- A new technology could revolutionize how everything from Alzheimer’s disease to autoimmune diseases and cancer are treated.
- Cancer has become an early focus for the technology, called targeted protein degradation or PROTAC, because there are many well-known drivers of cancer that modern medicine hasn’t been able to reach.
- At least $1 billion has been invested in the space by big pharmaceutical companies like Novartis and GlaxoSmithKline and biotech startups alike, one expert estimates.
- Visit Business Insider’s home page for more stories.
An experimental technology that’s been under development for almost two decades could upend treatment for conditions ranging from Alzheimer’s to lung diseases.
First, it’s coming for cancer.
Called targeted protein degradation or PROTAC, the tech is promising because it gives scientists new tools to destroy disease-causing agents, clearing them from the body. In cancer, that could put targets so elusive they’ve been dubbed “undruggable” and even the “Holy Grail” within reach.
Cancer will be a crucial testing ground for targeted protein degradation, which has only recently been tried in humans. There aren’t yet any treatments based on the technique, though one decades-old drug used to treat cancer was recently discovered to work in a similar way.
Roughly 30 companies are investing in the technology, including big pharmaceutical firms like Novartis, GlaxoSmithKline, Roche, and Boehringer Ingelheim and biotech upstarts. Excitement runs so high because the tech could vanquish the traditional limitations of making new drugs, opening up new possibilities, experts say.
“I would say that it is unlimited. And thats why I think there’s so much interest in this field, is that it can be applied to so many different exciting proteins that heretofore have not been druggable,” Craig Crews, the Yale professor who pioneered the field, told Business Insider. Cancer “is the first one out of the gate,” he said.
Not all the deals and rounds of funding around the cutting-edge field have been disclosed, so it’s hard to say exactly how much is being invested.
All told, the area has attracted “easily over a billion dollars,” estimated Randy Teel, vice president of corporate development at protein-degradation-focused biotech Arvinas. Crews founded Arvinas and serves as chief scientific advisor.
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Zooming in on cancer
KRAS. Myc. Beta-catenin.
In cancer, these are notorious names, just a few of many well-known drivers of cancer. But they have also long been unreachable by modern medicine.
Protein degradation could change that, in the process transforming the way that cancer is treated.
Most medicines that you take work in a similar way against disease. Imagine a light switch on a wall. A drug for high blood pressure, for instance, would switch “off” the bodily mechanisms driving the condition. In cancer, similarly, a drug might suppress proteins known to cause the disease.
But that switch model sets a high bar for potential new drugs. The approach doesn’t always work fully, and there’s plenty that scientists haven’t been able to reach, in cancer and beyond.
“Therefore, why don’t you just eliminate the switch, and rip out the wiring altogether?” Yale’s Crews explains.
Targeted protein degradation aims to do just that, tossing disease-causing proteins into the trash cans that naturally exist within our cells.
Obvious targets for that process are mutations in special proteins called transcription factors, because they are known to cause cancer. Drugs that employ targeted protein degradation could get rid of the mutated proteins.
Working there “would be an awesome way to treat many different diseases. This has been borne out many times,” John Tallarico, site head of the chemical biology and therapeutics department at Novartis Institutes for BioMedical Research, told Business Insider.
Scientists haven’t been able to affect this process with chemically-made pills. So drug companies have been increasingly looking to more complex medicines.
Among the startups researching protein degradation are Kymera, which has raised $95 million from investors like Atlas Venture, Pfizer Ventures, Amgen Ventures and Lilly Ventures; Vividion Therapeutics, which is valued at $295 million, and Nurix, valued at $227 million.
Novartis’s Tallarico tells an illustrative story about why so many are betting on protein degradation. Five years ago, Novartis scientists came up with a list of around 20 targets that they wanted to develop drugs for.
At the time, he figured that it would take a decade just to develop a drug for one of the 20 targets. Yet just five years later, thanks to the advent of protein degradation technology, he says Novartis might be able to find drugs for all 20.
The jury is still out on whether this approach will work, with drugs only beginning to get tested in humans.
“Could this perhaps provide a therapeutic solution for these aggressive cancers? There is exciting potential, but time will tell,” said Lynne Elmore, who is director of the Translational Cancer Research program at the American Cancer Society and has a doctorate in pathology. The cancer nonprofit recently awarded Crews a prestigious ACS Research Professorship.
Why a startup founded with this tech didn’t start with ‘undruggables’
Founded in 2013 to focus on protein degrader development, Connecticut-based biotech Arvinas is the first to test it out in humans, to treat prostate cancer.
You might think, then, that the biotech is focused on cancer mutations that medicine traditionally hasn’t been able to touch. Those “undruggable” targets include KRAS, Myc, and Beta-catenin.
But instead, Arvinas sidestepped them, at least in the beginning. Venturing out on into uncharted territory would have been too risky for initial tests of the technology, two top leaders explained to Business Insider.
Instead, Arvinas’ drugs are focused on the androgen and estrogen receptors, two well-established places where a signaling process gone awry can lead to cancer.
For the company, there was “some temptation to go after the undruggables” first, said Ian Taylor, the biotech’s chief scientific officer. But these are “clinically validated by drugs that have been working for a long time. These targets have been validated for decades.”
And “because the industry has never been able to effectively inhibit [undruggables], we don’t really know what will happen when we destroy the protein,” Teel said. “But obviously we are all excited to find out.”
The biotech probably won’t say which of those more challenging targets it’s working on publicly until next year, Teel said.
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