Summit highlights promise and challenges of radiopharmaceuticals

In the Gartner cycle of hype — a graph charting the progress of emerging technologies — radiopharmaceutical therapy has traversed the peak of inflated expectations, waded through the trough of disillusionment and climbed the slope of enlightenment to reach the plateau of productivity.

That was the take of Dr. Norman “Ned” Sharpless, UNC School of Medicine professor of cancer policy and innovation, and co-chief executive officer of Jupiter BioVentures, during his opening remarks at Eshelman Innovation’s 2024 Radiopharmaceuticals Summit, held May 23 at the North Carolina Biotechnology Center in Research Triangle Park (RTP).

Radiopharmaceuticals are radioisotopes that bind with biological molecules for targeting specific human tissues or cells. These radioactive drugs can be used to both diagnose and treat diseases — sometimes together, a groundbreaking concept known as theragnostics.

“After some false starts, I think this therapy class has arrived,” said Sharpless, an Eshelman Innovation steering board member who has served as both director of the National Cancer Institute and acting director of the Food and Drug Administration.

As evidence, he pointed to important scientific advances in radiochemistry and agent pharmacology, a better supply of isotopes, a growing commitment nationally to develop the radiopharmaceutical infrastructure and the recent approval of a blockbuster drug, Novartis’ Pluvicto, for treating metastatic prostate cancer.

“Oncology is already an interesting therapeutic class for investors, and now radiopharmaceutical therapy, being something new in oncology, is going to get a lot of attention,” he said.

Eshelman Innovation, located within the UNC Eshelman School of Pharmacy, partnered with the N.C. Biotechnology Center to host the event. The summit brought together university researchers, industry leaders and biotechnology investors to discuss the state of science and manufacturing strategies that can help the N.C. research ecosystem develop a vision and long-term strategy for addressing unmet needs.

“The goal was to engage stakeholders early to find out the needs and opportunities in radiopharmaceuticals,” said summit organizer Sumitra Pati, commercial strategy director for Eshelman Innovation’s Therapeutics Accelerator. “By taking a problem-driven approach, we bring concepts to investigators at the ecosystem level.”

“The field of radiopharmaceuticals is incredibly complex. There are so many different things that are involved — the radiochemistry, the choice of ligand, how these components affect metabolism in the body,” said Duke University Professor Michael Zalutsky, director of Duke’s Radiopharmaceutical Chemistry Laboratory. “But the good news is radioactivity can be monitored by imaging. So, unlike many types of therapy, you actually know where your drug is going. That puts us at an incredible developmental advantage over a lot of older therapies.”

The panelists moved from an overview of the field to deep dives into topics such as clinical indications and tissue-targeting strategies, as well as radionuclide isotopes and manufacturing.

There are challenges — and, therefore, opportunities — across the industry, from federal regulations and infrastructure to manufacturing and workforce development, the panelists said. Among other things, they pointed to outdated FDA safety guidelines, a lack of radio chemistry expertise, manufacturing supply chain shortages and the short half-life of radioisotopes.

“Are you making an imaging agent or are you making a therapeutic, or is it both together?” asked Jeff Kovacs, vice president and head of biology at Aktis Oncology. “The power of the field is in the combination of the two, but that poses some unique regulatory challenges. There’s not a lot of precedent, at least in the U.S., for developing two agents together.”

Similarly, there is uncertainty about which part of the combination therapy can be patent protected.

“I think the linker can be the intellectual property protection asset,” said Jeff Schaal, senior vice president for theragnostics at Solve Therapeutics, referring to pharmacokinetic-modifying linkers, part of the chemical scaffold that helps build radiopharmaceutical agents.

Patrick McConville has experienced the radiopharmaceutical boom firsthand. “The interest exploded around four years ago,” said the vice president for scientific and commercial strategies at the imaging company Invicro, a leading radiopharmaceutical clinical research organization. “Technologies are coming out of universities and being acquired by mid-level biotech companies and also large pharmaceutical companies. It’s a bandwidth issue, where the recent interest is outstripping the infrastructure that exists.”

The demand isn’t surprising, he said, given the advantages radiopharmaceuticals offer the major health care stakeholders. For patients, radiopharmaceuticals eliminate unnecessary or ineffective treatments through imaging, he said. Physicians benefit from the enhanced ability to diagnose and stage disease, select optimal therapies and monitor response. And payers — insurance companies and governments — benefit from reduced costs associated with sub-optimal diagnostics and treatments.

This is where Eshelman Innovation comes in — to help achieve those benefits for patients, physicians and payers by accelerating the development of the radiopharmaceutical industry in North Carolina. The summit was just a start. Eshelman Innovation plans to make strategic grants to university researchers to advance the technology.

“With the help of the North Carolina Biotechnology Center, we would like to continue the dialogue and maintain the connectivity,” said Eshelman Innovation Executive Director John Bamforth. “We think there’s an opportunity here for North Carolina. Academically, the Research Triangle has strengths. It has strengths in the CRO and manufacturing spaces. We think radiopharmaceuticals is a business that could thrive in this state.”