New Haven Biotech Firm Targets Late-Stage Breast Cancer with New Drug

CT Examiner – Tuesday, November 12, 2024
By Emilia Otte

NEW HAVEN — A local biotech firm is developing a drug targeting late-stage breast cancer that could be available as soon as 2026.

Instead of binding to certain receptor sites and blocking cancer cells from replicating, the PROTAC technology used in the new drug, called ARV-471, degrades the actual receptor so that it can no longer signal.

Noah Berkowitz, chief medical officer at New Haven-based Arvinas, explained that with more traditional drugs, cancer cells often mutate and become resistant. However, the new technology is designed to be effective even when the cancer has resisted other treatments.

“You bring the protein towards the garbage disposal, and then you start tagging that protein for degradation and you can reduce — depending on the target — we can reduce it 80% to probably a hundred percent,” he said.

In 2021, the company made a deal with Pfizer to split the costs for the drug development and any future profits. The initial plan was to run clinical trials that would use ARV-471 in combination with other drugs, including a Pfizer drug called Ibrance. But Berkowitz noted they are now exploring ARV-471 as a singular therapy for people who haven’t responded to other treatments. For patients undergoing initial treatment, he added, it would be combined with either Ibrance or a new drug that Pfizer is currently developing.

Arvinas isn’t the first biotech firm to use PROTAC technology to go after particular diseases. The first clinical trials using the technology began in 2019, and by the following year, it became evident PROTAC could effectively target two receptor sites: estrogen for breast cancer and androgen for prostate cancer.

According to Berkowitz, the clinical trials showed promise. He said people who had taken part in them, all of whom had undergone multiple treatments, had experienced few side effects compared to other cancer drugs.

“Patients didn’t have nausea, vomiting, diarrhea, reduction in white blood cell counts, which are seen with many other therapies that are used in that setting,” he told CT Examiner.

Berkowitz said patients were getting, on average, an additional three to five months of survival without the disease progressing.

He added that the company was also developing a drug to target a protein involved in the formation of B-Cells, which could be used to treat certain types of lymphoma. Next year, it will begin developing a drug that targets a protein called KRAS, whose mutations are found in pancreatic cancer, non-small-cell lung cancer and colorectal cancer.

“For a small company, I’m excited to be here because they’re really talented people with a great mission, but what great science that we could go after these different cancers,” he said.

Berkowitz said Arvinas has recently set its sights on drugs to treat certain neurodegenerative diseases like Parkinson’s, which are now being tested in human beings. The drug works by degrading a compound called LRRK2, which, in mutated form, can leave toxic proteins building up in the brain.

“There’s tremendous passion internally here to take this really innovative platform and be able to just address the unmet medical need wherever it is,” he said. “There are some people in the company that would love to go further, but right now we know targeting cancer and neurodegenerative disease is quite ambitious in its own right. And so that’s where we’re headed right now.”

Access this article at its original source.