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University of Missouri

Skinnovation

A product developed at MU could revolutionize the aesthetic medicine market.

eternogen

Backed by MU research, the biotech startup EternoGen is preparing two collagen-based dermal fillers to treat facial wrinkles. One of the products employs gold nanoparticles and has medical applications beyond aesthetics.

Five years ago, Sheila Grant helped found a company. It felt strange. As a professor in the department of biological engineering, a dual program between the College of Agriculture, Food and Natural Resources (CAFNR), and the College of Engineering, her job and aspirations had always been institutional: perform well in teaching and research, earn tenure, and publish in important journals. Jumping into a startup was a sweaty-palm moment. But she wasn’t on her own. She had promising lab research behind her, a host of Mizzou programs to support her and a team of collaborators to bring with her. Five years in, her company has raised $2 million from investors and is about to launch a product that could revolutionize the multibillion-dollar aesthetic medicine market.

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Rebecca Rone kept telling her colleagues in the Biodesign and Innovation Program that they had to see Sheila Grant’s research. Rone, BS BE ’06, had worked in Grant’s lab as an undergraduate and knew it had product development potential. So did Grant’s husband, Dave Grant, a research engineer who sat on the biodesign program’s committee.

The biodesign program is a collaboration between the School of Medicine and College of Engineering. It brings together doctors, engineers and businesspeople for a one-year fellowship, challenging them to identify a medical need in the operating room and develop technology to meet it.

In 2005, Grant published her first paper on how nanoparticles enhance the structural integrity of collagen, the most abundant protein in the body. By 2009, she was fashioning a promising collagen gel into an improved mesh — a porous patch — for hernia repair surgery but was making slow progress.

When Rone and her biodesign fellows visited the lab, Grant held up her gooey creation to explain what she was trying to do. The surgeon on the team immediately recognized its potential as a dermal filler — injectable solutions that reduce skin wrinkles and folds. The team’s business fellow agreed aesthetics was the market to pursue. That same year, with a dream of smoothing fine lines — and ultimately developing therapies for brittle bones and bone loss — EternoGen was born.

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Smoothing the Way

The meeting of Rone, her biodesign team and Grant was no accident. In a way, it had been planned for decades. Just as collagen provides structure to support youthful-looking skin, Mizzou has developed a network of programs to support successful startup businesses.

The idea of university-as-economic-development-engine has been around less than a century, and it only became widespread in 1980 with the passage of the federal Bayh-Dole Act. That act allowed universities to own the patents that resulted from federally funded research and to exclusively license the patented technologies to businesses.

Since then, an entire entrepreneurship, innovation and business development ecosystem has evolved at MU. The Office of Technology Management and Industry Relations, directed by Chris Fender, identifies, markets and protects commercially viable intellectual property developed by faculty, including obtaining patents and negotiating license agreements. The office houses teams of intellectual property experts in places of likely innovation — the Christopher S. Bond Life Sciences Center, the School of Medicine and the College of Engineering — to give direct assistance to MU faculty.

In the case of EternoGen, the Biodesign and Innovation Program identified the commercial potential of Grant’s research. The Office of Technology Management and Industry Relations assisted with the patent applications, business incorporation and technology licensing. The MU Life Sciences Business Incubator at Monsanto Place, where EternoGen is one of about 20 startups, gave the company a safe place to launch and affordable rent. The Missouri Innovation Center, which runs the incubator, offers back-office support and business mentoring. The final piece was the emphasis on promoting entrepreneurship among students by the Trulaske College of Business, where EternoGen found Luis Jimenez.

In 2011, while a student in the Crosby MBA program, Jimenez, MBA ’11, studied high-growth ventures in a business class taught by Jake Halliday, former president and CEO of the Missouri Innovation Center. Students are paired with local startups, and Jimenez teamed with EternoGen to rebrand the company and develop its business proposals.

The collaboration went well. “He was graduating in December 2011, and we said, ‘If you want to come on board, you [fundraise] your salary,’ ” Rone remembers. “And that’s what he did.” Until that point, EternoGen had not attracted investors. No matter. With Jimenez’s leadership, the company raised $500,000 in 2012, another $1 million in 2013, followed by $500,000 in the first months of 2014. The 2013 total included $250,000 from CAFNR to support faculty research and commercialization efforts. The company is now in a position to turn its potential into profits.

EternoGen’s CG NanoMatrix features collagen augmented with gold nanoparticles, which protects the proteins from being quickly broken down. Injected into the face as a dermal filler, it forms a strong nanomatrix that helps rebuild the skin’s natural scaffolding and smooths facial lines and folds.

EternoGen’s CG NanoMatrix features collagen augmented with gold nanoparticles, which protects the proteins from being quickly broken down. Injected into the face as a dermal filler, it forms a strong nanomatrix that helps rebuild the skin’s natural scaffolding and smooths facial lines and folds.

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Magic Words

EternoGen’s message was short. It said something like: “We’re bringing collagen back to aesthetic medicine. Are you interested in discussing?”

It wasn’t delivered by an expensive headhunter or prestigious recruitment firm. Anna Tenstam Lundvall, a Swedish executive and one of the world’s foremost experts in commercializing dermal fillers, found it in her LinkedIn account, a social networking site for professionals.

Lundvall didn’t care that EternoGen was a two-year-old startup with zero dollars in sales. With the words “collagen” and “aesthetic medicine,” the company had her attention.

Those were the two things I needed,” says Tenstam Lundvall, now CEO of EternoGen. “I didn’t need any more than that.”

Each EternoGen team member had a background in science. Jimenez, former CEO and now chief operating officer, also had expertise in business management. Rone, director of clinical and regulatory affairs, had expertise in health regulations. But with Tenstam Lundvall, the team had a marketer who knew the industry and could get their product in front of the right people — and ultimately under their skin.

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 Collagen is the most abundant protein in the body and a major component of bone, giving it its tensile strength. The EternoGen team hopes to use its gold nanoparticle collagen to develop therapies to treat various medical conditions, including the brittle bones of osteoporosis.

Collagen is the most abundant protein in the body and a major component of bone, giving it its tensile strength. The EternoGen team hopes to use its gold nanoparticle collagen to develop therapies to treat various medical conditions, including the brittle bones of osteoporosis.

Breaking Bone Research

Although the biggest market for CG NanoMatrix is in aesthetics, the future also holds potential for nonaesthetic therapies.

Grant was originally working on improving hernia surgeries by developing a better mesh ­— like a patch — which helps reduce reoccurrences of the injury. But collagen is also a major component of bone. “We’re really interested in osteoporosis and osteoarthritis,” Grant says. “People always think of the mineral component of bone, hydroxyapatite, which is brittle in tension” as the main component of bone strength. But that tension is usually how bones break. “So you need more collagen, your structural protein, to prevent a lot of those fractures.” Collagen could also combat bone reabsorption around knee, hip or other implants.

Collagen is also a key component in wound healing, which is another area of application. Collagen fortified by a nanoparticle matrix could be useful in chronic wounds where an overabundance of protein-breaking enzymes prevent healing.

Anywhere collagen is used [in the body], there’s all these other applications,” says Rone.

Grant calls it a “platform technology.” The underlying science is the same, but the product can be tailored for many uses.

Beauty Is Skin Deep

Tenstam Lundvall’s biggest claim to fame is bringing hyaluronic acid to America — the beauty medicine equivalent of introducing the iPod. The product is delivered by syringe into the face to give a quick boost of volume, which smoothes deep lines and wrinkles and makes skin look younger. The procedure takes a few minutes to perform, and the effects last an average of six to 12 months. Americans are enamored. They injected their faces with it 1.9 million times in 2013, making hyaluronic acid the second most popular aesthetic medicine procedure to Botox.

But it’s no substitute for collagen.

Hyaluronic acid is naturally produced in the body and is found in the extracellular matrix that skin cells sit on. But unlike collagen, which makes up 70 to 80 percent of skin by dry weight, it is not a structural component of the skin itself. The loss of collagen as we age contributes to the condition dermal fillers are trying to correct: skin that has lost elasticity, volume and developed wrinkles.

Hyaluronic acid inflates the skin with moisture, but the skin soon deflates, whereas collagen is a natural scaffold for the skin that actually helps rebuild it.

But collagen is difficult to work with. Simply injecting it into the skin is not enough. In its natural state, injected collagen would be quickly broken down by collagenase, a natural enzyme found in the body. So what companies have done — and this treatment is only available in Europe — is to “cross-link” it. Collagen is composed of three peptide chains wrapped around one another in a triple-helix pattern. Linking multiple chains together extends collagen’s life, but it also causes it to bunch up, making it more likely that the body will treat it as a foreign object. Typical treatments last three to six months.

EternoGen has two collagen products developed to protect against collagenase. One is based on a technology the company licensed from Dale DeVore, a longtime expert in the dermal filler industry and now EternoGen’s chief science officer. Called Rapid Polymerizing Collagen (RPC), it’s a liquid that, when injected, integrates into the body and forms into tissue — “tissue in a syringe” is what they call it. Treatments are expected to last about a year.

By 2016, CG NanoMatrix, the company’s second collagen product, is expected to be released. Based on Grant’s research at MU, it features a nanomatrix containing gold nanoparticles that shields against collagenase, protecting it from breakdown while preserving its microstructure so the body accepts it. In addition, it further strengthens the collagen structure and promotes tissue regeneration. The team estimates the treatment will last as long as two years.

That’s a big deal in a market where Americans spent $2.5 billion on injectable procedures, according to a 2014 report from the American Society for Aesthetic Plastic Surgery.

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Bright Future

This year has been hectic at EternoGen. In March, the company launched a pilot study in London with its RPC filler. With those results in hand, the team began working with marketers to position it as a high-end, status-symbol product at a premium price. In June, distributors began building global distribution networks. By the end of the year, the team hopes to conclude clinical trials in Europe. By spring 2015, they anticipate they will launch in select markets in Europe and Asia, followed by Canada. Eventually they want to gain federal Food and Drug Administration approval to bring the product to the U.S.

The company has a manufacturing site in Columbia to supply product for the pilot and clinical studies but will likely expand to a site in St. Louis for the commercial phase. “We want to keep it in Missouri as much as possible,” Grant says. “Missouri gave us our start, so we want to hire Missourians to continue production.”

Once sales start, EternoGen’s fillers will join MU’s other licensed technologies that generate between $7 million and $10 million a year for the university, Fender says.

But perhaps even more important than revenue is the role that the successful Mizzou startup fills in society. “I really look at it as the evolution of the land-grant mission,” Fender says. “It’s all built off the legacy of service and seeing the research benefitting society.”

And if the fillers, developed and manufactured in the Show-Me State, become the next big beauty trend, Tenstam Lundvall sees a bright new industry here. “Missouri would be the new aesthetic mecca.”