Pilatus Biosciences, a clinical-stage biopharmaceutical company developing novel metabolic checkpoint immunotherapies for liver and gastrointestinal cancers, today announced the presentation of new preclinical data supporting the therapeutic potential of PLT012, its investigational anti-CD36 monoclonal antibody, in overcoming acquired resistance to PD-1 immunotherapy in hepatocellular carcinoma (HCC) at the Society for Immunotherapy of Cancer (SITC) 41st Annual Meeting, held November 4-8, 2026, in Phoenix, Arizona.

The research, conducted in collaboration with investigators at Zhongshan Hospital, Fudan University, identifies a previously underexplored mechanism of immunotherapy resistance in which sustained PD-1 treatment and selection lead to immunoediting-driven metabolic reprogramming in tumor cells, creating a lipid-rich, immunosuppressive tumor microenvironment. Increased expression of CD36, a key regulator of lipid uptake, was associated with impaired antitumor immune responses and acquired treatment resistance.

In preclinical models of PD-1-resistant liver cancer, PLT012 treatment counteracted CD36-associated immunosuppressive effects within the tumor microenvironment and significantly inhibited tumor growth, supporting CD36 inhibition as a potential therapeutic strategy for patients who develop resistance to existing checkpoint inhibitors.

“Acquired resistance to PD-1 immunotherapy remains a significant challenge in treating advanced liver cancer, with limited therapeutic options available once patients stop responding,” said Yi-Ru Yu, Ph.D., Head of Biology, R&D, Pilatus Biosciences. “Our findings highlight the critical role of lipid metabolic reprogramming in acquired PD-1 resistance and demonstrate the potential of PLT012 to tackle lipid-mediated immunosuppression, with tumor growth inhibition observed in preclinical models. These results provide further mechanistic validation of our approach and reinforce the potential of PLT012 to address an important unmet need in liver cancer.”

The study utilized a preclinical model of acquired PD-1 resistance, developed through three generations of consecutive anti-PD-1 treatment and selection, combined with multi-omic analyses to characterize changes in tumor metabolism and immune activity.

Key findings include:

  • Metabolic reprogramming drives treatment resistance: Acquired PD-1 resistance was associated with epigenetic and transcriptional changes that increased lipid metabolism in tumor cells, contributing to an immunosuppressive tumor microenvironment.

  • CD36 contributes to immune dysfunction: Increased CD36 expression on tumor-infiltrating immune cells was associated with reduced effector T-cell and natural killer cell activity, alongside increased immunosuppressive macrophage and neutrophil populations.

  • PLT012 demonstrates antitumor activity: Targeting CD36 with PLT012 mitigated lipid-associated immunosuppression and significantly inhibited tumor growth in preclinical models resistant to PD-1 treatment.

“These findings strengthen the scientific rationale for advancing PLT012 in HCC following prior immunotherapy,” said George E. Peoples, M.D., Chief Medical Officer, Pilatus Biosciences. “Our planned Phase 1/2 development will prioritize monotherapy dose optimization and rational combination studies, supported by biomarker analyses. By linking CD36 target engagement and changes in the tumor immune microenvironment with clinical outcomes, we aim to establish preclinical-to-clinical concordance and determine whether the immune effects observed in our models translate into durable antitumor activity in patients.”

Poster Presentation Details

Title: Immunoediting-Induced Lipid Metabolism Fosters Acquired PD-1 Resistance in Hepatocellular Carcinoma via CD36-Mediated Immune Suppression

Poster Number: 380

Conference: Society for Immunotherapy of Cancer (SITC) 41st Annual Meeting

Date: November 7, 2026

Location: Phoenix Convention Center, Phoenix, Arizona

About Pilatus Biosciences

Pilatus Biosciences is a clinical-stage biopharmaceutical company developing metabolic checkpoint immunotherapies 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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