Welcome to Partnology’s Biotech Leader Spotlight Series, where we highlight the remarkable accomplishments and visionary leadership of biotech industry pioneers. This series is about showcasing the groundbreaking strides made by exceptional leaders who have transformed scientific possibilities into tangible realities. Through insightful interviews, we invite you to join us in following the inspiring journeys of these executives who continue to shape the landscape of the biotech industry. This week we are recognizing:
Dr. John Byon is the Chief Medical Officer of Imugene Limited. He has extensive oncology drug development experience in the pharmaceutical and biotechnology industry. At Genentech, he worked on TecentriqÆ (atezolizumab) in hematological malignancies. For over the past 5 years, he has worked in the cell therapy space. First at Juno as the Global Development Lead for orvacabtagene autoleucel (JCARH-125) in Multiple Myeloma. Then at Lyell, working on next generation cell therapy products for solid tumors. Most recently, he was VP, Clinical Development Hematology at Fate Therapeutics, where he oversaw a portfolio of 5 iPSC-derived cell therapies (CAR-NK and CAR-T) in various hematologic malignancies (AML, MM, B-cell Lymphoma).
Walk me through your career, highlighting key moments or decisions that shaped your path toward becoming a biotech CMO:
I think the first big decision was actually to go into biotech. When I started my career, I always thought I would become an academic physician-scientist—running a lab and seeing patients. But as I was finishing my fellowship, around 2008–2009—during one of the more recent financial crises—grant funding dried up. That forced me to consider a career pivot.
I ultimately decided to go into biotech for two main reasons. First, one of the most frustrating aspects of being a hematologist-oncologist is how quickly you run out of treatment options for most patients. That became disheartening. The opportunity to work on medicines that could meaningfully improve patients’ lives was incredibly appealing.
Second, I’ve always been deeply interested in the science—not just the pathophysiology of cancer, but also the mechanisms behind treatments and drug development. So biotech felt like a natural fit.
In terms of career highlights, I started at Genentech, which was a fantastic training ground for learning drug development strategy and gaining exposure to commercial considerations—the full gamut. The next big step was leaving that large, resource-rich environment for smaller biotech companies, where resources are more limited, but decisions are made much more quickly. That was a significant leap into the unknown.
One especially formative experience was at Lyell Immunopharma, where I joined as employee number 17. It was a risky move, and I wasn’t sure how things would unfold. But I learned a lot—especially about how organizations grow and scale, and where the pain points typically emerge.
Each step in my career has given me the chance to work with talented people and learn about organizational dynamics—what makes companies succeed, where they struggle, and what to look out for. As I’ve moved up the career ladder, those experiences have really served me well—especially in preparing me to take that ultimate step into the Chief Medical Officer role.
Tell me more about Imugene Limited, what are you currently working on?
Imugene is an Australian company, with headquarters in Sydney. Most of the team works remotely, and the company has been around for about 12 or 13 years. I’ve been with Imugene for about two years now. What initially drew me to Imugene—beyond the people—was the portfolio. The company is developing three main assets: two oncolytic viruses for solid tumors and an allogeneic CD19 CAR T-cell therapy (azer-cel) for hematologic malignancies.
What’s especially exciting is our lead oncolytic virus program (CF33-CD19), which leverages a unique mechanism of action. Not only does the virus infect and potentially kill tumor cells, but it also has a transgene inserted that causes infected tumor cells to express a protein—CD19—on their surface. This creates a future opportunity to combine the oncolytic virus with our CD19 allogeneic CAR T therapy. It’s a very novel and high-risk approach, but the combination strategy is scientifically compelling.
Both programs are currently in Phase 1. The CF33-CD19 oncolytic virus program is being studied in combination with Amgen’s BiTE (blinatumomab) to establish safety and early proof of concept. Our allogeneic CAR T-cell program is currently in expansion, with two patient cohorts: one for individuals with large B-cell lymphoma who have relapsed after autologous CAR T-cell therapy, and another for patients who are CAR T-naïve.
We recently issued a press release sharing preliminary results for azer-cel: among 12 patients treated, all of whom received prior autologous CD19 CAR T therapy, we observed a 75% overall response rate and a 55% complete response rate, with some responses lasting over 15 months. That’s very encouraging, especially given the limited treatment options for patients who have relapsed after autologous CAR T therapy.
Looking ahead, we plan to expand into CAR T-naïve populations, particularly in lymphoma subtypes where CAR T is not routinely used. We’re excited to continue enrolling patients and to see how the data evolve.
You’ve worked on cutting-edge platforms, including CAR-T, NK cell therapies, and oncolytic viruses. From your perspective, what scientific or technological breakthroughs are most likely to redefine cancer immunotherapy in the next decade?
I actually think certain applications of AI are going to fundamentally change the field. For example, applying AI to understand tumor biology and the tumor microenvironment has the potential to unlock insights we haven’t been able to see before. Much of that falls into the realm of translational research, where AI can help reveal new patterns and mechanisms.
On the drug discovery side, I believe the next major breakthrough will be the use of AI to design novel proteins with entirely new functions. Multiple groups around the world are working on this, particularly in academia—most notably David Baker’s lab at the University of Washington. He won the Nobel Prize in Chemistry last year for his work in this area.
As these tools mature and become more sophisticated, the ability to custom-design proteins for specific functions could truly transform the landscape—even more so than AI-driven small molecule target discovery.
You’ve overseen programs from pre-IND to pivotal stages. What are the most underestimated aspects of early clinical development that can make or break a program?
I think there are a few key points. First, it’s about truly understanding the product candidate you plan to bring into the clinic. Often, for the sake of speed and getting the IND filed and enabled, teams follow a standard playbook—doing what’s been done before. That may get you past regulatory hurdles, but it can leave critical questions unanswered. And once you’re in a clinical trial, it becomes much harder—if not impossible—to go back and address those gaps, because certain aspects of the product weren’t fully interrogated. Spending that extra time and resources during the preclinical phase can pay major dividends once you’re in the clinic.
The second point is being strategic about your first indication. In the past, Phase 1 trials were focused primarily on safety, and efficacy wasn’t a big expectation. That’s changed dramatically. Now, there’s often an expectation—fair or not—that a Phase 1 trial will show strong, even compelling efficacy signals. But these studies were never designed for that. So, if you want to achieve early proof of concept, you need to be extremely deliberate about your first indication: what you want to see, how you define success, and how you communicate that definition to both internal and external stakeholders.
And finally—something that’s often overlooked—is the team. Are you empowering your people? Supporting them to be the best version of themselves? Teams are under constant pressure to generate data and respond to external expectations, and sometimes leaders respond by bombarding them with questions and directives instead of trusting them to do what they were hired to do. Ideally, you’ve brought together a group of experts. If they’re supported and given the space to collaborate, they’ll deliver. That’s why I believe so strongly in the idea that culture eats strategy for breakfast. You can have the best strategy in the world, but if you don’t have the right people and the right culture, it won’t matter—you simply won’t be able to execute.
What are some best practices you’ve developed for designing first-in-human oncology studies to balance risk, patient safety, and speed?
One key consideration is being thoughtful in how you write your protocol—building in enough flexibility to account for unknowns. Personally, I’ve moved away from the standard 3+3 dose escalation algorithm. Like many in the industry, I now favor some form of Bayesian design, which allows you to escalate, de-escalate, re-escalate, or expand dosing as needed. That flexibility is crucial. It reduces the need for frequent protocol amendments, which are both costly and time-consuming.
Another important factor is being strategic about your target patient population. You need to think carefully about which group will help you best understand your drug, while also aligning with your broader development strategy. Your first-in-human, early clinical trial sets the foundation for everything that follows—so the planning behind it needs to be rigorous. That doesn’t mean accounting for every possible scenario, but the more clarity you have up front—and the fewer amendments you need—the faster you’ll be able to move forward.
Looking back, what leadership lessons would you share with the next generation of physician-scientists aspiring to make an impact in biotech?
I think it starts with reflecting on the kind of leader you want to be and understanding your leadership style. A lot of it comes down to self-awareness—really knowing who you are, recognizing your gaps, and continuously asking yourself how you can improve as a leader. That might come through self-directed learning—reading books and articles, talking to people, finding mentors, or observing great leaders in action.
If there’s a leader you admire within your organization, don’t hesitate to reach out. Ask for a coffee chat and pick their brain. The more you do that—and the earlier in your career you start—the faster you can develop and refine your leadership skills.
