Where Others Have Failed, Genocea Sees Promise In T-Cell Vaccines

By Michael Goodman, Contributing Writer

Genocea Biosciences is at the forefront of companies harnessing T-cell immunity to conquer the most difficult infectious diseases. Founded in 2006 with antigen discovery technology out of Harvard University, the Cambridge, MA-based company has spent the past decade progressing GEN-003, an HSV-2 (genital herpes) therapeutic vaccine, through the clinic and launching a personalized cancer vaccine franchise that will file its first IND (investigational new drug) this year and enter the clinic in 2018.

Genocea says its antigen discovery platform, ATLAS, is the key to its success in developing T-cell vaccines. An antigen is a target on which vaccines or immunotherapies act to elicit an immune response. While other vaccine companies have tried to identify T-cell antigens by using predictive algorithms or by taking a guess, the ATLAS approach is based on natural human immune response observed in large, diverse populations.

While Genocea focuses on identifying the right target antigen, and its HSV-2 T cell vaccine is in Phase 3, several small-cap biotechs and some large-cap vaccine players appear to have abandoned their programs.

THE VACCINE MARKET: GROWING AND BUBBLING WITH M&As
The global vaccine market is growing at a CAGR of about 10 percent, far outpacing drugs and medical devices. We asked Genocea CEO Chip Clark whether he thought the vaccine market could sustain its torrid growth. “I do think it can continue to be robust for a couple of reasons. First, there remain many pathogens, such as those requiring a T-cell response, for which we don’t yet have good vaccines. And secondly, there are new ideas about what a vaccine is and where it can be useful.” Clark is referring to the revolution in immuno-oncology that is based on unleashing the power of T-cells to kill tumors. “We believe,” he says, “that personalized, so-called neo-antigen vaccines can be an effective complement to checkpoint inhibitors that have been approved to treat cancer.”

The vaccine market is also a hotbed of M&A activity. GSK, for instance, spent $7.8 billion in 2015 on Novartis’ vaccine business, while Pfizer spent north of $1.2 billion over the past three years, picking up vaccines from Baxter and GSK as well as acquiring RedVax AG, a spinout of Swiss vaccine specialist Redbiotec AG.

Genocea’s ATLAS technology and its Phase 3-ready HSV-2 candidate position it for a potential acquisition. Although Clark doesn’t rule out a buyout, he is more focused on finding a partner for GEN-003 before it enters Phase 3. He feels the time is ripe, having just released placebo-controlled lesion rate data at six months post dosing from GEN-003’s Phase 2B trial. In addition, the Phase 3 dose is set, and the company has a primary endpoint. “We think we have a package in hand that would be compelling to potential partners.”

Clark believes there are a number of ways the company can think about sharing its assets and technology. “The best solution will be one that provides the right intersection between furthering our goals — assuring that GEN-003 gets approved as widely and rapidly as possible — and maximizing shareholder benefit.” He would be open to a single global partnership or one that split the world into a couple of territories, say, U.S. and rest of world. Either option would admit a broad range of bidders. Clark is basically looking for a partner with sufficient financial resources and complementary capabilities (e.g., global regulatory, global clinical development, global commercialization). He’s also interested in a partner with experience selling to some of the key call points for GEN-003. For instance, in the U.S., and less so in Europe, that would be OB-GYN physicians.

THE INVESTMENT LANDSCAPE FOR VACCINES
The funding of vaccine development and, in less-developed countries, vaccine distribution is quite different from the funding of drugs or medical devices. In most cases, the primary investor is a public entity or increasingly public/private vehicles. Venture capital is largely absent from the financing or creation of vaccine startups.

Clark thinks the reason that VC has kept away is that the new wave of T-cell vaccines present novel technology challenges. Looking over the past century of vaccine development, there have been significant successes — flu, measles, and mumps — but there has also been a flattening of the return curve. Clark explains, “We now have vaccines that can prevent infections caused by roughly 40 different pathogens. But that’s the low-hanging fruit. Most approved vaccines work through B-cell responses, but the pathogens of many diseases such as HSV or EBV (Epstein–Barr virus) are largely invisible to disease-fighting antibodies. That’s because they are in places where T-cells can go but antibodies cannot.” Genocea claims to have the only validated platform for finding the right target antigens of T-cell response. Technologies like ATLAS for discovering T-cell antigens, and novel adjuvant delivery systems, are all quite new. Clark feels that VC investors are waiting for more decisive validation before jumping in.

READY FOR THE FUTURE
GEN-003 has been through a rigorous Phase 2 program designed to demonstrate its activity against the genital herpes virus and to home in on the safest, most effective dose of antigen and adjuvant. These trials have shown that GEN-003’s ability to reduce viral shedding (when the virus is active and shedding at the site of infection) and lesion rates is durable (i.e., shown efficacy) out to 12 months. Genocea believes GEN-003 can capture much of the HSV-2 market — a global peak $2 billion opportunity — currently held by the generic oral antivirals famciclovir, valacyclovir, and acyclovir. These drugs are often used episodically to treat HSV-2 outbreaks; however, infected individuals continue to shed, or transmit, the virus even when they are asymptomatic. An HSV-2 vaccine administered once each year would reduce viral shedding continuously. Compliance would be greatly improved.

Genocea’s three major assets — ATLAS, the infectious disease pipeline, and the cancer vaccine pipeline — are rapidly evolving. Now all eyes are on its HSV-2 candidate. But its three cancer research collaborations — with Dana Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Checkmate Pharmaceuticals — are all based on the ability of ATLAS to discover antigens of T-cell response.

What if in the next five years ATLAS’ capabilities became more in demand by research institutions and Big Pharma? Or if the neo-antigen cancer vaccines started showing eye-popping data? Would Clark consider reorganizing the business around such a development?

He feels that in five years GEN-003 should be on the market, and a cancer vaccine could be near an approval decision. “We’re always thinking about the best use of Genocea resources, whether it’s to develop the assets on our own, to partner them, or to sell the company. And the way to solve for that is to look at value, time, and risk, and to solve for the right outcome. I can’t forecast where we’ll be in five years, but I think we’ll have great options.”

"We believe that personalized, so-called neo-antigen vaccines can be an effective complement to checkpoint inhibitors that have been approved to treat cancer."

Chip Clark
CEO, Genocea Biosciences

For the rest, Genocea meets with the FDA this quarter to plan for GEN-003’s Phase 3 trial; it expects to initiate the pivotal trial in the fourth quarter of 2017. The company is confident the FDA will accept its lesion-rate data as a primary endpoint instead of the recurrence-free endpoint used by the current standard, the oral antivirals. “It’s not just about whether you’ve had an outbreak,” notes Clark, “it’s about whether you’ve had a durable reduction in the number of days with lesions.”

Clark points to Cubist as a company to emulate. “They were smart drug developers,” he says, “and they had a unique and compelling work culture. Those are two things we’ve strived to focus on as we’ve built this company.”