Novel CAR T Therapies Help Celyad's CMO Bring Hope to Fearful Patients
Celyad Oncology CMO Charles Morris, M.D./Courtesy Celyad Oncology.
Immuno-oncology has seen fantastic advances in terms of efficacy and outcomes during the past few years. The challenge, however, is to find ways to identify and add new targets and modalities to bring those advances to even more patients.
For Charles Morris, M.D., CMO of Celyad Oncology, that challenge is what makes his work so exciting.
“I’ve been in the industry 26 years. After graduating from Sheffield University Medical School in the U.K., I spent six months in a number of rotations, including one in hematological oncology at the Manchester local infirmary," Morris said. “I found, on a personal, emotional level, that you’re dealing with patients who are frightened by their diagnosis, uncertain of their prognosis, and we – the medical staff – were the people who gave them hope. In that way, I found something enjoyable. I liked the work and trying to understand the science of it.”
In the 1990s, when he entered oncology, treatment nearly always was confined to chemotherapy. The field had potential – and a dire need – to advance.
“Cancer is a difficult nut to crack, and I saw there was potential for things to evolve,” he said. With the combination of bringing value to patients as individuals and as a collective, and the inevitable evolution of the science of oncology, Morris had found his calling.
Celyad is focusing on advancing chimeric antigen receptor T cell (CAR T) therapies.
“Approved cell therapy products have a very, very high response rate,” he said. "The challenge is in expanding that therapy from hematologic malignancies to other targets – in particular, to solid tumors – where we, as a field, haven’t yet cracked the code.”
As he elaborated, “all the approved cell therapies are in hematologic malignancies, where the cancer is very accessible to the treatments that are given.” Because the targets that are expressed on myeloma and B cell malignancies aren’t expressed in many other places, the targeting is very specific. Targeting solid tumors, however, is more complex. “Solid tumors are less accessible and have a microenvironment” which complicates the issue.
Celyad, therefore, is addressing the challenge from two fronts. Initially, it developed an autologous therapy program for acute leukemia, which is in clinical trials now.
“The challenge is that autologous treatment involves a long process,” Morris said.
That, effectively delays treatment delivery to patients. Therefore, the company is transitioning to allogeneic CAR T cell therapy, an ‘off-the-shelf’ approach using donor cells rather than the patient’s own cells.
“We believe there is a greater opportunity to treat patients with allogeneic therapy,” Morris said. “From the patients’ and physicians’ perspectives, allogeneic therapy is only possible if we minimize the risk of graft versus host disease by knocking down the T cell receptors so they can’t attack normal cells.”
From a developer’s perspective, this approach is advantageous, too. There is an almost unlimited supply of cells and the product can be available off-the-shelf or out-of-the-freezer, more like a drug. Because it can be continuously developed, it can be readily available.
“A number of companies are pursuing gene editing to develop CAR T therapies, but we have some different techniques,” Morris said, that make Celyad’s approach unique. Specifically, Celyad uses either T cell inhibitory molecules (TIM) or short hairpin RNA (shRNA) to knock down the T cell receptors. “shRNA is our proprietary platform and will do most of the work, although the TIM platform is further advanced.”
As CMO, Morris is balancing the concerns of multiple stakeholders. “Physicians, patients, board members, development teams and investors all want effective therapies, and they each have expectations as to how quickly they can be developed and at what costs. Sometimes you have to go slowly to ensure safety. So, balancing expectations is a critical part of what a CMO must do.” One of the strategies Morris uses to do that is to “explain the development process in ways that keep people engaged and excited. A product is great, looking back, when it succeeds, but getting it to that point takes a lot of planning.”
Morris counts his first drug approval as the one professional success that will live with him the longest. “The first time you’re part of a team that gets a drug approved, there’s a sense that we developed something that will really help people,” he said.
For him, that drug was Faslodex® (fulvestrant), which treats metastatic breast cancer. It was developed while he was with AstraZeneca.
“I occasionally meet someone who was treated with it, and I take satisfaction in knowing we are still helping people many years after the interaction with the (regulatory) agencies ceased,” Morris said.
Since then, he has been instrumental in the development programs at Radius Health, PsiOxus Therapeutics, ImmunoGen Inc., Allos Therapeutics and Cephalon, Inc. Morris helped Cephalon gain approval for Treanda® (bendamustine), its first oncology drug.
His professional success is rooted in truly enjoying his work. To maintain that enjoyment, “continue to find new approaches and new things to do,” he advised. The emphasis on new approaches was one of the key attractants of Celyad. “We have a great team that’s working on the leading edge of science, and we enjoy working together.”
There’s more to a successful career, of course.
“You also must listen to multiple stakeholders, because it’s not all about the medical role," Morris said. "You have to be confident in your ability to make decisions. If you maintain a patient-centric approach, you can make the right decision, but keeping everything in focus is a balancing act.”
As with many companies, that balancing act is multinational. Many of Celyad’s senior executives are based on the U.S. East Coast while “most of the company” is located near Brussels. Morris will make his first trip to meet the Belgian team in person soon.
“There’s a value in getting together in the same room, getting to know people socially,” he said. “That’s hard to do through Zoom.”
Balance is an integral part of Morris’ life. “Having interests and distractions – walking, running, cycling, listening to music, watching soccer and football – are important. They help make sure people don’t become robots, obsessed with one thing. For me, walking is a little escape. During COVID, I started calling my walks ‘mental health walks’. They give one thinking time.”