Sanofi SA put the power of its Sunrise Initiative behind start-up Dice Molecules SV LLC with the goal of creating a next-generation approach to small-molecule drug discovery. The partners rolled directly into a five-year global collaboration to discover therapeutics for up to 12 discrete targets encompassing an eclectic array of indications of strategic interest to the Paris-based pharma, which Kathy Bowdish, head of Sanofi Sunrise, cited as oncology, cardiovascular disease, rare diseases and diabetes.

The partnership is structured to exploit the intricacies of Dice's technology platform, which leverages the use of directed evolution in chemistry to select and optimize low molecular weight compounds against any target. The platform's capabilities include the potential to unlock protein-protein interfaces that were previously intractable for oral therapies.

Dice's technology selects and optimizes drug-like ligands to any given target, beginning with libraries containing billions of individual molecules. The technology restores the libraries to their original ligand concentration after each round of screening, revealing the full landscape of binding molecules and allowing for easy selection for enhanced potency, selectivity and drug-like properties through testing with proprietary assays.

Sanofi pledged initial funding in excess of $50 million to cover equity, up-front, target exclusivity, technology access fees and research services – along with in-kind support – plus up to $184 million in research, clinical and regulatory milestone payments per target, putting the deal's potential value at more than $2.26 billion. San Francisco-based Dice also is set to receive undisclosed royalty payments based on net sales of each compound developed by Sanofi.

Dice – the company's name is a contraction for Directed Chemical Evolution – is the brainchild of co-founder Pehr Harbury, a Stanford University professor who also chairs the company's scientific advisory board. In typical small-world biopharma fashion, Harbury was a post-doc in the same University of California, Berkeley lab with Kevin Judice, who went on to become vice president of chemistry at Theravance Inc., of South San Francisco, where he led the discovery of Vibativ (televancin). Judice also co-founded Achaogen Inc., of South San Francisco, and Cidara Therapeutics Inc., serving as chief scientific officer at both companies.

Dice's back story also involves co-founder and Chief Scientific Officer Phil Patten, who worked with Judice at Achaogen, where he was senior vice president of biology, and also served as vice president of technology at Maxygen Inc., a company that pioneered the field of directed protein evolution via gene shuffling.

Patten, who had been involved in the practice of directed evolution in biology for more than 30 years, put the bug in Judice's ear about the potential of applying directed evolution in chemistry. In 2012, when Harbury and Patten began seriously thinking about forming a company around the technology, they turned to Judice for advice.

"We had a really fun dinner and I asked them blue sky questions, like 'What's going to make you happy?' and 'What do you want to see happen?'" Judice recalled. "But as I helped them to think through the concept, I got more and more interested in the technology."

Judice was already committed to helping launch Cidara, "but I knew that wasn't going to be a permanent gig, because I live in the Bay Area and they're in San Diego," he said. So Judice transitioned out of Cidara and into the role of CEO and co-founder at Dice, which opened its doors toward the end of 2013.


The company began working quietly to "industrialize" Harbury's science to prepare it for a biopharma environment. In 2015, Dice raised approximately $4.5 million, according to an SEC filing, and began talking with potential partners.

"I can't tell you how happy we are to have the Sanofi deal," Judice told BioWorld Today. "Not only is it a big deal that represents money and progress, but Sanofi Sunrise is somewhat unique in their approach to partnering in that they take a collaborative and supportive attitude that we have found to be terrific."

Sunrise allows Sanofi to invest at the ground floor in transformative technologies that align with its core development and commercial expertise. For example, in 2014 Sanofi inked a similar, though smaller, deal with Third Rock Ventures-backed Myokardia Inc. for three discovery-stage assets targeting hypertrophic cardiomyopathy and dilated cardiomyopathy. (See BioWorld Today, Sept. 18, 2014.)

The Dice technology allows the discovery of multiple targets in parallel – the company generated 10 targets in parallel with just five researchers in its lab. The Sanofi deal will allow Dice to staff up, eventually to about 25 employees, and as the discovery work progresses Judice expects to generate on the order of 20 targets in parallel at a time.

"Some of those will be ours, and some will be Sanofi's," he said, noting that Dice sat down with Sanofi scientists to develop a list of targets across a broad range of therapeutic indications. A joint steering committee composed of representatives from both companies is overseeing the work.

Since Dice is still dabbling with the technology, the Sanofi partnership also will allow the company to test its problem-solving abilities. At a molecular level, the targets intentionally involve everything from "relatively easy" enzymes to more challenging protein-protein interfaces, Judice said.

"We think it's got a lot of power," Judice said. "We'd like to demonstrate that over the next couple of years with hard data and hit some milestones for Sanofi."

Solving the more complex challenges could provide the framework to develop entirely new categories of oral drugs, with both Dice and Sanofi benefiting from the learning process.

"We spent a year working on our own, and we learned a lot that's going to help at least three or four of the targets where Sanofi has interest to get off to a very fast start," Judice said.

Bowdish agreed. "This platform, for us, has the potential to deliver much greater breadth and depth in terms of the number and qualities of molecules that could emerge against a particular target," she told BioWorld Today.

Bowdish, who also is vice president of global R&D at Sanofi, took a personal interest in the platform since her background in biologics gave her insight into the development of technology to select and enrich very large libraries in biologics.

But the technology "never really applied to small-molecule chemistry," Bowdish said. "So moving the work of Pehr Harbury, along with Phil Patten and Kevin, into an applied setting and being able to do selection and enrichment for small molecules was, in my mind, revolutionary."

The partnership also fit the objectives of Sunrise, which seeks to ally early and work with founders of transformative technology "to change the delivery of patient care," she added.

One way that could occur, Judice suggested, might be the application of Dice molecules to precision medicine.

"For any given kinase inhibitor launched on the market, you can set your watch by a certain time period before mutations appear in tumors that will block the effectiveness of that kinase inhibitor," he said. That process requires a second-generation drug, "but the problem is that you don't know which mutations are going to pop up."

The Dice platform has proven that "we can make some super-selective molecules very quickly," Judice continued. "If you could quickly generate selective molecules for the same target, you'd have, in a sense, a palette of kinase inhibitors for treating patients," enabling clinicians to start patients on a first-generation drug and move them, as needed, to other drugs targeted to each type of mutation.

"The key is that you have to have this drug or that drug waiting in the wings," he pointed out, "and that necessitates a certain expeditious pathway to multiple drugs on closely related targets. Dice is exquisitely powerful for doing that kind of work."

But Dice doesn't aim to become all things for all targets, planning instead to stay relatively small, independent and capital-efficient.

"This deal, combined with our angel funding, should keep us going for the next five years," Judice said. "We'd like to do one more deal like this but probably not more than one. In three or four years, we hope to have enough success internally that we can begin partnering our internal molecules as single assets and use those revenues to continue driving the company and beginning to pay back our investors and other shareholders, including employees, as we generate windfalls via milestone payments."

Ultimately, Dice may own "a small piece of a bunch of different assets that are being developed by other companies," he added. "The upside will be much lower than if we had developed it ourselves, but the risk will also be much lower. I like this model. It's a little bit more financially modest, maybe, but it feels like it could be sustainable."