On November 3, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported it will present further preclinical proof-of-concept data on its logic-gated CD3 Switch-DARPin T cell engager (TCE) with CD2 co-stimulation in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2025 meeting, taking place in National Harbor, MD, USA from November 5-9.

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Clinical development of TCEs for solid tumors is often limited by systemic toxicity in the absence of specific enough tumor antigens and by impaired efficacy due to insufficient T cell activity. To address this, Molecular Partners designed a logic-gated Switch-DARPin TCE using an AND-gate to achieve conditional tumor-localized immune activation targeting mesothelin (MSLN) and epithelial cell adhesion molecule (EpCAM), which are highly co-expressed in ovarian cancer and other solid tumors. The Switch-DARPin TCE is designed for the CD3-engaging DARPin to be unmasked ("Switch" on) and activate T cells only upon binding to both MSLN and EpCAM (AND-gate).

Preclinical data to be presented at SITC (Free SITC Whitepaper) show that the Switch-DARPin demonstrated selective T cell cytotoxicity against cells co-expressing both tumor-associated antigens, with attenuated activity against cells in healthy tissues expressing only MSLN or only EpCAM. In addition, T cells repetitively exposed to CD2/CD3 Switch-DARPin showed a fundamentally improved activation and proliferation profile as compared to CD3 engagement alone, highlighting the potential of CD2/CD3 Switch-DARPin to overcome T cell exhaustion. Finally, the Switch-DARPin induced significant tumor regression in a xenograft mouse model expressing MSLN and EpCAM without causing systemic cytokine release, indicating a favorable safety profile.

"These data further underline the potential of Molecular Partners’ wholly-owned logic-gated and co-stimulated T cell engager program, which allows for targeted, conditional immune activation only in the presence of defined targets. The Switch-DARPin only activates T cells when both tumor-associated antigens are bound, and remains inactive in circulation, which allows the addition of a CD2 DARPin for co-stimulation of T cells. This approach is an opportunity for novel cancer treatments through logic-gated tumor-directed immune activation with increased efficacy and safety over modalities targeting a single tumor antigen," said Martin Steegmaier, Ph.D., CSO of Molecular Partners.

Details of the presentation

Title: A next-generation conditional Switch-DARPin T cell engager with CD2 co-stimulation enabling selective activity against solid tumors which co-express mesothelin (MSLN) and EpCAM

Abstract number: 829

Time: November 7, 2025

Location: Gaylord National Resort and Convention Center – Lower Level Atrium – Prince George’s ABC

(Press release, Molecular Partners, NOV 3, 2025, View Source [SID1234659287])