Jessai Flores

As New Haven’s biopharmaceutical sector continues to grow, the startup Arvinas is making waves with its advancements in cancer and neurodegenerative disease treatments.

Headquartered in New Haven, Arvinas achieved two drug development milestones last month. The breast cancer drug that it is jointly developing with Pfizer, called vepdegestrant, received “fast-track” federal review from the U.S. Food and Drug Administration. The company also administered the first human test dose of another drug, labeled ARV-102, which targets neurodegenerative illnesses such as Parkinson’s disease.

Arvinas credits its success to a proprietary technology called PROTAC, an abbreviation for the term ‘proteolysis-targeting chimeras.’ The drugs, taken orally, use cells’ biological machinery to break down disease-causing proteins within the body — an approach that creates a promising avenue for treating a wide range of diseases including cancer and certain neurological disorders.

Arvinas scientists say that the distinct protein-breakdown approach targets proteins that are widely recognized to cause disease, taking the guesswork out of choosing a biological target that might have unintended consequences — or none at all.

“We’ve proven that PROTAC will be a product … a drug that shows up in a bottle on a pharmacy shelf that someone can buy and take,” said Ron Peck, Arvinas’ former medical officer.

The FDA’s fast-track process is designed to accelerate the development and approval of drugs that are considered to potentially meet an unmet medical need. The drugs also must have sufficient data to show that they would be an important and effective potential therapy — criteria that Arvinas’ and Pfizer’s vepdegestrant could meet, said Ian Taylor, the company’s chief scientific officer. 

The breast cancer therapy is currently being evaluated in Phase 3 clinical trials that are evaluating its effectiveness in patients with advanced, or metastatic, breast cancer who have previously been treated with endocrine medications that affect hormones in the body. Vepdegestrant is also being tested in other Phase 3 clinical trials as a combination therapy with other medications, including the breast cancer drug palbociclib.

Meanwhile, Arvinas’ drug for neurodegenerative diseases, ARV-102, dosed its first human subject at the end of February. In a news release, the company detailed how the medication, in preclinical studies, targets a protein called leucine-rich repeat kinase 2, or LRRK2. 

Research suggests that increased expression and activity of LRRK2 are associated with brain diseases like Parkinson’s. In primate studies, the company says, ARV-102 reached deep into the brain to degrade LRRK2 by up to 90 percent.

Arvinas’s recent drug development advancements mirror a broader trend of growth within New Haven’s burgeoning biotech landscape. With its proximity to research institutions like Yale University and a supportive ecosystem for startups, Peck and other biotech entrepreneurs believe that the Connecticut area has emerged as a hub for pharmaceutical companies to innovate.

“Connecticut is a great place to do drug discovery and drug development,” said Martin Mackay, co-founder of the New Haven-based biopharmaceutical company Rallybio. “There is great talent here. We thought we’d be able to really build partnerships with top academics … we thought we could hire great people here.”

Founded in 2013, Arvinas spun off from the lab of Yale biochemist and professor Craig Crews, employing a group of 20 individuals. Since then, the company has ballooned in size to 450, said Taylor. Today, the company has four drugs in development, including vepdegestrant and ARV-102, and has been publicly traded on the stock market since 2018.

For Taylor, the fact that New Haven has a less-saturated biopharmaceutical industry than other cities has helped the company thrive. In a less crowded field, he said, startups have a greater opportunity to establish themselves as key players and expand their operations over time.

Compared with established biotech hubs like Boston or San Francisco, lower rent and overhead costs help startups with limited funding allocate more resources towards research and development, Taylor added.

Mackay described the significance of partnerships between academia, industry and local government in fueling innovation. Rallybio, for instance, launched out of the University of Connecticut’s technology incubator program in Farmington, giving the company access to the university’s offices and laboratories.

He highlighted how university and government partnerships helped Rallybio gain footing during the drug development process.

“I think it starts off with the state government being attractive to come into Connecticut: you feel wanted,” Mackay said. “There was a recognition that there were great people here, that you could actually build companies. Very welcoming local government and local politicians make it a great place to discover new medicines and develop the biotech industry.”

But Arvinas’s researchers still face challenges in drug development, including regulatory hurdles, funding constraints and scientific challenges.

New biopharmaceutical startups face high costs associated with running clinical trials. Though trial costs vary widely, a 2018 analysis found that the median expense for a single Phase 3 trial reached $19 million, with the most expensive multi-thousand patient trials reaching upwards of $340 million.

New Haven’s biopharmaceutical companies are no exception, even if rent costs are lower than in other cities. Rallybio, for instance, laid off nearly half its workforce last month, shrinking from 44 employees to 23. The money that Mackay’s company saved was used to obtain clinical trial data on pregnant mothers.

“You can pay in biotech dearly because you can’t raise the money that you need so easily,” Mackay said. “To extend the runway, we needed to make our money last longer. The people that we parted with were truly great human beings and great individuals, and it was kind of really hard for us to make those decisions. But we needed to make sure that we can get the data to see if this program is going to work”

According to Peck, researchers developing a new drug also face a fundamental obstacle: uncertainty that the molecules or biological mechanisms the drug targets will have positive outcomes for patients. 

But scientists like Taylor remain optimistic, particularly about the promise of Arvinas’ PROTAC technology. The technique, he believes, creates a new way to hit disease-causing proteins, over 80 percent of which are considered to be “non-druggable” by traditional drugs known as inhibitors. 

“The challenge is getting the molecules to have drug-like properties,” Peck said. “Would these things actually work in humans? It’s looked great in laboratory systems, but do they really work?” 

Arvinas is located at 395 Winchester Ave.

JANICE HUR
Janice Hur covers the Yale New Haven Hospital for the SciTech desk. From Seoul, Korea, she is a sophomore in Morse majoring in Biomedical Engineering.