After some ‘tough years,’ Frontier’s CEO is ramping up ambitions for precision med platform

Biotech After some ‘tough years,’ Frontier’s CEO is ramping up ambitions for precision med platform By Will Maddox Aug 27, 2026 9:50am Frontier Medicines Artificial Intelligence Oncology proteomics After announcing the “tough but necessary” decision to lay off some employees last year, Frontier Medicines is looking to the future by advancing more cancer drugs into the clinic while continuing to find partners to leverage its AI chemoproteomics platform. The biotech remains tight-lipped about exactly how many employees were let go under the February 2025 announcement, having explained at the time that the restructuring was a result of a need “for greater efficiency, focusing resources where they will have the greatest impact.” Reflecting on the company's journey since then, Frontier CEO Chris Varma, Ph.D., acknowledged the biotech “did have the downside, but [we] have come back from that.” “It is always very difficult to do,” he added, pointing out that the layoffs occurred in what was a difficult time for the wider industry. “This is a good year,” Varma explained in an interview with Fierce.

“Last year was not so good. The year before that—maybe even worse. There were some tough years.” When times are hard, Varma remembers advice he's received from his friend and mentor Mark Levin, co-founder of biotech venture capital firm Third Rock Ventures: “Biotech is about survival.

What we do is innovative, novel science and it's risky. But when it works, it can pay off for patients and shareholders alike.” Fierce sat down with Varma at Frontier's base in Boston's Seaport neighborhood. The 1900s-era brick building, which has been converted to modern lab space, houses around 60% of Frontier's approximately 60-strong workforce, with the rest based in San Francisco.

Varma explained that the layoffs allowed the company to consolidate its lab functions in Boston in order to scale its AI drug discovery capabilities. He pointed to the company's advancement of its lead drugs and a fresh partnership this year as evidence of the impact. Frontier’s platform is built on chemoproteomics, which focuses on the 20,000 proteins in a human cell that drive everything in our biology.

At any given time, 8,000 to 12,000 of those proteins are being expressed, Varma explained. Chemoproteomics introduces small molecules into the cell to see which proteins they bind to. An advanced mass spectrometer helps Frontier's scientists see which compounds bind to which proteins and where.

“That simple experiment—done at massive scale and throughput—allows us to interrogate the entire human proteome to link drugs, small molecules and proteins,” the CEO said. Varma is no stranger to tackling tricky targets, having co-founded Blueprint Medicines and headed up the company for three years. The rare immunological disease-focused biotech went on to be acquired by Sanofi for more than $9 billion in 2025.

Varma founded Frontier in 2018 with University of California, Berkeley professors Daniel Nomura, Ph.D., and Roberto Zoncu, Ph.D. From the beginning, the aim was to target cancer-causing proteins that had been previously considered undruggable. Frontier has been screening different cancer cells with its chemical library of small-molecule compounds, generating a terabyte of data per week for the past seven years.

Varma said the result has been 300 million compound-protein interactions. “For 8,000 of the 20,000 proteins, we have small-molecule chemical matter at the ready to go drug that target if we choose to,” Varma said. “That is more than the industry has been able to drug to date.” Varma noted that these compounds are not yet drugs and require significant work to get them there, but “it gives you a real hold on that protein target that you're going after.” To bankroll these plans, Frontier launched with $67 million in series A funds from the likes of Deerfield and RA Capital, before following that up with an $88.5 million series B in 2021 and, most recently, an $80 million series C in 2024.

Varma recalled that the series C was “one of the hardest financings I’ve ever done,” attributing the difficulty in part to a resurgent tech sector siphoning off early-stage investors. He also had to convince the company's backers that Frontier's lead asset was unique from its competitors. That lead candidate is an oral, covalent dual inhibitor developed to target the on and off states of the KRAS G12C mutation.

Dubbed FMC-376, the drug is currently in a phase 1/2 trial for patients with advanced unresectable or metastatic solid tumors. The company shared preclinical data last year, claiming FMC-376 demonstrated anti-tumor activity and deeper inhibition of KRAS downstream pathways compared with Amgen’s Lumakras, which targets the same pathway. Frontier plans to share data from the phase 1/2 trial at the European Society for Medical Oncology conference in Spain in October.

Next in line is a covalent allosteric inhibitor dubbed FMC-242, which is designed to disrupt the interaction between PI3Kα and RAS to target cancer drivers. FMC-242 is heading to the clinic this year, according to Varma. In April, South Korean biopharma LG Chem purchased worldwide rights outside of China to another of Frontier's preclinical candidates, FMC-220.

The covalent activator of the mutant p53 Y220C protein is being evaluated for the treatment of solid tumors with TP53 loss-of-function mutations. Frontier's most high-profile partnership to date has been the 2020 pact with AbbVie to develop E3 degraders against difficult-to-drug targets. Frontier's pipeline currently lists an unnamed transcription factor candidate in the discovery phase that is a result of the partnership, which saw the biotech receive $55 million upfront.

All the candidates are examples of targeting previously undruggable targets, Varma said. “Pharma companies will come to us and say, ‘Here is 30 targets we haven't been able to drug for 30 years. Can you guys help us with this?’” “It's pretty cool to have a conversation and say, ‘Yep.

With our fully AI-enabled tech that's accessing seven years of data, let's pull all the information while you’re sitting here.’” “For a number of years at Frontier, we were shy about our AI capabilities,” the CEO added. “Part of that shyness was exactly because [the AI hype] was so overblown. We feel like now is the time for us because of the ...

high-quality, unique data sets. That's why we're more open about it.” At the J.P. Morgan Healthcare Conference in January, Frontier announced it was spinning out a company called Vulcan Bio, which Varma said would be equipped with 20 targets developed by Frontier and would be working on target degradation for inflammatory conditions and aging.

“We'll look to explore more opportunities like that and try to get creative,” he told Fierce. Regarding how the company will be leveraging its platform for future partnerships, Varma said Frontier is still trying to figure out the balance between licensing out its drugs and nurturing them in-house. So far, this double-pronged strategy has brought in $200 million from partnerships compared to the $250 million raised from investors, he said.

In the meantime, the CEO has more clarity about his goals for moving candidates into human trials. “As a small company, if we could get even close to delivering one new molecule into the clinic per year, that would be a huge run rate,” he said. “I keep telling my team: ‘Let's do this!’” Varma added.

“It’s a lot of work, but it's an exciting goal.” Frontier Medicines Artificial Intelligence Oncology proteomics Biotech