Scientific pioneer, Molecular Partners, is driven by innovation in cancer treatment
As a leader in protein engineering, Molecular Partners leverages innate properties of the drug class it invented, DARPins, to develop therapeutics for medical challenges other drug modalities cannot readily address. Sparked by a major scientific discovery over 20 years ago, the company sees ongoing success. Alex Zürcher, Chief Operating Officer at Molecular Partners, begins: “Molecular Partners AG is a clinical-stage biotech company pioneering and developing Designed Ankyrin Repeat Protein (DARPin) therapeutics for patients. Researchers at the University of Zurich, Switzerland, formed Molecular Partners AG in 2004. These scientists discovered and developed the DARPin technology and have been the leaders in the field ever since. We are a team of approximately 180 dedicated and passionate colleagues with operations in Switzerland and the US.
“Through our leadership and together with partners, we have developed seven clinical-stage DARPin candidates, treated over 2,500 patients globally, demonstrated clinical value of DARPin therapeutics across several therapeutic areas, and reached late-stage clinical development, including registration stage with ensovibep (antiviral DARPin) and abicipar (a long-acting anti-VEGF DARPin for ophthalmology). Molecular Partners became a publicly traded company in November 2014, when it was listed on the SIX Swiss Exchange. Since July 2021, the company has been listed on the Nasdaq in the US, also under the ticker symbol MOLN.”
DARPins themselves are unlike anything else available in the industry, as Alex details: “DARPin therapeutics are a new class of custom-built drugs based on natural binding proteins with the potential to overcome several limitations of current protein-based therapeutics. Through our 20 years of leadership and innovation with DARPins, we have advanced the versatility of DARPin therapeutics for the benefit of patients. The platform has been optimized to enable rapid and cost-effective cell line generation and high-yield production of DARPins in E. coli and we have secured our intellectual property position covering evolutions of and improvements to the DARPin platform with around 400 patents and patent applications filed. We continue to improve upon our learnings and have twice manufactured DARPin therapeutics up to commercial scale manufacturing: with Allergan for abicipar, which was preparing for commercial launch, and with Novartis for ensovibep, as we filed for an Emergency Use Authorization during the worst of the COVID-19 pandemic.
“Our DARPin platform has vast applicability across a range of diseases, with clinical value demonstrated in ophthalmology, virology, and oncology. Our R&D pipeline presently focuses on oncology, with two clinical programs and a suite of preclinical projects and proprietary DARPin platforms, designed to improve patients’ lives. MP0533 is a tetra-specific T cell engager for the treatment of acute myeloid leukemia (AML) patients and has been in phase 1 since January 2023. MP0533 has a unique avidity-driven mode of action which allows it to activate T cells, a key type of immune cell, to kill AML cells by targeting three antigens that are preferentially co-expressed on cancerous cells, while sparing healthy cells that normally express one or none of the targets. MP0317, our second clinical DARPin candidate also in phase 1, is a tumor-localized, bi-specific CD40 agonist for the treatment of patients with advanced solid tumors. MP0317 is designed to activate immune cells specifically within the tumor microenvironment by binding to FAP (fibroblast activation protein) on cancer-associated fibroblasts and to thereby circumvent severe toxicities in peripheral organs as seen for other CD40-directed drugs.
Radio-DARPin Therapy
“In addition, several programs of our Radio-DARPin therapy (RDT) and Switch-DARPin platforms are currently in pre-clinical stage.
Radio-DARPins are designed to deliver radioactive payloads to a broad range of tumor targets while sparing healthy tissues. We have designed our candidates to minimize kidney retention, a historic challenge for the approach, while increasing tumor uptake through precise control of how long the RDT candidates stay in the body. Our first RDT program, MP0712, is a DLL3-targeted and 212Pb-labeled Radio-DARPin Therapy candidate for small cell lung cancer patients, with initiation of a first in human clinical trial foreseen in 2025, in collaboration with our partner Orano Med. Our RDT portfolio includes additional programs, as well as a collaboration with Novartis.”
Switch-DARPins
Continually pushing the boundaries of what’s possible means Molecular Partners has been able to apply DARPin therapies to a variety of conditions. As Alex describes: “One of our greatest innovations, the multi-specific Switch-DARPin candidate MP0621 is the first program of the Molecular Partners’ Switch-DARPin platform for targeted and conditional immune cell activation. It is designed as a therapeutic drug and next-generation conditioning regimen for hematopoietic stem cell transplantation (HSCT) in AML and other conditions with in vitro and in vivo proof of concept established earlier in 2024.
DARPin therapeutics 
“DARPins were discovered and developed by our founders while at the University of Zurich, and from this discovery we have pioneered a new class of therapeutics with potential to treat a wide range of diseases. Today we are the global leader of DARPin therapeutics. With vast libraries of over one trillion potential DARPins, each of which can bind their own biologic target and be rationally and rapidly combined and screened, we are constantly working to expand our technical capabilities and further unlock the potential of DARPins to create novel therapeutics for patients.
“There is great need to deliver disease-specific solutions for diverse conditions. As our understanding of the mechanisms of various diseases deepens, the opportunity for DARPin therapeutics is greater than ever. To innovate and stay ahead of the curve, we are active on several fronts. We have built a clinical team and we partner with leading investigators and specialized centers to ensure optimal clinical development with the objective to have early clinical readouts in relevant patient populations.”
As Molecular Partners marks 20 years of DARPin leadership and innovation in 2024, the pursuit, consolidation, and meaningful use of knowledge remains central to the company’s mission. Moving into the future, Molecular Partners has added cutting-edge AI tools to its DARPin generation process. “While we at Molecular Partners are building a therapeutics company leveraging DARPins and their unique advantages, we acknowledge that DARPins are a class of drugs, just like antibodies or small molecules, and we can’t do everything on our own. Accordingly, a long-term goal will be for universities and pharma companies, and everyone in between, to feel that this is a modality they should explore and leverage. There is so much more than can be done, and we want to facilitate learning wherever possible,” Alex concludes.