Perseverance is the foundation of impactful scientific discoveries, and is a core value that Precision BioSciences’ newly-appointed chief medical officer, oncology giant Alan List, shares.
Precision BioSciences’ newly-appointed chief medical officer, Alan List.
Perseverance is the foundation of impactful scientific discoveries, and is a core value that Precision BioSciences’ newly-appointed chief medical officer, oncology giant Alan List, shares.
“Anyone involved in scientific research knows that success only occurs when one perseveres and adapts to unexpected results,” he told BioSpace.
List, known as the father of Revlimid®, pegged his career on improving cancer therapies in ways that are meaningful to patients. The story of Revlimid is an example:
“My laboratory at the Arizona Cancer Center identified an angiogenic circuit that was important in the self-renewal of malignant stem and progenitor cells in a disease called myelodysplastic syndromes (MDS). We screened many different compounds and biologics that targeted the pathway…and one compound stood out. Celgene called this an immunomodulatory imide drug (IMiD), specifically CC-5013.”
Safety and efficacy studies involving MDS patients showed that, “Shockingly, a subset of patients with the most common chromosome abnormality in that disease – chromosome 5q deletion [del(5q)] – was profoundly sensitive. In the vast majority of patients who experienced complete remissions, the chromosome abnormality disappeared.
“Celgene quickly launched an international multicenter trial and confirmed that 75 percent of patients experienced major hematological improvement. Two-thirds became transfusion-free and normalized their blood counts with remissions that lasted more than two-and-a-half years. The FDA approved Revlimid® for Del(5q) MDS in 2005. It now is used to treat many different hematologic malignancies, including myeloma and lymphoma. Its 2020 sales exceeded $11 billion.”
Today, gene editing in on List’s mind.
“Precision BioSciences’ ARCUS gene editing technology genuinely amazes and excites me. It’s unique in the gene editing space,” he said, because of its size and ability to make specific edits, likely with minimal off-target editing. “It’s an exciting time, overall, in this space.”
As examples, List cited data presented recently at the American Society of Clinical Oncology (ASCO) annual meeting, including Precision’s allogenic CAR T cell therapy targeting CD19 for patients with non-Hodgkin’s lymphoma.
“If you look at clinical trials of autologous CAR Ts, up to 30% of the patients screened to participate never received their infusions. That’s because, while waiting weeks with high grade, relapsed lymphomas, the disease doesn’t sit tight. Ultimately, many patients become too sick to participate. With allogeneic CAR Ts that are ready to go or ‘off the shelf,’ the minute you see the need, you can intervene for the patient. This is going to transform cancer care.”
For List, finding better ways to treat cancer is personal. When he was growing up, “A cousin had acute lymphoblastic leukemia. She survived for years with that disease, and it was devastating to watch her suffer,” he said. That experience propelled him to study biology, and to complete his bachelor’s and master’s degrees together, in four years.
Before joining Precision Biosciences, List served as CEO of the Moffitt Cancer Center in Tampa.
“I’ve been advising Precision on its clinical trial programs for nearly a year and, with some exciting milestones coming up, I couldn’t pass up the opportunity to work with the team on what I feel could have a profound impact on cancer care, perhaps of a similar impact as Revlimid.”
List sees his role as CMO as that of a physician- scientist. That’s a role in which he has flourished throughout much of his 40+ year career, as leader and mentor as well as physician and researcher.
“We have an amazing team of researchers at Precision, and a big part of my job is to help each of them develop and reach their potential,” he said. “I feel that my background has prepared me for the role – I’ve been driving advances in cancer care for a long time. But ultimately, it is a team effort, and it is the science that will determine whether you are successful or not.”
The importance of the team mustn’t be underestimated. During his residency, Phil Scheerer, M.D., a hematology attending physician, “opened my eyes to the opportunities to make an impact in hematologic malignancies,” by directly interpreting bone marrow findings (which are readily accessible for laboratory research) and making clinician managing care decisions.
Sydney Salmon, M.D., founding director of the Arizona Cancer Center, was also influential.
“He was a pioneer in multiple myeloma… and brought in faculty who had a foot in the clinic as well as the lab,” List said. “That was key to discovering and developing more effective therapies. His guidance solidified my career focus.”
A full life involves more than career success. Weekends often find List with his wife, Kim, exploring the highways and byways of North Carolina. Until about a year ago, the soundtrack to their explorations was the distinctive growl of their Harley-Davidson motorcycles.
“Kim had a beautiful denim blue Softail Deluxe, and I had a black Road King Classic. We loved riding in the country… and through the Blue Ridge Mountains. Unlike driving in a car, riding a motorcycle through the mountains is a fully immersive experience. You smell the wildflowers on the side of the road and feel the wind on your face.”
Although the Lists sold those Harleys last year, they still enjoy the wind in their faces…but now from touring bicycles. “The greenway paths in the Raleigh/Durham area are just phenomenal for biking.”
World War II history is another great interest. “My father served in the Battle of Anzio, which he really never spoke about,” List said. To help fill in that gap, List read Rick Atkinson’s Liberation Trilogy, which tells how the Allies liberated Europe from the Nazis. “Reading that taught me a lot about his experience and the role soldiers from York (Pennsylvania, his hometown) played as the point of the spear invading Nazi Germany, because of the local fluency in German.”
It’s a lesson in determination and flexibility, and one that List knows well. Perseverance and adaptation – in science, in life, and in war – is a touchstone for great accomplishments.
