CAPTN-3 platform is a platform of masked tri-specific antibodies that simultaneously target tumor-associated antigens while engaging both T cells and NK cells. Proprietary capping technology confines immune activation to the tumor microenvironment by masking the CD3-binding arm in circulation and activating it only at the tumor site, significantly expanding the therapeutic window versus unmasked T-cell engagers.

The cap is designed to be cleaved-off by multiple TME-specific proteases, which increase the likelihood for cleavage by many tumor types. Upon removal of this cap, the anti-CD3 moiety of the molecule is freed to bind and activate T lymphocytes via CD3.

The third arm targets NKG2A, an inhibitory receptor on NK cells and cytotoxic T cells. Tumors evade immune attack by expressing HLA-E, which engages NKG2A and switches those cells off. By blocking that interaction in the same molecule that recruits T cells, CAPTN-3 releases the innate arm of the immune response alongside the adaptive one. To our knowledge it is the only platform that engages both T cells and NK cells while incorporating a masking technology. The rationale rests on transcriptomic analysis of approximately 11,000 primary human tumors, work performed by Dr. Amir Horowitz at the Icahn School of Medicine at Mount Sinai, our research collaborator on the platform.

The platform’s lead candidates, IM1240 (targeting 5T4) and IM1305 (targeting TROP2), are in preclinical development.

This technology presents a novel mechanism of action by unleashing both innate and adaptive immune systems at the TME to induce an optimal anti-tumor immune response.

The platform’s lead candidate, IM1240 (targeting 5T4) is advancing toward the clinic and IM1305 (targeting TROP2) is in preclinical development. IM1240 targets 5T4 as TAA, which is expressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness and poor clinical outcome. IM1240 is directed towards 5T4 (also known as trophoblast glycoprotein (TPBG). 5T4 is an oncofetal surface protein that is not found on adult healthy tissues but is abnormally expressed in several cancer types. This specific expression pattern as well as the correlation with poor prognosis in different cancer diseases such as lung, gastric, head and neck and other cancers makes it an ideal TAA for various therapeutic approaches.

Non-human primate studies showed IM1240 was tolerated at doses up to 300-fold higher than an equivalent non-capped antibody, with an approximately 8-fold longer half-life, 16-fold greater exposure and minimal cytokine release. In patient-derived tumor samples resistant to checkpoint inhibition, IM1240 induced tumor cell killing in all seven samples tested, with the NKG2A arm contributing a measurable improvement in therapeutic index.

IM1240 has completed non-GLP toxicology and achieved a commercially viable manufacturing yield. We expect to initiate a first-in-human trial in 2027.