDL2's Mechanism

Research shows that tumor cells often express PD-L1 as a strategy to avoid being attacked by the immune system. When PD-L1 binds to PD-1 receptors on T cells, it effectively inactivates these immune cells, diminishing their ability to combat cancer. Traditional therapies such as pembrolizumab (Keytruda®) and nivolumab (Opdivo®) help counteract this inhibition using monoclonal antibodies. However, a significant of clinical cases reflect that patients often fail to respond or relapse after such treatments, mainly due to post-translationally modified forms of PD-L1, present not only on the surface of tumors but also within the cytoplasm and nucleus. These resistant forms contribute to cancer's progression and evasion from therapy.

The innovative NDL2 compound diverges sharply from existing therapies. This novel bicyclic peptide is engineered to recognize and degrade these resistant forms of PD-L1, utilizing the body’s natural cellular disposal mechanisms. By binding to PD-L1 and facilitating its breakdown, NDL2 aims to eliminate these protective pathways that antibodies cannot reach, thereby restoring T-cell functionality and immune responses against tumors. This groundbreaking method holds promise for both primary non-responders and those who have relapsed following antibody therapies.

Promising Preclinical Evidence

In preclinical studies involving aggressive triple-negative breast cancer (TNBC), NDL2 demonstrated remarkable efficacy. It not only showed substantial tumor reduction when used alone but also enhanced the effectiveness of anti-PD-1 treatments. Treated tumors exhibited significant reductions in T-cell exhaustion alongside improved immune activity—validation of NDL2’s dual-action capability. Encouragingly, no toxicity has been reported during preclinical assessments. Kazia and QIMR are concurrently collaborating with top oncological peptide manufacturers to enhance the stability and effectiveness of the NDL2 formulation.

Future Development Pathways and Combinatorial Approaches

The initial targets for the NDL2 program are advanced breast cancer and non-small cell lung cancer (NSCLC), where PD-1/PD-L1 agents are prevalent yet often meet resistance. Scheduled studies that enable Investigational New Drug (IND) applications are projected to commence within the next six months. The hope is to initiate first-in-human trials within 15 months. Moreover, Kazia plans to investigate potential synergistic effects by pairing NDL2 with existing projects such as paxalisib—a pan-PI3K/mTOR inhibitor—and EVT801—a selective VEGFR3 inhibitor—leveraging their complementary mechanisms in altering the tumor environment.

Dr. John Friend, CEO of Kazia Therapeutics, emphasized the strategic significance of this partnership, noting that NDL2 is poised to represent the forefront of next-generation immuno-oncology breakthroughs. Similarly, Professor Sudha Rao, who spearheads the PD-L1 degrader research at QIMR, acknowledged the potential of NDL2 in revolutionizing immunotherapy by systematically targeting and dismantling all functional forms of the PD-L1 protein.

Terms of Collaboration and Licensing Details

Under the terms of the agreement, Kazia will provide an upfront payment of approximately $1.39 million just 15 business days post-signing, assuming all development costs associated with NDL2. The company will then share a portion of any commercialization revenue, including proceeds from potential out-licensing to third-party entities.

About Kazia Therapeutics

Based in Sydney, Australia, Kazia Therapeutics is dedicated to developing innovative therapies for various cancer types. Their lead product, paxalisib, is an investigational therapy targeting the PI3K/Akt/mTOR pathway and addresses multiple cancer forms, with a noteworthy focus on glioblastoma. With ongoing trials and partnerships, Kazia is positioned to make impactful advancements in cancer therapy.

For further information, visit Kazia Therapeutics or follow them on Twitter @KaziaTx.