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War, Surgery, and Cancer Vaccines: Meet San Antonio’s George Peoples
August 19, 2016

 

David Holley, Xconomy Texas

San Antonio-Cancer surgeries are long, arduous, and require detailed planning. There are always surprises. One measure of a surgeon is how he or she handles the unexpected. Just ask George Peoples-he's operated on more than a thousand tumors.

"You're going to deal with certain anatomical structures that most people will avoid like the plague," says Peoples (pictured), the former chief surgeon at Brooke Army Medical Center in San Antonio, who spent 30 years in the U.S. Army. "The liver just bleeds. Once you start poking the skunk, you know... now all of a sudden you got bleeding. How are you going to deal with it?"

Peoples has experience in trauma, too: As a part of the 274th Forward Surgical Team, he led the first group of U.S. surgeons into war in Afghanistan in 2001 and Iraq in 2003. He's been deployed seven times during his career, in war and on humanitarian missions.

Removing a tumor is actually similar to operating on a trauma victim, Peoples says. The better you plan, and the more scientifically you think about your work, the better the result.

Peoples ended his work as a surgeon and retired from the military in 2014, and he's since taken on an entirely different mission. As an oncology researcher-work that he's done on the side since he left medical school-he's now dedicated himself full-time to developing cancer vaccines. Two companies, Galena Biopharma (NASDAQ: GALE) and Elios Therapeutics, have experimental vaccines based on Peoples' research.

The cancer vaccine work is proving to be as much a challenge as he's ever had-a point of both pride and pain. But it's also helping him earn wider recognition.

Earlier this month, Peoples was named the winner of the BioMed SA 2016 Award for Innovation in Healthcare and Bioscience. Previously known as the Julio Palmaz Award, it has been accepted in years past by scientists such as Robert Langer of MIT and Nobel Prize winner W.E. Moerner of Stanford University.

In awarding Peoples, the San Antonio life sciences advocacy organization specifically noted Peoples' "groundbreaking work" in cancer immunotherapy, as well as his surgical and wartime achievements.

Yet less than a week after the award announcement, Peoples was reminded how hard it is to turn his oncology work into a vaccine that benefits cancer patients. Galena, the company testing a cancer vaccine he helped develop, NeuVax, decided to end a Phase 3 trial for good after disappointing results.

"It's still another negative," Peoples says, referring the longstanding difficulty researchers have had in finding success with cancer vaccines. "It's very frustrating, to say the least."

Peoples is working through the disappointment the way he usually does: by asking questions. What's working, and what's not? What do I know, and what do I need to figure out? What are the next steps?

It's a practice he honed throughout his life in the operating room and on the battlefield.

From ‘Bama to Brooke Army

Originally from Alabama, Peoples received his medical degree from Johns Hopkins University in Baltimore in 1988 after graduating from the United States Military Academy at West Point. He interned at Walter Reed Army Medical Center, and spent most of his surgical training at Harvard Medical School's Brigham and Women's Hospital, following it with a brief stint at MD Anderson Cancer Center in Houston. That ended in 1998, when he joined the staff of Walter Reed, where he eventually became the chief of surgical oncology in 2001.

The military transferred Peoples in 2006 to Brooke Army Medical Center in San Antonio, which calls itself the largest military healthcare organization under the Department of Defense. Peoples retained his position as surgical oncology chief, while also taking on leadership roles in committees on cancer.

"Technically speaking, he is the single best surgeon I have ever known," wrote Major John Barry, chief resident at Brooke Army Medical Center, in a letter of recommendation for Peoples to receive the BioMed SA award. "Unflappable, always steady in hand and in thought, he makes surgery look easy."

Peoples applied his scientific training in battle as well. In Afghanistan and Iraq, even as war raged around him, Peoples focused on how his team of doctors, nurses, and medics treated the wounded. His group was part of a mobile unit that followed army soldiers into war zones. Every unnecessary tool was a burden, so he tracked what his group used, how they used it, and what could and couldn't be left behind. Peoples and his team also established standards-which they later wrote and published books about-on topics such as when to operate on wounded fighters and when to send them away on a transport.

Atul Gawande wrote about that work in a 2004 article published in the New England Journal of Medicine. Gawande is now a famous physician at Boston's Brigham and Women's Hospital and author, but when he first met Peoples, Gawande was a surgical intern at that same hospital in the 1990s. In the NEJM article, Gawande wrote that during Peoples' service, the death rate among injured U.S. soldiers was the lowest among any prior wars the U.S. was involved in. (NPR interviewed them both.)

"I know of no one in medicine I hold in higher esteem," Gawande wrote in a recommendation letter.

Peoples had an interest in vaccines throughout his career. He had published some 17 papers on vaccines by the time Gawande met him, and has the same number of patents under his name for his vaccines work, dating back to 1994. In 2000, he started an Army program to encourage research collaborations on cancer vaccines, both in the military and elsewhere. NeuVax was originally developed at MD Anderson, and Peoples helped develop it before it was licensed in 2004 by the company that eventually became Galena.

Peoples retired from the army in 2014 as a colonel and turned his full attention to oncology research. That year, he started a contract research organization, Cancer Insight, focused on cancer immunotherapy. He is aiding a nonprofit, the Metis Foundation, that aims to help military researchers gain federal and private funding for medical research. And he is the chief medical officer of a San Antonio startup, Rapamycin Holdings, which has an experimental treatment for cancer.

Cancer Vaccines: Past Failures And New Hope

Peoples' transition to oncology has been a tough one, now headlined by the stinging failure of the breast cancer vaccine NeuVax. The vaccine, which has long had skeptics, made it all the way to Phase 3 testing before Galena disclosed that NeuVax failed badly. It performed worse than a placebo at preventing the recurrence of tumors in breast cancer patients, causing independent data monitors to recommend to Galena in June to halt the study. The trial was officially closed on Aug. 10, and Peoples says he is still having trouble making sense of what happened.

NeuVax isn't alone, however. Several experimental cancer vaccines have flopped in trials run by a variety of drug developers, from GlaxoSmithKline to Merck to Celldex Therapeutics. The only cancer vaccine to win FDA approval was Dendreon's sipuleucel-T (Provenge), and it had such a disappointing launch that Dendreon filed for bankruptcy in 2014 and later sold itself to Valeant Pharmaceuticals.

Nonetheless, investments in cancer vaccines have continued, as they're one of many tools that researchers and biotech companies are trying to use in concert to spur the immune system to fight cancer. Likewise, Peoples says he remains invested and is moving forward, even if he questions his decision to make cancer research his sole focus.
"I'm still not sure it's the exact right decision," Peoples says about the decision. "Nevertheless, unfortunately, it's somewhat of a necessary one."

What's next?

Peoples began dissecting the what he might do were NeuVax to fail, even before the data was released. Harkening back to the same questions he might have during a surgery or at war, he wondered, what's working, and what's not? The answer he's come up with is a popular sentiment regarding cancer immunotherapy: combination therapy looks like the key to better results.

A cancer vaccine's goal is to stimulate an immune response against a tumor. And NeuVax, specifically, was meant to train T cells-the immune system's attack dogs-to seek out and kill cells expressing a specific protein, HER2, that helps cancer cells grow. The hope was this strategy would help prevent breast cancer from recurring after treatment with chemotherapy or surgery, making both more effective.

That idea-making a good therapy better-got Peoples to consider another question: What other therapies, especially other immunotherapies, might also work well with vaccines? The answer he came to was checkpoint inhibitors.
Checkpoint inhibitors are immunotherapy drugs that help T cells see tumors that they otherwise wouldn't. The ‘checkpoints' themselves are proteins that tumors can mask themselves with; by blocking checkpoints, these drugs reveal tumors' true identity.

Over the past five years, four checkpoint inhibitors from Bristol-Myers Squibb (NYSE: BMY), Merck NYSE: MRK), and Roche's Genentech unit have racked up approvals in cancers of the skin, lung, bladder, head, and neck. In the process, they've invigorated the field of immunotherapy, but also revealed their own limitations. Checkpoint blockers still only work for a fraction of patients, and will likely need help from other drugs to boost their effectiveness. That's why Bristol and Merck, for instance, have a slew of combination trials underway pairing their checkpoint blockers with other drugs.

Cancer vaccines are a possible pairing partner for checkpoint drugs as well, and that's where Peoples sees an opportunity. He's developed a vaccine with Elios Therapeutics, an Austin, TX-based biotech that is owned by Orbis Health Solutions, of Greenville, SC. Elios is studying the vaccine in one trial currently, and expects to start two more by the end of the year.

"There's just a natural marriage between checkpoint inhibitors and vaccines," he says. "Everything scientifically lines up to show this synergistic effect."

Peoples isn't the only one with this idea. He co-authored an article in the Expert Review of Clinical Immunology in June that cited 18 ongoing trials where vaccines are being studied with checkpoint inhibitors. One, for example, is a Phase 2 study combining a vaccine from Seattle-based Immune Design (NASDAQ: IMDZ) with a checkpoint inhibitor from Genentech.

A Long-Term View

Despite all the past failures suffered by cancer vaccines, Peoples still believes they can and will work. He said Dendreon's journey epitomizes the field's progress: For every good, there's a bad.

That can take its toll, as Peoples can attest. It was easy to be motivated in the Army and on the battlefield saving lives, or performing a successful surgery and getting personal feedback from patients and families, he says. Research lacks the same immediacy. And the failures are easy to come by.

"I know it's a bigger picture and a longer-term view, and I've already said I have that view. But you oftentimes don't get the immediate feedback and successes of doing it," Peoples says. "I just want to find the right place for cancer vaccines to make an impact."

Family has been instrumental in helping him push forward, he says. He has five children. His wife, Kathy, is a former professor with degrees in business and early child development, who let go of her career to support the family at home.
"Having that family foundation, it's really kind of the rock that everything else is built on. My wife is a saint," Peoples says. "I was deployed seven times, gone for three and a half years. All of a sudden, everything falls on her. Without her, I don't know what I would do."

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