Penn’s infrastructure in both supporting clinical research and forging commercial partnerships smooths the way from idea to approval.
By Karen L. Brooks
In the sea of smiling faces at Penn Medicine’s August 2017 flash mob celebration, John Swartley, MBA, PhD, was beaming as much as everyone else — but not just because the Food and Drug Administration had just approved Kymriah, the first cellular immune therapy for cancer, that had been developed at Penn. His grin was sparked by memories of one of the first meetings he had at Penn, right after joining the institution in 2007.
The meeting was with a “very frustrated” Carl June, MD.
“Carl was struggling to find funding for this phase one study — the study that eventually became the New England Journal of Medicine article that kicked off the whole CAR T revolution,” Swartley remembers. “Fifteen to 20 years ago, you really could not raise money for cell and gene therapy. But he knew the world was going to wake up to it, and part of my job was to believe him before everyone else did.”
Carl June, MD, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017
Swartley was hired into Penn’s Center for Technology Transfer (CTT), a “more or less traditional, transactional tech transfer group” that managed the patenting and licensing processes for any intellectual property developed university-wide. Gradually, he helped to transform it into the Penn Center for Innovation (PCI), which still serves those functions but is now equally focused on building relationships between faculty innovators and the private sector.
“Faculty know to disclose big discoveries to us, but also to come to us if they’re looking for sponsored research or thinking that maybe they should start their own company — whatever’s the best way to take their program forward and get it to patients,” says Swartley, who today is associate vice provost for research at Penn and PCI’s managing director. “PCI comes in at the earliest stages of these discussions and also brings opportunities to faculty without being asked. We’re the matchmaker, the intermediary — the enzyme that helps make a reaction happen. But we’re not consumed in the reaction, so then we go off and find another partnership to build.”
The Slow Motion of Drug Development
These days, PCI handles around 750 commercial agreements annually, about three-quarters of which involve Penn Medicine and the Perelman School of Medicine (PSOM). Such agreements can prime early discoveries like new medicines for success years — sometimes decades — before the words “FDA approved” are ever uttered.
Drug development generally moves at a snail’s pace, with therapies taking an average of 10 to 15 years and costing upwards of $1 billion to trudge from concept to market. For every drug that “makes it,” more than 5,000 fail.
Anyone working in academic medical research is aware of the long and winding pathway an experimental therapy must traverse before securing approval. Often, the journey begins once a disease mechanism is identified, and then the search for a target molecule to fix it begins in the laboratory. Testing begins in cells outside the body before progressing in animal models. A small-scale phase 1 clinical trial then examines a compound’s safety in humans, followed by a phase 2 trial that measures its effectiveness and a large-scale phase 3 trial studying it in various populations, dosages, and combinations with other drugs.
While PCI manages all of the intellectual property coming out of Penn as a whole, Penn Medicine has its own discrete resources for supporting faculty research efforts as they push new therapies through the pipeline. The dozen staff members on the PSOM Office of Clinical Research’s (OCR) regulatory team, all of whom have regulatory backgrounds and graduate degrees in biomedical science, guide researchers in designing their projects with a view toward FDA approval — offering know-how that doesn’t exist in most academic organizations, according to Emma Meagher, MD, senior vice dean for clinical and translational research, who oversees PSOM’s clinical research infrastructure.
That regulatory expertise is a layer on top of the support that clinical research offices routinely provide academic health centers for the essential elements of simply running a clinical trial, which is not simple at all. Services range from participant recruitment and staff training to financial planning to legal guidance through compliance and contracting for corporate-sponsored trials. By streamlining all of the processes involved in clinical research, Penn’s OCR empowers faculty to conduct higher-impact trials that boost clinical discovery and offer patients more advanced treatment options and opportunities.
“As academics, we write grants, we publish papers, we execute research — but we don’t necessarily do that through the lens of, ‘How would this actually get reduced into clinical practice? What are the requirements I need to demonstrate to get there? How would this be manufactured, and what would scale-up look like?’” Meagher says. “There has been an enormous investment in taking Penn’s scientific heft and enabling its translation toward product development by hiring people who have a deep understanding of how regulatory authorities consider new drugs and devices.”
Working with Commercial Partners and Biotech Startups
The expansion of PCI — now about three times the size of its predecessor, the CTT — has empowered researchers to accelerate the advancement of their discoveries by positioning them as active research and development partners with pharmaceutical and biotech companies.
“We’re no longer just a contracting entity whose work ends with throwing a discovery over the fence. We're officially joint developers of our own technologies, especially when it’s something like a groundbreaking cell or gene therapy, because without our faculty members’ skills and expertise, these types of transformative innovations don’t work,” Swartley explains. “Penn helps its faculty embrace roles as collaborative co-development equals rather than waiting for an outside company to swoop in and take over.”
In many cases, PCI’s role is to support faculty in founding their own biotech startups. Successful Penn Medicine spinout companies developing cellular therapies such as Tmunity (now a division of Kite, a Gilead Company), Carisma Therapeutics, and Capstan Therapeutics, are all excellent examples of this, Swartley points out. Further developing promising technologies through a biotech startup can be a wiser strategy for commercializing the technology than immediately licensing it to an existing company, he says, because startups (and the types of firms that invest in them) are often more comfortable with the myriad risks inherent in early-stage product development. And because startup companies need early financial investment to grow, since 2018, Penn Medicine has supported a growing number of these faculty-led spinoff companies through the Penn Medicine Co-Investment Program. As of the end of the 2022 fiscal year, the program had invested over $35.5 million in nine Penn Medicine spinouts that have gone on to cumulatively raise over $1.4 billion in capital.
Jon Epstein, MD, executive vice dean and chief scientific officer in the Perelman School of Medicine, remembers that early in his own career as a basic scientist, he routinely imagined “somebody else — probably a pharmaceutical company — taking my discovery and running with it.”
“I thought someday they’d read a paper I’d written and go make a new medicine,” Epstein recalls. “But being at Penn has changed me. Now, I think I could make a new therapy here.”
No matter how far down the testing and development pathway an investigator’s project perseveres, Meagher says it demands doggedness and drive to navigate the laboratory, clinical, and entrepreneurial routes involved in drug discovery: “It takes a combination of incredible passion for and curiosity in the science, an unbelievable sense of optimism, and being able to take the knocks — to have an inherent resilience to bounce back up again even if nothing is ever going to go the way you want it to go.”
Except sometimes, eventually, things do go the way a researcher wants — like they did for June. Two years after first lamenting to Swartley about his lack of funding, June secured just enough private funding to treat three patients in an initial trial. Then, in 2012, two years after those remarkable first results were published — with support from Swartley and his team — Penn signed an agreement with Novartis to accelerate research, development, and commercialization of CAR T cell therapies.
Five years after that, their voices joined the chorus of cheers at the CAR T approval flash mob event.
And the rest is history that is still making history.
More About Penn’s Medical Advancements Leading to FDA Approvals
Making What’s Next in Medicine: Why Research at Penn Powers Many FDA-Approved Treatments. Since 2017, the FDA has approved more than two dozen new therapies with roots at Penn Medicine — almost half of which are first-in-class for their indications. Becoming a hub for drug research and development took a lot more than luck.
Why New Cancer Treatment Discoveries are Proliferating. The approval of CAR T cell therapy ushered in a new era for cancer treatment.
Putting Biomedical Research Advances Within Reach. Treatments and vaccines are only useful in the hands of the people who need them.