On April 8, 2025 Manhattan BioSolutions, Inc. ("Manhattan Bio" or "MABS"), an emerging biotechnology company developing new classes of precision biologics, reported a significant milestone with the successful validation of its proprietary legumain (LEG)-cleavable linker-payload platform across multiple oncology programs and subsequent securing of expanded rights to this breakthrough antibody-drug conjugate (ADC) technology (Press release, Manhattan BioSolutions, APR 8, 2025, View Source [SID1234651835]). Manhattan Bio’s innovative platform directly addresses the most critical challenges facing current-generation ADCs, particularly premature payload release that leads to off-target toxicity and narrow therapeutic windows. The technology leverages the lysosomal protease legumain, which is frequently overexpressed in various tumor types. The LEG-cleavable platform has now been successfully validated across three distinct oncology programs, first with conventional auristatin payloads and subsequently with novel topoisomerase I inhibitor (TOP1i) payloads derived from exatecan, positioning the company at the forefront of next-generation ADC development.
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In rigorous preclinical studies, the company’s LEG-TOP1i ADCs demonstrated complete tumor regression with strong durability in multiple difficult-to-treat solid tumor xenograft models. These compelling efficacy results were accompanied by favorable pharmacokinetic properties. The platform’s enhanced stability in circulation, with reduced premature payload release, represents a potentially significant advancement over certain existing ADC technologies that often suffer from systemic toxicity due to payload release in plasma. Upon completion of this comprehensive validation program, Manhattan Bio finalized an agreement that considerably expands its rights to the technology. This strategic transaction enables the company to broadly apply its LEG-cleavable platform across an extensive range of therapeutic targets and cancer indications, substantially enhancing its ability to build a diverse pipeline of next-generation ADCs. The expanded rights significantly strengthen the company’s commercial position and open new avenues for high-value strategic partnerships.
"By solving the fundamental stability and selectivity challenges that have limited current ADCs, we’ve created a versatile platform with potential applications across numerous high-value oncology targets," said Dr. Borys Shor, Chief Executive Officer of Manhattan Bio. "This agreement dramatically increases our ability to build internal pipeline assets and establish strategic collaborations that could accelerate bringing important new medicines to patients."
Manhattan Bio is rapidly applying its proprietary technology to high-value oncology targets using both conventional single-payload ADC approaches and innovative dual-payload designs. These next-generation configurations leverage the enhanced stability and tumor-selective activation properties of the company’s LEG-cleavable platform, with proprietary LEG-TOP1i linker-payload technology at their core.