Jessica McBride, Office of the Vice President for Research
Kourosh Parham, MD, Ph.D. has come up with a blood test that can detect hearing loss far sooner than existing tests. Early detection can potentially prevent further hearing loss, Parham told a group of medical practitioners, faculty and students from engineering, business, medicine and other UConn graduate programs at Healthcare Solutions Night, held recently at UConn Health.
Many people suffer from hearing loss, but hearing tests are limited and fail to capture the full range of hearing, he said. Researchers are working on medications to prevent further hearing damage – once it has been detected. But, at this point, he can’t give patients their test results until he has 90 blood samples to test at once. He was seeking someone to help him find a way to test blood samples individually.
As soon as he finished his presentation, people in the audience suggested ideas and offered to collaborate.
A biodegradable force sensor developed by Dr. Thanh Duc Nguyen from the Department of Mechanical Engineering
Parham was one of five clinicians and researchers at the recent cross-pollination event aimed at developing solutions to pressing health-care problems. He and the other presenters had devised a potential solution to a problem and came hoping others with different skills could help bring the ideas to market. In addition, Thanh Duc Nguyen, Ph.D., a member of the department of mechanical engineering who invented an implantable, dissolvable sensor, was looking to partner with clinicians who could apply his biodegradable sensor to their practice. He knew he had a great idea, but needed to demonstrate its ability to positively impact medical conditions.
Teams that formed during the team-building portion of the event will compete for two $1,500 Healthcare Solutions Seed Grants offered through the Accelerate UConn program. Accelerate UConn is a joint operation of the Office of the Vice President for Research and the Connecticut Center for Entrepreneurship & Innovation. Accelerate UConn’s goal is to build and support cross-disciplinary teams that improve the likelihood of commercial success of UConn technologies. The funds are intended to help the winning teams begin working together and prepare for future competitions where they can win additional funding and business development support.
“Sometimes you get unexpected solutions when you mix the crowd together,” said Mostafa Analoui, Ph.D. executive director of Venture Development, Office of the Vice President for Research and the evening’s host. Anne Diamond, CEO of UConn John Dempsey Hospital and Dr. Bruce Liang, dean of the School of Medicine, welcomed and encouraged the attendees, a mixture of medical students, graduate students, faculty and clinicians. “This is a great way to spur an accelerated effort to commercialize academic research,” Liang said.
The other presenters were Dr. Santhanam Lakshminarayanan, Division of Rheumatology; Dr. Joel Levine, Colon Cancer Prevention Program; Dr. Courtney Townsel, Department of Maternal-Fetal Medicine; and Heather Spear, M.S.N., A.P.R.N., Department of Psychiatry.
Dr. Courtney Townsel is a Maternal Fetal MedicineFellow at UConn. She is developing a non-invasive treatment for cervical cerclage. (Janine Gelineau/UConn Photo).
After Parham and other presenters explained their concepts, attendees from the various disciplines were invited to approach whichever presenter they felt they could help, given their various disciplinary expertise or interest. Evan R. Jellison, Ph.D., assistant professor, immunology, who runs the Flow Cytometry lab at UConn Health, met with Parham to discuss ideas for an alternate, more efficient and individualized blood test method.
“We are planning to apply for the Healthcare Solutions Seed Grant to fund our collaboration,” Parham said following the meeting.
Another presenter, psychiatric nurse Heather Spear, held her son’s teddy bear while explaining her idea for a device that could be imbedded into a stuffed animal to help sooth delirious patients. She outlined the problem faced in hospitals nationwide, pointing out that as Baby Boomers age, the challenge will snowball.
More than 40 percent of the patients admitted to UConn John Dempsey Hospital are over 65, and nationally, about 35 percent of admitted patients are at least age 65. About 10 to 31 percent of patients 65 and older come to hospitals in a state of delirium, said Spear, a leader in the NICHE (Nurses Improving Care for Healthsystem Elders) program at UConn Health. Once they arrive, another 11 to 42 percent develop delirium.
As a result, these patients’ hospital stays are prolonged, increasing their risk of infection, decline, continued confusion and death. These factors lead to increased costs and decreased quality of life.
Spear hopes to create a hospital-acceptable bear that has a four-quadrant, digital panel imbedded in its belly. When patients touch the bear, whether intentionally or accidently, they would see and hear either a video of a loved one, the date and time, video clips of TV shows from their younger years or music from their youth. The bear has to withstand being thrown, since delirious patients can become agitated, anxious or disoriented.
During the team-building portion of the event, electrical engineer Insoo Kim, Ph.D., assistant professor, department of medicine at the UConn Health, offered Spear new ideas to advance her product’s development. “The solution to your idea is a software design rather than a device,” he said with confidence. “We can program the tablet. A student can write an app.”
“To me, it was rocket science,” she said later. “I was thinking, ‘This is exactly why I came to this event.’ ”
She’s had this idea for a few years, but jumped on the chance to present it to colleagues with different skills, she said.
“I was somewhat nervous, but I knew that I only had to present what I know,” Spear said. “It was a very welcoming audience. They’re there because they want to be there. They’re hoping to hear something they can jump in on and invent and make.”
It was comforting to see a few other nurses in the audience, she said. She wasn’t sure her idea would gain any traction and was thrilled at the response. Other nurses who work with dementia patients felt it would help their patients who experience memory loss.
Kim invited Spear to attend the Senior Design Pitch Day on March 27, where third-year biomedical engineering students hear about different ideas that they could work on for their senior design projects. Energized, she’s working on her application for the Healthcare Solutions Seed Grant offered through the Accelerate UConn program.
Accelerate UConn is the University’s National Science Foundation Innovation Corps (I-Corps) Site. Its mission is to bring scientific discoveries and capabilities from the lab to the marketplace. Participating teams receive $3,000 in seed funding for their new ventures and an introduction to the most critical elements of the I-Corps Curriculum and Lean Launchpad methodology. Over seven weeks, teams learn how to assess the market opportunity for their product or technology.
Each workshop provides hands-on training in the basics of business planning and is delivered by entrepreneurs and faculty members. These coaches provide personalized guidance and feedback to help teams construct an evidence-based business model and market-entry strategy. Participating teams also receive $3,000 in seed funding for their ventures. Accelerate UConn is open to all university faculty and students. For more information, visit www.accelerate.uconn.edu.
February 27, 2017 – Colin Poitras – UConn Communications
Chris Clark, Research Scientist; Tom Jarvie, CEO; Mark Driscoll, CSO; and Ryan Beach, Research Scientist. Jarvie and Driscoll are discussing the manufacturing process for the kits. (Janine Gelineau/UConn Health Photo)
Biochemist Mark Driscoll is trying to crack open a stubborn microbe in his lab at the UConn technology commercialization incubator in Farmington, Conn.
He needs to get past the microorganism’s tough outer shell to grab a sample of its DNA. Once he has the sample, Driscoll can capture the bacterium’s genetic ‘fingerprint,’ an important piece of evidence for doctors treating bacterial infections and scientists studying bacteria in the human microbiome. It’s a critical element in the new lab technology Driscoll and his business partner, Thomas Jarvie, are developing.
But at the moment, his microbe isn’t cooperating. Driscoll tries breaking into it chemically. He boils it. He pokes and pushes against the outer wall. Nothing happens. This drug-resistant pathogen is a particularly bad character that has evolved and strengthened its shell over generations. It isn’t giving up its secrets easily.
Stymied, Driscoll picks up the phone and calls Peter Setlow, a Board of Trustees Distinguished Professor at UConn Health and a noted expert in molecular biology and biophysics. Setlow has been cracking open microbes since 1968.
A few hours later, Driscoll jumps on a shuttle and takes a quarter-mile trip up the road to meet with Setlow in person. He explains his predicament. Setlow nods and says, “Here’s what I would do …”
And it works.
That brief encounter, that collaboration between a talented young scientist and a prominent UConn researcher working in Connecticut’s bioscience corridor, not only results in an important breakthrough for Driscoll’s and Jarvie’s new business – called Shoreline Biome – it leads to a proposal for more research, a new finding, and at least one patent application.
If we were on our own … there would be no place to go to ask questions. But inside this environment at TIP, you can wander around and just ask people. … Even if they can’t give you an answer, chances are they know someone who can. — Mark Driscoll
In a broader sense, it also exemplifies the collaborative relationships that UConn and state officials hope will flourish under the University’s Technology Incubation Program or TIP, which provides laboratory space, business mentoring, scientific support, and other services to budding entrepreneurs in Connecticut’s growing bioscience sector. At incubators in Storrs and Farmington, TIP currently supports 35 companies that specialize in things like health care software, small molecule therapies, vaccine development, diagnostics, bio-agriculture, and water purification.
The program has assisted more than 85 startup companies since it was established in 2003. Those companies have had a significant impact on Connecticut’s economy, raising more than $50 million in grant funding, $80 million in debt and pay equity, and more than $45 million in revenue.
“This is not a coincidence,” Driscoll says as he recounts his microbe-cracking story in a small office across the hall from his lab. “This is what government is supposed to do. It’s supposed to set up an environment where these kinds of things can happen.”
A Bold Idea
Driscoll and Jarvie, a physical chemist and genomics expert, arrived at UConn’s Farmington incubator in June 2015 with a bold business concept but virtually no idea of how to get it off the ground. Both had worked in the labs at 454 Life Sciences in Branford, Conn., one of the state’s early bioscience success stories. 454’s development of a next generation genome sequencing process in 2005 was a huge success, and led to the company being acquired by international healthcare conglomerate Roche two years later. In 2013, Roche announced it was closing 454’s Connecticut offices and moving the operation to its diagnostics division near San Francisco, Calif.
Driscoll and Jarvie decided to stay. They had talked about starting a business based on new technology that, if developed properly, would allow researchers and medical professionals to more quickly and precisely identify different strains of bacteria in the human microbiome, the trillions of good and bad microorganisms living in our bodies that scientists believe play an important role in our health and well-being. The study of the microbiome is a rapidly growing area of biomedical research. There are currently more than 300 clinical trials of microbiome-based treatments in progress, according to the National Institutes of Health, and the global market for microbiome products is estimated to exceed $600 million a year by 2023.
Driscoll says Shoreline Biome is “the most frightening thing” he has ever done: “As scientists, we know that nine out of 10 new companies fail. That sound you constantly hear in the back of your head is the ‘hiss’ of money being burned. The pressure is intense. You have to reach the next level before your money goes to zero, because when the money’s gone, you’re done.”
Driscoll and Jarvie say it was fortuitous that their decision to launch a bioscience company came at a time when Connecticut and UConn were committing resources to strengthen the state’s bioscience research sector.
As part of Gov. Dannel P. Malloy’s Bioscience Connecticut initiative approved in 2011, Connecticut’s legislature allocated $864 million to efforts that would position the state as a leader in bioscience research and innovation. That initiative included the expansion of UConn’s technology incubator site in Farmington, the opening of The Jackson Laboratory for Genomic Medicine (JAX Genomic Medicine), and major upgrades at UConn Health to boost its research capacity.
Those resources came at just the right time for a fledgling bioscience company like Shoreline Biome. Driscoll and Jarvie remember the early days when company ‘meetings’ took place at a local Starbucks. The company’s official address and warehouse was Driscoll’s Wallingford garage, now stocked with leftover lab equipment and supplies acquired from Roche during the move. The pair didn’t even have a lab.
But they did have a vision of what Shoreline Biome could be. They knew that George Weinstock, one of the world’s foremost experts in microbial genomics, had just arrived at The Jackson Laboratory’s new Connecticut research site. They reached out to Weinstock, who had been one of their customers at 454 Life Sciences, with an offer to collaborate. He not only agreed, he became their principal scientific advisor.
About the same time, Driscoll and Jarvie began exploring the possibility of renting space at UConn’s TIP in Farmington because of its proximity to people like Weinstock and Setlow.
“If you’re looking to start a bioscience company, in some parts of the state the cost for commercial space is going to be more than your will to live,” says Driscoll. “But here, the rent is graduated. So we were able stay here in the beginning for just a few hundred bucks a month.”
Along with the pre-seed investment funds, Connecticut Innovations’ experienced staff helped guide Driscoll and Jarvie through the early stages of business development and introduced them to the investment community. And, as part of the arrangement, CBIF member Patrick O’Neill sits on Shoreline Biome’s board. O’Neill’s business savvy has been crucial in helping the company achieve its early success, says Driscoll.
But Shoreline Biome’s good fortune isn’t limited to timely infusions of cash and access to outside investors – although both certainly help. The company also benefits from the internal camaraderie and technical expertise provided through UConn’s TIP.
“If we were on our own in Wallingford or Branford, there would be no place to go to ask questions,” says Driscoll. “But inside this environment at TIP, you can wander around and just ask people. Companies that are ahead in the process are mentoring those just starting. They can help if you have questions about finding a patent attorney, or writing up a workplace hygiene plan, or getting business insurance. Even if they can’t give you an answer, chances are they know someone who can.”
As part of its services, UConn’s TIP holds monthly business meetings at its incubators where CEOs can exchange ideas, ask questions about anything from accounting practices to business law, and hear presentations from different state agencies and research departments at UConn that might help them.
“To channel Donald Rumsfeld, there are things that you know, things that you don’t know, and things that you don’t know you don’t know,” says Jarvie. “This environment is the type of place where you can find out what those unknown unknowns are and start to address them.”
Outside investors also are invited to visit with startups and learn more about them. The fact that CBIF had other scientists and business professionals screen and approve Shoreline Biome’s new technology and business plan prior to making its investment, bolsters the company’s standing with potential investors.
Using the TIP location also allowed Driscoll and Jarvie to save money on purchasing high-end lab equipment. When they need to run a DNA sequencing test on a bacteria sample, they just walk down the hall to a UConn researcher’s lab. Located in UConn’s Cell and Genome Sciences Building, the Farmington TIP shares space with the University’s Stem Cell Institute.
“We need certain types of equipment to process our samples and they have one of those up the hall,” Driscoll says. “They use it maybe once a day and the rest of the time it is sitting there. So we asked if we could use it for like five minutes a day and they said, ‘Sure, just pay us a little bit of money to help keep it maintained and we’ll let you do that.’ They get a little bit of cash in the door and we get access to a machine we couldn’t possibly buy ourselves.”
Tracking the Bad Guys
The lab kit Driscoll and Jarvie are currently testing is a low-cost, off-the-shelf tool that replaces hours of painstaking hands-on processing of patient samples for bacteria DNA testing. Rather than processing one sample at a time, the kit can extract dozens of DNA samples at once. It then identifies all of the good and bad bacteria species in those samples within minutes rather than taking hours or days. Its state-of-the-art sequencing technology allows users to see not only all of the different species of bacteria in a sample, but their subspecies as well. It represents a major step forward in the rapidly advancing field of microbiome diagnostics and research.
It’s about getting DNA out of the bacteria from a complicated environmental sample and doing that in a fast, cheap, and comprehensive way, explains Jarvie.
Researchers and medical professionals have previously relied on targeted testing and laboratory cultures to identify different bacteria strains. But many bacteria species are hard to grow in the lab, making identification and confirmation difficult. Even when scientists can confirm the presence of a bacteria such as salmonella in a patient sample, the findings are often limited, which can impact diagnosis and treatment.
“The DNA fingerprint region in a bacteria is about 1,500 bases long,” says Jarvie. “Most of the sequencing technologies out there are only getting a fraction of that, like 150 bases or 10 percent. It’s like relying on a small segment of a fingerprint as opposed to getting the entire fingerprint. You can’t really identify the organisms that well.”
Jarvie describes the difference this way. Say you are running tests for mammals on three different samples. Current sequencing technology would identify the samples as a primate, a canine, and a feline. With Shoreline Biome’s technology, the results are more definitive. They would say, “you have a howler monkey, a timber wolf, and a mountain lion.”
That level of specificity is important to researchers and medical professionals studying or tracking a bacteria strain or disease. Driscoll says the kit is not limited to identifying harmful bacteria like salmonella, listeria, or MRSA. It also can assist researchers investigating the microbiome’s role in maintaining the so-called ‘good’ bacteria that keeps us healthy as well as its role in other ailments such as diabetes, multiple sclerosis, and even mental health disorders like schizophrenia.
For example, the kit easily lets a researcher compare 50 bacteria samples from individuals with multiple sclerosis and 50 samples from individuals who don’t have the disease to see whether the presence or absence of a particular bacteria in the microbiome plays a role in impacting the body’s nervous system.
“If you don’t make it cost-effective, if you don’t make it practical, people won’t do it,” says Driscoll. “It’s like going to the Moon. Sure, we can go to the Moon. But it takes a lot of time and money to build a rocket and get it ready. With our kit, all that stuff for the Moon shot is already pre-made. We provide the whole system right off the shelf. You don’t need to know how to extract DNA fingerprints, or use a DNA sequencer, or analyze DNA, all you have to do is buy our kit and turn the crank.”
As part of their product testing, Shoreline Biome is working with researchers at UConn Health and JAX to learn more about a particularly toxic and potentially fatal intestinal bacterium, Clostridium difficile, otherwise known as C. diff.
“People who track this disease, especially in hospitals where it is a problem, want to know how it gets in there,” says Driscoll. “Does it come from visitors? Does it come from doctors? You have all these spores floating around. You can answer that by looking at the bacteria’s genetics. But if you can’t get to the bacteria’s DNA, you can’t identify it.
“Our tool cracks open the microbes so you can get at their DNA and fingerprint the bugs to see what you have,” says Driscoll. “It lets people see everything. And we’ve simplified the software so you don’t have to be a skilled microbiologist to do it. A person in the lab can sit down and with just a few clicks, all of this stuff comes up and tells you these are the bad guys, the infectious organisms that are present, and these are the good guys.”
Deer in the Headlights
Initial product testing on Shoreline Biomes’ lab kit has exceeded expectations and the company is continuing to line up investors.
While their focus is certainly on growing Shoreline Biome, Driscoll and Jarvie also have come to appreciate Connecticut’s broader effort in building a strong bioscience research core to help drive the state’s economy. Providing scientist entrepreneurs with an affordable base of operations, working labs, access to high-end lab equipment, and a cadre of science peers ready to help, takes some of the pressure off when launching a new company.
“This is all part of a plan the governor and the legislature have put together to have this stuff here,” Driscoll says. “You can sit around and hope that companies form, or you can try to make your own luck. You set up a situation where you are likely to succeed by bringing in JAX, opening up a UConn TIP incubator across the street, and setting up funding. Is that going to start a company? Who knows? But then you have Tom and I, two scientists kicked loose from a company, and we notice there are all these things happening here. We could have left for California or gone to the Boston-Cambridge research corridor, but instead, we decided to stay in Connecticut.”
Mostafa Analoui, UConn’s executive director of venture development, including TIP, says the fact that two top scientists like Driscoll and Jarvie decided to stay in Connecticut speaks to the state’s highly skilled talent pool and growing innovation ecosystem.
“Instead of going to Boston or New York, they chose to stay in Connecticut, taking advantage of UConn’s TIP and other innovation programs provided by the state to grow their company, create jobs, and benefit society with their cutting-edge advances in microbiome research,” says Analoui.
As the state’s flagship university, UConn provides critical support to ventures at all stages of development, but it is especially important for startups, says Jeff Seemann, vice president for research at UConn and UConn Health.
When asked if they still have those moments of abject fear that they aren’t going to make it, Driscoll and Jarvie laugh.
“Every day is a deer-in-the-headlights moment,” says Driscoll. “Even when things are going well, it’s still a huge risk.”
Adds Jarvie, “It never goes away.”
But during a recent visit to the Shoreline Biome lab, both men are in good spirits. The company met the 12-month goals set in their CBIF funding agreement in just six months. For that effort, Driscoll and Jarvie received another $250,000 check, the second of their two CBIF payments.
In the world of business startups, however, there is little time for extended celebration. The two scientists mark the milestone with smiles and a fist bump, then turn around and get back to work.
Within the inner ear, thousands of hair cells detect sound waves and translate them into nerve signals that allow us to hear speech, music, and other everyday sounds. Damage to these cells is one of the leading causes of hearing loss, which affects 48 million Americans.
Each of us is born with about 15,000 hair cells per ear, and once damaged, these cells cannot regrow. However, researchers at MIT, Brigham and Women’s Hospital, and Massachusetts Eye and Ear have now discovered a combination of drugs that expands the population of progenitor cells (also called supporting cells) in the ear and induces them to become hair cells, offering a potential new way to treat hearing loss.
“Hearing loss is a real problem as people get older. It’s very much of an unmet need, and this is an entirely new approach,” says Robert Langer, the David H. Koch Institute Professor at MIT, a member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the study.
Jeffrey Karp, an associate professor of medicine at Brigham and Women’s Hospital (BWH) and Harvard Medical School in Boston; and Albert Edge, a professor of otolaryngology at Harvard Medical School based at Massachusetts Eye and Ear, are also senior authors of the paper, which appears in the Feb. 21 issue of Cell Reports.
Lead authors are Will McLean, a recent PhD recipient at the Harvard-MIT Division of Health Sciences and Technology, and Xiaolei Yin, an instructor at Brigham and Women’s and a research affiliate at the Koch Institute. Other authors are former MIT visiting student Lin Lu, Mass Eye and Ear postdoc Danielle Lenz, and Mass Eye and Ear research assistant Dalton McLean.
Noise exposure, aging, and some antibiotics and chemotherapy drugs can lead to hair cell death. In some animals, those cells naturally regenerate, but not in humans.
The research team began investigating the possibility of regenerating hair cells during an earlier study on cells of the intestinal lining. In that study, published in 2013, Karp, Langer, Yin, and others reported that they could generate large quantities of immature intestinal cells and then stimulate them to differentiate, by exposing them to certain molecules.
During that study, the team became aware that cells that provide structural support in the cochlea express some of the same surface proteins as intestinal stem cells. The researchers decided to explore whether the same approach would work in those supporting cells.
They exposed cells from a mouse cochlea, grown in a lab dish, to molecules that stimulate the Wnt pathway, which makes the cells multiply rapidly.
“We used small molecules to activate the supporting cells so they become proliferative and can generate hair cells,” Yin says.
At the same time, to prevent the cells from differentiating too soon, the researchers also exposed the cells to molecules that activate another signaling pathway known as Notch.
Once they had a large pool of immature progenitor cells (about 2,000-fold greater than any previously reported), the researchers added another set of molecules that provoked the cells to differentiate into mature hair cells. This procedure generates about 60 times more mature hair cells than the technique that had previously worked the best, which uses growth factors to induce the supporting cochlea cells to become hair cells without first expanding the population.
The researchers found that their new approach also worked in an intact mouse cochlea removed from the body. In that experiment, the researchers did not need to add the second set of drugs because once the progenitor cells were formed, they were naturally exposed to signals that stimulated them to become mature hair cells.
“We only need to promote the proliferation of these supporting cells, and then the natural signaling cascade that exists in the body will drive a portion of those cells to become hair cells,” Karp says.
Because this treatment involves a simple drug exposure, the researchers believe it could be easy to administer it to human patients. They envision that the drugs could be injected into the middle ear, from which they would diffuse across a membrane into the inner ear. This type of injection is commonly performed to treat ear infections.
Some of the researchers have started a company called Frequency Therapeutics, which has licensed the MIT/BWH technology and plans to begin testing it in human patients within 18 months.
Jeffrey Holt, a professor of otolaryngology and neurology at Boston Children’s Hospital and Harvard Medical School, says this approach holds potential for treating hearing loss, if its safety and effectiveness can be demonstrated.
“The ability to promote proliferation of inner-ear stem cells and direct their maturation toward an auditory hair cell fate is an important advance that will accelerate the pace of scientific discovery and facilitate translation of regenerative medicine approaches for restoration of auditory function in patients with acquired hearing loss,” says Holt, who was not involved in the research.
The researchers also hope their work will help other scientists who study hearing loss.
“Drug discovery for the inner ear has been limited by the inability to acquire enough progenitor cells or sensory hair cells to explore drug targets and their effects on these cell types,” McLean says. “We hope that our work will serve as a useful tool for other scientists to more effectively pursue studies of supporting cells and hair cells for basic research and potential therapeutic solutions to hearing loss.”
Karp, Langer, and Yin are also working on applying this approach to other types of cells, including types of intestinal cells involved in insulin regulation and control of the gut microbiota.
The research was funded by the National Institutes of Health, the European Commission, the Harvard-MIT IDEA2 Award, the Shulsky Foundation, and Robert Boucai.
February 21, 2017 – Kim Krieger – UConn Communications
Dr. Bruce Liang, center, reviews a patient’s case with physicians from the Pat and Jim Calhoun Cardiology Center. (Lanny Nagler for UConn Health Center)
Heart failure is a big problem. But cardiologist Bruce Liang believes it could be fixed with a small molecule.
Liang’s startup, Cornovus Pharmaceuticals, is developing a new drug based on a small molecule that could save people in the advanced stages of heart failure, people who would otherwise worsen and die. The potential medicine has been found effective in mice and in dogs, and could soon be tested in humans. But first it needs to get approval from the Food and Drug Administration (FDA) as an investigational drug.
Hundreds of thousands of people in the U.S. and Europe have advanced heart failure but cannot, due to age or infirmity, get heart transplants or implants to help their hearts pump better. The outlook for these patients is grim. And for Liang, that’s unacceptable.
Liang is the dean of UConn’s medical school, but he’s also a researcher and practicing cardiologist. He became a cardiologist in part because of the immediate results it can give: a cardiologist can do a surgery that clears a clogged artery, or prescribe a drug that nudges blood pressure to a better level and give someone a brand new lease on life in just days. As a cardiologist, he’d like to be able to help even the sickest heart patients. He is constantly motivated by these sickest of patients, for whom a new medication is sorely needed.
So Liang, collaborating with National Institutes of Health (NIH) chemist Kenneth Jacobson, co-invented a potential new drug that may help even the most difficult cases of advanced heart failure. It has worked well in mice with heart failure conditions, and later in dogs, larger animals that are closer to human physiology. The drug seems to prevent heart cells from dying by affecting nitric oxide, a signaling molecule. And it does this without lowering blood pressure, which is a big disadvantage of similar drug candidates.
“That’s a big advantage, because that means if it’s true in humans with end-stage heart failure, you could go ahead and give it without worrying about dropping their blood pressure, which is a big no-no because they could die from low blood pressure,” Liang says. “To our knowledge, there’s not another drug out there in development that has this unique property.”
The new medication is a small molecule, which means it can be chemically manufactured (think of aspirin or penicillin) instead of having to be grown in a bacterial or animal cell (like insulin). Small molecules are easier to manufacture and potentially more affordable for patients than more complex drugs, and Liang’s new drug could potentially help many people. More than 500,000 people in Europe and the U.S. suffer from advanced heart failure that cannot be treated with surgery or other options. And less advanced disease affects more than five million people in those same regions.
But even small molecules need big money to become medicines. Cornovus has secured about $3.5 million in funding from Connecticut Innovations and from longtime UConn supporters Ray ’56 (CLAS) and Carole Neag. And the young company received critical early-stage support from UConn’s Office of the Vice President for Research to seek patent protection and establish a startup. Cornovus rents space in UConn’s Technology Incubation Program (TIP) facility at UConn Health in Farmington.
Cornovus is also receiving funding for chemical manufacturing process development from the NIH through the Science Moving towArds Research Translation and Therapy (SMARTT) program. If all goes as planned, the company’s compound could get investigational new drug status from the FDA in summer 2018. With that in hand, they could start testing the drug in humans – and hopefully someday soon, providing a better option for even the sickest heart patients.
Accelerate UConn, an NSF I-Corps Site to move technologies more quickly and successfully from the lab to the market
Dr. Jeff Seemann, UConn/UConn Health Vice President for Research, and Dr. Timothy B. Folta, Professor of Management and Faculty Director of the Connecticut Center for Entrepreneurship and Innovation, are pleased to announce the teams selected to participate in the Spring cohort of Accelerate UConn, the University’s National Science Foundation I-Corps site. The following teams will receive special training and a $3,000 seed grant to help understand whether and how their technology might create customer value:
Dr. Abhishek Dutta, Ashwini Srishyla & Alexei Sondergeld (Faculty & Graduate Students), Drought Water Generator, School of Engineering, Department of Electrical and Computer Engineering
Dr. Sandra Weller, Dr. Dennis Wright & Dr. Lorry Grady(Faculty & Postdoctoral Fellow), Small Molecule Inhibitors, Schools of Medicine & Pharmacy, Departments of Molecular Biology & Biophysics and Pharmaceutical Sciences
Dong Yu & Susan Jacob(Graduate Students), High Rate BioGas Conditioning, School of Business, MBA Program
Katie Boyle (Faculty), Novel Underarm Scrub, Center for Public Health & Health Policy
Caseem Ward (Undergraduate Student), Project Mobo, School of Business
Dr. David Han, Dr. Poornima Hegde & Veneta Qendro (Faculty & Graduate Student), Therapeutic Antibodies for Triple Negative Breast Cancer, School of Medicine, Departments of Cell Biology and Pathology and Laboratory Medicine
Dr. George Lykotrafitis & Kostyantyn Partola(Faculty & Graduate Student) WBV Rheometer Project, School of Engineering, Department of Mechanical Engineering
Dr. Rampi Ramprasad, Dr. Huan Tran, Chiho Kim & Arun Mannodi Kanakkithodi(Faculty, Postdoctoral Fellows & Graduate Student), Polymer Genome Project, Institute of Materials Science
Faizan Khan, Ishita Banerjee & Natalie Miccile (Undergraduate & Graduate Students), Dermatat, Schools of Medicine & Business, College of Liberal Arts & Sciences, Departments of Mathematics, Physics, Immunology and MBA Program
The program includes seven weeks of intensive training to evaluate their business ideas and conduct customer discovery activities.
In cases where a single faculty member or student was accepted into the program, the AU staff helped identify appropriate Academic or Entrepreneurial Leads or Industry Mentors to round out the team.
The Office of the Vice President for Research (OVPR) and the Connecticut Center for Entrepreneurship and Innovation (CCEI) jointly operate Accelerate UConn (AU). As an NSF I-Corps Site program, AU was formed to foster entrepreneurship resulting in technology commercialization. I-Corps Sites are academic institutions that catalyze the engagement of multiple, local teams in technology transition and strengthen local innovation.
Rocky Hill, Conn. – February 2, 2017 –Connecticut Innovations (CI), the leading source of financing and ongoing support for Connecticut’s innovative, growing companies, today announced that it invested $12.2 million in equity investments in 31 companies and scientific projects during the three months ending December 31, 2016.
The investments leveraged an additional $58.4 million in capital to further support the growth of these companies. Of the $12.2 million, CI invested $6.6 million in bioscience and $5.6 million in information technology.
“We were pleased to be able to fuel the growth of more than 30 companies in bioscience and information technology throughout the quarter,” said David Wurzer, executive vice president and chief investment officer at Connecticut Innovations. “This quarter, we closed a deal with the inaugural VentureClash winner, Dream Payments.”
The second quarter of the fiscal year also included a number of key deals. CI closed:
A $1 million investment with the inaugural winner of VentureClash 2016, Dream Payments;
A $250,000 investment with Biohaven Pharmaceuticals, which leveraged an additional $39.8 million; and
A $1 million investment with CaroGen, a company that has been funded through CI’s pre-seed fund and the Connecticut Bioscience Innovation Fund.
February 9, 2017 – Jessica McBride, Office of the Vice President for Research
UConn’s new director of venture development, Mostafa Analoui, right, speaks with Ying Liu of ReinEsse LLC at the Cell and Genome Sciences Building in Farmington. Analoui says Connecticut has all the right ingredients for success in commercializing university research. (Peter Morenus/UConn Photo)
Mostafa Analoui joined UConn as executive director of venture development last October after an extensive national search, and now also serves as head of the UConn Technology Incubation Program. He has previously worked in academia, the corporate world, and investment banking, as well as launching a startup that is still in business today.
Mostafa Analoui, executive director of venture development, speaks with Kashmira Kulkarmi, chief scientist, and Alex Tikhonov, senior scientist at Azitra’s technology incubator lab at the Cell and Genome Sciences Building in Farmington on Feb. 8, 2017. (Peter Morenus/UConn Photo)
Mostafa Analoui, executive director of venture development, center, speaks with Kashmira Kulkarmi, chief scientist, left, and Alex Tikhonov, senior scientist at Azitra’s technology incubator lab at the Cell and Genome Sciences Building in Farmington. (Peter Morenus/UConn Photo)
He has been tasked with leading UConn’s efforts to identify disruptive technologies that are ripe for venture development, recruit entrepreneurs and talent to lead these startups, and raise early-stage and follow-on funding to grow these companies.
“We are thrilled that a seasoned entrepreneur and business leader like Mostafa Analoui is at the helm of UConn’s growing venture development efforts, including the Technology Incubation Program,” says Jeff Seemann, vice president for research at UConn/UConn Health. “UConn’s research and innovation pipeline is a critically important part of economic development in the state. It helps drive Connecticut’s innovation economy by commercializing life-saving technologies, supporting new companies, and creating high-wage jobs.”
Analoui has already begun working closely with faculty in Storrs and at UConn Health in Farmington. He recently discussed the special challenges and benefits of trying to develop new ventures in a university setting, and what it means for UConn and the state of Connecticut.
Q: Why is it important for universities to play a role in venture development?
A: Academic research is a powerful engine that generates innovative ideas for products and services with commercial potential. There are currently close to 10,000 patented products being sold based on technologies that originated in academic research labs. This potential offers a source of capital that can allow researchers to extend their work beyond basic research, and see their discoveries transformed into tangible products and solutions that could benefit society. Converting these ideas into solutions supports the University’s mission to enhance the social, economic, cultural, and natural environments of the state and beyond. It is also a reason that the state continues to provide support for growth programs like UConn 2000, Bioscience Connecticut, and Next Generation Connecticut.
The innovative research being conducted at academic institutions like UConn and UConn Health is also an important economic driver for the state and the nation. In the past 20 years or so, universities have launched approximately 11,000 companies that created 3.8 million jobs. The majority of these companies remain in the state where the original research was conducted and make important contributions to that state’s economy. To convert these ideas into products and companies, academic researchers need support from experts and access to resources that are common in the venture world, but are not traditionally available in a university environment. With my experience in academia, corporate settings, the startup world, and investment banking, I know I can help bridge that gap.
Q: What is different about venture development in a university setting? What are the biggest challenges?
A: What makes venture development at a university unique may also be its greatest challenge. By definition, research institutions are places where discovery and innovation happen daily. There is a constant flux of fresh ideas from great minds. This provides a unique environment where some of the greatest challenges facing our society are being tackled. The biggest challenge within a university setting is converting these ideas and discoveries into tangible solutions that can be used to address societal needs. The overall expectation for faculty is to educate, explore new ideas, and to further knowledge, but not generally to execute this conversion process. Federal research funding is increasingly competitive and typically does not support commercialization, but working to translate such research does present alternative funding options and offers the added, special reward of seeing a discovery applied to solve a real-life problem. That is another reason why support services like those provided through Technology Commercialization Services within the Office of the Vice President for Research are so critical to help advance research discoveries made at UConn to the marketplace.
Q: You have a background as an academic researcher in engineering. How did you end up in venture development?
A: Along with my teaching responsibilities, when I was a young assistant professor I was leading a major research program in oral and maxillofacial radiology. This work was successful using the standard measures of academic achievement: grants, publications, and training graduate students. But I was always intrigued to see that some of these scientific discoveries had transformative applications in the real world. It was also empowering to know that if our research demanded certain tools and devices that did not exist, we had the ability to try and develop them ourselves.
I gradually began to do more hands-on work, implementing some of the research ideas, collaborating with companies that were active in my areas, and learning about the business aspects of transforming scientific discoveries into commercial products. Soon a patent was issued for our work (“stereotactic radiography”), but because there were no university-based support services at that time, I had to form a startup on my own to commercialize the technology. Focused on product development and clinical services, this company is still in business today.
Although I received academic promotions and was awarded tenure, my work took me out of academia into the corporate world. This allowed me to increase my focus on innovation and product development with more robust resources. After going through some key corporate roles and transactions, I eventually found myself in the world of investment banking, primarily focused on company formation and funding. I’ve really enjoyed being engaged in multiple innovative companies, and am happy to continue this work at a top university like UConn.
Q: What is UConn’s reputation for innovation and entrepreneurship?
A: UConn has made positive gains in this arena, especially in regard to the growing Technology Incubation Program (TIP), which currently supports 35 startups in various fields. Since its inception in 2003, TIP has supported over 85 companies that have raised more than $50 million in grant funding, $80 million in debt and equity, more than $45 million in revenue, and have created over 100 full- and part-time jobs in the past year alone. With unprecedented investments from the state in initiatives like Next Generation Connecticut and Bioscience Connecticut, the momentum is building. We need to continue to support and grow the programs that currently exist at UConn and UConn Health to establish the University as a leader in research, education, service, and also commercialization.
Q: How does TIP fit in?
A: TIP is an established program in Connecticut that is known to improve the likelihood of startup success. The program provides a supportive environment with comprehensive startup services for UConn and UConn-related entrepreneurs that need access to state-of-the-art lab space and business resources to transition early-stage R&D projects into prototypes, products, and services. With the right support, these projects can grow and become a stand-alone company, or they can be very successful as technologies licensed to established corporations.
The access to state-of-the-art facilities and research infrastructure that TIP provides to member companies is unrivaled in Connecticut. The cutting-edge equipment and access to expensive scientific instrumentation is critical for our startups, who are working in a variety of highly specialized fields. The fact that our two major facilities are located on UConn campuses means that TIP companies can easily collaborate with the world-class researchers in Storrs or at UConn Health in Farmington, which keeps progress moving.
TIP provides valuable business support services at little or no cost to member companies. TIP startups have access to entrepreneurs-in-residence with proven track records who play a hands-on role to assure their scientific and financial goals are met. TIP also provides access to legal and financial resources for member startups, and often hosts internal educational events for startup CEOs and their employees. One of TIP’s most attractive benefits to startups is the visibility companies get in the investment community and among corporate players.
Q: What is the interest level from outside investors in university-based technologies? What can UConn do to increase this interest?
A: One of the key challenges for UConn and all Connecticut spinoff companies is limited sources of local investment capital. The quality of the research and technologies is not the problem. While Connecticut Innovations and a few local venture capital firms are actively engaged in reviewing and supporting UConn entrepreneurs, a larger and broader set of investment pools to address this critical need would help a larger number of promising technologies to reach the market. Currently, we are in the process of reviewing and interviewing an expanded group of regional investors in Connecticut, New York, and Massachusetts to engage them in TIP and other new ventures at UConn.
Q: What role does UConn Health play in UConn’s ability to commercialize technologies, support existing industry, and create new companies?
A: UConn is in a very special position, given its basic and applied research capabilities in Storrs and at the Schools of Medicine and Dental Medicine at UConn Health. UConn Health covers a broad range of clinical and research areas across multiple disciplines. The recent investments from the state through Bioscience Connecticut have also significantly expanded its depth and reach, which has led to many unique opportunities for venture development. In fact, a large portion of our current TIP companies have health care or biotech focuses. These companies rely on direct and indirect involvement from UConn Health, as well as other collaborations with UConn faculty in Storrs. Based on my initial observations and conversations with academic and research leaders, I anticipate a significant increase in the quality and quantity of UConn Health-related ventures.
Q: Most recently, you were based in New York City, but you chose to take a job in Connecticut. What is your perception of the current climate for innovation in the state? What is the impact of initiatives like Bioscience Connecticut, and JAX Genomic Medicine locating at UConn Health?
A: In my opinion, the state is primed for big growth in this field. Top research institutions like UConn and Yale are engaged in many innovative research areas, with extremely high commercial value and potential returns. Combine that with the significant long-term investment made by the State of Connecticut to create and support an environment that is conducive to innovation and entrepreneurship, and the potential is there. Then consider the fact that JAX Genomic Medicine and a number of diverse biomedical, technology, industrial, and service corporations are also in Connecticut, and you have all the right ingredients for success. Achieving such success requires a targeted effort in the areas that can differentiate Connecticut in the competitive regional and national race, such as technologies that rely on microbiome research, for instance.
Q: What is your advice to faculty, students, postdocs, etc. who are interested in commercialization or forming new startups? What can they do to increase their chances of success?
A: I would recommend they seek the help of experts who can support them in this endeavor, because it requires a completely different skill set than those necessary to be a successful researcher or educator. I am always available, as are my colleagues in Technology Commercialization Services, to assist entrepreneurial faculty with their questions about the commercialization process and the market potential of their technologies. I would also encourage them to take advantage of the existing programs and resources offered at the University, which are intended to provide educational and follow-on support for students and faculty considering commercializing their innovations.
Venture development is a high-risk endeavor, with a rocky road full of surprises. It requires vision, tenacity, and the ability to work with a large and diverse network of experts with diverse personalities. While the journey starts with a great idea and recognition of societal needs, you also need to hit the road pitching the idea, as well as listening to and implementing feedback. In the end, it takes a team to convert novel ideas into tangible products, so get out there, shake hands, and network.
Q&A talks with Dr. Mostafa Analoui, a life sciences entrepreneur and investment banker, who recently became executive director of venture development at UConn.
Q: You recently joined UConn to help lead efforts to increase venture development activity at the university. What is involved in your new role?
A: The primary goal is to help faculty and student entrepreneurs launch and grow new technology ventures based on the innovative research they conduct at UConn and UConn Health. This includes working with academic and research leaders across all UConn campuses to develop mentoring/educational tools and recruiting outside industry experts, investors and business leaders to participate in new and existing UConn ventures.
This entails collaborating with various entrepreneurship initiatives at the university, leading the UConn Technology Incubation Program (TIP), and collaborating closely with our technology commercialization team.
Q: What is the Technology Incubation Program?
A: UConn’s Technology Incubation Program, also known as TIP, is the only university-based technology incubator in the state. The program provides high-value technology startups with a suite of business services, state-of-the-art labs, fully-equipped office space, and UConn’s research infrastructure to grow their businesses.
A unique and highly valued aspect of TIP is the access it affords our companies to the extensive R&D capacity at UConn, such as core research facilities and faculty expertise, that is often unattainable for a fledgling startup.
Q: How many companies have come through the TIP program?
A: Since it was established in 2003, TIP has accelerated the growth of over 85 technology startups led by UConn faculty, students, and external entrepreneurs who collaborate with the expert researchers at UConn and UConn Health. These companies have raised more than $50 million in grant funding, $80 million in debt and equity, more than $45 million in revenue, and have created over 100 full- and part-time jobs in the last year alone.
Q: How do you determine which technologies have commercial potential? How do you turn a technology into a successful product or company?
A: The key ingredients for the success of any innovation-based venture are: accurately identifying the market demand; establishing a clear and realistic business plan that covers technology development, finances, strategic partnerships, etc.; and recruiting an experienced team to execute the plan.
As a standard of practice, we rigorously evaluate each innovative concept developed by our faculty to identify potential opportunities, and more importantly, to assist and support them throughout the commercialization process, either through new company formation or licensing. To do this, we depend on internal experts like our licensing directors and industry liaisons, and we also reach out to external contacts from the investment community, other technology-based startups, and successful entrepreneurs and business leaders.
Q: What are the biggest challenges in your new position?
A: What makes venture development at a university unique may also be its greatest challenge. By definition, research institutions are places where discovery and innovation happen daily. There is a constant flux of fresh ideas from great minds. This provides a unique environment where some of the greatest challenges facing our society are being tackled. The mandate for faculty is to educate, explore new ideas, and to further knowledge. They are not expected to know how to start a company or market a technology.
Also, academic research requires a different type of capital to adequately support venture development from university technologies. Ideally, investors want to work with ventures that are close in proximity. This can be challenging for Connecticut-based startups, since there is a limited presence of venture capitalists in the state.
Yet even before this stage, we need to tackle the funding gap that exists between the federally funded research projects and applied R&D activities. To make a technology attractive to investors and partners, it is critical to have data to prove a concept. While there are a few federal programs for applied R&D, they are highly competitive and can take quite some time to access.
Our challenge is to move at a pace that keeps us ahead through easily accessible funding at this very early stage — sometimes even prior to company formation — that will allow us to attract investors and partners.
Q: There are currently 35 companies located at TIP’s two major locations in Storrs and at UConn Health in Farmington. What are the prospects for growth in these sites?
A: Currently our TIP facility at Storrs is fully booked, but we expect some companies to graduate and make room for one or two new companies in the spring of 2017. The number of clients in Farmington has increased quickly since the state invested $19 million through Bioscience Connecticut to expand the facility in Jan. 2016, and we anticipate high-quality companies from UConn, Connecticut, and beyond will fill the remaining space soon.
Published on Hartford Business Journal / January 11, 2017
East Hartford’s Sustainable Innovations Inc. (SI) and UConn’s Center for Clean Energy Engineering are developing a hydrogen fuel quality sensor to help ensure reliability of hydrogen vehicles.
The sensor they are designing would rapidly assess whether a fuel supply stream is meeting a vehicle’s operating needs. It has been shown in laboratory testing to be highly accurate in its detection of potential contaminants in a vehicle’s hydrogen supply stream, said Trent Molter, SI president and CEO.
Within seconds, the sensor sends a signal to shut off the dispenser if a damaging contaminant is detected. The sensor is also cheap and needs little maintenance, he said.
SI has received a $1 million contract award from the U.S. Department of Energy to develop a commercial variation of the sensor.
January 11, 2017 – Jessica McBride, Office of the Vice President for Research
Kepeng Wang, assistant professor of immunology, right, works with research associate Kasandra Rodriguez in the lab at CaroGen Corp. in the technology incubator at Farmington. (Peter Morenus/UConn Photo)
The University of Connecticut and emerging immunotherapy company CaroGen Corp. have begun a collaboration to develop a vaccine for treatment of patients with colon cancer.
CaroGen’s proprietary technology platform will be applied to a specific target studied by UConn Health researchers Kepeng Wang, assistant professor of immunology, and Anthony T. Vella, professor and Boehringer Ingelheim Chair in Immunology.
CaroGen Corp.’s platform is a transformative virus-like vesicle (VLV) technology developed at Yale University School of Medicine and exclusively licensed by CaroGen for the development and commercialization of immunotherapies worldwide.
Colon cancer is the second leading cause of cancer-related deaths in the United States. It is expected to cause over 49,000 deaths during 2016, and the risk to individuals increases with age. Wang’s target, Interleukin-17 (IL-17), a pleiotropic pro inflammatory cytokine, can promote cancer-elicited inflammation and prevent cancer cells from immune surveillance.
“While the death rate from colon cancer has been dropping for several decades thanks to screening and improved treatment, our goal is to reach close to a 100 percent survival rate,” said CaroGen’s President and CEO, Bijan Almassian. “By combining our platform with Dr. Wang’s very promising target, we hope that a new powerful immunotherapy will be developed to provide patients with that assurance.”
The company will have the right to exclusively license intellectual property developed by UConn through this collaboration, for human and animal health use.
The company is one of 21 biotech startups now housed at the Technology Incubator Program (TIP) on the UConn Health campus in Farmington, which helps develop new biotechnology concepts into businesses. CaroGen is leveraging the resources of the program to develop a portfolio of immunotherapies, with a lead program in chronic hepatitis B viral infection in collaboration with researchers from Yale University School of Medicine and Albany Medical College.
It is also working on the development of VLV immunotherapies against C. difficile bacterial infection in collaboration with Kamal Khanna, assistant professor of immunology at UConn Health, and a vaccine against the Zika virus with Paulo Verardi, associate professor of pathology at UConn Storrs.
“CaroGen is proving to be both a scientific and entrepreneurial leader in Connecticut,” said Dr. Jeff Seemann, UConn’s vice president for research. “Dr. Almassian has led multiple efforts to apply the CaroGen technology in collaborations with UConn researchers where critical and urgent health care needs exist. We are very excited about this latest endeavor, which we believe will yield significant therapeutic and commercial opportunities through the combined expertise of UConn Health’s Department of Immunology and CaroGen.”
UConn’s Technology Incubator Program is a key component of BioScience Connecticut, the state’s initiative to position Connecticut to be a leader in bioscience research, boost the economy, and improve residents’ access to world-class medicine.