Title:From innovation to impact

When Jill P. Smith gets frustrated by the lack of medical breakthroughs in pancreatic cancer, she derives motivation from the collection of pins on her white coat.

Each of what she calls her “angel pins” represents a patient who has passed away from the disease. Smith, a gastroenterologist and professor of medicine at the School of Medicine is impatient to be able to offer her patients something beyond what is currently available.

“My patients need more than what we can currently offer them. They tell me, ‘Dr. Smith, please don’t give up, keep trying,’” says Smith, who sees patients at MedStar Health and the DC Veterans Affairs Medical Center. “They really want us to participate in the research, even if they realize it won’t benefit them personally.”

As a physician-scientist who maintains an active research portfolio, Smith is passionate about ensuring scientific discoveries do not remain in the lab. This means working tirelessly to advance scientific discoveries to clinical trials with the goal of helping improve patients’ prognosis and survival.

If caught early, pancreatic cancer can be curable, but it is often diagnosed too late. Around 90% of precancerous lesions of the pancreas are not seen on routine imaging scans because they are microscopic, leading to more cases being diagnosed at stage 3 or later, when the cancer has spread.

“If we just go with the flow of what everyone else is doing, we will not shift the field,” Smith says. “There have been no major breakthroughs in pancreatic cancer in 50 years, no new drugs in over 10 years, and very little improvement in overall survival. We need to be looking for the next big thing.”

Cradle of Innovation

Universities and other academic institutions are often thought of as cradles of scientific innovation, with vast amounts of federal funding coming in to support research.

Nearly 83% of the total budget of the National Institutes of Health (NIH) funds extramural research at universities and other research institutions. In fiscal year 2023, the NIH allocated nearly $35 billion for extramural research funding.

Yet while ideally situated to pursue big ideas, universities are not set up to fully translate discoveries into products or drugs that can be manufactured and commercialized at a large scale.

Ensuring academic discoveries can have a broader impact on human health requires a process known as technology transfer—or the translation of scientific discoveries together with industry partners into a marketable product or service. At Georgetown, all technology transfer functions are housed in the Office of Technology Commercialization (OTC), which was created over 20 years ago to help researchers protect their discoveries and, hopefully, move them into the licensing and commercialization phase.

“Universities are innovation engines where researchers are free to explore their passions and their ideas to tackle the world’s problems,” says Tatiana Litvin-Vechnyak, vice president of technology commercialization at Georgetown. “We want to understand the mechanism of disease, but we are not in the business of manufacturing products at a global or even a national scale.”

That’s where industry comes in. The OTC works closely with researchers to build that bridge—beginning once a discovery is made to protect that intellectual property through patenting, copyrights, or trademarks, and then moving through the process of commercialization via partnerships with private companies.

The steepest learning curve for researchers who work in academia is to regard their discoveries as potentially valuable intellectual property, and not just matters of scientific interest. The OTC works to ensure that they disclose any potential intellectual property prior to going public with their findings, for example, in a journal or at a conference.

“Intellectual property is absolutely the key to all of this. Once an idea is out in the public domain, we are no longer able to protect it through patenting,” Litvin-Vechnyak says. “It’s a real culture shift that we are working on with researchers.”

A Legislative and Cultural Shift

To understand the scope of scientific advancements at Georgetown, one must first look back 45 years.

In 1980, the landmark Bayh-Dole Act was enacted, prompting a seismic shift at universities and research institutions across the United States.

Formally known as the Patent and Trademark Act Amendments, the law established a federal policy that enabled universities to identify and effectively work with potential industry partners interested in moving discoveries of new drug targets and devices into commercial development. The government reserves a royalty-free, non-exclusive license to use any such invention for government purposes.

Before this law’s passage, universities were not able to own or outlicense research innovations made possible by federal funding. Therefore, few inventions were actually commercialized—meaning the impact of federal funding did not reach the public.

“The Bayh-Dole Act transformed our space so that universities, research institutions, and companies could own their intellectual property,” Litvin-Vechnyak explains. “With that has come the responsibility to advance those discoveries to make sure they end up benefiting the public. This is also core to Georgetown’s mission and values.”

With a surge in university-driven innovations, universities began to create dedicated offices and roles to respond to the new demands of technology transfer. Over the decades since, the space has become increasingly multidisciplinary, attracting professionals in law, science, and business.

The OTC’s 10 staff members, led by Litvin-Vechnyak, who is trained in pharmacology, include experts in biotechnology, biochemistry, intellectual property law, mechanical engineering, data sciences, marketing, and business entrepreneurship.

The team’s remit includes evaluating inventions, navigating the patent and copyright process, pursuing licensing, and supporting the establishment of startup companies, among other needs. These steps can take years—establishing a commercial relationship is just the beginning.

“It’s not like you set it up, hand it off, and forget about it,” says Litvin-Vechnyak. ”We often work with companies for a very long time.”

Cultivating an Entrepreneurial Mindset

Samir N. Khleif, a professor of oncology and director of the Center for Advanced Immunotherapeutic Research at Georgetown’s Lombardi Comprehensive Cancer Center, says he has an entrepreneurial mindset within the academic environment. Moving towards spinning out companies from his inventions has been a “natural progression” over the years, as his research in developing novel immunotherapy drugs for cancer has evolved. This has led to the launch of two therapeutic biotechnology companies.

Khleif ’s research forms the basis of three clinical trials currently underway at Georgetown, testing new ways of combining three drugs to treat immunotherapy-resistant cervical, ovarian, lung, and pancreatic cancers. His goal is to understand how to improve a tumor’s response to immunotherapy, which despite much progress, is still effective in only about 15% of patients with advanced cancer.

For one of the trials, Khleif ’s team forged a unique collaboration with three different pharmaceutical companies: Janssen Pharmaceuticals, Bristol Myers Squibb, and Targovax. Each company had one of the drugs needed for the proper treatment, but none had all three.

“Because we are able to take this highly unusual route, we have been able to translate some of the findings that we have had in the lab into patient care,” he says.

Adopting an entrepreneurial mindset creates much wider avenues for impact, Khleif adds.

“You can invent, and you can publish. But finding a way to translate this into patient care is the difference between universities that foster discoveries to benefit humanity and those that are essentially cemeteries for invention,” he says.

A Whole Ecosystem Approach

The OTC launched the Faculty Entrepreneurship Academy in Spring 2024 to explore the fundamentals of translating research discoveries into business ventures.

The sessions bring expert speakers to support and educate faculty on the process of commercialization and entrepreneurship.

According to Litvin-Vechnyak, the academy encourages faculty cohorts to explore questions such as whether their discovery can become a viable product, if the market actually needs the proposed therapy or device, and what the regulatory approval process entails. The sessions are also an opportunity to bring awareness of Georgetown’s research portfolio by inviting people from local and regional agencies, such as the Maryland Department of Commerce and the District of Columbia Deputy Mayor’s office.

“As we look at our opportunities for translation of our research for broader impact, it takes all these entities in the ecosystem to help us advance it,” she said.

Faculty also learn how industry works, including topics such as why companies operate the way they do, how they think about fundraising, milestones, and reporting, and the importance of shareholder obligations “The idea is that they’ll be better informed about the players and the white space that might exist for them to bring something new forward,” Litvin-Vechnyak says.

From the bedside to the bench

Two collaborators, basic scientist Anton Wellstein and transplant surgeon Alexander Kroemer, attended the Faculty Entrepreneurship Academy this past October—their interest piqued by their own experience working to commercialize their joint discoveries.

Wellstein, a professor of oncology and pharmacology at Georgetown Lombardi, and Kroemer, a transplant surgeon at MedStar Georgetown University Hospital and director of the Center for Translational Transplant Medicine at Georgetown University Medical Center, have uncovered a new way to detect problems in a transplanted liver as early as the time of transplant. By offering an important indication of whether and where something has gone wrong, their discovery holds promise for pinpointing liver tissue failure—and ultimately improving the viability of liver transplant procedures.

While translational research often goes from “bench to bedside,” in this instance the researchers are working from the bedside to the bench—taking blood samples from Kroemer’s liver transplant patients and analyzing them against a “library” of cell fragments called cell-free methylated DNA developed in Wellstein’s lab.

The researchers are working to identify a partner to commercialize their technology and develop it for clinical use, Wellstein said. At the same time, the team is continuing to dive deeper to identify more subtypes of liver cells for more precise diagnoses, as well as looking to apply the technology to organs beyond the liver.

Despite their success, Wellstein and Kroemer have seen that the road to commercialization is not always a straight line.

“Having great science does not guarantee that you will have great success commercially,” Kroemer says. “If you want to move towards commercialization, you realize how many other elements are required.”

Wellstein agreed, and noted that he has been sharing insights he has gleaned about the process with his graduate students.

“I want them to understand that it’s not enough to sit in an ivory tower thinking beautiful thoughts and making beautiful discoveries,” Wellstein said. “We have a societal responsibility to make our research useful and available.”

Real-world implications

In her lab focusing on pancreatic cancer and liver disease, Smith is also acutely aware of the importance of shaping the next generation of researchers—particularly in connecting the dots between their work in the lab and the real-world impact on human health. She stresses that even the tiniest miscalculation can have even graver consequences than pancreatic cancer.

“When I lecture graduate students who are conducting research, I emphasize to them over and over again to be meticulous in their work, all the way from cell culture up to human clinical trials,” Smith says. “Even one decimal point error in your work could cost the lives of patients if it gets to the clinic.”

Smith feels she is fighting the clock to commercialize her lab’s findings so that more patients can beat the disease. Her lab has identified a receptor that, while normal in non-cancerous pancreases, is over-expressed in pancreases with cancer. This target is receptive to a drug called proglumide, which was originally developed 30 years ago for peptic ulcers. Smith and collaborators have also developed a fluorescent biodegradable nanoparticle that can selectively bind to the receptor—making cancerous cells visible through existing technologies and also offering the possibility of targeted therapies.

These findings, though published in top-tier journals, have been challenging to commercialize because of pancreatic cancer’s status as an orphan disease. An orphan disease is one that affects fewer than 200,000 people in the United States, and which most companies do not consider profitable and thus are reluctant to invest in development.

Proglumide now has received orphan drug designation for pancreatic cancer, a status that affords certain incentives to companies, and a company called CCKr Therapeutics has recently licensed the innovative technology along with the corresponding intellectual property.

Smith is hopeful about the opportunity to change the narrative around pancreatic cancer as an orphan disease. Having received support through the Georgetown University Medical Center Gap Fund, established in 2021 through a $1 million gift from Bill (C’54) and Ruth Baker (Parents ’80, ’84, ’88) to support innovative biomedical research initiatives, as well as through the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown, Smith says her breakthroughs demonstrate that it doesn’t always take an enormous investment to make a difference.

“I may be out on a limb, but I’m feeling hopeful that we’re making real progress, and that this will bring a change in this disease’s terrible record,” she says.

Martha D. Gay, assistant professor of medicine at Georgetown University School of Medicine, is inspired by watching Smith navigate the intersection between basic science and clinical research. Smith is lead mentor on Gay’s Mentored Research Scientist Development Award from the NIH for early-career investigators.

Gay’s passion lies in the lab—she studies the mechanism of action of drugs to treat metabolic dysfunction-associated steatohepatitis (MASH), an advanced stage of fatty liver disease that includes inflammation and fibrosis. Yet having worked on two phase 1 clinical trials, she admires Smith’s focus on ensuring that her research can benefit patients as soon as possible.

“I love being in the lab, but I also need to be connected with who I’m doing this work for,” Gay says. “It helps me stay focused and remain rigorous in my research when I know that there is a person behind that petri dish.”

She also enjoys spending time working in the community, particularly among underrepresented minority populations, communicating about the importance of scientific research and clinical trials. She views this as a different type of translational research—translating her research and that of her colleagues for the general public.

These interactions remind Gay of the people at the other end of the research continuum.

“Sometimes experiments require extensive troubleshooting, you don’t get accepted by that top-tier publication, or you don’t get the grant. But my pursuit of facilitating and improving liver health outcomes through my research keeps me working towards my overall goal—to enhance the health of those impacted by MASH.”