With $55M, Neon Wants To Make the Cancer Vaccine “Problem” Personal

Xconomy Boston — 

One year ago, in a paper in the journal Oncoimmunology, three cancer researchers wrote this: “After many years of best efforts and countless dollars, but unmet expectations, cancer vaccines have become a long-standing problem.”

The problem has apparently become an opportunity. Those same three researchers are now lending their expertise, along with four other leading scientists, to a new cancer vaccine company, Neon Therapeutics. Neon launches today with $55 million in funding—not quite countless dollars, but an enormous sum for a new biotech. The money comes from Boston-based Third Rock Ventures and entities controlled by Len Blavatnik, a broad-ranging investor and the richest man in the U.K.

So what has changed? In that same 2014 Oncoimmunology paper, the authors Edward Frisch, Catherine Wu, and Nir Hacohen—all with Harvard University and affiliated entities—wrote that a new approach they and others had been working on, to harness the immune system against the unique genetic fingerprints of tumors, could be “the paradigm shift needed for cancer vaccines.”

Those three, as well as Eric Lander of the Broad Institute, James Allison of the M.D. Anderson Cancer Center, Robert Schreiber of Washington University, and Ton Schumacher of the Netherlands Cancer Institute are listed as Neon scientific cofounders.

“The founders we brought together are the folks we believe have driven the field,” said interim CEO Cary Pfeffer (pictured), who is also a partner at Third Rock.

The idea is to fight cancer the way we’ve been trying to ward off the flu for decades. A flu vaccine contains tiny bits of the virus strains expected to cause the most infections. Our immune system notices those bits as bad actors and builds a defense against them. When the real flu comes around, we hope it matches, and that the immune defense kicks into gear. A cancer vaccine wouldn’t prevent cancer, but it aims to prime a patient’s immune system to attack the cancer already growing. Many have tried, but not a single one has worked over the years. (One vaccine for the grevious brain cancer glioblastoma is in Phase 3 and should produce data by early next year, according to its developer Celldex Therapeutics.)

However, the type of cancer vaccine Neon and its backers hope to create takes its cue from the past decade’s breakthrough work in cancer immunotherapy known as checkpoint blockade. James Allison just won a prestigious Lasker award for his work in the checkpoint blockade field.

Checkpoints are a family of proteins that tumors produce to mask themselves from the immune system. Block the checkpoints, and the tumors are unmasked, so to speak. Sometimes this method works in spectacular fashion, and four drugs have been approved to fight severe forms of skin and lung cancer. As Allison noted at a recent immunotherapy conference, in one of the earliest checkpoint studies a decade ago, people with a dire form of skin cancer were given a single dose of ipilumumab, which was approved years later as Yervoy; 22 percent were still alive a decade later.

But checkpoint inhibitors are far from perfect. Even when tumors are unmasked, T cells—the attack dogs of the immune system—don’t always find them.

In exploring the question why, researchers have found that the responsive T cells were zeroing in on pieces of the tumor cells, or antigens, that were the result of new, unique mutations as the tumor grew. These “neoantigens” present a complex picture of a living, growing, changing tumor. They are part of the discovery in the age of genome sequencing that tumors are collections of cells with varying DNA sequences, not a genetically uniform mass.

Neon believes the immune system can be trained to spot neoantigens, attack, and remember them—because T cells have memory—in case the tumors reoccur. Here’s how Pfeffer described the process: Neon would sample a patient’s tumor and sequence the exome, which is the tiny percentage of the DNA that codes for proteins. Based on comparisons to normal tissue DNA, Neon would identify not just the neoantigens, which make the tumor unique, but more specifically the neoantigens that are responsible for driving tumor growth. There’s a lot of heavy … Next Page »

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