Purple Biotech's CAPTN-3 Platform Shows Promise Against Treatment-Resistant Cancers with Dual Tri-Specific Antibodies
核心洞察
Purple Biotech (搜索) presented new preclinical data at ESMO-IO 2025 demonstrating that two CAPTN-3 (搜索) tri-specific antibodies, IM1240 and IM1305 (搜索), achieved significant anti-tumor activity across different tumor antigens and treatment-resistant models.
IM1240 showed anti-tumor activity in PD-1-resistant patient-derived explants from NSCLC and HNSCC, with transcriptomic analysis of ~11,000 TCGA samples supporting the inclusion of the NKG2A (搜索) arm in the platform design.
The new TROP2 (搜索)-targeting candidate IM1305 (搜索) demonstrated potent tumor cell killing at low concentrations across multiple cancer types including triple-negative breast, gastric, pancreatic, and head and neck cancers.
Purple Biotech (搜索) has reported positive preclinical data from its CAPTN-3 (搜索) tri-specific antibody platform at the ESMO Immuno-Oncology Congress 2025, demonstrating significant anti-tumor activity across two distinct compounds targeting treatment-resistant cancers. The data, generated in collaboration with Dr. Amir Horowitz's laboratory at the Tisch Cancer Institute (搜索) at Mount Sinai, showcases the platform's versatility in addressing immune failure in solid tumors (搜索).
Lead Compound Shows Activity in PD-1-Resistant Models
The company's lead CAPTN-3 (搜索) program, IM1240, demonstrated significant anti-tumor activity in three PD-1-resistant ex-vivo models, including new results in head and neck squamous cell carcinoma (搜索) (HNSCC) patient-derived biopsies. In these studies, IM1240 induced tumor cell apoptosis, with anti-tumor activity dependent on both CD3 (搜索) and NKG2A (搜索) arms.
IM1240's immune-mediated anti-tumor activity in PD-1-resistant non-small cell lung cancer (搜索) (NSCLC) patient-derived explants was evidenced by a significant increase in IFN-γ secretion. The compound targets the 5T4 (搜索) antigen, which is expressed in various solid tumors (搜索) and associated with advanced disease, increased invasiveness, and poor clinical outcomes.
"Immune failure is one of the biggest obstacles in treating solid tumors (搜索), and CAPTN-3 (搜索) was built to address that challenge," said Gil Efron, Chief Executive Officer of Purple Biotech (搜索). "The data we presented at ESMO IO shows that IM1240 can activate an immune response even in tumors that no longer respond to PD-1 therapy."
Platform Versatility Demonstrated with TROP2-Targeting Candidate
The company's new TROP2 (搜索)-targeting candidate, IM1305 (搜索), further validates the adaptability of the CAPTN-3 (搜索) platform. IM1305 demonstrated high-affinity binding to both TROP2 and NKG2A (搜索) with an EC₅₀ of approximately 2 nM.
Potent peripheral blood mononuclear cell (PBMC)-mediated tumor cell killing was observed at low concentrations (EC₅₀ 1-5 pM) across multiple tumor types, including triple-negative breast, gastric, pancreatic, and head and neck cancers. In humanized triple-negative breast cancer (搜索) mouse models, IM1305 (搜索) induced sustained tumor regression at low doses (p < 0.0001).
Like IM1240, IM1305 (搜索)'s anti-cancer activity and CD3 (搜索) binding were fully restored after cap cleavage, a critical component of CAPTN-3 (搜索)'s conditional activation design.
NKG2A Arm Provides Strategic Advantage
Transcriptomic analysis of approximately 11,000 TCGA (The Cancer Genome Atlas) human samples showed that NKG2A (搜索) expression co-occurs with 5T4 (搜索) in solid tissues, providing rationale for inclusion of the αNKG2A arm unique to the CAPTN-3 (搜索) platform.
"The NKG2A (搜索)/HLA-E axis is emerging as a key post-treatment resistance mechanism," said Dr. Hadas Reuveni, VP Research and Development at Purple Biotech (搜索). "The added value of the aNKG2A arm in IM1240 design, shown both in vivo and in vitro through reactivation of suppressed immune cell subsets, is now further supported by enhanced anti-tumor activity in PD-1–resistant patient-derived explants."
Platform Technology and Mechanism
The CAPTN-3 (搜索) platform produces conditionally activated tri-specific antibodies that engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound's therapeutic activity to the local tumor microenvironment, potentially increasing the anticipated therapeutic window in patients.
The technology presents a novel mechanism of action by unleashing both innate and adaptive immune systems to mount an optimal anti-tumoral immune response. The platform is designed to unite three functional mechanisms—T-cell engagement and activation, enhanced by NKG2A (搜索)-mediated innate and adaptive immune activation, and tumor-antigen targeting—into a single tri-specific molecule intended to coordinate a synergistic immune response.
Purple Biotech (搜索)'s broader oncology pipeline also includes CM24, a humanized monoclonal antibody that blocks CEACAM1 (搜索), and NT219, a dual inhibitor targeting IRS1/2 (搜索) and STAT3 (搜索). The company completed a Phase 2 study for pancreatic ductal adenocarcinoma (搜索) with CM24 in combination with nivolumab and chemotherapy, demonstrating improvement across all efficacy endpoints.