On September 3, 2025 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance, reported its second CAPTN-3 trispecific antibody, targeting TROP2 in development (Press release, Purple Biotech, SEP 3, 2025, View Source [SID1234655733]).

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Purple Biotech has advanced development of a tri-specific antibody targeting TROP2 from its unique CAPTN-3 platform. Through activation of both the innate and adaptive immune systems, CAPTN-3 platform candidates can generate synergistic responses within the tumor microenvironment (TME) and overcome the immunosuppressive environment, which remains a major challenge in treating solid tumors.

IM1305 (capped-CD3xTROP2xNKG2A) contains a masked anti-CD3 arm, as well as an anti-NKG2A arm, and an anti-TROP2 arm. The potent anti-CD3 arm is masked at the periphery with a cleavable cap, designed to be removed specifically in the TME, which is expected to reduce the risk of off-target cytokine release and potentially enables higher dosing to achieve increased efficacy.

Encouraging preclinical results targeting TROP2 have demonstrated sustained tumor regression of human triple negative breast cancer (TNBC) in a mouse model, with no detectable tumor recurrence following treatment completion. Significant cell death induction was demonstrated in multiple tumor types, including TNBC, tongue and hypopharyngeal cancers, pancreatic and gastric cancers, at remarkably low doses (EC50 1-5 pM).

TROP2 is broadly expressed across major solid tumors (e.g., breast, lung, gastrointestinal, ovarian) and is associated with poor prognosis. Supported by prior clinical validation from approved TROP2-directed antibody-drug conjugates (ADCs), the broad potential of targeting TROP2 makes it a compelling target for the CAPTN-3 platform.

Unlike ADCs or monospecific antibodies, CAPTN-3 combines selective TROP2 binding with multi-effector immune recruitment (T and NK cells). This immune synapse–driven cytotoxicity is expected to potentially be independent of TROP2 density, providing a strong rationale for activity in non-ADC settings and across diverse tumor types.

"We are expanding our portfolio with the development of this novel tri-specific antibody to leverage our accumulated knowledge and technological advancements from the development of IM1240. By optimizing the CAPTN-3 platform, we are able to accelerate the time of development for the new TROP2 targeted tri-specific antibody." said Gil Efron, CEO of Purple Biotech Ltd." There is growing interest in TROP2 as a therapeutic target and excitement around next-generation engagers, and we believe our TCE platform is uniquely positioned to capitalize on this momentum. CAPTN-3 is a platform that can potentially generate multiple programs and expand our partnering opportunities."