As a pulmonary physician scientist, Avi Spira is driven to get his breakthroughs in molecular biomarkers for the early diagnosis of lung cancer and chronic obstructive pulmonary disease (COPD) into clinical care. “I’m a doctor, I want to help people,” says Spira, a professor of medicine, pathology, and bioinformatics at the Boston University School of Medicine (MED). “The question is, ‘How do you get these discoveries into patients?’ You have to work with companies and industry. How do you do that when you’re an academic?”
With the support of BU President Robert A. Brown and BU’s Technology Development (TD) office, Spira, who is the director of the BU-Boston Medical Center (BMC) Cancer Center, has spent much of the past eight years figuring out the answer to that question. In 2007, he founded his own company to develop a relatively noninvasive molecular test for early detection of lung cancer. The test grew out of Spira’s research at BU. Getting the company off the ground, and running the large clinical trials needed to validate the test, meant raising millions of dollars in private funding.
Spira says he and his partner, Jerome Brody, a MED professor emeritus of medicine, had no clue about business. They blew their first meeting with venture capitalists by showing up with an 80-slide scientific presentation—and no firm funding goal in mind.
“We could tell within three minutes that no one in the room was listening,” says Spira. Three minutes later, they were shown the door.
They eventually raised more than $10 million in venture capital financing to run two successful clinical trials. In 2014, their company, Allegro, was acquired by a San Francisco molecular diagnostics firm, Veracyte, which made an early lung cancer diagnostic test (PerceptaTM), based on Spira and Brody’s biomarker, available for the first patients in 2015 (Medicare coverage recently became available for the test).
“Jerry and I could never have done that on our own,” says Spira, who, in recognition of his success with Allegro, was named BU’s Alexander Graham Bell Professor in Health Care Entrepreneurship. “Bob Brown and TD have created an entrepreneurial culture that is very supportive of startups as well as industry collaborations with our laboratory and others.”
A different approach to collaboration
Now, Spira has entered into a promising partnership with Janssen Research & Development, LLC—one of the Janssen Pharmaceutical Companies of Johnson & Johnson, the pharmaceutical group of the New Jersey–based health care giant—and the company’s venture capital subsidiary, Johnson & Johnson Innovation—JJDC, Inc. Janssen is investing more than $10 million in Spira’s research into biomarkers for the early detection of COPD and lung cancer. Spira says he views his collaboration with Janssen as part of an emerging new paradigm for how industry and academia can work together. In this new model, industry not only gets involved earlier in the disease but also earlier in the initial discovery process.
“The traditional model was one where academia did almost all of the discovery,” he says. “You make a finding, figure out how to protect the intellectual property, and then try to license it to a pharmaceutical company or another partner, who will then hopefully move it into patients.”
“The challenge is that the initial discovery process is expensive and risky, and it’s hard to know how to develop the technology and hand it off to someone else who is going to apply it to the clinic,” says Spira, who started Allegro with Brody after failing to interest an existing company in licensing their biomarker discovery. “Part of what Janssen is doing with my lab is becoming involved directly in the process as a partner from the very beginning. It’s science done with application in mind at the earliest stages—not science for science’s sake.”
Spira’s research on biomarkers for the early detection of COPD and lung cancer is part of his work within DECAMP (Detection of Early Lung Cancer Among Military Personnel), a US Department of Defense–funded consortium of researchers at military facilities and veterans’ hospitals that Spira leads as principal investigator.
As part of the Janssen-funded effort, Spira’s team will also study how the immune system behaves in the development of lung cancer and determine whether approaches that boost the immune system have the potential for stopping the progression to disease. The team will also evaluate the molecular and radiological features in the airways and lungs of hundreds of smokers to identify biomarkers that can pinpoint individuals who are likely to develop COPD.
“I’m very encouraged about Dr. Spira’s partnership with Janssen Research & Development,” says Brown. “We’re committed to fostering efforts—such as this one—that quickly translate research into effective therapies and diagnostic tools. Industry support is critical to translating the results of our research into better health care.”
Janssen is additionally supporting Spira’s collaborations with scientists Mary Reid and Samjot Dhillon at Roswell Park Cancer Institute, in Buffalo, NY, to develop a pre-cancer genome atlas (PCGA). The PCGA would provide comprehensive genomic profiling of pre-malignant lesions for lung cancer and identify the key molecular pathways that lead pre-cancer lesions to progress to invasive and lethal lung cancer. The National Cancer Institute is helping to expand this work by providing an additional investment for the PCGA in collaboration with Steven Dubinett, a professor of medicine and molecular and medical pharmacology at the University of California at Los Angeles. Finally, with Janssen and James Hogg of the University of British Columbia, Spira and Marc Lenburg, a MED professor of medicine, are working to identify new therapies and therapeutic targets that can reverse or stop the progression of COPD-related lung pathologies.
The traditional model for working with industry, where a company comes in toward the end of the academic discovery process, “is very dependent on federal funding of the early discovery work, which is very competitive, and is probably not sufficient to take advantage” of today’s vast scientific opportunities and potential, says David Coleman, Wade Professor and chair of the MED department of medicine. The new model that Spira and BU have embarked upon with Janssen is one that has been discussed by many people in both academia and industry in the last few years, Coleman says.
“I think this is a very important model to find new and productive ways for academia and industry to successfully develop products that contribute to public health,” he adds.
Partnerships for progress
As a research university, BU helped generate Spira’s breakthroughs in the lab, as well as his partnership with Janssen, says Mike Pratt, TD interim managing director. “Our community of innovators and portfolio of discoveries are accessible,” he says. “This open access enables innovators like Avi by giving them the freedom to be creative and to form partnerships with key stakeholders that share his vision for treating disease.”
As part of its collaboration with Spira, through JJDC, Johnson & Johnson Innovation is providing an equity investment into Metera Pharmaceuticals, a company that Spira founded in July 2016 with two MED colleagues, Lenburg and Joshua Campbell, an assistant professor of medicine. They hope to develop a diagnostic to identify patients who show early signs of possible COPD and a drug that could potentially treat and even reverse the disease (and perhaps other lung diseases, as well). With this financial backing, Spira can bypass the usual financially driven venture capitalists, at least in the early stages.
“This is a really nice model for more efficient drug development and commercialization,” Spira says. “We don’t have to go out and raise traditional venture capital, which is challenging, is primarily focused on financial returns, tends to look for later-stage molecules, and already comes with ties. JJDC is getting involved very early and helping us to advance this important program due to their primary strategic goal of bringing medicines to patients. What’s exciting is that we get industry guidance early in the process, in areas such as designing and developing a drug and clinical trials, expertise that we don’t have within academia. These are things drug companies do well. We get access to that knowledge base while getting to remain actively involved.”
Janssen’s $10 million research collaboration in Spira’s work on early detection and intervention in lung cancer and COPD is part of the company’s ambitious, multi-partner effort to move from what it calls disease care to health care. Called the Disease Interception Accelerator (DIA), the partnership is also focusing on type 1 and gestational diabetes; cataracts and presbyopia; perinatal depression; and cancers of the cervix, mouth, and throat caused by human papilloma virus. The goals are to find biomarkers for the earliest signs of disease and to develop affordable diagnostics as well as therapeutics to stop an individual’s progression to disease.
With Janssen’s support, Spira will expand on his DECAMP project and test hundreds of high-risk smokers to identify biomarkers that predict who will eventually develop lung cancer and COPD. The study will also work to discover whether there are biomarkers that can be used to guide current and future therapeutic approaches.
Advances in genomics and bioinformatics have made Janssen’s DIA project possible, and Spira’s groundbreaking work in both fields—as well as his focus on early detection of disease and his extensive network of scientific collaborators—helped bring him to the company’s attention. “We’re trying to find the Avi’s of the world to work with,” says Benjamin C. Wiegand, DIA global head. “He’s a phenomenal visionary. He loves health care challenges. He’s working with researchers around the world—leading microbiome experts, some great pulmonary researchers—and because he can articulate his vision, he brings others along with him. He’s building his ecosystem and we’re glad to add him to our ecosystem as well.”
Spira first connected with Janssen in 2012 when a senior research scientist at the company, Patrick Branigan, heard Spira’s talk on COPD research at the American Thoracic Association’s annual meeting. Branigan then invited Spira to meet with Janssen’s COPD and oncology teams in Philadelphia. “Most of the research and development in Big Pharma is focused on people who are already sick,” Spira says. “What got me aligned with Janssen is that they’re interested in disease prevention and—a word I love—disease interception. In the lung cancer space, a lot of companies are developing very effective drugs that keep you alive longer with late-stage disease. That’s very important, but I would argue that we should be focusing earlier in the disease process. Prevention is always better than a cure. Janssen was very clear that this vision was aligned very well with our lab.”
One of the tasks ahead for Metera is figuring out how to move from these interesting data to a true drug in a precision medicine way, says Spira. “Part of it would be to generate novel drug-like molecules and effectively deliver them to the lung,” he says. “It’s very challenging. Janssen has the expertise in how to do this and we have been very fortunate to work closely with world-class scientists, like Chris Stevenson at Janssen, who have been instrumental in moving compounds toward the clinic.” Stevenson leads the DIA COPD team at Janssen.
Reversing the risk
Spira, who practices at BMC, says his experience managing patients with advanced lung cancer and COPD helped spur his focus on translational research into ways to diagnose disease as early as possible. Lung cancer, which is the leading cause of cancer deaths in the US and around the world, is extremely difficult to diagnose, and by the time most people exhibit symptoms, the cancer has metastasized. “As a physician, by the time I see patients with either COPD or lung cancer, the vast majority of them have late-stage disease and it is too late for a cure,” Spira says.
“We don’t want to treat people at the end of the disease,” Spira says. “We want to catch it early or even prevent it. That’s what our lung cancer test is about. It applies to COPD, too, we believe. This is a disease we need to prevent. We need to get people before they get the disease and then intercept and reverse the risk.”