BU Paves Way for MED Prof’s $10M Plus Partnership with Industry

By Brianna Leigh Freeman April 7th, 2017 in Research Highlight

Monday, April 3, 2017
Written by: Sara Rimer | Source: BUToday

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 (ENG’02), a School of Medicine professor of medicine, pathology, and bioinformatics. “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, director of the BU-Boston Medical Center (BMC) Cancer Center, has spent much of the past eight years figuring out the answer to those questions. In 2007, he founded his own company to develop a relatively noninvasive molecular test for early detection of lung cancer, a test that 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.

“Bob Brown and TD have created an entrepreneurial culture that is very supportive of start-ups, as well as industry collaborations with our laboratory and others.” —Avi Spira

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 (Percepta^TM), 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. In recognition of his success with Allegro, he 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 start-ups, as well as industry collaborations with our laboratory and others.”

A different approach to collaboration

Spira has now 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 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, N.Y., to develop a precancer genome atlas (PCGA). The PCGA would provide comprehensive genomic profiling of premalignant 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 University of California at Los Angeles professor of medicine and molecular and medical pharmacology. 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 their 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 D. Campbell (ENG’12), a MED 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, multipartner 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.

“This is a really nice model for more efficient drug development and commercialization. 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.”
—Avi Spira

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 Avis 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 Patrick Branigan, a senior research scientist at the company, heard Spira’s talk on COPD research at the American Thoracic Society 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 disease—a word I love—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 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, Spira says. “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 United States 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. 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.”

Finding Lung Cancer in the Nose

By Brianna Leigh Freeman March 7th, 2017 in Research Highlight

Tuesday, February 28, 2017
Written by: Barbara Moran | Source: BUToday

Lung cancer is the deadliest form of cancer in the United States—and in the world. According to the National Cancer Institute, it accounts for more than a quarter of cancer deaths in this country, killing about 158,000 people in 2016.

Because lung cancer is so lethal, many current and former smokers undergo precautionary CT scans of the chest. These scans can detect small lesions in the lungs that may be an early sign of cancer, but false positives can lead to invasive and unnecessary lung biopsies. New research points to a better path to diagnosis: a genomic test that may eventually require only a simple nasal swab. The findings appeared online in the Journal of the National Cancer Institute (JNCI) on February 27, 2017.

“The idea that we can sample cells from the nose and tell if someone has lung cancer—that is sort of out there,” says JNCI paper senior author Marc Lenburg, a School of Medicine professor of medicine. “To sample cells that far from the tumor and still find a genetic signal is really exciting.”

The findings build on previous research led by Lenburg and JNCI paper corresponding author Avrum Spira (ENG’02), Alexander Graham Bell Professor in Health Care Entrepreneurship and a MED professor of medicine, pathology, and laboratory medicine. In 2015, the researchers reported in the New England Journal of Medicine that a genomic test they’d developed could detect lung cancer in a section of the bronchial airway far removed from the tumor. The test, now called Percepta, was acquired by the genomic diagnostics company Veracyte, released that year, and received Medicare approval in late 2016.

Lung cancer’s “field of injury” extends well beyond the tumor. New work by Avrum Spira and colleagues demonstrates genetic changes in nasal cells of patients who went on to develop lung cancer. Courtesy of Avrum Spira

The problem, says Spira, is that “there is a subset of people with pulmonary lesions who do not undergo a bronchoscopy as part of their diagnostic workup,” either because the suspicious lesions are very deep in the lung and inaccessible to the bronchoscope or because the patient suffers from other conditions—like heart failure or emphysema—that make a bronchoscopy difficult or dangerous. But if people with lung cancer have genomic alterations in the cells in the nose too, a nasal swab could potentially serve the same purpose as a bronchial brush.

To explore this possibility, Spira and Lenburg analyzed genomic changes in nasal swabs from patients recruited for the Percepta clinical trials. “We had previously collected the nasal samples,” says Spira. “But we thought that genomic changes in the nose that associate with lung cancer would be more difficult to detect than those found in the bronchial airway.” This proved to be true, but recent improvements in computational approaches to genomic data analysis allowed the team to find a lung cancer signal in the nasal samples. They found 535 genes that were expressed differently in the nasal passages of patients who went on to develop lung cancer, but not in patients with benign lesions. Of those genes, 30 were sufficiently distinctive to be useful as a diagnostic biomarker.

The researchers say that the nasal test needs additional testing. “The people in the original study were already at substantially elevated risk for lung cancer,” says Lenburg. “We need to confirm that these results are valid for a wider population.” Nevertheless, the researchers hope that their findings will eventually lead to a widely used test.

“In the short term, we’ll use the nasal biomarker as a diagnostic test for people who have something suspicious on a CT scan of the chest, but are not undergoing bronchoscopy,” says Spira. “But eventually, the nasal test could impact a lot more people as a mass screening tool for lung cancer. That’s the really exciting potential.”

Six Junior Faculty Receive Career Development Awards

By Brianna Leigh Freeman September 27th, 2016 in Research Highlight

Written by: Amy Laskowski | Source: Bostonia

Jerry Chen received quite a present just three months after arriving at BU. Chen, a College of Arts & Sciences assistant professor of biology, is the winner of this year’s Stuart and Elizabeth Pratt Career Development Professorship, which highlights excellence within CAS. A neuroscientist who uses the sensory input from the whiskers of mice to study the relationship between local circuits and long-range networks in the brain’s neocortex, Chen says he hopes his research will help him better understand the central nervous system in mammals.

“I was a bit surprised and honored to find out I received this development award,” says Chen, who earned a bachelor’s in molecular and cell biology at the University of California, Berkeley, and a PhD in biology from MIT. He says his professorship will help him develop a novel microscope system and allow him to hire students and postdoctoral researchers to help with his work. “I consider it to be very generous and a nice welcome gift.”

Chen is one of a select group receiving this year’s annual Career Development Professorships, which recognizes junior faculty who have been at BU less than two years and have been identified as emerging future leaders in their respective fields. Made possible by the support of donors, alumni, and BU’s Technology Development office, these professorships emphasize the caliber and potential of the University’s faculty. Awards, nominating procedures, and selection vary based on the professorship and the unit administering the honor. All awards are for three years, and go towards the recipients’ salaries and research and scholarly work.

Bostonia’s recent story about several new Career Development Professorships established this year and their winners can be found here.

The annual University-wide Peter Paul Career Development Professorships have been awarded to Charles Chang, a CAS assistant professor of linguistics; Daniel Cifuentes, a School of Medicine assistant professor of biochemistry; and Arturo Vegas, a CAS assistant professor of chemistry.

Chang’s research explores the dynamics of language acquisition and development, focusing on the ways individuals’ native languages influence, and are influenced by, the phonological systems of heritage or later learned languages. Chang does this by using behavioral experiments, acoustic analysis, and statistical modeling. He is working on several projects in his lab; one examines variations “to which native language pronunciation changes during immersion in a foreign language environment,” he says, while another, done in collaboration with colleagues at the University of Maryland, addresses the hypothesis of a “critical period” for native language loss, and investigates how speech perception in native language declines among immigrants who came to America at different ages. Chang is a graduate of Harvard University and earned a master’s and a doctorate in linguistics from the University of California, Berkeley.

As a biochemist and developmental biologist, Cifuentes examines the early stages of embryo formation and the role RNA plays during this period, with a “long-term goal of understanding how we develop from a single egg into a whole new organism,” he says. He uses small, four-centimeter zebrafish to study these basic mechanics of development, because the fish are “very easy to maintain in the lab and highly prolific,” he says. “The embryos are transparent and together with their fast development—we can already observe the heart beating, the blood flowing, and the muscles twitching the day after the eggs are fertilized—it is a great experimental system.” Cifuentes graduated from the University of Barcelona, where he earned a doctorate in biochemistry. He completed postdoctoral training at Yale.

Vegas uses his research in synthetic biology to develop novel chemical tools, materials, and approaches for targeting therapeutics to diseased tissues, with a focus on cancer and diabetes. Specifically, he says, his lab works to develop chemical technologies “that can serve as a guidance system for a therapeutic payload, delivering drugs to the cells in the body that have disease, while avoiding normal cells entirely.” He hasn’t yet decided how he’ll use the funding from his Peter Paul Professorship, but says the award “could go far in helping us cover the costs of some expensive experiments we’ve been thinking about.” Vegas holds a bachelor’s degree in biology from Cornell and a doctorate in chemistry from Harvard.

The Reidy Family Career Development Professorship, which recognizes College of Engineering and Questrom School of Business faculty, goes his year to John Ngo, an ENG assistant professor of biomedical engineering. The Ralph Edwards Career Development Professorship, given to MED junior faculty, has been awarded to Joshua Campbell (MED’12), a MED assistant professor of computational biomedicine.

Ngo’s research applies principles of evolution, chemistry, and engineering to develop new tools for visualizing, measuring, and controlling biomolecules in cells and organisms. Currently, his lab studies how proteases—proteins that “chop up” other proteins—are used by cells to regulate gene expression in response to different biological signals.

He says his Career Development Professorship came as a complete surprise, and that upon learning that he had been selected, he immediately wrote to thank his former mentors. “As somebody who is just starting an independent career, I know that much of my success is owed to the scientists who coached me along the way,” says Ngo, whose undergraduate degree is from the University of California, Santa Barbara, and PhD in biochemistry and molecular biophysics from the California Institute of Technology. “To me, this award is a big reminder of how lucky I am to have been trained by such great teachers. So, in honor of my mentors, I’m going to pay it forward and use this award to enhance the training environment of my lab for my own students.”

Using bioinformatics, Campbell’s research in DNA and RNA sequencing works to help detect and treat lung cancer and chronic obstructive pulmonary disease (COPD) at an earlier stage by identifying unique genomic mutations and then targeting them with novel therapies. Working at the BU-BMC Cancer Center, he says, he has an ambitious plan in place to apply single cell genomics to a variety of tumor types.

Campbell earned a doctorate in bioinformatics and completed postdoctoral training at BU. He has been on the MED faculty just this year, and he says that receiving a Career Development Professorship instantly validated his decision to teach and do research at BU. “The assistance I have had in my first several months has been very encouraging and shows the level of support BU gives to early investigators,” he says.

“The junior faculty members we recognize this year with Peter Paul, Stuart and Elizabeth Pratt, Reidy Family, and Ralph Edwards Career Development Professorships are all engaged in exciting research, scholarship, and creative endeavors,” says Jean Morrison, University provost and chief academic officer. “Their efforts range from enhancing our understanding of the way we learn new languages to using leading-edge technologies to detect and fight disease and yield vital insights into the human body and its development. By crossing disciplines, making critical discoveries, and helping forge entirely new fields of study, they exemplify the breadth and caliber of rising talent across our campuses. We believe strongly in their potential and are delighted to support their scholarly success here at BU.”

New Consortium to Study Environmental Causes of Breast Cancer

By Brianna Leigh Freeman August 17th, 2016 in Research Highlight

Written by: Rich Barlow | Source: BU Research

Cancer researcher David Sherr is gunning for a disease that has upended his life. His wife died from multiple myeloma 15 years ago.

So when the Art beCAUSE Breast Cancer Foundation, a nonprofit supporting research into the environmental causes of breast cancer, approached him for ideas to accelerate progress, Sherr, a Boston University School of Public Health (SPH) professor of environmental health, was ready.

“Dr. Sherr has long been a friend of ours and a supporter,” says Eleanor Anbinder (SED’62), who cofounded the foundation with Joyce Creiger (CAS’62) in 2001. “One day, I said to him, ‘How can we speed this research up?’” Sherr suggested a four-laboratory collaboration, two from Tufts and two from BU: his own, which researches the mechanisms through which environmental chemicals suppress the immune system, among other topics, and the lab of Stefano Monti, a BU School of Medicine associate professor of computational biomedicine, who also has an appointment at SPH. The two from Tufts are led by Gail E. Sonenshein, a Tufts professor of developmental, molecular, and chemical biology, and Charlotte Kuperwasser, an associate professor of developmental, molecular, and chemical biology.

“The rest,” Anbinder says, “is history.”

Art beCAUSE has given a three-year, $5 million grant to the new Art beCAUSE Breast Cancer Research Consortium and is hoping to attract matching grants from other donors. The idea for such a multilab consortium, says Sherr, consortium director, “was something I stole from lots of literature about team science. It’s much harder to do science by yourself. It has to be team science if you really want to get somewhere.”

One of every eight American women gets breast cancer, and 40,000 a year die from it, says Sherr. He shared his hopes for the consortium with BU Research.

BU Research: Why this consortium?

Sherr: The idea is to build evidence that the environment really is contributing majorly to breast cancer. Gail Sonenshein and Charlotte Kuperwasser are major breast cancer researchers.

Do we know that environmental factors can cause breast cancer?

There’s always an argument going on in the literature about to what extent the environment plays a role. The estimates are that anywhere from 33 to 85 percent of cancers are influenced in some way by environmental chemicals. We can attribute about 10 percent of cancers to inheritance of bad genes. That doesn’t mean there aren’t other genes we haven’t found yet, but it’s becoming less and less likely. Of the other 90 percent, some of them might be just random and you can’t do anything about it, but I think more than half are due to some environmental exposure.

How many chemicals do you think are registered for use in consumer products by the Environmental Protection Agency? About 84,000. About 2 percent have been tested to see if they are carcinogens. Of those 2 percent, about 30 percent are carcinogens. Say the overall carcinogen rate is 0.5 percent. That’s about 400 carcinogens that we’re exposed to all the time.

Why not test the rest?

That’s exactly what Stefano Monti is doing, trying to find a very rapid, economical protocol to screen thousands of chemicals at once to get certain characteristics in a short time. Those characteristics go into a database, and then he identifies which set of characteristics is common to carcinogens and which is common to everything else that’s not carcinogenic. He thinks he’ll be able to identify a profile of a carcinogen.

Part of the problem is actually getting the chemicals to test. It’s taken us two years to collect 300 of them. And there’s an added problem, which is that one might not be a carcinogen and another might not be a carcinogen, but together they might be carcinogenic.

What else might the consortium research?

Gail Sonenshein has developed ways to detect cancer that may be growing anywhere by looking in blood for genetic pieces of the cancer. This is a very sensitive mechanism for detecting a cancer. She thinks that using this technique, she can determine whether somebody’s been exposed to something carcinogenic—the environmental factor. If Gail can come up with a way to test somebody’s blood to be able to say, ‘You were exposed to these five chemicals recently, and they’ve caused this change,’ that could be used by epidemiologists to say your disease might be caused by these chemicals.

Will we find therapies or a cure in our lifetime?

I don’t see that happening, but I’m not sure it’s because of the science. It’s the economics of developing therapeutics. The other side is, there are 84,000 chemicals, and we all want to have a new car with a new car smell and we all want to sit in chairs that are flame-retardant. We’re all passively agreeing that we want companies to make these chemicals; we all use Tupperware and all that stuff. So then it becomes an economic issue, to go after the chemical companies that could substitute something that’s not carcinogenic. That’s daunting.