Pilatus Biosciences Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its leading molecule, PLT012, for the treatment of liver and intrahepatic bile duct cancer (HCC/ICCA). This designation, awarded in November 2024, marks a significant advancement in developing innovative therapies for these malignancies.
PLT012 is a humanized anti-CD36 antibody with a dual mechanism of action, disarming immunosuppressive cell populations while amplifying effector cell functions. The drug has shown potential against multiple tumors with unmet medical needs and is set to advance to its first U.S. IND submission and first patient dosing in 2025.
Targeting Metabolic Checkpoints in Liver Cancer
According to Pilatus Biosciences, metabolic reprogramming plays a crucial role in promoting tumor progression in HCC and ICCA by modifying the tumor microenvironment (TME) to support tumor growth and immune evasion. PLT012 leverages metabolic checkpoint targeting to reprogram the TME, offering a unique therapeutic approach.
"We are honored to receive Orphan Drug Designation for PLT012, a milestone that reflects our dedication to addressing the urgent need for innovative therapies in liver and intrahepatic bile duct cancer," said Dr. Raven Lin, CEO and Co-founder of Pilatus Biosciences. Prof. Ping-Chih Ho, Chair of the Scientific Advisory Board and Co-founder of Pilatus Biosciences, added, "This designation highlights the promising scientific discoveries and results we have achieved in addressing the underserved area. It further motivates us to accelerate PLT012’s development and collaborate globally to bring this promising treatment to patients with limited options."
PLT012's Mechanism of Action and Preclinical Data
PLT012 demonstrates anti-tumor efficacy in both immune 'hot' and 'cold' tumor models, with a significant augmentation in GzmB-expressing CD8+ T cells and reductions in both intratumoral Tregs and pro-tumorigenic macrophages. Additionally, PLT012 treatment alters the exhaustion features of cytotoxic CD8+ T cells by increasing the populations of progenitor- (Texprog) and terminal-exhausted T cells (Texterm), highlighting enhanced anti-tumor immunity when combined with immune checkpoint blockade therapies, such as PD-1 or PD-L1 inhibitors.
Orphan Drug Designation Benefits
The FDA's Orphan Drug Designation program provides orphan status to drugs intended for the treatment, diagnosis, or prevention of rare diseases affecting fewer than 200,000 people in the United States. ODD qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and 7 years of marketing exclusivity upon FDA approval.
The Need for New Treatments in HCC and ICCA
The two most common types of liver and intrahepatic bile duct cancer are hepatocellular carcinoma (HCC, 80-90% of cases) and intrahepatic cholangiocarcinoma (ICCA, 10-15% of cases). For HCC, the most common first-line systemic therapies include either a combination of a PD-L1 inhibitor and a VEGF inhibitor or a combination of a PD-L1 inhibitor and a CTLA-4 inhibitor. However, the recurrence rate of HCC has been reported to be as high as 88%, and most patients require multiple lines of treatment. PLT012 emerges as a promising candidate, demonstrating a dual MOA that synergizes with existing treatments and provides immune-stimulating effects in the TME, potentially enhancing therapeutic outcomes.
Pilatus Biosciences is actively engaging with regulatory authorities and stakeholders to expedite the availability of PLT012.
