Researchers at the University of Zurich, Switzerland formed Molecular Partners AG in 2004 while studying monoclonal antibodies. These scientists discovered and developed the DARPin technology and launched the company using this platform. Molecular Partners became a publicly traded company in November 2014, when it was listed on the SIX Swiss Exchange. As of 2018, Molecular Partners has two cancer assets currently going through clinical testing.
DARPins
DARPins are genetically engineeredantibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding. They are derived from natural ankyrin repeat proteins. Repeat proteins are among the most common classes of binding proteins in nature, responsible for diverse functions such as cell signaling and receptor binding. DARPins constitute a new class of potent, specific and versatile small-protein therapies, and are used as investigational tools in various therapeutic and diagnostic applications. The simplest format of a DARPin is the mono-DARPin, consisting of one DARPin domain with specificity for one target. The molecular mass of a mono-DARPin is about 15 to 20 kDa, depending on the exact design. Several mono-DARPins can be linked to multi-DARPins, which then combine multiple activities in one therapy. This approach enables the design of medicines that can inhibit multiple disease-specific targets and may improve outcomes for patients living with cancer, ophthalmic diseases and other disorders. Currently, Molecular Partners has two DARPin molecules in clinical development and a broad pipeline of molecules in preclinical development.
Areas of Focus
Molecular Partners is currently focusing its DARPin platform on the fields of oncology, immuno-oncology, ophthalmology, and immunology. Oncology Molecular Partners’ lead candidate in oncology is MP0250, a proprietary multi-DARPin designed to inhibit VEGF and hepatocyte growth factor. In a poster presentation at the in Boston, Mass. on Saturday, November 7, 2015, a team of independent researchers presented the first demonstration in patients of the potential role of DARPin-based therapy in oncology. Data from the Phase I study demonstrated good tolerability, favorable pharmacokinetics, and sustained exposure over multiple applications of MP0250 in a preliminary analysis in patients with solid tumors. In January 2016, the Company announced plans for a Phase II trial of MP0250, a multi-DARPin® drug candidate targeting vascular endothelial growth factor and hepatocyte growth factor, in combination with bortezomib and dexamethasone in patients with multiple myeloma who have developed resistance to at least two prior regimens. The Phase II trial is expected to be initiated in the second half of 2016. In preclinical studies, MP0274, a proprietary multi-DARPin with broad anti-HER2 activity, has shown promising data in model of HER 2-positive breast cancer, including those with lower levels of HER2 expression. Molecular Partners agreed to pair MP0250 with Tagrisso in a phase I lung cancer trial, working with AstraZeneca on the EGFR-inhibiting candidates. Immuno-Oncology In March 2016, the Company announced its strategic plan to expand its immuno-oncology pipeline by naming the first two development programs. The first is for a multi-DARPin® that inhibits the programmed cell death protein 1 and VEGF-A, while also binding to human serum albumin. This tri-functional DARPin® is designed to normalize the tumor vasculature by inhibiting VEGF and increasing tumor-penetration and intra-tumor expansion of effector T-cells. Additionally, the DARPin® binding domain to serum albumin is expected to yield a long half-life and to allow for potentially increased tumor penetration. The second immuno-oncology program is for the development of a highly specific activator of T-cells in the tumor stroma. It binds to co-stimulatory agonists on the surface of T-cells without activating them when bound in circulation – only once the T-cells enter the tumor microenvironment, the agonist is clustered via the DARPin® having a second specificity for a densely expressed target in the stroma. This selective activation of T-cells is typically not seen for antibodies as they tend to directly cluster agonists through their Fc part and clustering on widespread Fc-receptors. Ophthalmology Molecular Partners’ most advanced clinical candidate is abicipar, an anti-VEGF DARPin in late-stage development, in partnership with Allergan. In Phase 2b studies, abicipar was shown to provide equal or potentially higher vision gains with fewer injections in patients with wet AMD, compared to standard anti-VEGF treatment with ranibizumab. Currently, abicipar is being investigated in four different clinical trials. The first two are Phase 3 safety and efficacy studies in patients with wet AMD; the aim of these studies is to test the safety and efficacy of abicipar in patients with wet AMD. Molecular Partners anticipates clinical read-outs from these studies in the summer of 2018. The third clinical trial is a Phase 2 safety and efficacy study in patients with wet AMD, designed to establish comparability between Japanese and non-Japanese patients. The fourth study is a Phase 2 safety and efficacy of abicipar in patients with diabetic macular edema. Allergan is also advancing the other DARPins in the ophthalmology agreement, which includes an earlier-stage multi-DARPin® targeting VEGF and platelet-derived growth factor in wet AMD. Immunology Molecular Partners is developing DARPins against several targets important for the treatment of inflammatory and auto-immune diseases. Its lead compound targets both IL-13 and IL-17 with long systemic half-life and potential use in pulmonary indications.
Partnerships/Business Development
Molecular Partners has negotiated three agreements with Allergan to develop therapies for ophthalmology, one in 2011 and two in 2012. In 2011, the Company licensed its lead asset MP0112, now called abicipar, to Allergan. In 2012, Molecular Partners and Allergan expanded their relationship by signing two separate new agreements to discover, develop, and commercialize proprietary therapeutic DARPin products for the treatment of serious ophthalmic diseases.
