Greg Verdine.

Health

Finding ways to ‘drug the undruggable’ diseases

Greg Verdine, a force behind pancreatic cancer progress, learned from a devastating family accident the value of improvisational thinking

Sy Boles

Harvard Staff Writer

June 22, 2026

6 min read

Part of the
Profiles of Progress
series

Chemical biologist Greg Verdine was driving from his North Shore home to his office in Cambridge when he had to pull over to the side of the road.

Verdine was listening to the podcast “Interesting Times with Ross Douthat.” The guest was former U.S. Sen. Ben Sasse, who has metastasized stage 4 pancreatic cancer. Few with the diagnosis survive beyond a year.

Sasse sounded surprisingly upbeat as he described an experimental drug that had reduced his tumors by 76 percent and helped him beat survival expectations (though not cure him, he noted).

“I did that,” Verdine, the Erving Professor of Chemistry, emeritus, recalled thinking. “I made that possible.”

The drug was daraxonrasib, which has garnered attention in recent months for the unprecedented success of its Phase 3 clinical trial. The treatment roughly doubled overall survival time from 6.7 months to 13.2 months, a precious increase for patients like Sasse and the estimated 60,000 other Americans who are diagnosed with pancreatic cancer each year.

“It’s a chink in the armor of a very difficult cancer,” Verdine said. “We can get patients six months, and now everyone is talking about how we get from six months to nine months and so on.”

Daraxonrasib’s success is owed to a kind of molecular glue that can help two proteins adhere when they wouldn’t.

For decades, conventional wisdom held that KRAS, a protein that is a major driver of cancer in humans, couldn’t be drugged. It took years, but Verdine’s innovative approach to binding proteins ultimately led to the discovery that made this possible.

It’s not the only time one of Verdine’s seeming long-shot ideas turned out to have sticking power.

Verdine made a career “drugging the undruggable” — creating not just new medications, but new kinds of medication — both from his lab at Harvard and later at a series of companies he founded, led, and sold.

One of those companies, Parabilis, is advancing research from Verdine’s Harvard lab with zolucatetide, a first-in-class anti-cancer therapeutic that is also performing well in clinical trials.

“You might be familiar with the term ‘me-too drugs’ in biotech and pharma, where minimal improvements are made to existing therapeutics,” said Curtis Keith, chief scientific officer at Harvard’s Blavatnik Biomedical Accelerator, which supported some of Verdine’s early work with funding and business development consulting.

By contrast, Keith said, “Greg has the rare distinction of having created what are fundamentally new drug modalities. Not many people can say that.”

Verdine traces his entrepreneurial streak to early lessons after a family tragedy.

When he was 5, his father, Richard, suffered an accident and was paralyzed from the neck down. The event dramatically rearranged life for the blue-collar family in New Jersey’s rural Pine Barrens.

Beginning at age 7, Verdine began to skip school periodically to help his father with certain projects, like retrofitting a van to accommodate Richard’s wheelchair.

“There was a lot of improvisation in that, and I didn’t realize it until many years later,” Verdine said.

As he grew older, Verdine did well in school and was encouraged to pursue higher education. He began as an English major at St. Joseph’s University, but he found a familiar sense of improvisation in the organic chemistry lab and was hooked.

Verdine liked that he could take molecules apart and put them back together in new ways for his own ends.

By the time he went to graduate school at Columbia University, he was working at the borderline between chemistry and biology, figuring out the mechanism by which an anticancer drug, mitomycin, interacts with DNA.

The research would put him on Harvard’s radar, eventually leading to a professorship in 1988.

Verdine was then beginning to identify a problem in the drug development process that would become his life’s work.

Science had largely written off most human proteins as “undruggable” for two reasons.

First, the proteins were located inside a cell, meaning protein therapeutics would have to be small enough to pass through the cell membrane to reach them. Secondly, the proteins lacked the textured edges or “sockets” that would allow a drug to bind with them.

Verdine’s idea was to distill protein therapeutics to their essential elements, the shortest possible chains of amino acids that could accomplish their disease-targeting objectives while still passing through a cell membrane.

But those tiny amino acid chains were floppy. They needed a sort of chemical “staple” to hold them in the perfect helical shape to slip through a cellular membrane and then cling to the surface of a protein.

“You can see how risky that was,” Verdine said. “It could have all been wrong.”

It was risky enough that securing federal funding would have been a challenge. Instead, Verdine turned to Harvard’s Blavatnik Biomedical Accelerator, which supports innovative research in its preliminary stages.

The BBA’s Curtis Keith said that projects like Verdine’s sit at the edge of gaining interest from traditional funding mechanisms, and that’s exactly where the BBA can help.

“The idea is that within universities, people working on highly innovative science need to be able to get funding. Often the NIH is not there to fund this kind of work, and a small amount of money can go a long way at that stage,” he said.

Beginning in 2011, the BBA awarded Verdine three grants totaling $450,000.

“Even relatively modest amounts of money, a few hundred thousand dollars, can make a huge difference at the early stages of developing a technology, de-risking it, showing proof-of-concept data that is then going to attract outside investors to put in much more significant money,” Keith said.

And it worked. The technique, which Verdine called stapled peptides or helicons, proved versatile at targeting a wide variety of proteins. Verdine spun the technology into a private company, Fog Pharmaceuticals, since renamed Parabilis.

In November 2025, the FDA granted fast-track designation to Parabilis’ leading drug candidate, zolucatetide, for the treatment of patients with desmoid tumors.

Zolucatetide, which builds on Verdine’s helicon technology, slips inside cells and binds to a protein called beta-catenin. There, it inhibits a chain reaction that activates cancer growth genes — a chain reaction that drives a wide spectrum of cancer types.

Until zolucatetide, beta-catenin was considered undruggable.

A Phase 1 and 2 clinical trial of zolucatetide demonstrated tumor reductions in a remarkable 100 percent of patients with desmoid tumors.

On June 10 — Verdine’s birthday — Parabilis went public, bringing in a record venture-backed biotech haul of $770.5 million for the company to further advance zolucatetide and other therapeutic programs.

Of the drug, the BBA’s Curtis Keith said, “It has the potential to become one of the most important therapeutics coming out of Harvard in recent decades.”

Verdine’s experience with the pancreatic-cancer drug daraxonrasib and zolucatetide has convinced him that improvisational, blue-sky thinking is necessary for the future of medicine. “We should be funding crazy stuff, because the crazy stuff is what changes the world,” he said.