Pipettes, Pitches, and Patents

When Holly Wobma, an MD-PhD student at the Vagelos College of Physicians & Surgeons, began her PhD research on stem cells, she had no interest in business—she was a scientist, she thought, and wanted little to do with the commercial side of medicine. But a year into the work, her mindset started to shift.

“As data came in, I started to think that our idea had potential. I wanted to see it help somebody,” says Wobma. “If you want your findings to be translated into a therapy, you can publish and maybe someone will pick it up, but you can also try translating it yourself.”

The people whom Wobma is trying to help have graft-versus-host disease (GvHD), a potentially severe condition that can occur in patients who receive a bone marrow transplant. In these cases, GvHD arises when immune cells in the donor’s bone marrow recognize the patient’s tissues as foreign and attack. GvHD affects 30 percent to 70 percent of bone marrow transplant patients, even when patients are given preventive therapies such as immunosuppressive drugs. For those who develop a steroid refractory version, the mortality rate is very high.

Wobma and her colleagues are trying to prevent GvHD by adding additional cells from another donor. These cells—mesenchymal stem cells (MSCs)—naturally have immunosuppressive potential and may be able to subdue the attack by the graft. The idea isn’t new—MSC therapies have been tested in hundreds of clinical trials for a range of conditions—but no therapy has earned FDA approval due to lack of consistent efficacy. This motivated Wobma to work on a better solution.

MSCs get “educated”—and more effective

A clearer scientific understanding of MSCs has emerged more recently, Wobma says, and that’s opened the door to improving upon prior therapies.

“We know that MSCs have to be ‘educated’ beforehand by the right environmental cues to behave in an immunosuppressive way,” she says. “If you put uneducated MSCs in a patient, maybe some of them will adopt the behavior over time, but realistically your therapy could be suboptimal.

“Our vision is to have 100 percent of the cells educated and highly therapeutic from the start, so when you put them in a patient, they immediately start quenching that immune response that is causing the disease.”

The schooling of the cells is what sets the new therapy apart. The idea is to culture allogeneic, or human, MSCs with a set of proprietary factors, which primes the MSCs to more effectively suppress a harmful immune response.

The results of Wobma’s preliminary in vitro experiments, conducted with then-undergraduate Mariko Kanai in the lab of Gordana Vunjak-Novakovic, PhD, showed consistently promising results that were hard to ignore. More than 75 percent of educated MSCs highly expressed key immunosuppressive proteins, compared with less than 20 percent of uneducated MSCs, which had low, if any, expression of these proteins. Educated cells were also much better at limiting T-cell proliferation. In the summer of 2016, she submitted an invention report to Columbia Technology Ventures, a first step toward transforming her research into a business venture.

From benchtop to business

Then Wobma went to “boot camp.” Run by Columbia Biomedical Technology Accelerator, the program teaches teams how to take biomedical technologies from the lab to market. As part of the process, Wobma and Kanai (now a PhD student in Columbia’s Graduate School of Arts and Sciences) rounded out their team: Scientific advisors Dr. Vunjak-Novakovic, who also has three other business startups, and Hui Wang, MD, PhD, an expert in GvHD animal models, joined along with business advisor Anthony Curro, a Columbia MBA graduate, and Markus Mapara, MD, PhD, director of the Blood and Marrow Transplantation Program at Columbia University Irving Medical Center.

“It was a very eye-opening experience,” Wobma says. “You learn about what investors really care about. You learn how to think about who your customer is—which is usually the hospitals, not your patient—and about reimbursement. I also realized how naïve I was initially when it came to understanding what it takes to translate a clinical therapy.”

As the capstone of the course, Wobma and Kanai designed a “killer” experiment: a study that would either convince investors that the technology is worth investing in or push the team toward an early exit. Wobma and Kanai were awarded funds to perform this study—a test of their educated MSCs in a mouse model of GvHD—which they have been conducting in collaboration with Wang and Mapara.

The team also won $10,000 for their company, Immplacate, in last year’s Columbia Venture Competition, where they pitched their idea to venture capitalists and business leaders. Shortly after, the team incorporated the business and filed a nonprovisional patent—which provides intellectual property protection until the patent is granted—for the educated MSC therapy.

“The path to market for a therapy is long, and it’s expensive,” says Wobma, who is expecting costs in the millions. But the accelerator program and venture competition have helped the team build credibility and establish a network, she says, putting them in a better position to pitch to angel investors and apply for grants.

Looking ahead, Wobma plans to continue with animal experiments and raise funds, but she also hopes to hire outside scientists to work at Immplacate—an option that would advance the therapy but also free up time for her medical school studies, which she returned to in February, having completed her PhD earlier this year.

“Maybe it fails in the end, but to take something forward that may make a difference for people is exciting,” says Wobma. “It’s one of the most satisfying things I’ve ever done.”