Interim CEO Cary Pfeffer told BioWorld Today that Neon Therapeutics Inc.'s $55 million series A round will fuel the firm for "at least a couple of years," as researchers work to further exploit findings made possible by checkpoint inhibitors and target neoantigens in cancer. "It's a big number because this is a company that's about to enter clinical studies," said Pfeffer, a partner with Third Rock Ventures, which led the financing round, with Clal Biotechnology Industries and Access Industries joining.

Lead program NEO-PV-01 is a personalized neoantigen vaccine that builds on research by the Broad Institute and Dana-Farber Cancer Institute, which are collaborating in trials. Cambridge, Mass.-based Neon will launch a company-sponsored clinical development program next year, though Pfeffer would not say exactly when.

Constantly mutating tumors cause new proteins to turn up inside and on cell surface, with epitopes that are foreign to the body, thus not subject to the immune system's tolerizing mechanisms and therefore likely to excite a disease-fighting response. Checkpoint-therapy research discovered that patients' "T cells are actually responding to the neoepitopes of tumors," Pfeffer said, and NEO-PV-01 aims to take the science a step farther. "We know through some of the checkpoint mechanisms – CTLA4 and PD-1 specifically, but there are others obviously in the pipeline – that there are all sorts of regulatory mechanisms that the tumor is using to tamp down the immune response," he said. Neoantigens may provide the key to getting around those.

"When you say the term 'cancer vaccine,' because of the 30 years or more of failure in the space, people roll their eyes," Pfeffer said. But drug development in cancer has undergone "very significant changes," including the fairly recent understanding of neoantigens, which may "set the stage for success in the space," he said.

"Many of the cancer vaccines that have been tried in the past have not been successful because they have used tumor-associated antigens," approaches involving would-be immune stimulators that "are not completely new to the system," he said.

Neon also aims to develop personalized T-cell therapies and explore shared neoantigens that might permit development of an off-the-shelf therapy. Otherwise, "every patient is a new product," Pfeffer said.

"You've got to biopsy and sequence the tumor, do epitope selection" in order to know which neoantigens to develop the peptide against. "It's a process we're working to get expert at," he said.

The firm is not alone in exploring the potential of exploiting neoantigens, though Padlock Therapeutics Inc., also of Cambridge, Mass., focuses on autoimmune disorders. Padlock was formed more than a year ago by Michael Gilman, an Atlas Venture partner, co-founding the company with scientific founders Paul Thompson, professor and the director of chemical biology at the University of Massachusetts Medical School in Worcester, and Kerri Mowen, whose research at The Scripps Research Institute on the protein-arginine deiminases, or PAD, enzyme family serves as the basis for Padlock's science. PADs post-translationally modify arginine side chains on proteins to the non-encoded amino acid citrulline. In some patients, these citrullinated proteins are immunogenic, so PAD enzymes may be responsible for producing the antigens that drive disease in these individuals. Inhibiting PADs in these patients could help in rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and other conditions. (See BioWorld Today, Jan. 16, 2015.)

There's also Charlottesville, Va.-based Neoantigenics LLC, founded on discoveries made by John Herr at the University of Virginia School of Medicine, which in January 2014 entered an early stage research and development collaboration with Pfizer Inc., of New York, to develop antibody-based therapeutics and companion diagnostics targeting Neoantigenics' oocyte-associated biomarkers, selectively expressed on a wide array of human cancers.

In April, promising data were published in Science from a phase I study by Beatriz Carreno at Washington University in St. Louis that examined the role played by passenger mutations in tumor growth, specifically somatic mutations in melanoma as a source for patient-specific neoantigens that might spark an immune response. Outcomes suggested that aiming personal vaccines against the mutations could make the medicines work better.

"This is in the middle of immuno-oncology, the next generation of science that is exploding in this field," Pfeffer said. "From our perspective, that's really exciting because there's new science coming out every day. There are a lot of people that are interested or are going to be interested." With its heavyweight founders (including Ed Fritsch, who's been closely involved with the basic neoantigen research that led to Neon's launch), intellectual property, and a head start thanks to Dana-Farber and Broad, the new firm "could really be in the lead here," he said. In the latter part of 2014, a handful of papers on neoantigens turned up in major journals, "many of which [had] our founders' names on them," he said, and the publications "really worked to start blowing up in the field and convince some of the naysayers, but it clearly had been brewing before then as well."