Pilatus Biosciences Inc. has received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for PLT012, a drug candidate aimed at treating liver and intrahepatic bile duct cancers, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). The designation, granted in November 2024, is a significant milestone for the company, potentially expediting the development of this novel therapy for cancers with high unmet medical needs.
PLT012: Targeting the Tumor Microenvironment
PLT012 is a humanized anti-CD36 antibody that operates through a dual mechanism of action. It is designed to disarm immunosuppressive cell populations while simultaneously enhancing effector T cell functions. This approach aims to reprogram the tumor microenvironment (TME), making it more conducive to immune-mediated cancer cell killing. Preclinical studies have demonstrated PLT012's anti-tumor efficacy in both immune 'hot' and 'cold' tumor models, with observed increases in CD8+ T cell activity and reductions in pro-tumorigenic macrophages.
According to Prof. Ping-Chih Ho, Chair of the Scientific Advisory Board and Co-founder of Pilatus Biosciences, PLT012's mechanism leverages metabolic checkpoint targeting to reprogram the TME, offering a unique therapeutic approach.
Clinical Development and Future Plans
Pilatus Biosciences is actively advancing the development of PLT012, working closely with regulatory bodies to accelerate its availability. The company anticipates submitting its first U.S. Investigational New Drug (IND) application and initiating patient dosing in 2025. PLT012 has shown potential against various tumors with unmet medical needs.
Orphan Drug Designation: Incentives and Benefits
The FDA's Orphan Drug Designation program is designed to support the development of therapies for rare diseases affecting fewer than 200,000 people in the United States. The designation provides several benefits to the drug sponsor, including tax credits for qualified clinical testing, exemptions from prescription drug user fees, and seven years of marketing exclusivity upon FDA approval.
Liver and Intrahepatic Bile Duct Cancer: An Unmet Need
Primary liver cancer, which includes HCC and ICCA, often requires complex treatment strategies due to high recurrence rates. Metabolic reprogramming plays a critical role in these cancers, modifying the TME to support tumor growth and immune evasion. Current first-line systemic therapies for HCC include combinations of PD-L1 inhibitors with VEGF inhibitors or CTLA-4 inhibitors. However, most patients require multiple lines of treatment, with recurrence rates as high as 88%. PLT012's dual mechanism of action offers a potential strategy to synergize with existing treatments and enhance therapeutic outcomes through immune stimulation in the TME.
Dr. Raven Lin, CEO and Co-founder of Pilatus Biosciences, stated that the company is honored to receive the Orphan Drug Designation for PLT012, emphasizing the urgent need for innovative therapies in liver and intrahepatic bile duct cancer.
