Two scientists made huge bets on 'impossible' cancer treatments. They're finally paying off.
· Business Insider
Mike Coppola/Getty Images for Klick Health
- 2026 is the year of the cancer breakthrough, with innovations from Revolution Medicines and Moderna.
- "I'm almost tired of saying paradigm shift, but I haven't figured out a new phrase," one expert said.
- Innovators Greg Verdine and Tal Zaks pushed boundaries with risky, groundbreaking experiments.
Short sellers love to profit from biotech's big fails. The category remains their favorite to bet against because roughly two-thirds of publicly traded biotech companies ultimately go broke one way or another, losing money for investors.
Visit afnews.co.za for more information.
This summer, however, that strategy went bust. Biotech has experienced unusual success with some of the category's biggest, longest cancer moonshots coming to fruition.
On August 19, Moderna announced positive late-stage results from a melanoma trial, sending its stock surging 177% — up to $174 per share — on the promise of the very first personalized cancer vaccine. A week later, on August 26, another astounding development: The FDA approved a pill to help treat late-stage prostate cancer. The drug is a new molecular "glue" from Revolution Medicines, a Silicon Valley-based biotech company, and it's capable of drugging so-called undruggable cancer targets.
"This is a whole new era," Dr. Andrew Coveler, who directs the Fred Hutch Pancreatic Cancer Specialty Clinic in Seattle, said. "I'm almost tired of saying paradigm shift, but I haven't figured out a new phrase."
These medicines are both used in concert with existing drugs, and neither is considered a cure for cancer. Instead, they're seen as breakthrough options that open up a new playing field for fighting cancer, targeting different mutations, and training the immune system in new ways.
The moves prompted a huge surge of cash for investors in the companies, prompting celebration at corporate offices.
"We raised our glass of champagne, but now back to work," Dr. Alan Sandler, the chief development officer at Revolution Medicines, said.
The successes weren't always obvious, though.
Two innovators — a chemical biologist and an oncologist — had both the vision and the capital to finally make these groundbreaking ideas work, despite many failures before.
A chemist who raised $125 million to chase an idea inspired by nature
Greg Verdine is a chemical biologist and former Harvard professor turned biotech entrepreneur. He turned to nature for inspiration to design a new molecular "glue" to target cancer.Greg Verdine
In 2012, after four years of pleading for cash, Greg Verdine finally scrounged up the investors to give him $125 million for a cancer drug.
He didn't have a drug yet. In fact, he wasn't exactly sure how it could be made. He just had an idea inspired by nature for targeting one of cancer's most "undruggable" mutations, RAS.
The problem with RAS is that it is so smooth. Unlike other molecules, this protein has no characteristic sticky pockets or holes for a drug to glom onto. Even if you could figure out how to attach something to the smooth surface of this protein, you'd run the risk of having your therapy stick onto everything else in the body, too, potentially damaging healthy organs.
"People told me it was crazy. It'll never work"
- Greg Verdine
This is why most chemists before him gave up and called RAS an impossible mutation to target, even though it often drives tumor growth in some very tough-to-treat cancers, including pancreatic cancer, colon cancer, and lung cancer.
"I just found it totally unacceptable, pathetic, that we would say, 'Oh, well!' You've got all these patients," Verdine said. "We know exactly what's driving their cancer, but 'Oh, that's undruggable.' Come on!"
Verdine knew that molecular glues already existed in the natural world. Compounds produced by bacteria and fungi cause proteins to bind together, altering their function without completely destroying them. Some immunosuppressive drugs for organ transplantation take advantage of that biology.
The remaining question was: How can you engineer a new way to do that, targeting the "undruggable" RAS cancer mutation? By sticking the drug to another target, then gluing it onto RAS.
"People told me it was crazy. It'll never work," Verdine told Business Insider. "It's the combination of a target that's never been drugged before, and drugging it in a way that's never been done before. That sounds like compounding risks."
It turns out, Verdine is a pretty persuasive guy. He flew to France, where investors at Sanofi, a large French pharmaceutical company, were intrigued by his bullishness and agreed to pay 50% of his Series A funding round for his startup Warp Drive Bio.
"There was no IP. There was nothing. It was just an idea that we could drug RAS using molecular glue technology, and I had no idea how you might do it," Verdine said.
In 2018, the technology Verdine pioneered at Warp Drive was acquired by Revolution Medicines, where the chemistry was finessed further. Fourteen years after his initial bet, the FDA approved a drug by Revolution last week that does exactly what Verdine imagined.
Former Sen. Ben Sasse has late-stage, metastatic pancreatic cancer. He's been taking the new daily pill and says it helps.Nikos Frazier/Omaha World-Herald via Getty Images
Former Nebraska Republican Sen. Ben Sasse, who has stage 4 pancreatic cancer, calls Revolution's pill, which he's been taking in a clinical trial, a "miracle" worker for reducing both his pain and dramatically shrinking tumor volume.
"I have much, much less pain than I had four months ago, when I was diagnosed," Sasse told "60 Minutes" in April. "And I have a massive 76% reduction in tumor volume."
For now, the drug, called Rasonque, is chiefly recommended for patients with advanced cancer and is meant to be used after chemotherapy. It costs about $40,000 a month, before insurance, and side effects include rashes, mouth sores, and some diarrhea.
Taking a $450 million bet based on a belief
Zaks was confident a cancer vaccine could work. It was just a matter of timing it right for the immune system.Tal Zaks
For cancer doctor Tal Zaks, former chief medical officer at Moderna, the ambition was similar.
He knew a cancer vaccine could work. It just required the right architecture, asking the right questions, and conducting the right trial at the right time.
Oh, yes, and also lots of cash, including a $450 million deal with Keytruda-maker Merck to co-develop the technology.
"Where the naysayers are right in this regard is that for cancer vaccines, neither mice data nor phase 1 data even are indicative of whether it's going to work, so you're really taking a very large financial bet just based on first principle beliefs," Zaks said.
"The truth is that from a business perspective, this one was tough — it was a high risk, high reward type bet — it required a significant investment of capital."
He knew lots of cancer vaccines had failed before. He was confident there was a way to win, though, if the immune system was called up in the right way and at the right time.
"From a business perspective, this one was tough — it was a high risk, high reward type bet"
- Tal Zaks
Moderna's melanoma vaccine harnesses the genetic makeup of each patient's tumor — teaching the body to attack its own unique cancer mutations. It's administered after a patient's initial treatment and is designed to reduce the risk of cancer recurrence.
"That's really the success of Moderna. I was very adamant when we started this at Moderna that we either funded to the end of a randomized phase 2 or it's not worth doing," he said, referring to the mid-stage clinical trial where researchers tested their vaccine against standard methods for preventing relapse.
The results were a "wow," Zaks said, with Moderna's vaccine almost cutting in half the risk of skin cancer recurring. "This is not about curing mice or showing cool data for a scientific publication. This is about getting conclusive proof."
Moderna's new vaccine for melanoma patients is not FDA-approved, but could be on shelves as soon as 2027, pending a positive review. Common side effects include things you'd expect for a vaccine: some fatigue, chills, and mild pain at the injection site.
But there are caveats to this medication, too. It has to be taken in concert with Keytruda, a $12,000 to $25,000 IV immunotherapy. It also has to be used after a person's tumor has already been surgically removed.
40 years of discovery science also helped
A personalized cancer vaccine takes only a few weeks to produce, thanks to advances in genetic sequencing, and mRNA vaccine technology.Bloomberg/Getty Images
Of course, there were other discoveries along the way that helped shepherd these breakthroughs, including a far better understanding of cancer genetics, a few key technical solutions, and additional cancer drugs that work in concert with the new technologies. In short, decades of plodding, hard work by scientists across the country and around the world.
"It's taken at least 40 years," mRNA vaccine researcher Phil Felgner, a University of California, Irvine professor who helped develop early versions of the lipid nanoparticle technology that powers the new vaccines, said. "It's taken this much time for it to mature."
And the work isn't over. Revolution is testing a pill for lung cancer, and seeing how its drugs might compete head-to-head against chemotherapy. Moderna is testing vaccines for lung, bladder, and kidney cancers.
These are "approaches that, hopefully, over time will have less toxic side effects to patients, and more targeted effects on the cancer," Dr. Christopher Flowers, division head of cancer medicine at The University of Texas MD Anderson Cancer Center, said.
All accomplished with some new glue and a shot.
"Ideas sound simple once you get it out, and then there's elegance in that," Coveler, the pancreatic cancer doctor, said. "But I think the design and the specificity of these things was in no way easy to figure out."
Read the original article on Business Insider