Cancer vaccines got a bad name years ago. First, they don’t prevent cancer—they are supposed to stimulate the immune system to fight existing tumors. Early-generation cancer vaccines that made it to clinical trials couldn't stimulate enough immune firepower to kill tumors, cost too much to manufacture, or failed for other reasons.
But there's an ongoing revolution in cancer immunotherapy (see "Cancer Immunotherapy’s Amazing Four-Year Run: A Timeline of Events"). That has convinced Boston-based Third Rock Ventures that it’s time to take another shot.
Cambridge, Mass.-based Neon Therapeutics has all the hallmarks of a Third Rock play – big idea, big names, big money. The startup, making its public debut today, has raised $55 million in its Series A venture financing from Third Rock, Clal Biotechnology Industries, and Access Industries. James Allison of MD Anderson Cancer Center, a pioneer in cancer immunotherapy, and genomics leader Eric Lander of the Broad Institute are among the founding scientific advisors.
The concept at Neon Therapeutics is based on the biology of “neoantigens.” These are the proteins and peptide structures expressed on tumor cells that can essentially be waved in front of the immune system, to urge it to attack, like a matador waves a flag in front of a bull. Many biotech companies have tried to incorporate such antigens into vaccines that stimulate the immune system against cancer, and all have failed at one point or another—Dendreon being the most high-profile case. But the success of recent “checkpoint inhibitor” drugs from
The neoantigens come from the many genetic mutations that occur in tumors while they grow, and which are structurally seen as foreign substances to an immune system that’s trained by evolution to “tolerate,” or leave alone, similar structures on healthy cells. Part of the challenge with cancer vaccines of the past was getting them to fire up the immune system, and get over the barrier of tolerance that only serves to help protect the tumor.
Neon, led by Third Rock partners Cary Pfeffer and Bob Tepper, is seeking to come up with a mix of neoantigen-based treatment strategies. Part of the plan is to take tumor biopsies from patients, do quick exome scans of the 2 percent of the genome that contains code for making proteins, and identify the ‘personalized’ neoantigens that are like signatures on the tumor. While personalized approaches have promise, they can also be time-consuming and expensive. So Neon is also doing additional work on identifying more common neoantigens which could be given to all patients “off-the-shelf” if they have a certain type of malignancy. At first, Neon plans to go with patient-specific neoantigens in the form of peptides, building off some research from one of the scientific founders, Robert Schreiber of Washington University in St. Louis.
Like most companies backed by Third Rock, one of biotech’s best-known venture investors, Neon has been operating behind the scenes for months prior to today’s announcement. The company has now gotten its own lab in Cambridge, where it will set up a team of about 20 people to handle the biopsies, and hone its capabilities in immune system monitoring, selection of the neoantigens, and the strategy on how to possibly combine them with other treatments. The goal is to take the company’s first product candidate into clinical trials next year, said interim CEO Cary Pfeffer.
“With the checkpoint therapies, they don’t work in everybody, that’s clear,” he said. “There’s been a lot of work going on in past couple years, in terms of who they work in, who they don’t, and why.” Those gains in understanding are what made this an opportune time to start Neon, he said.
Dendreon, the Seattle-based company that won FDA approval for its prostate cancer vaccine and later went bankrupt, failed in part because its high manufacturing costs. Pfeffer said he and the team studied that case carefully, and they are aware that getting personalized neoantigens from patients will only work in a business if the antigens can be obtained and identified quickly and cost-effectively. The turnaround time now for delivering a personalized therapy is currently “a couple months.” That’s OK for clinical trials, but not nearly fast enough for a commercial-ready product, in which patients have a terminal illness and need something fast. “We think the turnaround time can be shortened dramatically,” Pfeffer said.
Mac Cheever, a longtime cancer immunotherapy researcher at the Fred Hutchinson Cancer Research Center who’s not involved with the company, said the time could be right.
“The basic thesis of Neon Therapeutics appears to be that identification of the neoantigens is possible and that vaccination to the neoantigens and/or T cell therapy directed towards the neoantigens will be therapeutically effective, especially when used in concert with checkpoint inhibition with anti-PD1, anti-PD1-L1 or other agents of this category,” Cheever said. “The thesis is likely to be correct. Identification of the neoantigens and construction of patient specific vaccines is feasible, likely to be practical and has a good chance of working in concert with anti-PD1 to increase the depth of response and/or render tumors responsive in more patients.”
Some of the work at Neon traces its origins to a collaboration between the Broad Institute and the
For in-depth analyses on cancer immunotherapy from Timmerman Report, see:
