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 computational lifting involved. When I asked Pfeffer for more details, he said, “These bioinformatics algorithms are complex and proprietary, and we are not disclosing how they are done.”)

Based on that information Neon could make a vaccine, personalized to each patient’s cancer, by producing synthetic versions of those neoantigens, perhaps as many as 15 or 20, and inject them into the body to activate the immune system against them.

Another possibility is to use the patients’ own T cells as a weapon. The T cell approach could be done in two ways, Pfeffer said. One method is to find T cells that have already recognized the key neoantigens, induce them to multiply outside the body, and then re-inject them into the patient. The other is to engineer a patient’s own T cells outside the body to be extra sensitive to those antigens, then reintroduce the cells back into the patient—something akin to the CAR-T cancer fighting products that Novartis, Juno Therapeutics, and Kite Pharma are racing to develop.

Production of personalized cancer treatments could be a time-consuming and expensive proposition, as immunotherapy pioneer Dendreon, bankrupted and sold off for pieces, found out. Pfeffer acknowledged Neon’s ambitions would require partners and collaborations to bring in key pieces, but that the field has progressed since the Dendreon days.

One technology Pfeffer said Neon can build in-house is immune monitoring—a deep understanding of the immune system’s interaction with cancer cells. It’s a specialty that Seattle’s Adaptive Biotechnologies has parlayed into hundreds of millions of dollars raised, building its own ambitions to become a drug developer. But Pfeffer said Neon isn’t working currently with Adaptive: “Perhaps we’ll partner with them or academic institutions, but we think we it’s a core capability inside our building.”

With either vaccines or T cell therapies, Neon’s products will likely be used in combination with drugs based on checkpoint inhibitors, Pfeffer said.

Neon’s scientific founders have already begun two clinical trials of neoantigen vaccines, one to treat glioblastoma, run by Catherine Wu at the Dana-Farber Cancer Institute, the other to treat melanoma.

But Pfeffer said Neon hopes to have the first of its own vaccine products in a clinical trial next year. I asked if Neon also had rights to the products being tested by Wu and others. He declined to comment on intellectual property matters. He also declined to say which cancers Neon will go after first.

Third Rock has provided the majority of Neon’s funding, but Pfeffer declined to give specifics. Coinvestor Blavatnik’s presence is no coincidence. He helped seed some of the work that Neon is built upon, giving $5 million in 2009 to support Wu and Hacohen’s cancer vaccine research. Blavatnik also gave Harvard $50 million from his family foundation two years ago to boost life science research.