Arvinas, a New Haven biotechnology firm founded by a Yale professor, announced on Thursday an agreement with the largest cancer-specializing pharmaceutical company in the world: Genentech.
Arvinas focuses on developing a new class of cancer drugs that have the potential for a wide variety of uses. Under the new agreement, Genentech will bring monetary support and research intel to its new partner. Arvinas will receive over $300 million in “milestone fees” from Genentech, according to a Thursday press release. Arvinas CEO Manuel Litchman MED ’86 said the two companies will collaborate on Arvinas’ research projects, which include a promising prostate cancer treatment that is set to move to clinical studies by next year. Litchman added that the agreement with Genentech will give Arvinas new access to a wide variety of research not previously available to them. The new access, Litchman said, will help Arvinas understand the treatment potential of its own technology.
“[The partnership] also affords us the opportunity to learn from a wide variety of cancer researchers that will hopefully help us with understanding our own technology better, and also expand the utility of our technology and the applications of our technology,” Litchman said.
Arvinas produces a class of drugs known as protein degenerators, which cause cancer cells to eliminate the proteins they use to replicate and reproduce, said molecular, cellular and developmental biology professor and company founder Craig Crews. By bonding to the “rogue proteins,” the drug causes the cell’s natural recycling mechanism to break down the targeted protein.
“Proteins are constantly being made and they are constantly being eliminated from cells,” Crews said. “What we want to do is recruit those rogue proteins to that machinery and cause an early death for those proteins. We just want to get rid of them.”
The drug, called a PROTAC, currently targets the androgen receptor — a protein critical to the growth of prostate cancer cells. The drug is a breakthrough, Crews said, because the protein degenerator class of drugs can be used for a huge range of diseases.
Since the PROTACs can be tooled to bind to proteins in any kind of cancer cell, the immediate next step is to develop drugs for other forms of cancer. But the opportunities do not stop there, Crews said.
“The nice thing about this approach is that it’s a platform technology, meaning that this idea of recruiting proteins you want to eliminate to the cell’s garbage can be applied to any number of proteins, like the ones that are driving prostate cancer, driving breast cancer, driving lung cancer,” he said. “We’d love to go after neurodegenerative diseases.”
Crews added that the drug could potentially be used for diseases like diabetes, inflammation and even neurodegenerative diseases like Parkinson’s and Huntington’s.
The announcement came as Alexion, one of the largest pharmaceutical companies in the country, relocates back to the Elm City from Cheshire, Connecticut. For many biotechnology companies, Yale is a primary draw to New Haven, said Sean Cassidy, Arvinas CFO. Cassidy added that the University provides talent as well as access to expensive, high-tech facilities such as nuclear magnetic resonance spectroscopy machines.
Still, New Haven is still a long way from becoming as vibrant a biotechnology hub as Cambridge or San Francisco, Cassidy said. Cassidy added New Haven could work on becoming a stronger magnet for biotechnology firms by building an airport larger than Tweed New Haven Airport and creating more lab buildings for scientific research.
If the company’s drug is successful, one of the key breakthroughs will be a substantial drop in the amount of medication necessary for certain cancer patients. That lower dose, said Crews, is the biggest change in the paradigm of cancer medication.
“We’re taking a rogue protein to a protein that is going to tag it for destruction, and so once we’ve brought it together, it’s tagged and it’s destroyed,” Crews said. “And then it’s sent off to do the same thing to another one, and another one, and another one. I view it as more of a seek-and-destroy drug that goes and just eliminates those proteins that are causing the problem.”
Each PROTAC molecule can be used to destroy many rogue proteins before the body naturally breaks it down. This recycling effect allows patients to receive a smaller and less invasive dose, he added, noting that tumors are not expected to build up resistance to PROTAC molecules over time the way they do to current medication options.
Ultimately, this new class of drugs will shift the paradigm of treatment from inhibition of the rogue proteins to degradation, directly destroying the proteins necessary for the cancer cells to replicate.
“The current therapy works for a while, but ultimately prostate tumor cells become resistant to the therapy,” he said. “One method they use to become resistant is that they make more of the androgen receptors. So eventually you just can’t take enough of the drug — it’s an arms race. We want to build a different paradigm. Not one that’s built on inhibition, but one that’s built on degradation.”
This year, the National Cancer Institute estimates that 27,540 men will die of prostate cancer in America, accounting for 4.7 percent of all cancer deaths.