Vividion Therapeutics Inc. has continued to build its roster of partnerships with a multitarget collaboration deal with Roche Holding AG that could be worth billions.

San Diego-based Vividion entered an exclusive worldwide option and license agreement with Roche to use its platform and small-molecule library to target E3 ligases and a range of oncology and immunology targets. Vividion gets $135 million cash up front and could receive, according to the company, “several billion” in payments based on hitting preclinical, developmental and commercial milestones.

Vividion could also receive royalties from sales of any commercialized products. Roche retains exclusive rights to license any compounds resulting from the collaboration at different development stages.

Vividion will handle early drug discovery and preclinical development up to proof of concept with an option to share development costs and split profits and losses in the U.S. with Roche.

The deal puts Vividion in a place its CEO, Diego Miralles, is comfortable with. Barely more than a year ago, the company reeled in a new series B financing worth $82 million. Just a little more than a year before that, it began a strategic research collaboration with Celgene Corp., in which Vividion received $101 million up front and an equity investment.

Diego Miralles, CEO, Vividion

“We have a very substantial balance sheet, over $250 million,” Miralles told BioWorld. “Through these partnerships, we are still able to retain wholly owned programs running in the clinic. Vividion is a true platform company.”

The platform, developed by scientific founders at The Scripps Research Institute in La Jolla, Calif., is designed to help discover and develop small-molecule medicines that drug traditionally inaccessible targets.

Vividion said it has discovered ligands that bind covalently to novel E3s and support targeted protein degradation. The company will make a presentation at the upcoming American Association for Cancer Research annual meeting in June about the discovery of drugs capable of covalently engaging E3 ligases and driving targeted degradation. Several molecules were able to degrade more than 50% of their target proteins at doses less than 1 mg/kg in mice, the company said.

“Because the covalent bond is irreversible, we are then able to break down proteins,” Miralles said.

E3 ligases are an important class of proteins responsible for directing target proteins to the proteasome for degradation and have the potential to unlock a wide range of valuable therapeutic applications, Miralles said.

“To the best of our knowledge, our program represents the first E3 ligase outside of cereblon and VHL that has been reported in a bifunctional construct to achieve in vivo degradation of multiple targets,” he added.

The company has additional evidence showing that, by leveraging covalent binding, it can achieve differentiated pharmacology with profound and long-lasting protein degradation, which may enable Vividion to offer an improved treatment compared to existing approaches, he added.

Many companies don’t have the capacity to run their own programs, so they partner with other companies, Miralles said, adding that the Roche deal validates Vividion’s platform, which is advancing a pipeline of multiple, selective small-molecule therapeutics for target proteins in oncology and immunology.

With Summit, N.J.-based Celgene, now owned by Bristol Myers Squibb Co., Vividion is pursuing a handful of small molecules against targets for a range of oncology, inflammatory and neurodegenerative indications. Terms of the arrangement call for four years of work, with Celgene potentially extending the pact for another payment, the amount of which the companies left unspecified. The pair is advancing small molecules that function through the ubiquitin proteasome system, modulating specific protein levels for therapeutic benefit.

Vividion pulled down $50 million in series A cash at the start of 2017. Founded in 2014, the firm is based on work that started with scientist Ben Cravatt, chair of the Department of Chemical Physiology at Scripps, whose efforts focused on getting beyond the conventional target-centric approach that typically nets a limited number of hits and leads.

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