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UConn TIP Company Uses Microbiome For Innovative Skin Treatments

Published by Chemical & Engineering News on 5/8/2017

Marc S . Reisch

“Love your bacteria.” That’s the tagline for Yun Probiotherapy’s line of skin cosmetics directed at those who have acne or athlete’s foot or who just want to keep their skin looking healthy. Yun’s product line, now entering the personal care market, incorporates “friendly” bacteria to help correct skin microbe imbalances.

Scientists have known for some time that the skin, like the human gut, is teeming with bacteria, fungi, yeast, and viruses, all actors in what is known as the microbiome. Some are beneficial, others are not, and some considered “good” may become harmful under the right conditions.

There’s also long-standing evidence of a connection between a healthy gut and the consumption of Lactobacillus-containing supplements and foods such as yogurt. Research firm Global Market Insights estimates that the food market for the beneficial microorganisms known as probiotics exceeded $36 billion in 2015.

However, little was known about the diversity of the “bugs” among us or their impact on human health until the Human Microbiome Project, a five-year, $157 million endeavor launched in 2008 and overseen by the National Institutes of Health. The effort teased out tantalizing details on the astounding variety of microbial communities living in our guts and on our bodies.

Now, cosmetic formulators are taking tentative first steps toward applying some of the lessons learned from the project to develop their own microbiome franchises. They are designing health-enhancing skin care products that contain live bacteria, bacteria extracts, or ingredients meant to enhance skin microbe activity.

Skeptics say not enough evidence exists to verify the benefits of creams and butters meant to farm the bugs living on human skin. They especially question the benefit of placing live microorganisms on the body without thorough testing, and they wonder how formulations containing live actors can even exist when regulations generally forbid the sale of “contaminated” products.

Personal care product formulators like Yun aren’t put off by such questions about the skin microbiome. They see many opportunities emerging from research that suggests a strong connection between a balanced microbiome and healthy skin.

Others targeting consumers with skin-microbiome-enhancing formulas include start-up firms such as AOBiome, maker of skin care products containing the ammonia-oxidizing bacteria Nitrosomonas eutropha, and Gallinée, a supplier of products containing probiotics as well as so-called prebiotics that feed skin microorganisms.

And the small innovators are not alone. Some of the big personal care firms are staking out a claim to the microbiome. Johnson & Johnson, for instance, is helping the biotech firm S-Biomedic develop a bacterial treatment for both therapeutic and cosmetic applications. The firm is now a resident of J&J’s JLINX start-up incubator in Beerse, Belgium.

Procter & Gamble has taken an interest in the skin microbiome, applying for a patent on a prebiotic composition to “improve the health of the skin microbiome.” L’Oréal, meanwhile, has patented the bacteria-derived ingredient vitreoscilla ferment, intended to “balance” the microbiome of dry skin. The firm has incorporated it into cosmetics sold under its La Roche-Posay label.

Forward-looking personal care ingredient makers are also looking into what could be the next big thing in cosmetics. For instance, prominent ingredient suppliers such as BASF and Givaudan have introduced products to enhance the microbiome and, along with it, skin health. Smaller firms such as Azitra, Greenaltech, and Vantage Specialty Ingredients are also looking to provide microbiome-focused ingredients.

Microbiome skeptics

Not surprisingly, the concept of microbiome-enhancing cosmetics has its doubters. Wilfried Petersen, managing director of the German preservatives specialist Dr. Straetmans, wonders if the developing fascination with the skin microbiome will amount to more than a hill of beans. “The story of the microbiome sounds nice, but the proof of benefit is lacking,” he says.

European Union regulations, Petersen points out, don’t allow for the intentional addition of bacteria to cosmetics. In addition, he asks, if beneficial bacteria are added, how do you preserve the formula and how can you be sure it won’t become unstable and spoil?

Dermatologist Patricia K. Farris points out that skin microbiome imbalances, such as the overgrowth of Propionibacterium acnes, are prevalent in many skin diseases. Correcting those conditions, perhaps with lactic acid or other bacterial derivatives, can provide relief for people with those conditions.

“But can we make people look 20 years younger by putting probiotics on their face? I’m not sure we’re there yet,” says Farris, who is on the board of the American Academy of Dermatology. More study is needed to determine if pre- and probiotics are worthy of the hype they are getting, she says.

Studies carried out as part of the Human Microbiome Project suggest that a person isn’t so much an individual as a complex organism composed of both human and microbial cells. Trillions of microorganisms inhabit the body, outnumbering human cells by 10 to 1. In all, those microorganisms make up 1 to 3% of the body’s mass, or anywhere from 1 to 3 kg on the body of a 100-kg adult.

But the challenge is to translate that general knowledge into health and disease conditions and then to specific treatments. Mapping out and sequencing the genetic identity of microbes at various locations on the skin is a complex undertaking, notes Nava Dayan, a skin research consultant to pharmaceutical and personal care firms. Even with the work undertaken to date, “we don’t fully understand the baseline of what a healthy skin microbiome is because it varies from person to person and even differs depending on a person’s age and environment,” she says.

Without a full understanding of what the baseline is, developing a personal care product to influence the skin microbiome “is like shooting a moving target,” Dayan says. Even if scientists learn how the skin microbiome changes and shifts over time, they are still missing a lot of information about how microbes influence human cells.

Testing personal care formulations for their effects on the skin poses another problem, Dayan says. Cultured human cell models now used in labs “are inherently sterile.” It will be some time before scientists can develop a human cell model that also incorporates skin microbes.

Probiotic possibilities

Still, cosmetic firms such as Yun, the company that exhorts customers to love their bacteria, see value in harnessing what is now known about the microbiome. The firm has worked with scientists at the University of Antwerp to develop its product line, which incorporates live Lactobacillus. It promises to make its research public soon.

At a microbiome workshop last month at the In-Cosmetics personal care ingredients show in London, Yun cofounder Tom Verlinden said the company avoids contaminating other ingredients in its formula by housing the dormant Lactobacillus inside a protective microcapsule.

When the cream is rubbed on the skin, the capsule breaks open and the bacteria are activated, according to Verlinden, who is trained as a pharmacist. The firm uses a “natural” pH-activated preservative system that turns off when it hits the skin’s pH, he added.

Asked if he thinks the market is ready for skin care products that contain bacteria, Verlinden said he would not have thought so two years ago on the basis of surveys his firm conducted. “Now, given the fear of chemicals,” he said, consumers are ready for a more “natural” product.

Some consumers have already given Yun a vote of confidence. The firm raised more than $20,000 on Indiegogo, a crowdfunding website, earlier this year.

Regulators are ready for live probiotics too, Verlinden claimed. The regulators Yun has spoken with gave the firm the go-ahead after they saw data indicating its products “can’t hurt,” he says.

Also adding live bacteria to its formulas is Cambridge, Mass.-based AOBiome, maker of a product called Mother Dirt. Speaking at the London workshop, Elsa Jungman, a product manager for the firm, explained that company founder David Whitlock uncovered the ammonia-oxidizing bacteria after being challenged to explain why horses roll in the dirt.

Whitlock, a Massachusetts Institute of Technology-trained chemical engineer, took a look at the dirt and eventually isolated Nitrosomonas. While studying the bacteria, he found they consume the ammonia in sweat and produce nitric oxide and anti-infective compounds that have a role in regulating inflammation, Jungman explained. Whitlock concluded that horses roll in the dirt for its skin-soothing benefits.

Nitrosomonas were once common on human skin, AOBiome theorizes, but with the widespread use of surfactants to clean skin, they have all but disappeared. Reestablishing them on the body promotes skin health and reduces the occurrence of skin pathologies such as acne, Jungman claimed.

Mother Dirt drew attention the year before it was launched when a 2014 New York Times Magazine article detailed reporter Julia Scott’s experience testing a spray mist containing AOBiome’s active ingredient. After a month of using the mist instead of showering, Scott said, she didn’t smell and her skin changed for the better.

The mist and other preparations containing the bacteria contain no preservatives and must be refrigerated, Jungman said. “Our customers tend to be afraid of chemicals,” she said, and they tend to have very sensitive and problematic skin. To date, she noted, “we have had no adverse event reports involving our product.”

The biotech firm Azitra, a 2014 spin-off from Yale University, has developed a skin-soothing recombinant microbe based on Staphylococcus epidermidis, a normal part of the skin microbiome.

Azitra’s bacteria express filaggrin, a structural protein often missing or underexpressed in people who have skin problems such as eczema, explains Travis Whitfill, a Yale School of Medicine research scientist and Azitra’s chief science officer. The protein binds to keratin fibers in the skin’s epithelial cells, regulating skin lipids and helping the skin retain moisture, he says.

Whitfill says filaggrin production is designed to be short-lived. After a day or two, the bacteria “kick out” the designer DNA Azitra inserted as they reproduce on the skin. The bacteria are still there, but the altered DNA decays in the environment, he says.

Azitra is struggling with how to keep the bacteria viable until the consumer uses a product containing them. Whitfill says the firm is considering drying the bacteria so they go dormant and delivering them in a waterless emollient to the consumer. Moisture on the skin would revive them.

So far, Azitra has raised nearly $4 million from the venture capital firm Bios Partners, in which Whitfill is also a partner. Azitra aims to qualify a consumer product for sale by 2019, hopefully with another firm, Whitfill says. Longer term, it wants to develop its recombinant bacteria to treat skin conditions such as eczema and rare genetic skin diseases, he says.

Gallinée distributes a cream in France and the U.K. that contains what the company describes as “deactivated bacteria from the Lactobacillus family” along with prebiotic fibers and sugars to support the growth of good bacteria, and lactic acid to optimize skin pH. The combination of ingredients is intended to repair the skin barrier and support the microbiome.

The firm’s founder, Marie Drago, who like Verlinden is a pharmacist, also spoke at the London conference. Changing her diet to include prebiotic and probiotic ingredients alleviated the gluten intolerance she had for years, she claimed. That led her to reason that “if such a treatment worked inside, it could work outside too.”

“We’re cleaner than we used to be, and that’s why you see so much disease,” Drago said.

Active ingredient approaches

Some personal care ingredient suppliers are leery of diving into materials that contain bacteria, either alive or “deactivated.” But they are interested in developing active ingredients that work to benefit the skin microbiome.

“We considered developing live bacteria strains with skin benefits,” says Boris Vogelgesang, a technical manager at BASF, the world’s largest chemical company. But the firm was concerned about regulations on microbial “contamination” of personal care products and the complications inherent in preserving creams and lotions while keeping good bacteria viable.

“Maybe we can learn from food regulations,” which do allow active microorganisms in products such as yogurt and cheese, Vogelgesang suggests. “Preservative regulations need to evolve to distinguish good from harmful bacteria.” That may happen with time, but for now “it’s a brand new topic,” he says, and BASF is taking a conservative approach.

That approach includes establishing a research group that is exploring how microbes are involved in a healthy skin barrier and how active ingredients affect them. “We want to better understand the role of each microorganism in skin beauty and build new skin models to study effects of active ingredients,” says David Herault, BASF’s head of global R&D for bioactives.

Together with the International Center for Infectiology Research in Lyon, France, BASF has been developing skin models embedded with bacteria. The firm hopes the models will help it launch active ingredients to treat aging skin, skin with pigment disorders, and skin exposed to pollution as well as to work with different skin types.

BASF’s work in skin modeling also involves Poietis, a French firm with which it is developing a three-dimensional printed model of human skin as an alternative to animal testing of cosmetics, which is banned in Europe. Vogelgesang says 3-D printing can layer cells and precisely seed growth factors and cell types.

The technique might be adapted to reproduce the cells and bacteria found in wrinkles, Vogelgesang suggests. Such a model could lead to microbiome-inspired techniques to reduce skin wrinkling. “There is a lot to discover about the skin microbiome,” he says.

As BASF sees it, exploring the microbiome for personal care opens up a brave new world. “For years we’ve tried to eliminate problematic bacteria by using antibiotics. But killing the bad bacteria could also damage beneficial bacteria,” Vogelgesang says. “We need an approach that recognizes the community of flora on the skin and that preserves beneficial bacteria.”

For now the firm is using in vivo methods to look at the effect of active ingredients on skin microbes. In doing so it has come up with an ingredient, called Relipidium, that rebalances the skin microbiome. Vogelgesang says Relipidium works by encouraging growth of the beneficial bacterial S. epidermidis and discouraging growth of Staphylococcus aureus, which is associated with dermatitis and dry skin.

Launched late last year, Relipidium is made by feeding a yeast extract to Lactobacillus plantarum, a type of lactic acid bacteria. After filtering out any microbes, what are left behind are beneficial proteins, amino acids, and short-chain fatty acids.

BASF expects to develop products that complement Relipidium in the future, Vogelgesang says, adding that the firm’s likely next microbiome-inspired targets are ingredients that address oily and sensitive skin.

The fragrance ingredient specialist Givaudan is also developing actives to enhance the skin microbiome. Its 2015 acquisition of the active ingredients maker Induchem brought with it an R&D center in Toulouse, France, with expertise in genetic analysis and the microbiome, explains Fabrice Lefèvre, marketing and innovation director.

Givaudan initially developed Revivyl, one of its newest ingredients, to “revive” the skin by stimulating cellular differentiation and exfoliation of older skin cells. But then “we also asked how this ingredient would affect the microbiome,” Lefèvre says.

Isolated about 10 years ago, Revivyl is an extract from Orobanche rapum, a chlorophyll-free parasitic plant that grows in Europe. Besides its skin-reviving characteristic, Revivyl “protects skin by balancing the skin microbiota” and prevents microbial imbalances. According to the firm’s literature, Revivyl also inhibits the Finegoldia genus of opportunistic skin pathogens.

In a concept it calls [Yu] for “you are unique,” Givaudan is promoting the incorporation of Revivyl into fragrances. Such a use would combine a sensory experience with microbiome protection to make users “feel and look beautiful,” Lefèvre says.

Beyond ingredients that maintain the skin microbiome, Lefèvre says, Givaudan is developing ingredients that the microbiome turns on. One is Brightenyl, a skin-lightening agent that is activated by the skin’s resident bacteria.

Developed two years ago, Brightenyl contains an α-glucoside derivative of trihydroxybenzoic acid that Givaudan calls THBG. When applied to the skin, THBG is converted by certain microbes into trihydroxybenzoic acid, a molecule that evens out and lightens the skin.

Practical prebiotics

Other ingredient makers aren’t yet ready to go as far as introducing microbes to the skin or even developing ingredients that depend on microbiome activity. Many are betting that getting the skin microbiome into better balance with prebiotics is the first course of action.

“We stay strictly with prebiotics and address the skin holistically,” says Michael Anthonavage, technical director of Vantage Specialty Ingredients.

The firm’s PreBio Defense is a blend of polysaccharides that “acts as a fertilizer bed” for good skin bacteria, Anthonavage says. Prebiotics in the formula include inulin and β-glucan, which are packed into cellulose microcapsules to make it easy for formulators to blend into their skin care products, he says.

Greenaltech, a Barcelona-based biotech firm, is offering Algaktiv BioSKN, a prebiotic derived from microalgae. Joan Tarraga, who heads business development for the firm, describes BioSKN as a carbohydrate derived from microalgae cell membranes.

The skin is subject to a variety of assaults, including “sun radiation, urban pollution, weather, and chemicals in the environment,” Tarraga argues. As a result, the epidermis thins “and our microbiome is altered, leading to inflammation,” he says. Incorporated into a cosmetic formulation, BioSKN helps beneficial bacteria grow and reduces the proliferation of harmful bacteria that can cause inflammation, he claims.

Skin research consultant Dayan says she expects that scientists and cosmetic ingredient formulators will over time look more deeply into the “cross talk between the microbiome and human cells.” Understanding the complex community of microbes resident on the skin—and comprehending how those microbes can vary from individual to individual—can lead to the next steps in skin product development, she suggests.

It’s uncharted territory for the personal care business. For years people have been taught to fear bacteria and knew of only the infections and illnesses they could cause. Time will tell whether the public is now ready to accept skin care products full of bacteria and turn microbiome-inspired cosmetics into the next big thing.

Science to Startup: A Connecticut Company Plays the Startup Game in the Land of Innovation

Published in UConn Magazine in the Summer ’17 Issue

Colin Poitras

Biochemist Mark Driscoll is trying to crack open a stubborn microbe in his lab at UConn’s technology commercialization incubator in Farmington, Connecticut.

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 Professor Peter Setlow at UConn Health. 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.

Breakthrough

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 — but also leads to a proposal for more research, a new finding, and at least one patent application.

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 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,” says Driscoll 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.”

Bold Moves

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, Connecticut, one of the state’s early bioscience success stories that ended up moving to the San Francisco area.

Driscoll and Jarvie decided to stay in Connecticut. They had talked about starting a business based on new technology that would 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.

“It’s the most frightening thing I have ever done,” says Driscoll with a chuckle. “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.”

Fortunately, Driscoll and Jarvie’s 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), and major upgrades at UConn Health to boost its research capacity.

Those resources were tailor made for a fledgling bioscience company like Shoreline Biome. Driscoll and Jarvie remember the early days when company ‘meetings’ took place at a local Starbucks, their official address and warehouse was Driscoll’s garage, and they 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 and one of their customers at 454 Life Sciences, had just arrived at Jax. They reached out to him with an offer to collaborate. Weinstock not only agreed, he became their principal scientific advisor.

About the same time, Driscoll and Jarvie began exploring the possibility of renting space at 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.”

The pair also obtained $150,000 in pre-seed funding from Connecticut Innovations, the state’s quasi-public investment authority supporting innovative, growing companies; and a $500,000 equity investment from the Connecticut Bioscience Innovation Fund (CBIF).

Along with the pre-seed investment funds, CBIF’s staff helped guide Driscoll and Jarvie through the early stages of business development and introduced them to the investment community. AndCBIF member Patrick O’Neill took a seat on Shoreline Biome’s board. O’Neill’s business savvy has been crucial to the company’s early success, says Driscoll.

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. 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

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.

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.”

“It never goes away,” agrees Jarvie. 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.

UConn Student Engineers Monitoring System for Bridges

Published on UConn Today / May 26, 2017

Claire Hall

Kevin McMullen, a structural engineering Ph.D. student at UConn, has designed a bridge-safety monitoring device.

Kevin McMullen, a structural engineering Ph.D. student at UConn, has designed a bridge-safety monitoring device.

In the middle of a June night in 1983, a 100-foot span of the Mianus River Bridge in Greenwich, Conn., collapsed, plunging two cars and two tractor-trailers into the river 70 feet below.

Three people died, three were seriously injured, and diverted I-95 traffic snarled local streets for six months. Inspections revealed that an undetected fatigue crack caused the catastrophic bridge failure.

Kevin McMullen, a structural engineering Ph.D. student at UConn, is too young to remember that tragedy. But he has designed a bridge-safety monitoring device that might have prevented it. He’s hoping his company, NexGen Infrastructure, can revolutionize transportation safety.

Using force-sensing pads that continuously monitor bridges, the system can warn engineers about a bridge that is overstressed. The pads can be installed on a new bridge or one that is being repaired. The system doesn’t replace human inspection, but can help establish priorities in a nation where one in 10 bridges is structurally deficient.

“Our hope is that if something is going drastically wrong with a bridge, engineers would be alerted that the bridge needs to be inspected right away,’’ he said. “We are anticipating that the federal government and state departments of transportation will feel it is a worthwhile investment.’’

McMullen recently received a $40,000 grant from the UConn School of Engineering in partnership with Connecticut Innovations. This award is given to engineering students with promising technologies, to help them enter the marketplace. Ironically, the award is called the Third Bridge Grant.

“Not much has changed in infrastructure over the last few decades,’’ McMullen said. “More recently, new technologies are being developed for infrastructure and civil engineering. This push towards innovation makes me know I’m in the right field.’’

McMullen, who earned a bachelor’s degree in civil engineering from UConn in 2015, smiles when asked how he developed his passion.

“As a kid, I built with Legos and loved creating things,’’ he said. “When I decided what to study at UConn, civil engineering was the choice for me. And for some reason, I’ve just always loved bridges.’’

He is working on a Ph.D. thesis about a new, streamlined bridge-repair process that would be more cost-effective and minimize traffic disruptions.

“Many people surrounding me at UConn, including Professor Hadi Bozorgmanesh, who teaches an entrepreneurship program for graduate students, and my adviser, Professor Arash Zaghi, have really pushed innovation and got me thinking out of the box,’’ said McMullen.

“UConn has been very instrumental in getting my company off the ground. The Third Bridge grant I was awarded is helping me to start my company and bridge ‘the valley of death,’ so when I leave UConn, I can hit the ground running.’’

UConn Research Innovation Newsletter – June 2017

Check out the latest UConn Research Innovation newsletter to learn about exciting technologies and startups with a UConn connection.

UConn TIP Farmington Startup Sets Sights on Curing Retinal-Disease Blindness

Published on UConn Today / May 24, 2017

Claire Hall

Nicole Wagner, president and CEO of LambdaVision, which was founded through support from UConn’s Technology Commercialization Services in 2009.

Nicole Wagner, president and CEO of LambdaVision, which was founded through support from UConn’s Technology Commercialization Services in 2009.

Tucked inside a small laboratory at UConn’s Technology Incubation Program (TIP) in Farmington, Conn., Nicole Wagner is trying to cure vision impairment and blindness for more than 30 million people worldwide.

Using a protein, grown in the laboratory and implanted behind the retina, this promising new procedure offers hope for patients with age-related macular degeneration (AMD) and other retinal diseases.

“These are terrible diseases that truly impact the quality of life for many people,’’ said Wagner, the president and CEO of LambdaVision. “To offer patients the possibility of restoring their vision provides them the chance to see a new grandchild, resume a golf game, drive again or read a favorite book. For many people, restored vision would allow them to return to an independent life.’’

LambdaVision uses a light-activated protein, bacteriorhodopsin, to stimulate the retina of patients suffering from impaired or lost vision due to retinal degenerative diseases. The protein, isolated from high-salt environments, including the Dead Sea, is grown and purified in the laboratory. The protein works by absorbing light and converting it into a signal that is picked up by specialized cells in the retina, relayed to the optic nerve and ultimately interpreted by the brain.

More than 31 million people worldwide suffer from irreversible vision loss caused by macular degeneration and retinitis pigmentosa. The incidence of blindness caused by retinal degenerative diseases is increasing at a rapid rate due to an increase in the global geriatric population, Wagner said.

LambdaVision’s implant can restore high-quality vision to those patients who are no longer candidates for traditional treatments and have end-stage retinal degeneration, Wagner said. Current treatments only succeed in slowing the progression of disease.

LambdaVision was founded through support from UConn’s Technology Commercialization Services in 2009. Dr. Robert R. Birge, distinguished professor of chemistry at UConn, led a research group that included Wagner.

The protein is in pre-clinical trials across the country to determine the stability and efficacy of the implant.

“LambdaVision has been incredibly fortunate to have the continued support of UConn and the State of Connecticut, and we owe much of our success to the incredible mentors that have helped us to propel the research and development and commercialization of the technology,’’ she said. “In the early stages of development, they were the believers.’’

LambdaVision has won many awards, including most recently: a 2016 UConn SPARK Technology Commercialization Fund Award and the prestigious 2016 MassChallenge CASIS-Boeing Prize for Technology, which allows the company to carry out experiments aboard the International Space Station. Since gravity can interfere with the uniformity of the retinal implant films, the hope is that work done in microgravity will be faster and yield improvements in the homogeneity and stability of the product.

The company also won the $15,000 Wolff New Venture Prize, sponsored by UConn’s Connecticut Center for Entrepreneurship and Innovation (CCEI) and a National Science Foundation Small Business Innovation Research Grant.

“To be on the brink of a new and exciting medical breakthrough is thrilling,’’ Wagner said. “I’m very eager to see this technology available in the medical community where it can make a difference in people’s lives.’’

UConn Technology Incubation Program Company, Torigen, Inc., among Other High-impact Startups Participating in MassChallenge 2017 Cohort

Published on MassChallenge / May 23, 2017

MassChallenge, the most startup-friendly accelerator on the planet, today announced the 128 early-stage startups that have been accepted into the 2017 MassChallenge Boston accelerator program. Selected by a community of more than 850 expert judges, this year’s competitive cohort represents the top 8% of applications from around the world, including 12 countries and 16 U.S. states.

Through a global network of zero-equity accelerators, MassChallenge helps the world’s highest-impact, highest-potential startups successfully launch, grow, and create impact across industries. This proven model has accelerated 1,211 alumni that have gone on to raise more than $2 billion in funding, generate approximately $900 million in revenue, and create over than 65,000 direct and indirect jobs.

“The quality of this year’s applicant pool is a real testament to the community’s efforts to inspire and support individuals who are working to solve some of the world’s biggest problems,” said Kiki Mills Johnston, Managing Director, MassChallenge Boston. “I’m excited to welcome the 2017 cohort to Boston this summer. This is just the beginning!”

Since March, top investors, serial entrepreneurs, corporate executives, academics, and more have evaluated over 1,500 applications based on each startup’s ability to demonstrate impact and potential, which ranges from scientific breakthroughs to industry disruptions. Many of these judges remain actively involved throughout the four-month MassChallenge Boston program as mentors, speakers, and even potential partners.

Of the 128 startups selected:

  • 30% are healthcare and life sciences
  • 29% are high tech
  • 20% are general, retail and consumer goods
  • 16% are social impact
  • 6% are cleantech and energy

As part of the 2017 cohort, startups will have unrivaled access to top corporate partners, expert mentorship, tailored curriculum, and more than 26,000 square-feet of co-working space in Boston’s dynamic Innovation and Design Building – all at zero cost and for zero equity. Entrepreneurs developing physical products also have an opportunity to take advantage of MADE @MassChallenge, the organization’s 5,000 square-foot research and development lab, which provides the equipment and support needed to design, develop, and scale hardware solutions.

The accelerator program will culminate on November 2, 2017 at the MassChallenge Boston Awards, where the most-promising startups compete for shares of more than $1.5 million in equity-free awards.

“Over the past seven years, MassChallenge has graduated more than 1,200 entrepreneurs from our intensive accelerator, enabling them to create enormous impact around the world,” said John Harthorne, Founder and CEO of MassChallenge. “We are proud to welcome such a high-potential class of startups to MassChallenge, and are excited to help them define their future and maximize their impact.”

Now in its eighth year, MassChallenge has continued to drive innovation around the world through its global network of accelerators in Boston, Israel, Mexico, Switzerland, and the U.K. In addition to existing programs, the organization experienced significant growth in 2016 with the launch of several new initiatives. Locally, MassChallenge Boston launched the Newton Innovation Center, a 5,000 square-foot co-working space in collaboration with CIC and the City of Newton, and PULSE @MassChallenge, a zero-equity innovation lab that connects digital health entrepreneurs to the region’s leading institutions, corporates, payors, and healthcare experts. Top startups from the first-ever PULSE @MassChallenge cohort will compete for shares of more than $200,000 in equity-free awards at PULSE Finale on June 13, 2017.

UConn TIP Company Finds Drug Triggers Immune System to Fight Cancer in Pets

Published on UConn Today / May 22, 2017

Claire Hall

Every time the veterinarian removed the cancerous tumor from the back of “BW,’’ a sweet-faced, well-loved, white cat, the malignancy would return two or three weeks later.

The cat’s owner opted to try a revolutionary veterinary cancer treatment, called VetiVax, which triggers the animal’s immune system to fight the disease. After the third treatment, the fibrosarcoma tumor didn’t recur, and “BW’’ has been healthy for 2½ years.

UConn alumna Ashley Kalinauskas is the CEO of Torigen Pharmaceuticals, the Farmington, Connecticut-based company that creates the new treatment. She is currently marketing it to veterinarians and is anticipating rapid growth for her startup.

“When I meet people whose family pets have been diagnosed with cancer, they are heartbroken,’’ Kalinauskas said. “They want the very best for their pet. But few people can afford to pay upwards of $5,000 for chemotherapy and radiation.’’

Each year over 8 million dogs and cats are diagnosed with cancer. Almost half of all dogs and cats over age 10 will die of one form of the disease.

Until now, the standard treatment was chemotherapy and radiation, which are both expensive and could potentially have negative side effects. Vetivax uses the animal’s own tumor and tumor-associated antigens to stimulate the pet’s immune system to fight the disease. The personalized treatment, a series of injections, costs about $1,200.

“For both pet owners and veterinarians, VetiVax is another tool in the toolbox,’’ she said. “It provides hope to have an affordable treatment option with limited side effects. The reaction from veterinarians has been very positive.’’

“Our end goal is extending the survival time for these animals and achieving remission,’’ Kalinauskas said. To date, more than 150 animals have been treated with 60 percent exceeding expected survival benchmarks.

The novel approach to treatment of cancer in pets has resulted in a successful preliminary response in 11 types of cancer. Fewer than 3 percent of the animals experienced side effects, and most were minor, including mild lethargy, irritation, and redness at the injection site.

Kalinauskas earned a bachelor’s degree in pathobiology and veterinary sciences at UConn, and then went to the University of Notre Dame for graduate degrees in science and business. There, she won second place in the Notre Dame McCloskey Business Plan Competition alongside her professor and inventor of this technology, veterinarian Mark Suckow. The business plan competition inspired the team to launch Torigen and VetiVax and bring them to the marketplace.

“Connecticut is my home and I wanted to return here,’’ she said. Through the UConn Technology Incubation Program (TIP), she has dedicated laboratory space, access to unique research and development facilities, and advice from business experts and investors that can help grow the company.

“We recently received $100,000 from the UConn Innovation Fund, and additional funding from Connecticut Innovations and private investors,’’ she said. “The funding from UConn is allowing me to collect and present additional clinical data to veterinarians.’’

“Veterinarians are ‘scientific skeptics’ and want to see evidence of results. When I show them what we’ve accomplished, they are very excited,’’ Kalinauskas said. “Immunotherapy is the future of cancer medicine, not only for animals but for humans as well.’’

UConn Technology Incubation Program Hosts Inaugural Investment Event

Published on UConn Innovation Portal / May 17, 2017

It was standing room only at the inaugural UConn Technology Incubation Program (TIP) Innovation & Investment Series event this week at UConn Health in Farmington. Startup CEOs, entrepreneurs and members of the angel and venture capital community from throughout New England were in attendance.

The UConn Technology Incubation Program was established in 2004 to accelerate the growth of technology-based startups with a strong connection to the university.  Since then, TIP has grown from its roots in Storrs with space for five companies to a three campus operation able to support up to 60 companies.

This first Innovation & Investment Series event marks a renewed commitment by UConn to support the growth of promising ventures that come out of university labs, as well as external startups.

In addition to active networking, guests heard from Canaan Partners venture capitalists, Colleen Cuffaro and Peter Farina. Canaan Partners is a global, early stage venture capital firm with more than $4 billion in assets under management, and that has invested in some of the world’s leading technology and health care companies.

Cuffaro and Farina offered an inside look at what makes a biotech company attractive for investors. According to Cuffaro, the partners at Canaan “really need to swing for the fences” to get a sufficient return on their investment.

UConn’s executive director of venture development, Mostafa Analoui, explained why events like the TIP Innovation & Investment Series are critical for startups.

“Insight from active venture capitalists from firms like Canaan Partners can mean the difference between winning funding to propel a startup towards success or halting R&D because of insufficient financing,” Analoui said. “The university is committed to supporting events like these that can expedite investments and increase the chances of success for high-potential ventures throughout the state.”

The VCs from Canaan also critiqued pitches from several current TIP companies:

Bioarray Genetics is a molecular diagnostics company focused on changing the way that cancer patients are evaluated and treated with tests that predict patient response to cancer treatments.

Biorasis is a privately held company co-founded by two UConn professors who developed a wireless, needle-implantable biosensor platform for real time, continuous glucose monitoring.

CaroGen Corporation is an emerging vaccine company with a platform technology involving virus-like-vesicle (VLV)-based nanoparticle vaccines to address a broad range of infectious and chronic diseases, such as Hepatitis B, colon cancer and Zika.

The event was sponsored by Locke Lord, LLP and took place at the TIP incubator facility in Farmington at UConn Health. A $19 million addition was completed at this facility in January 2016 as a part of the state’s Bioscience CT initiative. TIP is currently home to 33 companies – the most in the program’s history. Companies in the program had a record year in 2016, with almost $40 million raised in debt and equity. This is $15.5 million more than the previous record set in 2014.

In addition to Canaan Partners, investors from Axiom Ventures, Connecticut Innovations, Elm Street Ventures, Horizon Technology Finance, Jefferson Investors, Pickwick Capital and Vital Venture Capital came to the event to learn about UConn venture opportunities.

For more information about the UConn Technology Incubation Program and to find out about future events, visit ip.uconn.edu.

New UConn Butterfly Bushes Land on the Market

Published on UConn Today / May 11, 2017

Kim Colavito Markesich

Buddleia ‘Summer Skies’

With the arrival of the new growing season quickly approaching, plant enthusiasts may choose from several new butterfly bush (Buddleia) varieties for their gardening pleasure, thanks to the College’s plant breeding work headed by Mark Brand, professor of horticulture in the Department of Plant Science and Landscape Architecture.

During the summer of 2006, doctoral graduate student William Smith exposed Buddleia davidii seeds to ethylmethane sulfonate (EMS) in the hope of generating some novel traits in butterfly bush. EMS is a chemical that can be used to induce a higher rate of mutations in plants. When the treated seeds were grown in 2007, two were identified that Brand believed were important new plants.

The first plant was a variegated individual whose leaves had a yellow edge around a dark green center. Variegated plants are always popular because the foliage adds interest even when the plant is not in bloom, according to Brand. The foliage variegation pattern was very stable, which is not always the case with variegated plants, and light blue flowers were also produced during the summer. Spring Meadow Nursery in Michigan, a commercial grower, decided to license the new butterfly bush and include it in their Proven Winners® product line as “Summer Skies.” The plant was patented (USPP 22465) and also holds Canadian Plant Breeder Rights.

“Fortunately, 50 percent of the seedlings from the compact mutant plant retained the dwarf characteristic,” Brand notes. “We then selected out the plants with the best flower colors in each color group from hundreds of seedlings.” By 2010, Brand knew he had something special. He continued reproduction of the new plants using softwood stem cuttings, and since that time each plant has retained its unique features in successive generations. He filed for four patents in June of 2015.The second unique seedling was picked from the hundreds initially grown out from the EMS treatment was one with a unique growth form, low growing and compact, bearing thick stems, large leaves and a frosted appearance to the foliage. But the color of the flowers was lackluster. Brand wanted to retain the compact habit of the new seedling, but breed it to produce flowers that had stronger, more vivid colors. To do this, the compact butterfly bush was crossed with four standard-sized butterfly bushes that have vibrant flower colors.

“These new Buddleia are dramatically different in their appearance than anything else on the market,” Brand says.Brand sent the plants to Spring Meadow Nursery. The new butterfly bushes were first offered in 2016 exclusively at Walmart, as the Soda Pop series within the Better Homes and Garden line.

Unlike other dwarf plants, the UConn Soda Pop series have big leaves, big chunky stems and full-sized flowers on a plant that stays between three and four feet tall, even when left unpruned, says Brand. “That’s what makes them unique.”

The response to the new line was so positive that Spring Meadow bred the new cultivars with some deeper color plants to expand the line. These plants are part of their Proven Winners® line, under the Buddleia Pugster™ Series. “Our material was so impressive it led to an additional line of Buddleia touted as a major breakthrough in butterfly bushes,” Brand points out. “I expect there will be more future butterfly bush introductions that will trace their genetic roots back to the compact mutant that was produced in our breeding program.”

Royalty monies from plant cultivars help to fund continued research by students. So far, the royalty income has gone toward lab supplies and other necessities such as plant media, containers and fertilizer.

“I think the bulk of our royalty funding is yet to come,” Brand says. “We have quite a few cultivars out there including an ornamental switchgrass, several varieties of butterfly bush and some chokeberry. We also have a number of plants in trials with commercial growers and some, such as a compact form of purple-leaf sand cherry, and sterile barberries, are licensed and in the production pipeline.”Royalty monies from plant cultivars help to fund continued research by students. So far, the royalty income has gone toward lab supplies and other necessities such as plant media, containers and fertilizer.

This story was originally published in Naturally@UConn, a blog by the College of Agriculture, Health and Natural Resources.

UConn Researchers Team with Pharma to Combat Superbugs

Published on UConn Innovation Portal / May 12, 2017

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Photo: Dennis Wright, professor of pharmacaeutical science, at his lab (Peter Morenus/UConn Photo)

Creating antibiotics that kill a potentially deadly staph infection known as methicillin-resistant Staphylococcus aureus or MRSA, E. coli and other drug-resistant contagions known as “superbugs” is like trying to catch a ball rolling down an endless hill that keeps slipping out of reach.

Drug-resistant bacteria constantly morph and evolve, eluding efforts to kill them. The Centers for Disease Control and Prevention flagged them as an “urgent threat” because of their hard-to-kill nature and how easily they spread from person to person.

But after about a dozen years of persistence, a husband-and-wife team of medicinal chemists and their students at UConn’s School of Pharmacy have developed a group of experimental antibiotics that early tests suggest may be up to the job. Professors Dennis Wright and the late Amy Anderson found a weakness and exploited it in a way that may make the bacteria defenseless, they report in a recent issue of Cell Chemical Biology.

The researchers believe they have developed a drug that MRSA cannot evade and another antibiotic that proves effective against E. coli, which is even more challenging to fight. They tested hundreds of different compounds, altering each one’s chemical structure slightly with the hope of finding the weapon that would break through the drug-resistant bacteria’s defenses.

“I think the really exciting thing was being able to target these resistant forms of the bugs,” says Wright. With many other drugs, such as those that fight cardiovascular disease, “once you make it, that drug lasts forever. Because bacteria evolve, antibiotics lose function over time and work less and less as time goes on. You really have to stay one step ahead of them.”

Wright and Anderson had several candidates in the works when they asked colleagues at UConn Health and Hartford Hospital to collect antibiotic-resistant strains of MRSA as test cases. The local samples showed how fast antibiotic resistance is spreading. Two-thirds of the bacterial strains contained genes to resist common antibiotic treatments; these six strains had never been seen before in the U.S.

But the compounds forged by the Wright-Anderson team prevailed. They inhibited a particular enzyme in the bacteria so it couldn’t function or survive. Their goal is to create highly resilient antibiotics so that they can withstand mutations that lead to resistance.

Resiliency is crucial to combating the drug-resistant bacteria and to finding financial backers. Pharmaceutical companies may be more willing to invest in the development of an antibiotic if they know the drug will have staying power.

Wright’s lab has received more than $10 million in federal research support, including from the National Institutes of Health, to study these compounds.

Anderson’s and Wright’s discovery is licensed from UConn to a pharmaceutical company that was founded to develop novel antibiotics.

From a business perspective, pharmaceutical companies can’t make the kind of money on antibiotics that they can make on drugs for chronic illnesses such as high cholesterol or hypertension, since prescriptions are generally for 10 days and end. The research and development stage can take decades and cost millions before bringing an antibiotic to market. That’s why, Wright says, it’s so important for university researchers to work on creating antibiotics.

Wright’s lab is refining the antibiotics to improve their effectiveness and minimize side effects before the pharmaceutical company that holds the licensing agreement can apply to the Food and Drug Administration for clinical trials.