On June 22, 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") and Orano Med, a clinical-stage radiopharmaceutical company and a pioneer in the development of targeted alpha-particle therapies (TAT) with 212Pb (lead-212), reported the debut of MP0726, its Radio-DARPin candidate targeting mesothelin (MSLN) and will present preclinical data in an oral presentation at the 2025 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), taking place June 21-24 in New Orleans, LA, USA (Press release, Molecular Partners, JUN 22, 2025, View Source [SID1234654039]).

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The oral presentation outlines encouraging early preclinical proof-of-concept data showing that MP0726 binds with high affinity and selectivity to the membrane-proximal domain of MSLN without being impacted by shed MSLN. In vivo results in a MSLN tumor model show a favorable biodistribution with substantial uptake of the Radio-DARPin in MSLN-positive tumors, while other organs showed limited accumulation. At 24 hours post injection, tumor accumulation was up to 34%, resulting in a tumor to kidney ratio of up to 4.5.

MP0726 leverages the unique properties of DARPins to selectively bind membrane-bound MSLN, a promising target for ovarian cancer due to its differentiated expression profiles – high in tumor, and lower in healthy tissues. High levels of shed MSLN can act as a decoy receptor and have historically hampered the development of MSLN-targeted therapeutics. MP0726 is being co-developed under Molecular Partners’ strategic partnership with Orano Med.

"Our collaboration with Molecular Partners has been delivering substantial progress in a short time, reflecting the skills, passion and strong complementarity of our teams. This progress highlights the effectiveness of our joint R&D efforts, enabling us to identify and advance differentiated clinical candidates that address important unmet medical needs. With its world-class R&D capabilities, the ownership of a virtually unlimited supply of the starting isotope, and fully-integrated manufacturing supply chain, Orano Med is uniquely positioned to support the development of these important potential new medicines", said Arnaud Lesegretain, CEO of Orano Med.

"We are proud to advance our second Radio-DARPin candidate into development, together with our partner Orano Med, for patients with MSLN expressing cancers. The promising preclinical data indicate a favorable biodistribution profile and highlight the unique approach to targeting MSLN with MP0726," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

MP0726 represents the second Radio-DARPin program to move into pre-clinical development. The first Radio-DARPin program, MP0712 targeting DLL3, is on track to dosing the 1st patient in a Phase 1 study in the US in the second half of 2025.

Details of the presentation:

Preclinical characterization of a Lead-212 Radio-DARPin Therapeutic to selectively target membrane-bound mesothelin in solid tumors
Date & Time: 24 June 2025; 2:50-3:00 pm CST
Session: SS38 Radiopharmaceutical Oncology – Preclinical and Early Phase (2:30-3:45 pm CST)

About 212Pb-based Radio-DARPins
Molecular Partners’ Radio-DARPin platform is being developed to provide a unique and innovative delivery system for radioactive payloads, with exquisite targeting capabilities of DARPins combined with the optimally balanced safety and tumor killing of 212Pb. DARPins are ideal vectors for efficient delivery of therapeutic radionuclides to solid tumors, while overcoming some historic limitations of radioligand therapy approaches, thanks to their small size as well as high specificity and affinity. Molecular Partners and Orano Med are developing targeted alpha radio-therapeutics against up to ten targets, including the tumor-associated protein Delta-like ligand 3 (DLL3) and mesothelin (MSLN).