The power of neoantigens
Interim CEO: Cary Pfeffer
Based: Cambridge, MA
Clinical focus: Personalized therapeutic cancer vaccines
The scoop: When you think of cancer vaccines, you can’t help but think of failure both in the lab and in the manufacturing process, but Neon, led for now by Third Rock’s Dr. Cary Pfeffer, is seeking to create the next-gen therapeutic vax for a host of oncology targets. Its first trial, which will begin in the fall, will team its experimental vaccine with Bristol-Myers Squibb’s blockbuster PD-1 drug Opdivo (nivolumab) to help boost patients’ response to treatment.
What makes Neon Fierce: Pfeffer says: “We all know the impact that immunotherapy has had in oncology over the last 5 years. It’s been nothing short of incredible, and I’ve had the humbling experience to be involved in that in multiple different ways. Checkpoint inhibitors like Bristol’s Yervoy (ipilimumab) and the latest PD-1 and PD-L1 treatments have opened the door to immunotherapy by, in a sense, taking the brakes off the immune system and allowing the body to do its job.
“But, behind that door we now have neoantigens, which is our focus at Neon. These are the antigens that the immune system seems to be responding to when it actually does its work. What’s different here is that looking back over the 30 years plus of cancer vaccines that have been developed and, frankly, failed, is that we are now working on neoantigens, which are created by specific mutations in a patient’s tumor and so are completely novel to the system, unlike some of the other tumor-associated antigens--the things that have been used in other vaccines--which have gone through the immune system in a way that makes their use more accepted.”
The other key thing, Pfeffer explains, is the rise of checkpoint therapies that take the brakes off the immune system and allow it to react to the tumor the way it should. And the third element wedded to this is “immune monitoring,” where researchers can really start to understand what the T cells are bonding to.
What makes them different from other companies working in this area? “We’re going after personalized approaches both on the vaccine side as well as on the T-cell therapy side, and we are really becoming leaders I think in the space of some of the key components that you need to make this therapy effective. We’re becoming leaders in the whole area--such as immune monitoring to really understand what T cells are responding to--and that will build a complete therapy.”
Pfeffer wants to move on from former treatments, such as Dendreon’s Provenge, and create something new and better. “We know this is very different from Provenge. We are identifying the neoantigens from specific patients’ tumors; identifying the ones that we want (i.e., that are the most immunogenic) and the easiest to manufacture; then we are making them in peptide form and then putting them into a vaccine and giving them back to the patient.”
The company’s lead product is NEO-PV-01, a personalized cancer vaccine, which is set for the clinic this year after the biotech recently filed an IND. “That will start this fall and comes within a year of us founding the company, which is incredible given the short timelines.”
The first study will in fact be combined with Bristol-Myers Squibb’s PD-1 checkpoint drug Opdivo. “If the tumor is using the immune system to turn the brakes on, as we know that it does, well you’ve got to take those brakes off as well as enhancing the immune response. That’s the role our vaccine should play. In our study, patients will first be given Opdivo for 12 weeks and then their response will be measured. There will be plenty of people who do not respond optimally at this point, so then they will be given NEO-PV-01. The idea is that for those patients, we can turbocharge a response by giving back the neoantigens, then we should see an enhanced response and therefore turn the Opdivo response rate up.”
Pfeffer says you can think of the company’s pipeline in four ways. The first quadrant, he says, will be personalized therapeutic cancer vaccines that use neoantigens--antigens which are foreign to the body, found in cancer--that can be used to spur a specific immune system attack tailored to the individual patient.
The second will look for shared neoantigens that can be used for off-the-shelf therapeutic vaccines, looking for antigens that are shared across groups of patients.
The next quadrant will center on a personalized T-cell strategy, identifying T cells that are particularly suited to attacking cancer cells, extracting them from patients, priming them for greater effect and then expanding them for use in patients.
And the final quadrant will be an off-the-shelf T-cell product that can be used to greater effect among a broad group.
As is usually the case with Third Rock startups, Pfeffer, who helped launch a range of companies from Jounce to Agios ($AGIO), is steering the ship as an interim CEO while looking for a permanent captain.
Third Rock does, however, already boast of some major names involved in biotech, something which Pfeffer believes places it higher than anyone else in this field. The big names include:
- James Allison, MD Anderson Cancer Center
- Ed Fritsch, Neon Therapeutics
- Nir Hacohen, Broad Institute and Massachusetts General Hospital
- Eric Lander, Broad Institute of MIT and Harvard
- Robert Schreiber, Washington University School of Medicine
- Ton Schumacher, Netherlands Cancer Institute
- Dr. Catherine Wu, Broad Institute and Dana-Farber Cancer Institute
“The founder base is tremendous; these guys have spearheaded the neoantigen processes and we’ve had them with us from the beginning.”
Investors: Third Rock, Clal Biotechnology Industries and Access Industries