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Arvinas, a Startup Based on Yale Research, Is Positioned to Reinvent Drug Discovery

Craig Crews

By Brita Belli

A new startup company in New Haven, Conn. based on Yale research is reinventing drug discovery and developing an entirely new class of drugs. Arvinas is built around Yale-patented technology from Craig Crews, Lewis B. Cullman Professor of Molecular, Cellular and Developmental Biology and professor of Chemistry and Pharmacology at Yale.

"Currently, drugs act as inhibitors," Crews explained from Arvinas' new 10,000 square-foot headquarters at 5 Science Park in New Haven—which includes 9,000 square feet of lab space. "But many proteins in cells don't have a function that can be inhibited. Our novel approach is to remove the proteins, by inducing the cells' own protein degradation facility." It's these "rogue proteins" that are driving cancer and other important diseases, and the drugs Arvinas is developing work by getting rid of these proteins, potentially creating an entirely new class of drugs based around protein degradation.

Changing the Drug Paradigm

Traditional drugs work as inhibitors—binding to particular proteins in order to block their function. But that binding is not permanent. "To stop cancer, you need the drug binding site of a protein bound 95 percent of the time," Crews says. "This is often extremely difficult to achieve since it requires high drug levels thus creating potential complications."

The new drugs being developed by Arvinas would induce the cell's own protein-degradation capability—by binding to a protein and "labeling" it for degradation and thereby removing it from the cell. One key advantage of this approach is the ability to target proteins that are not currently "druggable." Whereas traditional drugs can only target 25 percent of the body's 20,000 proteins that can be inhibited, many other proteins that can't be inhibited can be degraded using Arvinas' approach, thus radically expanding the number of disease-causing "rogue" proteins that can become the targets of new drugs.

Arvinas' initial focus will be on cancer—in fact, images from Yale's Pediatric Oncology unit will adorn the lab and office walls as inspiration—but, Crews adds, "there are lots of wonderful targets" for these new drugs. Long-term targets include inflammatory, autoimmune and rare diseases, from rheumatoid arthritis to lupus.

Investing in Health — and New Haven

Tim Shannon, venture partner in Canaan Partners and CEO of Arvinas, says Arvinas offers an ideal platform for partnering with pharmaceutical companies and for helping big pharma to "unstick" many of their stalled projects.

Arvinas received $15 million in Series A financing from both local and outside investors, including Canaan and Boston-based 5AM Ventures. Of the 400 or 500 opportunities 5AM reviews each year, the firm makes an average of just four new investments. Kush Parmer, a venture capitalist at 5AM, says they focus solely on the best life science investment opportunities. "The theme has to be game-changing," Parmar says. "That's why we like Arvinas. It's a game-changing platform with the possibility to transform therapies and medicine."

And Shannon was committed to locating Arvinas in New Haven, Conn., where he lives, despite substantial interest from others to start the company in larger biotech hubs. "We have abundant talent in Connecticut and there is great merit in keeping this close to Craig and Yale. There is no reason to leave the area," Shannon says.

The Connecticut Department of Economic and Community Development offered $2.5 million in loan financing and Connecticut Innovations offered $1 million in equity funding as well as a bioscience facilities loan of $750,000 to keep the startup in Connecticut. "Our economic development team worked aggressively to keep this company—and this technology—in Connecticut," says Connecticut Governor Dannel P. Malloy. "Not only does the company represent great promise for the future of health care, but it will bring new jobs and expand New Haven's growing pharmaceutical presence. We're very pleased to have Arvinas call New Haven its long-term home."

New Haven continues to attract life science, bioscience and pharmaceutical companies, including the new global headquarters of Alexion Pharmaceuticals at New Haven's Downtown Crossing. Crews adds that the close proximity to his lab—where he spent the past five years developing the protein-degrading drug technology—is another bonus. Arvinas is currently in the process of hiring its first 25 employees.

Commercializing Yale Research

Crews has a history of commercial success with his drug discoveries. Ten years ago, his research into a specific molecule led to the development of Kyprolis™ (carfilzomib), a potent anti-cancer drug that targets multiple myeloma. Crews started a San Francisco-based company, Proteolix, to make the drug. In October 2009, Proteolix was acquired by Onyx Pharmaceuticals for over $800 million. Krypolis received Food & Drug Administration approval for the treatment of multiple myeloma in 2012, and the following year Amgen acquired Onyx for $10.4 billion, largely to get access to the blood cancer drug. Kyprolis™ is expected to reach sales of $1 billion by 2015.

As with the formation of Proteolix, Crews worked directly with the Yale Office of Cooperative Research (OCR) to secure the necessary intellectual property protection for his inventions and to develop and execute a strategy to form Arvinas to capitalize on the commercial potential. Yale OCR works side by side with faculty innovators to bring their novel technologies out of the laboratory and into real-world applications. "Although it is difficult to predict the future, we believe that we have put the same elements in place – first rate science, blue chip investors and experienced entrepreneurial management and technical teams – that brought success to Proteolix. But, this time, we have anchored the new venture in New Haven," says Jon Soderstrom, managing director of OCR.

The Arvinas team anticipates that they will have their first drug developed and ready to be tested in a clinic in three years. One early goal is to attract additional investment and expand. "The pharmaceutical and biotech industries are looking for innovation," says Shannon. "We have it."

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