The recent relocation of homegrown biopharma company Alexion to 100 College St. in New Haven, combined with the news that General Electric is moving its headquarters from Connecticut to Boston, highlights the paradigm shift from a reliance on larger Connecticut-based companies to a focus on smaller biopharma companies, according to molecular, cellular and developmental biology professor Craig Crews, who founded Proteolix and Arvinas, two biotech start-ups. In New Haven, health care innovation is driven by the interface between Yale professors and local biotech startups they found or guide through consultant and advising relationships.
“If we’re going to develop drugs that will actually improve the health of our patients, we have to engage with industry,” Yale School of Medicine Dean Robert Alpern said.
Crews and molecular biophysics and biochemistry professor Thomas Steitz are both research scientists who saw their decades of work through to commercialization by founding biotechnology companies.
Steitz’s lab at Yale focuses on the structural basis of DNA replication, transcription, protein synthesis and the structure of the ribosome. In 2001, he founded Melinta Therapeutics in New Haven to develop ribosome-targeted antibiotics for various infections, especially those considered drug-resistant, including acute bacterial skin and skin structure infections. The Crews lab at Yale focuses on discovering chemical applications to biology, for example cellular differentiation and cell signaling. Crews founded Proteolix, which brought a drug for multiple myeloma through to FDA approval in 2012. The company was acquired by Amgen — a biopharma company with 18,000 employees and a revenue of $20 billion per year — in 2013. Most recently, he founded Arvinas, which is developing novel drugs for cancers by degrading harmful proteins instead of just binding and inhibiting them as most drugs do, Crews said.
Steitz said his role with Melinta Therapeutics has changed over time. Even in the early years, he did not commit “a huge amount of time” to it and was primarily involved in hiring the executive staff, interacting with investors and then working as a consultant. He described attending meetings several times a year and checking in with lab staff to discuss their research.
“An advantage of a small startup company is that everyone is talking to each other, which leads to cooperation and a fun atmosphere to work,” Steitz said. When the company was founded, he insisted it be located in New Haven, rather than in California, so that he could easily stay involved without distancing himself from his research.
Steitz said he believes similar skill sets are required to do research in an academic and a biotech setting, but research in industry cannot be done in a university research laboratory because it involves too broad a scope of expertise. He said small company labs contain experts from several disciplines who would be dispersed across several departments at a university. He did say, however, that it is common for his colleagues at Yale to be involved with biotechnology companies as consultants.
When Steitz founded Melinta 15 years ago, he said there was little to no institutional support from Yale other than the requirement that professors seek approval from a patent office before founding a company.
“They’re more involved now,” he said.
Crews, who entered academia and the biotechnology sector afterward, can attest to that.
“There is institutional support for entrepreneurial efforts here at Yale and this is becoming an attractive feature for incoming students,” Crews said. He pointed to the 1980 Bayh–Dole Act as a turning point in biotechnology, making universities key drivers of innovation. Prior to the act, National Institutes of Health-funded research was owned by the government. Now universities own the research and are thus responsible for patenting and commercializing it. This led to the founding of Yale’s Office of Cooperative Research in 1982, which has grown in presence on campus, according to Crews, who has collaborated with the office.
Crews also said the Yale Entrepreneurial Institute — which supports undergraduates, graduate students, postdoctoral fellows and faculty with resources and education for entrepreneurship — has helped to create a culture of entrepreneurship on campus. Crews said he believes this culture shift is driven by a new paradigm in industry: outsourcing of research and development by big pharma companies to young biotech spinoffs from university laboratories, like his and Steitz’s, which have demonstrated commercial success.
“Large pharma companies need a robust pipeline of academic researchers starting biotech companies for the purposes of translating projects out of basic research labs. These new biotechs also provide landing spots for interested young researchers,” he said.
Steitz, Crews and Alpern all described an interdependence and mutually beneficial relationship between academia and biotech, although they do have differences.
“Biotech and big pharma companies want to work with and need academia but they may sometimes see us as inefficient,” Alpern said. “But they respect us for our science and we have a respect for their efficiency.”
He characterized industry as generally more team-oriented because, at a university, each professor is an independent researcher. But he believes this culture in academia is changing because technologies are becoming more advanced and diverse teams are necessary, as no single person can know all the technology a research project may need.
The two sectors also have different motivations.
“The focus in academia is following one’s scientific curiosity, whereas the focus in biotech is product development,” Crews said.
Similarly, Alpern said universities are more focused on the “advancement of science … rather than profit.” But both entities are focused on saving lives, he added.
The interface between biotechnology and academia, as well as between public and private sectors in health care innovation, is constantly developing. For example, Crews is leading an integrated Yale–University of Connecticut initiative called the Program in Innovative Therapeutics for Connecticut’s Health to create new local biotechnology companies out of academic research innovations. The initiative provides $10 million in funding over three years to bring together the resources of the Yale Center for Molecular Discovery — which is directed by Crews and evaluates the potential efficacy of molecules as drugs — and leaders in academia, biotechnology and the venture capital community.
“We’re de-risking academic projects and moving them a step or two closer to being sufficiently attractive for a venture capital firm to launch a biotech company,” Crews said. “The goal is to provide the infrastructure to help faculty become faculty entrepreneurs.”
Melinta has two drugs in phase three of development, and Kyprolis, a drug developed by Proteolix, is expected to reach $1 billion in sales in 2016.