Molecular Partners and Orano Med present preclinical data on mesothelin-targeting Radio-DARPin candidate MP0726 at SNMMI 2025
- Promising preclinical data showing high tumor accumulation (up to 34%) and favorable tumor-to-kidney ratio of 4.5
- Strategic partnership combining Orano Med's radiopharmaceutical expertise with Molecular Partners' DARPin technology
- MP0726 successfully overcomes the historical challenge of shed MSLN acting as a decoy receptor
- Company's first Radio-DARPin program (MP0712) advancing to Phase 1 trials in H2 2025
- Still in early preclinical stage with no human trial data yet
- Potential competition in the MSLN-targeting therapeutic space
- Success in preclinical studies doesn't guarantee clinical trial effectiveness
Insights
Promising preclinical data for Molecular Partners' mesothelin-targeting Radio-DARPin shows potential for treating ovarian cancer with favorable tumor targeting properties.
Molecular Partners has reached a significant milestone with its second Radio-DARPin candidate MP0726, demonstrating encouraging preclinical results for treating mesothelin (MSLN)-expressing tumors, particularly in ovarian cancer. The data reveals substantial tumor uptake of up to 34% at 24 hours post-injection and a favorable tumor-to-kidney ratio of up to 4.5—metrics that are particularly important for radiotherapeutics where selective targeting is essential to minimize off-target toxicity.
What makes this candidate particularly interesting is its ability to selectively bind to membrane-bound MSLN without being affected by shed MSLN. This overcomes a significant historical challenge in developing MSLN-targeted therapies, as shed MSLN has previously acted as a decoy receptor, reducing therapeutic efficacy. The DARPin technology platform appears well-suited to address this particular binding challenge.
The progress of this second Radio-DARPin program demonstrates the productivity of Molecular Partners' strategic collaboration with Orano Med, which combines DARPin engineering expertise with Orano's radiopharmaceutical capabilities. Notably, the partnership's first Radio-DARPin candidate (MP0712 targeting DLL3) is already advancing to Phase 1 clinical trials in H2 2025, establishing a pattern of pipeline progression.
This positive preclinical data represents an important de-risking step for the company's Radio-DARPin platform, though investors should recognize that considerable development work remains before potential clinical validation. The advancement of multiple candidates through their proprietary platform technology suggests a scalable approach that could yield additional therapeutic candidates targeting various tumor-associated antigens.
- MP0726, a Radio-DARPin candidate targeting mesothelin (MSLN) and intended for the treatment of ovarian cancer, is nominated for development under strategic partnership with Orano Med
- Promising tumor accumulation and attractive biodistribution shown in vivo, selective binding to membrane-bound MSLN with positive tumor to kidney ratio
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass. and PARIS, June 22, 2025 (GLOBE NEWSWIRE) -- Ad hoc announcement pursuant to Art. 53 LR 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), today announced 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.
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
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).
About Molecular Partners AG
Molecular Partners AG (SIX: MOLN, NASDAQ: MOLN) is a clinical-stage biotech company pioneering the design and development of DARPin therapeutics for medical challenges other drug modalities cannot readily address. The Company has programs in various stages of pre-clinical and clinical development, with oncology as its main focus. Molecular Partners leverages the advantages of DARPins to provide unique solutions to patients through its proprietary programs as well as through partnerships with leading pharmaceutical companies. Molecular Partners was founded in 2004 and has offices in both Zurich, Switzerland and Concord, MA, USA. For more information, visit www.molecularpartners.com and find us on LinkedIn and Twitter / X @MolecularPrtnrs
About Orano Med
Orano Med, a subsidiary of the Orano Group, is a clinical-stage biotechnology company which develops a new generation of targeted therapies against cancer using the unique properties of lead-212 (212Pb), an alpha-emitting radioisotope and one of the more potent therapeutic payloads against cancer cells known as Targeted Alpha-Emitter Therapy (TAT). AlphaMedix, its most advanced asset in development for GEP-NETs tumors, received Breakthrough Designation from the FDA in 2024. The company develops several treatments using 212Pb combined with various targeting agents. Orano Med has 212Pb manufacturing facilities, laboratories, and R&D centers in France and in the US. It is expanding its GMP-manufacturing capacities for 212Pb radiolabeled pharmaceuticals in North America and Europe and building a unique, independent, and fully integrated industrial platform to serve the needs of patients globally. For more information, please visit: www.oranomed.com.
For further details, please contact:
Molecular Partners:
Seth Lewis, SVP Investor Relations & Strategy
Concord, Massachusetts, U.S.
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361
Laura Jeanbart, PhD, Head of Portfolio Management & Communications
Zurich-Schlieren, Switzerland
laura.jeanbart@molecularpartners.com
Tel: +41 44 575 19 35
Orano Med:
Sophie Letournel
Head of Strategy, governance, and communication
sophie.letournel@orano.group
Tel: +33 6 38 44 34 11
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, including without limitation: implied and express statements regarding the clinical development of Molecular Partners’ current or future product candidates; expectations regarding timing for reporting data from ongoing clinical trials or the initiation of future clinical trials; the potential therapeutic and clinical benefits of Molecular Partners’ product candidates and its RDT and Switch-DARPin platforms; the selection and development of future programs; Molecular Partners’ collaboration with Orano Med including the benefits and results that may be achieved through the collaboration; and Molecular Partners’ expected business and financial outlook, including anticipated expenses and cash utilization for 2025 and its expectation of its current cash runway and the expected use of proceeds from the October 2024 offering. These statements may be identified by words such as “aim”, "anticipate”, “expect”, “guidance”, “intend”, “outlook”, “plan”, “potential”, “will” and similar expressions, and are based on Molecular Partners’ current beliefs and expectations. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Some of the key factors that could cause actual results to differ from Molecular Partners’ expectations include its plans to develop and potentially commercialize its product candidates; Molecular Partners’ reliance on third party partners and collaborators over which it may not always have full control; Molecular Partners’ ongoing and planned clinical trials and preclinical studies for its product candidates, including the timing of such trials and studies; the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with future clinical trials; the timing of and Molecular Partners’ ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Molecular Partners’ product candidates; the clinical utility and ability to achieve market acceptance of Molecular Partners’ product candidates; the potential that Molecular Partners’ product candidates may exhibit serious adverse, undesirable or unacceptable side effects; the impact of any health pandemic, macroeconomic factors and other global events on Molecular Partners’ preclinical studies, clinical trials or operations, or the operations of third parties on which it relies; Molecular Partners’ plans and development of any new indications for its product candidates; Molecular Partners’ commercialization, marketing and manufacturing capabilities and strategy; Molecular Partners’ intellectual property position; Molecular Partners’ ability to identify and in-license additional product candidates; unanticipated factors in addition to the foregoing that may cause Molecular Partners’ actual results to differ from its financial and business projections and guidance; and other risks and uncertainties set forth in Molecular Partners’ Annual Report on Form 20-F for the year ended December 31, 2024 and other filings Molecular Partners makes with the SEC from time to time. These documents are available on the Investors page of Molecular Partners’ website at www.molecularpartners.com. In addition, this press release contains information relating to interim data as of the relevant data cutoff date, results of which may differ from topline results that may be obtained in the future. Any forward-looking statements speak only as of the date of this press release and are based on information available to Molecular Partners as of the date of this release, and Molecular Partners assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.
FAQ
What are the key findings from MOLN's MP0726 preclinical data presented at SNMMI 2025?
How does Molecular Partners' MP0726 overcome the MSLN decoy receptor challenge?
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What is the strategic partnership between Molecular Partners and Orano Med?
What type of cancer is MP0726 being developed to treat?
