Dr. Israel Lowy remembers the days when he and his oncology immunotherapy colleagues were assigned tables in the distant east wing of the American Society of Clinical Oncology conference in Chicago. They would watch aficionados walk by, scoffing at these iconoclastic researchers pushing an alternative way to treat cancer.
“Some people thought we were deluded, like Don Quixote tilting at windmills,” he told Fierce Biotech at the Biotechnology Innovation Organization conference this week. “But we felt there was something there, and we needed to keep at it.”
Today, Lowy is a senior vice president and head of the oncology clinical development unit at Regeneron, and he spoke about the journey oncology immunotherapy has taken on its way to creating ubiquitous blockbuster therapies like Merck’s Keytruda and Bristol Myers Squibb’s Opdivo, approved for indications as diverse as lung cancer, melanoma and colorectal cancer.
Lowy’s early work treating AIDS patients in 1990s New York City helped shape his expertise in immunotherapy. He saw firsthand as the disease went from a near-certain death sentence to a manageable chronic condition. “These medications came out that stopped the virus in its tracks,” he said. “These people basically restored a lease on life.”
The power of immunotherapy to stop a previously devastating disease was a theme that stayed with Lowy. Later, he was approached by leaders at a company called Medarex that was developing an antibody drug targeting CTLA4 in tumors, and he asked whether the target would work in chronic infections. They said they had hoped he would ask, and he joined the company and later led his first clinical trial of an anti-CTLA4 drug for AIDS patients.
But he kept an eye on how the target was working in oncology, and he eventually switched to treating cancer. Unencumbered by the traditional mindset of most oncologists at the time, he believed biotech could develop drugs that trained the immune system to fight cancer, despite the well-established surgery, chemotherapy and radiation protocols that commanded most oncologists’ attention.
He would go on to design and lead the first clinical studies of anti-PD1 and anti-PDL1 drugs, as well as the first combination studies of anti-PD1 and anti-CTLA4 oncology immunotherapies. He remembers a presentation in the early 2000s when a lead scientist at Merck saw Medarex’s data. Merck had a PD-1 antibody that, Lowy says, the company was about to out-license because it didn’t know what to do with it.
“They saw our presentation, and they said, 'Don't out-license it,’” Lowy said. “That became Keytruda.”
Drugs like BMS’ Opdivo, Novartis’ Kymriah and Gilead’s Yescarta arrived in the years that followed.
“It’s very validating to see that this whole endeavor has blossomed, so that immunotherapy is now considered a core component of any approach to cancer care,” Lowy said.
Empowering the immune system to fight disease has been the centerpiece of Lowy’s career and has transformed both HIV and cancer treatment over the last 40 years. But Lowy noted the importance of remembering that what is standard of care today was once just a group of scientists who believed in an idea enough to toil in the backwaters of the oncology world for years before a breakthrough.
Biotech innovation and drug development, while slower than most would like, are moving faster than ever. Now, Lowy said he’d like to see oncology dig deeper into what is happening at the tumor site and within its microenvironment.
Earlier this month, Regeneron inked a $2 billion biobucks deal with CytomX to expand a previous agreement focused on the tumor microenvironment. Learning more could allow “a combination of anti-tumor targeted therapy and immune-targeted therapy to effectively combine to suppress the tumor,” he said.
Despite two late-stage immunotherapy trial failures in the last year, Regeneron has continued to seek out new immunotherapies, including a potentially $2.3 billion pact with Parabilis to develop an antibody-drug conjugate-like treatment.
Lowy sees the success of immunotherapy as an inspiration for future breakthroughs and a shift in thinking toward ideas off the beaten path. “Because of the success of immunotherapy, there's, for now, more willingness to entertain new ideas,” he said.
In a biotech world that remains a long game even for the most promising therapies, Lowy is among a group that persevered even when toxicity concerns and inertia made immunotherapy in oncology look like a long shot. “When you feel something in your bones, you stick with it,” he said.