Roche has terminated its cancer collaboration with Molecular Partners, as part of a retreat by the pharma giant away from its Pseudomonas exotoxin conjugate programs. The collaboration could have generated up to $1 billion-plus for Molecular Partners, which announced the termination today.

Roche’s retreat includes conjugate programs co-developed with the DARPin® biologics of Molecular Partners—which said it will assess whether to add DARPins from the Roche collaboration to its proprietary pipeline directly or repurpose them in other programs.

DARPins are non-antibody-based small proteins where a variable region has been engineered for target binding. Roche and Molecular Partners reasoned that DARPins were ideal targeting agents to deliver toxic agents to tumors to kill cancer cells. They based that reasoning on the DARPins’ small size and high binding affinity, designed to enable them to hone in on and penetrate deep into solid tumors.

Roche and Molecular Partners launched their DARPin collaboration in 2007 “for a variety of undisclosed applications,” with financial terms and other details not disclosed. The companies expanded their partnership in December 2013, with Roche receiving rights to develop “several” conjugates that combined DARPin products with the pharma’s toxic agents and Molecular Partners standing to gain more than CHF 1 billion (about $1.1 billion).

“The DARPin platform generated highly differentiated binders in short time, and it is unfortunate that Roche decided to discontinue these programs for reasons related to the toxin,” Molecular Partners CEO Christian Zahnd said in a statement. “We discussed other areas of mutual interest, but given our own proprietary focus on immuno-oncology, it made no sense to amend the current collaboration. This way, we can avoid working on potentially competing pathways.”

Zahnd did not say how many candidates were created through the partnership. In the company’s Annual Report for 2014, Molecular Partners mentioned “several DARPin-toxin conjugates we are developing with Roche,” and added that Roche accounted for about CHF 5 million ($5.2 million) of its CHF 26.6 million ($27.7 million) in total revenue in 2014.

Molecular Partners disclosed the termination in an announcement that reiterated its commitment to its pipeline of un-partnered candidates: “This includes advancing the clinical and preclinical development pipeline and ramping up the activities in immuno-oncology.”

The pipeline features several DARPin therapies in oncology—the most advanced of which is the Phase I candidate MP0250 for solid tumors. MP0250 is designed to inhibit both VEGF and HGF from binding to their receptors, thus blocking tumor growth and tumor spreading. “We believe that MP0250 has the potential to become a valuable treatment option in gastric, kidney, and liver cancers,” Molecular Partners states on its website.

The second most advanced oncology DARPin is the preclinical candidate MP0274, which according to Molecular Partners has broad anti-HER activity inhibiting both downstream HER2 and HER3-mediated signaling and leading to induction of apoptosis. Molecular Partners envisions MP0274 as a treatment for HER 2+ breast cancer patients, including those with low levels of HER2 expression.

In all, Molecular Partners has four compounds in various clinical and preclinical development stages, and “several” more in the research stage, with a current focus on oncology—as well as ophthalmology, where the company has partnered with Allergan on four programs, one of which has advanced to Phase III (abicipar for wet age-related macular degeneration).

On Tuesday, Molecular Partners said Allergan had expanded their 2–1/2 year-old ophthalmology alliance by agreeing to speed up $35 million in milestone payments. That partnership could generate up to $1.7 billion in aggregate development, regulatory and/or sales milestones, plus tiered royalty payments (up to the double digit percentage range) on any future product sales.

Molecular Partners has separately partnered with Johnson & Johnson’s Janssen Biotech on a discovery-phase immunology program.

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