Roche and Molecular Partners ally against cancer

Partnership will combine novel biologics with drug-conjugate technology

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BASEL, Switzerland—December brought together Roche and fellow Swiss company Molecular Partners AG in a research collaboration and licensing agreement to discover, develop and commercialize several proprietary therapeutics incorporating Molecular Partners’ DARPin biologics conjugated to toxic agents developed at Roche for the treatment of cancer.
The twist, though, is that the conjugates aren’t the antibody-drug conjugates (ADCs) that have made the news so often these days—instead of antibodies, the partners are engineering small proteins to carry out the work of delivering therapeutics where they are needed.
As Zürich-Schlieren-based Molecular Partners and Roche touted in their announcement of the deal,  DARPin-drug conjugates would be “an exciting new class of drugs offering the potential of enhanced efficacy with substantial patient benefit over existing therapies.” This is because DARPins are non-antibody-based small proteins in which a variable region has been engineered for target binding.
Reportedly, their small size and high binding affinity enable them to accurately target and penetrate deep solid tumors to deliver toxic agents designed to kill cancer cells. As a result of their ability to bind to different epitopes than antibodies do, and by binding to multiple epitopes or targets in parallel at the same time, DARPins will, the Swiss companies believe, have a higher selectivity for tumor cells compared to other biologics, including ADCs.
Noting that Roche is one of the top players in oncology and specifically the toxic payload field, Molecular Partners CEO Dr. Christian Zahnd says that by combining Roche’s technical and commercial expertise with his own company’s DARPin research and development expertise, “we can rapidly develop a pipeline of highly differentiated products offering a novel approach to treating patients far more quickly than we could do independently, offering new hope for patients with unmet medical need. The DARPin-drug conjugate is an exciting new product direction for us alongside our internal proprietary DARPins and our existing partnerships in ophthalmology and immunology.”
According to Sylke Poehling, head of large-molecule research at Roche, “In the field of drug conjugates, we have identified an excellent opportunity to combine our expertise with the leading company in non-antibody scaffold technology to develop transformative cancer medicines,” adding that the DARPin platform “is truly complementary to our internal capabilities in the large-molecule space.”
Roche will have rights to develop and commercialize several DARPin-based products under the terms of the agreement, with Molecular Partners eligible to receive upfront and initiation payments of as much as 55 million Swiss francs, or around $61 million, in addition to research funding and earnings that could exceed $1.1 billion if all development and sales milestones are met for all potential products. Should any products make it to market, Molecular Partners will receive tiered royalties in the double-digit percentage range.
The specific oncology targets were not disclosed, though Roche has indicated it plans to target liquid and solid tumors. In speaking with various media, Zahnd has noted that the final indications are still a work in progress, as are the specifics of the linker technology that will ultimately be used, and that is where the collaborative effort between his company and Molecular Partners will first play out. No timelines have been set, though reportedly the companies are looking to establish clinical proof of concept quickly.
The deal is a another big step for Molecular Partners, which in 2012 inked a development deal with Allergan that could pay out as much as $1.5 billion for the use of DARPins to treat wet age-related macular degeneration.
In an investor commentary at the Motley Fool, Stephen D. Simpson characterized the deal as one of the more “significant” ones Roche has forged in recent months, not just because it boosts Roche’s oncology pipeline but also because “it builds on some already significant immunotherapy assets under Roche's roof. Roche is looking to cover multiple bases in immunotherapy, from conjugated antibodies to checkpoint agents and vaccines.”

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