For decades, Fred Hutchinson Cancer Research Center has been known for innovative approaches that use the immune system to treat cancer and save lives.
Now, the Hutch is advancing its legacy in immunotherapy by means of a new Seattle biotechnology company that is a unique collaboration among scientists at the Hutch, Memorial Sloan-Kettering Cancer Center in New York and Seattle Children’s Research Institute.
With financial support from investors ARCH Venture Partners and the Alaska Permanent Fund, the three institutions have combined to found Juno Therapeutics, Inc., which is being launched with one of the largest biotech startup Series A financings ever ― $120 million.
That funding, and the immunotherapy expertise of the founding institutions, give Juno the ability to bring new therapies to clinical trials more quickly.
“Bringing together the cutting-edge technology of the Hutch, Memorial Sloan-Kettering and Children’s creates incredible potential to develop new forms of immunotherapy that could help cancer patients not just in Seattle and the United States, but worldwide,” said Fred Hutch President and Director Dr. Larry Corey.
Dr. Michel Sadelain, Juno co-founding scientist and Memorial Sloan-Kettering faculty member, said, “The therapy Juno is developing has the potential to revolutionize cancer treatment and save untold numbers of lives. The pursuit of that goal will be well-served by combining guidance from world-renowned researchers.”
Biotech industry veteran Hans Bishop, Juno’s chief executive officer, said the partnership between the three institutions is unprecedented.
"The field of immunotherapy is highly competitive, but the Hutch, Memorial, and Seattle Children’s saw the value of working together," he said. “Combining the extraordinary amount of knowledge at these centers gives us the best chance of progressing toward our shared goal of developing curative treatments for adult and pediatric cancers."
Faster treatments from bench to bedside
Hutch researchers have been making exciting advancements in immune-based cancer therapies that build on the center’s groundbreaking work in bone-marrow transplant decades earlier. In the past year, the one millionth bone marrow transplant was performed. Bone marrow transplants were pioneered by Dr. E. Donnall “Don” Thomas, a Nobel Prize-winner who called the Hutch home until his death in 2012.
The Hutch’s immunology research has been catalyzed by a $10 million gift in 2009 from the Bezos family. The donation was used to advance the Hutch’s immunotherapy program and galvanized a community of additional supporters, which together helped evolve and expand the cutting-edge research that now serves as Juno’s foundation.
Hutch researchers are working to advance a form of immunotherapy known as adoptive T-cell therapy. The approach involves removing T cells, a type of white blood cell, from patients and uses genetic engineering to allow the cells to recognize specific antigens, which are proteins on the surfaces of invading cells. The engineered T cells are grown in a laboratory, and then infused back into patients to attack cancer cells.
By selecting the right type of T cells, investigators can infuse cells that will have potent and sustained anti-tumor activity. Since immunotherapy can specifically eliminate tumor cells without destroying healthy ones, the approach has the added benefit of causing fewer side effects than chemotherapy, radiation and surgery.
But as promising as immunotherapy seems, a new funding approach was needed to move it forward, Hutch Board Chair Paula Rosput Reynolds said.
“No matter how worthy our cause is, we all recognized that philanthropy alone wasn’t going to be sufficient to accelerate a cure,” she said. “We needed to develop a new model that aggregated the science of several institutions and used that research in an environment that can more rapidly validate therapies and make them available to more patients.”
The therapies Juno will use are already being tested in clinical trials at the Hutch, Memorial Sloan-Kettering and Seattle Children’s, targeting patients who have not had success with chemotherapy, radiation or transplants. More than 25 patients have enrolled in the trials so far.
In June, the National Cancer Institute, one of the National Institutes of Health, announced that as of October 2013 it would no longer fund phase 3 clinical trials for cancer treatments. Dr. Michael Jensen, who heads the pediatric cancer immunotherapy program at Seattle Children’s and is leading one of the clinical trials with genetically engineered T cells, said that decision underscores the importance of the startup’s funding approach.
“We are in a funding crisis in this country for academic research,” he said. “Despite the clear therapeutic opportunities, our ability to move forward without partners like this would be significantly restricted.”
Corey and others believed that immunotherapy had the potential to cure a range of cancer types. But transforming those technologies into viable treatments took time, Corey knew, and time meant lives.
In an era of shrinking federal funding, the Hutch’s president and director reasoned, the center needed a bold new strategy – one that would allow it to freely pursue innovation without being slowed down by a grants process that, while useful in providing pilot data, would not be large enough to enroll and follow the number of patients required to develop an adequate clinical profile for a novel cancer therapy – even if it was curative.
In 2012, Corey and the Hutch’s board of trustees began talking about the need to revise the center’s strategic plan. They agreed that the Hutch’s priorities going forward should include a heightened focus on immunotherapy.
Those conversations continued at the board’s two-day strategic planning process in January 2013. There a former board member and adviser, Ed Fritzky, suggested that the Hutch needed to bundle its technologies together and seek a long-term investor in order to get novel therapies – particularly cellular therapies – to market.
A serendipitous meeting
Corey was mulling over that suggestion as he headed to the Boston airport in March 2013 to fly home to Seattle after a board meeting.
Standing in line at the airport, he ran into a friend. They got to chatting, and the friend introduced Corey to David Fallace, senior portfolio manager at Alaska Permanent Fund Corp.
Corey told Fallace about his ideas on how to incubate the Hutch’s cellular immunotherapy technology. The pair talked extensively during the flight and were so immersed in the conversation that at one point a flight attendant had to shoo them back to their seats to free a path to the plane’s restrooms.
A few days later, Corey got an email from Fallace indicating he was intrigued and asking if he’d be available to meet with Alaska Permanent Fund Executive Director Mike Burns and Chief Investment Officer Jay Willoughby, who were coming to Seattle.
That meeting set in motion events that led to the launch of Juno and, after considerable vetting, a promise of investment from Juno’s two primary funders, ARCH Venture Partners and the Alaska Permanent Fund. Robert Nelsen, ARCH’s co-founder and managing director, said he was compelled to invest in Juno after reviewing initial data from the clinical trials.
“In 27 years of starting biotech companies, this is the most exciting data I’ve seen,” said Nelsen, who is on the Hutch’s board of trustees. “We have seen complete responses with no signs of residual cancer at a molecular level in clinical trial patients who had advanced disease. "I think Juno has the potential to have a major impact on the treatment of cancer.”
Dr. Stanley Riddell, a member of the Hutch’s Program in Immunology said, “More time is needed for definitive results, but the responses in the initial patients with B cell leukemia and lymphoma are overwhelmingly positive. We’re very optimistic that T-cell immunotherapy will be a major advance for treating cancer.”
Dr. Phil Greenberg, who heads the Hutch’s Program in Immunology, is leading another clinical trial that is also showing encouraging results.
“We are treating very sick adult patients with acute myelogenous leukemia, a very tough disease,” said Greenberg, who has been working on T-cell therapies since the 1970s. “We are seeing results that are changing the paradigm of what immunotherapy can do.”
Therapy with engineered T cells is a relatively new approach to fighting cancer, and the technologies being developed by Juno represent the next frontier in cancer immunotherapy. Typically, T-cell therapies use whatever combination of cells is extracted from each patient, which can result in varying effectiveness and duration of treatment response.
In contrast, Juno’s therapies will use specific combinations of extracted T cells that are most effective in providing a long-lasting response against particular cancer cells resulting in more consistent and predictable behavior in clinical trials.
The cells used include memory T cells, which can last throughout a patient’s lifetime and reactivate if cancer returns, rapidly reproducing cells that aggressively fight off the disease in subsequent recurrences.
“We’ve worked out the technologies to rapidly isolate very specific subsets of T cells,” Riddell said. “That’s one of the advantages we think Juno has.”
Juno’s founders include Hutch scientists Riddell and Greenberg; Jensen of Seattle Children’s; and Memorial Sloan-Kettering researchers Sadelain, the director of MSKCC’s Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory; Dr. Isabelle Rivière, director of the MSKCC Gene Transfer and Somatic Cell Engineering Facility; and Dr. Renier J. Brentjens, an MSKCC oncologist specializing in the treatment of acute and chronic leukemias.
Juno’s scientists each have long-standing independent, successful and complementary research efforts that are focused on the design and implementation of cell therapies for cancer. By leveraging their broad scientific expertise and combining cell-processing capacity in Seattle and New York, Juno can test promising new treatments in patients more quickly than a typical biotech startup.
Juno will initially focus on blood cancers including acute leukemia and aggressive lymphomas. But its discovery efforts and breakthroughs in T-cell engineering provide the foundational platform that will be expanded to fight solid-tumors cancers such as breast, lung, and other common cancers. In fact, a lung cancer study is scheduled to start in 2014.
“Juno brings together some of the nation’s brightest minds in immunotherapy,” Corey said. “Working together, we believe we have the ability to develop innovative T-cell therapies that could cure a variety of cancers.”