FDA Grants Fast Track Designation to PLT012 for Hepatocellular Carcinoma Treatment

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PLT012, a first-in-class anti-CD36 monoclonal antibody for the treatment of hepatocellular carcinoma (HCC). Pilatus Biosciences Inc., a biopharmaceutical company developing novel metabolic checkpoint immunotherapies for liver and gastrointestinal cancers, is also developing PLT012 in additional solid tumor indications.

FDA Fast Track designation is intended to facilitate the development and expedite the review of therapies that treat serious conditions and address unmet medical needs. The designation enables more frequent interactions with the FDA and potential eligibility for rolling review, priority review, and accelerated approval pathways.

PLT012 is a first-in-class metabolic checkpoint antibody designed to block CD36-mediated lipid uptake and immune suppression within the tumor microenvironment. CD36 is an immune-metabolic regulator highly expressed on exhausted T cells, NK cells, regulatory T cells, and tumor-associated macrophages, but far less prevalent in healthy tissues. By targeting CD36, PLT012 is engineered to invigorate innate and adaptive effector cells, reduce immunosuppressive cell populations, and promote stronger anti-tumor immune responses.

The co-founder and CEO stated that receiving FDA Fast Track designation for PLT012 is an important milestone that reinforces the potential of the checkpoint therapy approach to transform the treatment of HCC. PLT012 was designed to address the metabolic adaptations that drive immune evasion in cancer. With IND clearance already secured and the Phase 1 trial open for patient enrollment, this designation will help accelerate clinical development and advance towards delivering a novel therapeutic option for patients, both in HCC and other solid tumors where patients do not benefit from existing immunotherapies.

The Phase 1 study (NCT07337525) is currently open for patient enrollment at clinical sites in Dallas and Houston, Texas. The study will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary signs of clinical activity, with expansion cohorts planned for tumor types strongly influenced by CD36-mediated metabolic dysregulation. In preclinical models, PLT012 demonstrated monotherapy activity across both immune-inflamed and immune-excluded tumors and showed potential synergy with PD-1/PD-L1 inhibitors, supporting development as both a single agent and a combination therapy.

Pilatus has also received FDA Orphan Drug Designation for PLT012 for the treatment of liver and intrahepatic bile duct cancers.

The Chair of Scientific Advisory Board and Co-founder stated that targeting CD36 represents a promising new way to reshape the tumor microenvironment, and importantly, the company is also starting to reveal its superior activity on treating metabolic disorders. PLT012 has the potential to redefine how the MASH-to-HCC continuum is approached by intervening at the metabolic root of disease to treat and prevent progression.

Beyond oncology, PLT012's mechanism of action may also address upstream drivers of liver disease progression. By targeting CD36-mediated lipid uptake, PLT012 has demonstrated promising preclinical activity in metabolic dysfunction-associated steatohepatitis (MASH), including reductions in inflammation and fibrosis. By addressing the full disease continuum, from early hepatic dysfunction to advanced malignancy, PLT012 is well-positioned to intervene at the metabolic root of disease and potentially slow or halt progression.

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. By targeting lipid metabolism, PLT012 exerts a unique mechanism of action: it reduces immunosuppressive cell populations, including Tregs and pro-tumor macrophages, while simultaneously enhancing anti-tumor activities of intratumoral NK cell and cytotoxic CD8+ T cell that are otherwise susceptible to lipid-induced exhaustion. In preclinical studies, PLT012 has demonstrated potent monotherapy efficacy in models of liver malignancies, with a favorable safety profile across species.

Hepatocellular carcinoma remains difficult to treat, particularly for patients whose disease progresses after standard therapies. Although immune checkpoint inhibitors and targeted therapies have improved outcomes for some patients, many do not respond or eventually develop resistance. Fast track designation reflects the significant unmet need in this setting.