Not long ago making an effective cancer vaccine seemed like a dead-end proposition, but that sentiment is changing. The latest evidence: Gritstone Oncology, which makes its debut today with a massive Series A financing.
Gritstone has raised a $102 million Series A round led by Versant Ventures and The Column Group. Others pitching in include Clarus Ventures, Frazier Healthcare Partners, Redmile Group, Casdin Capital, and a special purpose vehicle for private investors called “Transformational Healthcare Opportunity.” The company is run by former Clovis Oncology (NASDAQ: [[ticker:CLVS]]) chief medical officer Andrew Allen, who helped found the Colorado-based cancer drugmaker with CEO Pat Mahaffy.
“We were just doing less of the early stage stuff, which is what I really enjoy,” says Allen, who left Clovis in August. Clovis could begin selling its first drug next year, a lung cancer drug called rociletinib. Mahaffy, meanwhile, agreed to become chairman of Allen’s new venture when the time came.
That venture is San Francisco-based Gritstone, and it’s the second company, along with Cambridge, MA-based Neon Therapeutics, to announce itself this month to develop vaccines containing what are known as “neo-antigens”—genetic fingerprints left behind by tumors as they mutate.
Allen became intrigued by this concept last year, after reading a paper published in the New England Journal of Medicine by researchers at Memorial Sloan-Kettering Cancer Center, Timothy Chan and Naiyer Rizvi. (Rizvi has since moved on to Columbia University.) The paper concluded that a melanoma patient’s response to “checkpoint inhibitors”—a new type of cancer drug that unmasks tumors to the immune system—depended on the presence, and abundance, of neo-antigens. These neo-antigens are little protein sequences that, in these patients, the immune system could see. That’s important, because the body could then find and wipe out tumors with these proteins.
“This is, to me, a massive, massive advance,” Allen says. “[It’s a] completely rational, totally understandable, and potentially exploitable insight into how tumors can be cleared by the human immune system.”
First, a little background why this is potentially a big deal. Traditional vaccines essentially train our immune system to spot a foreign invader and attack if it arrives. Despite numerous attempts, this approach has not worked with cancer—albeit one prospective brain cancer vaccine from Celldex Therapeutics (NASDAQ: [[ticker:CLDX]]) in Phase 3 testing has the chance to be the first.
The failures have piled up, according to Allen, for a simple reason. “They just had the wrong antigen,” he says. “If you’ve got the wrong antigen, it doesn’t matter how good the vaccine technology is.”
Allen believes genetic sequencing technology and advances in immunology have led scientists to the right antigens. Breakthroughs in these fields have already begun to change the way cancer is treated. Methods of spurring the immune system to recognize and fight tumors have produced remarkable results against cancers of the skin and lung, namely so-called “checkpoint inhibitors” like nivolumab (Opdivo) and pembrolizumab (Keytruda).
But checkpoint inhibitors only work for a fraction of patients. In their NEJM paper, and later in an article published in Science in March, Chan and Rizvy aimed to show that the answer to the limited effectiveness was held by neo-antigens. The more neo-antigens—or, genetic fingerprints—they found on tumors, the better pembrolizumab fared in patients with lung cancer or melanoma.
The researchers hypothesized that training the immune system to better spot the important neo-antigens—the ones that drive a cancer cell’s growth—would help checkpoint inhibitors work in more patients.
That’s the thinking behind Gritstone. Allen aims to make vaccines that contain groups of these so-called neo-antigens. The hope is that these therapies would improve how effective checkpoint inhibitors can be. They’d also be somewhat individualized treatments—meaning they’d be made up of a group of, say, 10 neo-antigens that are deemed to be critical to the growth of a specific person’s tumor.
Gritstone will start with vaccines for non-small cell lung cancer, which accounts for about 85 to 90 percent of cases, according to the American Cancer Society. Lung cancer is the most common cause of cancer death, and while checkpoint drugs have shown promise here, Allen says they work only in about 20 percent of patients. That means it’ll be easier for Gritstone to
