“We went through tough times and got back up”: Frontier accelerates cancer drug development

U.S. biotech company Frontier Medicines is moving faster on cancer drug development after overcoming the challenges of restructuring.

In an interview with U.S. biotech publication Fierce Biotech on the 27th (local time), Frontier Medicines CEO Chris Varma said, “This is a good year,” adding, “Last year was not good, and the year before that was worse. We went through tough times.”

In February last year, the company carried out a restructuring that included layoffs “to increase efficiency and focus resources where they can have the greatest impact.” It did not disclose the exact number of employees affected at the time.

Varma said restructuring is “always very difficult,” but assessed that the company “went through a downturn and got back up.”

The restructuring consolidated Frontier’s research functions in Boston and expanded its artificial intelligence (AI) drug discovery capabilities. About 60% of the company’s roughly 60 employees now work in Boston, with the rest in San Francisco.

Frontier’s platform is based on chemoproteomics. Of the 20,000 proteins that make up human cells, 8,000 to 12,000 are expressed at a given time. The approach involves introducing small-molecule compounds into cells and determining which proteins they bind to.

“This simple experiment, performed at scale and high speed, lets us explore the entire human proteome and connect drugs and small molecules with proteins,” Varma explained.

Over the past seven years, Frontier has generated 1 terabyte (TB) of data each week and amassed 300 million compound-protein interactions. “We have small-molecule chemistry that can immediately drug 8,000 of the 20,000 proteins,” Varma said. “That’s more than the industry has drugged to date.”

The company’s lead candidate is FMC-376, an oral covalent dual inhibitor that targets both the active and inactive states of KRAS G12C. It is currently in a phase 1/2 trial in patients with advanced unresectable or metastatic solid tumors.

Last year, Frontier released preclinical data showing that FMC-376 had greater antitumor activity and more effectively inhibited downstream KRAS signaling pathways than Amgen’s Lumakras, which targets the same pathway. Phase 1/2 data are expected to be presented in October at the European Society for Medical Oncology (ESMO) Congress in Spain.

The next candidate is FMC-242, a covalent allosteric inhibitor that blocks the interaction between PI3Kα and RAS. The company plans to advance it into clinical trials this year.

In April, South Korea’s LG Chem acquired worldwide rights outside China to Frontier’s preclinical candidate FMC-220. FMC-220, a covalent activator of mutant p53 Y220C, is being evaluated as a treatment for solid tumors with TP53 loss-of-function mutations.

In 2020, Frontier signed a deal with AbbVie to develop E3 degraders against challenging targets and received $55 million upfront. The current pipeline includes an undisclosed transcription factor candidate from the collaboration that is in the discovery stage.

“Pharmaceutical companies come to us saying, ‘There are 30 targets that haven’t been drugged in 30 years. Can you help?’” Varma said. “With fully AI-based technology that gives us access to seven years of data, we can pull out information on the spot.”

“For years, we were cautious about our AI capabilities,” he added. “That was because there was so much AI hype, but now we have a high-quality, unique data set, and it’s time to be more open.”

At the J.P. Morgan Healthcare Conference in January, Frontier announced that it would spin out Vulcan Bio, a subsidiary focused on research into inflammatory diseases and aging using targeted protein degradation technology.

Varma said the company is working to find a balance between technology transfer through partnerships and developing drugs in-house. To date, it has raised $200 million through partnerships and $250 million from investors.

“For a small company, getting even one molecule into clinical trials each year would be an incredible pace,” he said. “I keep telling the team, ‘Let’s do it.’ It’s a lot of work, but it’s an exciting goal.”