Pilatus Biosciences Unveils Preclinical Data on CD36 Antibody PLT012 for Liver Cancer
Pilatus Biosciences, a biotechnology company dedicated to developing next-generation immunometabolic therapies for cancer, has announced the publication of a pivotal preclinical study in Cancer Discovery, a leading peer-reviewed journal published by the American Association for Cancer Research. The study outlines the mechanism of action and robust anti-tumor activity of the company’s lead investigational therapy, PLT012, a humanized antibody targeting the lipid transporter receptor CD36.
The publication, titled “PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Anti-Tumor Immunity Against Liver Cancer and Liver Metastasis”, provides compelling evidence for the therapeutic value of targeting CD36, a receptor that plays a key role in the metabolic reprogramming and immune suppression seen in several solid tumors. Pilatus’ data illustrate how PLT012 can overcome the hostile, lipid-rich tumor microenvironments (TMEs) that often drive immune cell dysfunction and resistance to standard immunotherapies, particularly in liver cancer and colorectal cancer with liver metastases.
A New Frontier in Cancer Immunotherapy: Targeting Immunometabolism
In recent years, the concept of immunometabolism — the interplay between cellular metabolism and immune cell function — has emerged as a crucial area of oncology research. Tumors, especially those of the liver, are known to be metabolically aberrant environments that are often flooded with lipids and inflammatory signals. These factors can blunt immune responses by promoting the infiltration and survival of suppressive immune cells such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), while reducing the cytotoxic activity of CD8+ T cells.
CD36, a scavenger receptor known for its role in fatty acid uptake and metabolism, has emerged as a key mediator of this immunosuppressive phenotype. It is upregulated in immune cells exposed to lipid-rich tumor environments and has been linked to dysfunctional T cell states and poor prognosis in multiple solid tumor types.
Pilatus Biosciences has taken a bold step forward by engineering PLT012, the first humanized monoclonal antibody specifically designed to block CD36. The company’s research shows that by inhibiting CD36, PLT012 can disrupt lipid uptake pathways that promote immune evasion, thereby restoring a more pro-inflammatory, anti-tumor immune landscape.
Study Highlights: Efficacy in Multiple Preclinical Models
According to the newly published Cancer Discovery paper, PLT012 demonstrated strong preclinical efficacy in various mouse models of hepatocellular carcinoma (HCC) — the most common form of liver cancer — as well as in models of colorectal cancer liver metastases. Notably, the therapy was effective in both immune-inflamed tumors, which already contain some immune cell infiltration, and immune-excluded tumors, which typically resist immune therapies due to physical and metabolic barriers.
One of the most compelling findings came from experiments involving β-catenin–driven HCC models. These tumors are notoriously resistant to checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 therapies. PLT012 monotherapy induced significant tumor regression in these models, suggesting its potential utility even in refractory disease settings.
When combined with other immuno-oncology agents — specifically anti-PD-L1 and anti-VEGF therapies — PLT012 significantly enhanced overall tumor control, leading to increased rates of complete responses. This indicates that PLT012 could be an effective partner in combination regimens designed to overcome resistance mechanisms and amplify immune responses.
In addition, PLT012 demonstrated the ability to remodel the macrophage compartment in colorectal cancer liver metastases, pushing TAMs toward a more inflammatory, anti-tumor phenotype. These results further underline the versatility of the antibody across different cancer indications where immunometabolic suppression plays a critical role.
Translational Evidence and Human Validation
In an effort to bridge the gap between animal models and human disease, the Pilatus team also conducted ex vivo experiments on fresh human liver tumor samples obtained from hepatocellular carcinoma patients. Treatment with PLT012 led to measurable increases in CD8+ T cell activation in nearly half (45%) of patient samples, and reduced Treg populations in over 80% of cases.
These data provide early translational validation for PLT012’s mechanism of action and support its potential clinical benefit in human cancers with similar metabolic profiles.
Favorable Safety Profile and Path to the Clinic
Beyond demonstrating strong anti-tumor efficacy, PLT012 has also cleared important safety hurdles. Non-human primate toxicology studies revealed no dose-limiting toxicities or adverse immune responses at dose levels up to 200 mg/kg, establishing a solid preclinical safety profile as the company prepares for human trials.
As a result of these promising findings, PLT012 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of hepatocellular carcinoma and intrahepatic bile duct cancer — two aggressive malignancies with limited treatment options and poor prognoses.
Pilatus Biosciences is currently conducting Investigational New Drug (IND)-enabling studies and plans to submit its IND application by the end of 2025. If approved, this would pave the way for the initiation of first-in-human clinical trials in 2026.
Expert Perspectives from the Pilatus Team
“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,” said Dr. Yi-Ru Yu, Lead Scientist at Pilatus Biosciences and co-first author of the publication. “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.”
Raven Lin, CEO and Founder of Pilatus Biosciences, emphasized the broader implications of the findings: “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. These important milestones highlight PLT012’s potential to transform treatment for patients with advanced solid tumors.”
Dr. Ping-Chih Ho, Co-Founder and Chair of the Scientific Advisory Board at Pilatus and a globally recognized leader in immunometabolism, added further perspective on the scientific innovation behind PLT012. “The ability of PLT012 to reprogram the tumor microenvironment by overcoming metabolic immune suppression marks a major advancement for the field of immuno-oncology. 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.”
Dr. Ho recently presented the data at the 2025 American Association for Cancer Research (AACR) Annual Meeting, drawing significant interest from both academic and industry audiences.
The publication of this landmark study in Cancer Discovery marks a major milestone for Pilatus Biosciences and its novel immunometabolic strategy. As the company accelerates its efforts to transition PLT012 from bench to bedside, it joins a growing wave of biotech innovators rethinking cancer treatment through the lens of metabolic-immune interactions.
With its first-in-class approach, robust preclinical validation, and a clear path toward clinical trials, PLT012 could offer new hope for patients with tumors that have proven resistant to conventional immunotherapies — particularly those facing limited options due to the immune-hostile microenvironments of liver and metastatic cancers.
As the field of immuno-oncology continues to evolve, targeting CD36 and similar metabolic pathways may soon become a cornerstone of combination therapy regimens, reshaping the therapeutic landscape for some of the most difficult-to-treat cancers.
