Third Rock’s Latest, Jounce, Grabs $47M For Cancer Immunotherapy

Scientists have been striving for decades to find a way to stimulate the immune system to fight cancer, with only a couple of recent success stories to show for it. Now Third Rock Ventures, the Boston firm drawn to the biggest and edgiest ideas in biotechnology, is making its biggest up-front investment yet on cancer immunotherapy.

Cambridge, MA-based Jounce Therapeutics is the newest startup to come from Third Rock’s team, emerging from stealth mode today with a $47 million Series A financing commitment. The concept at Jounce is to build a pipeline of antibodies and other injectable protein drugs that can spark the immune system to fight cancer cells, much like it fights off viruses and bacteria that people encounter all the time.

While many companies have tried and failed to deliver on the promise of cancer immunotherapy, there have been a couple of important advances in the field the past few years. Seattle-based Dendreon (NASDAQ: DNDN) won FDA approval in 2010 for the first treatment to actively stimulate the immune system to fight prostate cancer. New York-based Bristol-Myers Squibb (NYSE: BMY) won FDA clearance a year later for an immune-based treatment against melanoma. Bristol-Myers also turned heads at last year’s American Society of Clinical Oncology meeting with an experimental immunotherapy for melanoma that scientists believe may disable a cloaking mechanism that tumors use to avoid immune detection.

While cancer can be bewilderingly complex at the molecular level, and differ dramatically from patient to patient, many once-skeptical scientists and drugmakers have come to believe that immunotherapy could someday become a standard approach for fighting various cancers, much like traditional surgery, radiation, chemotherapy, and targeted molecular medicines. About 1.7 million people are expected to be diagnosed with some kind of cancer in the U.S. this year, and about 580,000 are expected to die from it, according to the American Cancer Society.

“Here there’s an incredible opportunity because the immune system has memory,” says Cary Pfeffer, Jounce’s interim CEO and a partner at Third Rock. “The way the immune system works, there’s potential to provide really durable benefit to patients. It’s an incredible shift we’re seeing.”

Cary Pfeffer is interim CEO of Jounce Therapeutics and a partner at Third Rock Ventures

Mitch Gold, the former CEO of Dendreon and now the founder of Seattle-based Alpine Biosciences, said that as recently as five years ago, there was little interest among Big Pharma companies or venture capitalists in cancer immunotherapy. But Third Rock’s investment in 2013 comes as little surprise, he says.

“The immune system is a very effective way of fighting cancer,” Gold says. “Just like with monoclonal antibodies, you’re going to see the next wave of immunotherapy technologies come out. Every pharmaceutical company is interested now in an immunotherapy platform. As far as they are concerned, you can’t not have it.”

Third Rock picked the name Jounce because it stands for a jolt or dramatic change in position, both in lay English and in a technical sense in physics, Pfeffer says.

The company traces its origins back about 16 months, when James Allison of the University of Texas MD Anderson Cancer Center talked about cancer immunotherapy at a Third Rock scientific advisory board meeting, Pfeffer says.

That got the venture team excited, he says, and work began on bringing together what a “dream team” of founders. They include James Allison and Padmanee (Pam) Sharma of MD Anderson; Tom Gajewski of the University of Chicago; Drew Pardoll of Johns Hopkins University School of Medicine; and Louis Weiner of Georgetown University Medical Center. Third Rock has three senior executives working on Jounce, including Pfeffer as interim CEO, Bob Tepper as chief scientific officer, and Bob Kamen as chief technology officer.

Rather than zero in specifically on one kind of immunotherapy, Jounce is looking to build a portfolio of product candidates that work in different ways. The company is intending to make antibody drugs and other kinds of targeted protein molecules that can bind with a variety of different targets, Pfeffer says. Jounce isn’t disclosing specifically what those molecular targets are, but Pfeffer said they come from three main categories—checkpoint inhibitors, co-stimulatory molecules, and those in the tumor microenvironment.

The first category, checkpoint inhibitors, is where immunotherapy evangelists have had the most success. Bristol-Myers’s drug ipilimumab (Yervoy) falls into this camp, as a drug that inhibits a target called CTLA-4, which acts like a brake on the immune system. The drug, designed to release that brake and allow an immune attack on tumors, has shown an ability to help people live longer with melanoma. It has also been a commercial success, as the drug generated $706 million in worldwide sales in 2012, its first full year on the market, and saw 47 percent growth in the most recent quarter.

Bristol-Myers is following up on that success with an experimental drug called BMS-936558, which homes in on a target called PD-1. That drug showed some impressive ability to shrink tumors in a study of 240 patients released at last year’s American Society of Clinical Oncology meeting. One oncologist from Johns Hopkins, Julie Brahmer, told Bloomberg News at the time that PD-1 acts like an “invisibility cloak” tumors use to avoid an immune system attack.

Jounce’s scientific founders believe that there could be more of these sorts of cell checkpoint inhibitors, Pfeffer says. Yervoy and the anti-PD-1 drug are “the tip of the iceberg,” he says.

The second type of treatments on Jounce’s radar are co-stimulatory molecules. If checkpoint inhibitors are drugs that release a brake on the immune system, then co-stimulatory molecules are ones that essentially push down on the immune system accelerator pedal.

Lastly, Jounce is concentrating on the tumor microenvironment, and which molecular switches might be involved in rendering tumors “open” for immune system surveillance and attack, and which ones make tumors “closed” off. Gajewski brings considerable expertise in that particular area of immunotherapy, Pfeffer says.

The work here is at very early stages by biotech industry standards. Jounce has obtained, and is in the process of obtaining, licenses to develop technology from the institutions where its scientific founders work. The company has just under 10 employees, and will now set out to build up a bigger team of people with expertise in tumor immunology, antibody drug discovery, translational science, and early drug development, Pfeffer says.

There are lots of competitors seeking to build expertise in various aspects of what Jounce is trying to do. Bristol-Myers Squibb is the “big gorilla” in the field, and Merck has an immunotherapy molecule as well, Pfeffer says. Other smaller players in the field include Seattle-based Oncothyreon (NASDAQ: ONTY), Denmark-based Bavarian Nordic, and Seattle-based VentiRx Pharmaceuticals, which recently struck a partnership with Celgene (NASDAQ: CELG).

For those willing to stretch the definition of immunotherapy a bit, you can also consider standard antibody drugs like Genentech’s trasztuzumab (Herceptin) and rituximab (Rituxan) as members of the class, because scientists know they tend to work in part through antibody-dependent cellular cytotoxicity (ADCC) which essentially means the drug stimulates an immune response to tumors.

What’s different about Jounce, Pfeffer says, is that it’s attempting to cast a wide net around a variety of technologies and approaches, rather than bet the farm on just one drug or biological target. By casting a wide net, Jounce could be attractive to partners from its early days. Even before the company issued its first announcement that it was in business, Jounce got a number of inquiries from people who want to talk about collaborating, Pfeffer says.

“What’s exciting to me, as business development professional for 20 years, is the amount of inbound interest from larger companies interested in the space. It’s really been off the charts, even before we launch the company,” Pfeffer says. He adds: “There are a lot of small companies out there, and big companies out there. But what folks are doing today is the tip of the iceberg, and there’s plenty of opportunity.”

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