ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., and Paris, France – January 5, 2024 – In a significant move within the biotech industry, Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a leader in developing innovative protein-based drugs, and Orano Med, a pioneer in targeted alpha therapy, have announced a groundbreaking co-development agreement. This collaboration aims to create novel Radio-DARPin Therapeutics (RDTs) for cancer treatment, leveraging the unique strengths of both companies. The partnership will combine Molecular Partners’ expertise in DARPin® (Designed Ankyrin Repeat Protein) technology with Orano Med’s cutting-edge capabilities in targeted alpha therapy using lead-212 (²¹²Pb) radioisotopes.
This strategic alliance is set to explore multiple oncology targets, with an initial focus on DLL3 (delta-like ligand 3), a promising target particularly prevalent in small-cell lung cancer. The companies anticipate rapidly advancing these novel RDTs into clinical trials, with first-in-human studies projected for 2025. The collaboration marks a significant step forward in the fight against cancer, promising more precise and effective treatment options for patients.
Revolutionizing Cancer Treatment: Understanding Radio-DARPin Therapeutics
The core of this collaboration lies in the development of Radio-DARPin Therapeutics (RDTs). To fully appreciate the potential of RDTs, it’s crucial to understand the individual components that Molecular Partners Ag and Orano Med bring to the table.
DARPin Technology: Precision Targeting of Cancer Cells
Molecular Partners AG has established itself as a frontrunner in protein therapeutics with its proprietary DARPin technology. DARPins are a novel class of custom-built proteins engineered to exhibit high target specificity and binding affinity. Unlike traditional antibodies, DARPins are smaller and more stable, offering significant advantages in drug design and development. Their unique architecture allows for multi-functional designs, enabling them to target multiple disease pathways simultaneously. In the context of cancer therapy, DARPins can be engineered to precisely target tumor cells, minimizing off-target effects and enhancing treatment efficacy.
Targeted Alpha Therapy (TAT) and Lead-212: A Potent Payload
Orano Med specializes in Targeted Alpha Therapy (TAT), a revolutionary approach in cancer treatment that utilizes alpha-emitting radioisotopes to selectively destroy cancer cells. Alpha particles are highly potent in killing cells due to their high linear energy transfer. Lead-212 (²¹²Pb), the radioisotope at the heart of Orano Med’s technology, emits alpha particles with a very short range, limiting damage to surrounding healthy tissue while maximizing impact on cancer cells. Orano Med has developed significant expertise in the production and application of ²¹²Pb, ensuring a reliable supply for therapeutic development.
Synergy of RDTs: Combining Precision and Potency
Radio-DARPin Therapeutics (RDTs) represent the synergistic fusion of Molecular Partners’ precision-targeting DARPin technology and Orano Med’s potent alpha therapy. By conjugating ²¹²Pb to DARPins, the collaboration aims to create therapeutics that can precisely deliver alpha radiation to tumor cells. Preclinical data has indicated that this approach offers a highly differentiated profile, demonstrating strong binding to target proteins, effective tumor uptake, and importantly, the potential to minimize kidney damage—a known side effect associated with some protein-based radioligand therapies. This improved safety profile, combined with the potent cell-killing capability of alpha radiation, positions RDTs as a promising new class of cancer therapeutics.
Targeting DLL3 and Expanding Oncology Applications
The first oncology target under this co-development agreement is DLL3. DLL3 is a protein that exhibits low expression in healthy tissues but is significantly overexpressed in various tumor types, including small-cell lung cancer, neuroendocrine tumors, and some other cancers. This differential expression makes DLL3 an attractive target for cancer therapy, allowing for selective targeting of tumor cells while sparing healthy cells.
Molecular Partners AG and Orano Med will exclusively co-develop DLL3-targeted RDTs. While the initial focus is on DLL3, the agreement encompasses multiple oncology targets, highlighting the broad potential of this collaborative approach to address a range of cancers. Molecular Partners retains the option to explore DLL3 for targeted therapies beyond radiotherapy, further maximizing the therapeutic potential of their DARPin technology.
Strategic Partnership and Future Directions
This co-development agreement is a landmark achievement for both Molecular Partners AG and Orano Med. It represents Molecular Partners’ first co-development deal and underscores Orano Med’s commitment to expanding the applications of its ²¹²Pb technology through strategic collaborations. Both companies will share the costs of preclinical and clinical development, demonstrating their mutual commitment to bringing RDTs to patients. Furthermore, the agreement includes provisions for the supply of respective materials and sets the stage for future agreements regarding the commercialization of successful RDT programs.
The anticipated first-in-human studies in 2025 signal a rapid pace of development, reflecting the urgency in addressing unmet needs in cancer therapy. This collaboration not only diversifies the therapeutic pipelines of both companies but also accelerates the translation of innovative science into potentially life-saving treatments.
Executive Perspectives on the Collaboration
“Orano Med provides extensive expertise and a secure supply of a powerful, highly focused source of radiation for precision cancer treatment, expanding our RDT portfolio in new directions,” stated Dr. Patrick Amstutz, CEO of Molecular Partners AG. “While we have been able to demonstrate the potent and highly selective targeting of tumor cells by DARPins, it is imperative that we align ourselves with partners who have the scientific, technical, and logistical expertise to develop, manufacture, and supply radiotherapeutics. Having worked with the Orano Med team, we are excited and confident in their expertise and capabilities, as well as by their ambition to co-develop molecules in the clinic. We look forward to working jointly to bring these RDT programs into the clinics as rapidly as possible.”
Julien Dodet, CEO of Orano Med, added, “We are extremely excited to start this collaboration with Molecular Partners and to unlock the full potential of their DARPin platform in the field of radioligand therapies. We have been impressed by the versatility of the DARPin platform and by their in-house expertise in optimizing DARPins for applications in targeted alpha therapies. This collaboration enables us to meet the 3 key success factors in this field: leveraging a safe, convenient, and potent radioactive payload, achieving effective vectorization, and mastering the intricacies of the supply chain. This collaboration will further diversify our targeting approach, which combines the unique properties of ²¹²Pb and Orano Med’s unparalleled global manufacturing supply chain. It will expedite the development of ²¹²Pb-based radiotherapies to bring new breakthrough solutions for patients living with cancer.”
About Molecular Partners AG
Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, a novel class of protein drugs designed to overcome limitations of conventional modalities. The company collaborates with leading pharmaceutical entities to advance DARPin therapeutics across oncology and virology, with a diverse pipeline spanning various stages of clinical and preclinical development. Learn more at www.molecularpartners.com and follow them on LinkedIn and X: @MolecularPrtnrs.
About Orano Med SAS
Orano Med is a biotechnology company in the clinical stage, dedicated to creating next-generation targeted cancer therapies. Utilizing the unique attributes of lead-212 (²¹²Pb), a rare alpha-emitting radioisotope, Orano Med is at the forefront of Targeted Alpha-Emitter Therapy (TAT). The company is developing multiple ²¹²Pb-based treatments using diverse targeting agents and operates ²¹²Pb manufacturing facilities, R&D centers, and laboratories in both France and the US. Orano Med is actively expanding its GMP manufacturing capabilities in North America and Europe to meet the growing demand for ²¹²Pb radiopharmaceuticals.
About DARPin Therapeutics
DARPin therapeutics represent a new frontier in custom-built protein therapeutics. Inspired by natural binding proteins, DARPins introduce unprecedented multi-functionality and multi-target specificity to drug design. A single DARPin can engage over five targets, and their adaptable structure and small size offer advantages over other protein therapeutics. Clinically validated in thousands of patients across various indications, including the development of abicipar for ophthalmological conditions, the DARPin platform is a rapid and cost-effective engine for drug discovery, yielding drug candidates with optimized properties and high production efficiency.
About Targeted Alpha Therapy
Targeted alpha therapy (TAT) is based on the principle of combining biological molecules that target cancer cells with the potent, short-range cell-killing capabilities of alpha-emitting radioisotopes. Alpha decay involves the emission of a helium nucleus (alpha particle) with high linear energy transfer and a limited emission range of only a few cell layers. This results in irreparable DNA damage specifically in cells adjacent to the alpha emission area, maximizing cytotoxicity to cancer cells while minimizing harm to nearby healthy tissues. Alpha emitters are recognized as exceptionally powerful payloads for targeted therapies in oncology.
