LyGenesis Out to Prove the Age of Organ Regeneration Has Arrived
By Mike Yeomans
In a recent episode of the long-running ABC television show “Grey’s Anatomy,” the lead character, Dr. Meredith Grey, experiences an epiphany in her quest for an idea to enter into her hospital’s innovation competition.
As she examines an MRI scan of a patient on whom she had recently performed a splenectomy surgery she is shocked to discover several functional mini-spleens that have regenerated inside the woman’s abdomen. As she mulls the discovery with other doctors a “eureka” moment occurs when she realizes the concept could be translated to treat another of her patients who is dying of liver cirrhosis. It strikes her that liver cells could be inserted into the abdomen and stimulated to regenerate functional mini-livers that could prolong his life.
If that sounds like science fiction, think again, as the idea originates from the lab of Eric Lagasse, Pitt Associate Professor in the Department of Pathology, and has been licensed to a startup company under the leadership of an Innovation Institute entrepreneur in residence.
When Lagasse received a phone call several months ago from moonlighting physician consultants for “Grey’s Anatomy” wanting to pick his brain for a story line they were developing on the concept of “ectopic” organs he was caught slightly off-guard, but happy to oblige.
After all, he had poured eight years of research into the concept and had recently achieved his own radical breakthrough when he discovered that when hepatocyte cells, which make up as much as 85 percent of a liver’s mass, are introduced into the lymph nodes of mice and pigs, the nodes act as bioreactors that incubate the growth of functional liver mass.
“I was happy to see that in the show they really captured the science correctly, and the potential impact for patients suffering end stage liver disease if this concept can be successfully carried out in humans,” he said.
At the suggestion of Pitt transplant surgeon Paulo Fontes, who like Lagasse, has an appointment to the McGowan Institute for Regenerative Medicine, Lagasse replicated the experiment in pigs, and got the same amazing result: fully-functioning vascularized liver tissue aiding in digestion and producing hormones.
On the heels of his discovery, Lagasse has been collaborating with the Innovation Institute to translate it for real-world impact. The spinout created from his discovery, LyGenesis Inc., became the 16th startup to be formed around Pitt research discoveries in the current fiscal year, breaking the University record of 15 set just last year.
(Re) Generating Home Grown Management
LyGenesis is being led by Michael Hufford, a veteran biotech researcher and executive who received his master’s and Ph.D degrees from Pitt and helped launch a Pitt spinout, invivodata, nearly 20 years ago from his doctoral research.
Hufford has left and returned to Pittsburgh three times, having done stints in drug development in San Diego and Chapell Hill. His most recent boomerang occurred two years ago when a company he was operating was sold. About a year ago he joined the Innovation Institute as an entrepreneur-in-residence. In this role he evaluates the Pitt intellectual property portfolio to help prioritize commercialization opportunities and works with faculty interested in exploring commercialization of their discoveries to develop a go-to-market strategy.
Hufford was recruited to work with Lagasse by fellow entrepreneur in residence Lorenzo Soletti, who had been consulting with Lagasse before leaving to launch another McGowan Institute-generated startup, Renerva.
“The thing that attracted me to this opportunity is that it is just jaw-dropping science,” Hufford said. He also liked that Lagasse and Fontes had been deliberate about their research strategy to begin building a strong regulatory case for the Food and Drug Administration.
One of the first things Hufford did upon signing on to LyGenesis was pursue a pre-Investigational New Drug (IND) meeting with the FDA to demonstrate the maturity of the pre-clinical work Lagasse and Fontes had done and to obtain the regulatory agency’s guidance on next steps in preparing for an IND application.
“I’m a big believer in getting FDA input early and often,” he said.
Last November, the FDA issued new guidance around the field of regenerative medicine, including the simplification of regulatory requirements for regenerative medicine advanced therapies, which is the designation Hufford in pursuing.
Hufford said the FDA has recommended a final pre-clinical study for the technology, and if successful, a trial in humans could be begin in 2019. Hufford is seeking investment for an A-round of venture capital investment to IND-enable the technology and lay the foundation for a clinical trial in patients with end stage liver disease.
He attended the annual J.P. Morgan Healthcare Conference, one of the largest healthcare investment symposiums, in San Francisco in January, attracting what he said was serious interest from potential investors.
“There was a lot of excitement around our story,” Hufford said.
If successful, the treatment would allow a single donated liver to help treat 75-150 people instead of just one. Lagasse said there are about 20,000 people waiting for liver transplants, which represents only a fraction of people suffering from liver disease who could benefit from the treatment. Depending on the stage of the disease, ectopic liver generation treatment could serve as a bridge to a transplant, or if done early enough in the disease progression, eliminate the eventual need for a transplant.
Researching With an Eye Toward Commercialization
Lagasse is no stranger to industry and academic technology transfer. Raised in France, he earned a pharmacy degree and worked at a predecessor company of the pharmaceutical giant Novartis. He did a stint as a postdoctoral researcher at Stanford under the mentorship of an entrepreneurial faculty member, and then joined a cell transplantation startup where he spent seven years before coming to Pitt.
“All of the projects in my lab are oriented toward a practical approach to science,” he said. “The goal of science to me is to develop new therapeutic approaches that can have an impact outside of the lab.”
His on-again, off-again research into growing ectopic organs was temporarily shelved as he sought additional funding when he decided to begin exploring commercial opportunities. He entered the Innovation Institute’s First Gear commercialization program, during which he interviewed numerous surgeons to confirm that the solution he was developing would be welcomed as meeting an unmet clinical need.
“As an academic I always thought the idea is the most important thing. Of course it is important, but First Gear reminded me that investors who have the capital to bring your idea to life need to hear all of the elements of how a business can be built around the idea,” he said.
Now Lagasse is turning his research apparatus to proof of concept studies around regenerating insulin producing pancreatic islet cells, kidneys and thymus, a lymphoid organ that produces T-cells, the bodies primary defense against foreign invaders and hoping to experience more eureka moments.