Study demonstrates PLT012 reprograms tumor immunity by targeting metabolic suppression in hepatocellular carcinoma (HCC) and liver metastases
Findings establish proof-of-concept for CD36 as a novel immunometabolic checkpoint in solid tumors
PLT012 has received FDA Orphan Drug Designation for liver and intrahepatic bile duct cancers with IND submission expected by end of 2025
Pilatus Biosciences, a biotechnology company developing immunometabolic therapies for cancer, today announced a preclinical publication in Cancer Discovery detailing the mechanism and therapeutic potential of its lead candidate, PLT012.
The paper, titled: "PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Anti-Tumor Immunity Against Liver Cancer and Liver Metastasis," establishes PLT012 as the first humanized antibody to target CD36, a lipid scavenger receptor implicated in immune dysfunction in metabolically hostile tumor microenvironments and highlights its efficacy in restoring anti-tumor immunity in hepatocellular carcinoma (HCC) and colorectal liver metastases.
CD36 is upregulated in immune cells exposed to lipid-rich, inflammatory environments and has emerged as a key driver of immune suppression in solid tumors. By blocking CD36-mediated lipid uptake, PLT012 reduces intratumoral Tregs and pro-tumor macrophages, while enhancing CD8+ T cell infiltration, survival, and cytotoxicity.
"Liver cancer presents a unique opportunity to improve patient outcomes by addressing the underlying immunometabolic suppression that can limit the effectiveness of current checkpoint inhibitors," said Yi-Ru Yu, Ph.D., Lead Scientist of Pilatus Biosciences and co-first author of the study. "Our data show that PLT012, our lead CD36-targeting immunometabolic therapy, restores immune function at its metabolic core to reprogram the tumor environment to enable effective and durable anti-tumor responses."
Key Findings from the Cancer Discovery Study:
- PLT012 monotherapy drives tumor regression in both immune-inflamed and immune-excluded HCC models, including ß-catenin-driven tumors resistant to checkpoint blockade.
- In combination with anti-PD-L1 and anti-VEGF therapies, PLT012 significantly improves tumor control and increases complete response rates.
- In colorectal cancer models with liver metastases, PLT012 restores responsiveness to PD-1 blockade and reprograms macrophage phenotypes.
- Ex vivo validation in human HCC samples showed increased CD8+ T cell activity in 45% of patient samples and decreased Tregs in 82% of samples treated with PLT012.
- Toxicology studies in non-human primates confirmed a favorable safety profile, with no adverse effects observed at doses up to 200 mg/kg.
"This work validates CD36 as a tractable target in immuno-oncology and positions PLT012 as a first-in-class therapeutic with broad potential across solid tumors characterized by metabolic immune suppression," said Raven Lin, CEO Founder, Pilatus Biosciences. "These important milestones highlight PLT012's potential to transform treatment for patients with advanced solid tumors."
"The ability of PLT012 to reprogram the tumor microenvironment by overcoming metabolic immune suppression marks a major advancement for the field of immuno-oncology," said Ping-Chih Ho, Ph.D., Co-Founder and Chair of the Scientific Advisory Board at Pilatus Biosciences, who presented the data as an oral presentation at AACR 2025. "Our findings validate CD36 as a novel immunometabolic target and demonstrate the broad potential of PLT012 to restore effective anti-tumor immunity across solid tumors. I look forward to seeing Pilatus bring this important new therapeutic approach into clinical development."
PLT012 has received FDA Orphan Drug Designation for the treatment of HCC and intrahepatic bile duct cancer, reinforcing its potential to address rare, aggressive liver malignancies with limited treatment options. Pilatus is advancing PLT012 through IND-enabling studies, with plans to file an IND by end of 2025 to initiate clinical development next year.
About PLT012
PLT012 is a humanized monoclonal antibody designed to selectively block CD36-mediated lipid uptake, a key mechanism driving immunosuppression and immune exclusion within the tumor microenvironment. PLT012 simultaneously reduces Tregs and pro-tumor macrophages while enhancing anti-tumor activities of intratumoral NK cell and cytotoxic CD8+ T cell. The antibody has demonstrated potent monotherapy and combination activity in preclinical models of HCC, liver metastases, and high-fat-diet-induced tumor progression, with a favorable safety profile across species.
About Pilatus Biosciences
Pilatus Biosciences is a biotechnology company developing immunometabolic therapies to address unmet medical needs in cancer and immune-related diseases. Founded in 2022 from the Ludwig Institute for Cancer Research, and supported by the Cancer Research Institute, Pilatus operates internationally with R&D teams in Switzerland and Taiwan. The company's lead program, PLT012, targets CD36 to reprogram the tumor microenvironment and restore anti-tumor immunity in solid tumors. For more information, visit www.pilatusbio.com.
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