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 Tod Smeal.
Dr. Tod Smeal has served as Chief Scientific Officer (CSO) of Cardiff Oncology since January 2022. Previously he was CSO at Hexagon Bio (2020-2021), CSO of Cancer Biology at Eli Lilly and Company (2015-2020), Director at the Oncology Research Unit of Pfizer (2003-2015), and Senior Group Leader at the Sugen site of Pharmacia and Upjohn and Sugen (1998-2003). When Pfizer closed the Sugen site in 2003, Dr. Smeal continued his oncology research efforts on targeted therapies and their resistance mechanisms with Pfizer at their San Diego oncology research site. Subsequently in 2015, Dr. Smeal joined Eli Lilly where he led their oncology research efforts at Lilly Research Labs in Indianapolis. During his over 20 years in industry working on targeted therapies, Dr. Smeal has played key leadership roles in delivering about 20 FHD/NMEs and several FDA approved drugs (e.g., Lorbrena, Xalkori, Vizimpro and Nirogacestat). Dr. Smeal’s work in developing cancer therapies has been focused on intracellular signaling, kinases, drug pharmacology, and targeted therapies and their resistance mechanisms. He has over 45 publications which include high-impact publications in Cell, Nature, New England Journal of Medicine, JCO, Cancer Cell and Cancer Discovery.
From 1994 to 1998, Dr. Smeal was a post-doctoral fellow of the American Cancer Society and a senior post-doctoral fellow of the MIT-Merck fellowship program. Dr. Smeal holds a B.S. in Biology from the Massachusetts Institute of Technology and a Ph.D. in Biology from the University of California, San Diego.
Walk me through your career journey, highlighting pivotal moments, decisions or challenges throughout:
Like many, the decision about where to attend college was a significant one. I was strong in science, math, and chemistry, which led me to MIT. Initially, I started as a chemical engineering major. During my sophomore year, however, I was introduced to biology. It was an exciting time for the field, with breakthroughs in the 1970s and 1980s, so it truly felt like a revolution. I came across a new textbook on The Molecular Biology of the Cell by Alberts, which inspired me greatly.
Pursuing biological sciences would be a long path, requiring a Ph.D. instead of just a bachelor’s degree, but I felt drawn to it. I asked myself three main questions: What was I passionate about? What felt like a good fit? And did I forsee exciting growth and opportunity in this field? I’ve always been a conceptual thinker, less analytical, so fields like accounting didn’t appeal to me. Instead, I thrive on discovery and innovation, always wanting to be at the cutting edge.
As it happened, there were several places in the world ideal for the biological revolution of that era (1980s), the Bay Area (Stanford, UCSF, Berkeley), San Diego (UCSD, Salk, Scripps) and Boston (MIT, Harvard), where I was already based. The vibrant, inspiring atmosphere at MIT, with Nobel laureates and groundbreaking work, fueled my passion for the biological sciences, and I decided to focus on cancer research. Cancer was personally relevant, as it was prevalent in my extended family, and scientifically, I was fascinated by cell signaling and how cells respond to their environment—an area critical to understanding cancer. I’ve been especially fortunate throughout my career in working with world class scientists. After MIT, I was a graduate student at the department of biology UCSD and did my thesis work with Michael Karin (Professor of Pharmacology, School of Medicine, UCSD) and collaborated with Tony Hunter (Salk Institute) both are Nobel caliber scientists. Michael is a force of nature who has made many seminal discoveries in transcription and cell signaling and working in his lab was an inspiring, challenging, and a defining career experience for me. Also, another important influence on me during my graduate studies, was working with Tony Hunter who is best known for discovering protein tyrosine phosphorylation. Tony is a scientific visionary who was a great collaborator as well as thesis committee member.
From there, I moved into biotech. My exposure to Big Pharma started at MIT during my postdoctoral fellowship, where I was a senior fellow in the Merck-MIT program. This program, a collaboration between Merck and MIT, opened my eyes to the pharmaceutical industry and posed a career question: should I pursue academia or industry? Ultimately, I leaned toward industry but preferred a smaller company for more impact and career flexibility. This and Sugen’s focus in cancer, kinases and cell signaling, were areas I was very much passionate about and focused on during my academic years, led me to Sugen, which ironically eventually became part of Big Pharma due to Sugen being acquired by Pharmacia, Monsanto, and later Pfizer.
The first phase of my career was dedicated to discovering new cancer targets. At Pfizer, my focus shifted to developing the best drugs for those targets. In the third stage of my career, especially at Cardiff, I’ve been focusing on identifying the patient populations who would benefit the most from these best-in-class drugs. So, the arc of my career has progressed from finding the best targets, to developing the best drugs, to targeting the right patients.
What motivated you to jump from big pharma into biotech? How did you find that transition and what were some key lessons?
As I mentioned, my career has evolved gradually, beginning in biotech, transitioning to Big Pharma, and eventually circling back to biotech. The first phase of my career focused on innovative ideas, identifying new cancer targets, and exploring the causes of cancer. In the middle phase, with Big Pharma, I shifted to developing the best drugs to target those discoveries, leveraging new technologies to create effective treatments. It’s a natural progression; many of my peers also reach a point where they’ve gained extensive experience in pharma and want to apply that knowledge in a smaller company where they can make a bigger impact and work on cutting-edge ideas.
Though I stayed in pharma longer than I initially expected, opportunities for advancement at companies like Pfizer and Eli Lilly opened at just the right time. As you move up the ladder, especially in areas that matched my career interests, major roles at large pharma companies are relatively rare. To my surprise, my career development led me to Indianapolis, Indiana with Eli Lilly, even though I’ve mostly lived on the coasts. My experience with Eli Lilly was a very positive and rewarding opportunity to work with a very strong science focused R&D group in oncology in a company that is striving to transform itself into a 1st tier pharmaceutical company (which Eli Lilly achieved going from ~ 12th to the 1st pharma in the world by market cap). In biotech, there are several main hubs: San Diego, the Bay Area, and Boston, which collectively host a large number of oncology-focused biotechnology companies. Of course, there is also outstanding research in many other places as well but I especially enjoyed my time at Sugen and UCSD. So, when the right biotech opportunity emerged, I knew I wanted to return to California.
In the later stage of my career, I’m focused on applying everything I’ve learned to make a greater impact at a smaller company where the risks and rewards are more impactful on the success of the company. At this stage, I’m not working for a salary alone but more for the satisfaction of delivering transformative therapies that positively contribute to extending patients’ lives and improving their quality of life.
Career growth in biotech and pharma requires balancing immediate goals with the long-term development of skills and expertise. Early in your career, working for a smaller company can provide diverse experience. However, to gain deep expertise in drug development—taking a drug from discovery to clinical trials through to approval—larger companies offer the necessary resources and scale. Once you have that comprehensive experience, returning to a smaller company allows you to maximize your impact.
Reflecting on my journey, a key lesson from transitioning between academia and industry is the importance of interdisciplinary work in drug development. In oncology, advancements have come not just from biological sciences but also from computer science, DNA sequencing diagnostics, and medicinal chemistry. Together, these fields have enabled the development of highly specialized, next-generation drugs that offer patients long-term benefits. A prime example is the evolution of HER2-targeting drugs for breast cancer: from Herceptin to T-DM1 and now Enhertu. Each new generation of these drugs has significantly extended patients’ lives, showing how advances in both biology and technology can transform treatment outcomes.
Tell me more about Cardiff Oncology – what are you currently working on?
Much of my early career was in cell signaling, focusing heavily on a protein class called kinases. My first biotech company Sugen specialized in this area. Additionally, Sugen turned out to be a great training ground for me and other future drug discoverers. Many successful biotech scientists and executives as well as successful drugs can be traced back to Sugen. Founded in the 1990s, Sugen pioneered the discovery and development of ATP competitive inhibitors for the treatment of human disease including cancer.
Currently, I’m working on a kinase called Polo-like kinase 1 (PLK1), which is part of a class of kinases that regulates the cell cycle. At Cardiff Oncology, we’re developing onvansertib, a next-generation, highly selective PLK1 inhibitor. Currently in Phase 2, initial data demonstrate upside potential and our hope is for onvansertib to eventually become a best-in-class option, offering promising therapeutic benefits for cancers dependent on PLK1. This drug class differs from traditional oncogenic driver inhibitors, like those targeting EGFR mutations. With cell cycle inhibitors, the focus is on specific patient populations rather than mutations. For example, CDK4/6 inhibitors are effective in ER-positive breast cancer, whereas we’re developing onvansertib for KRAS-mutant metastatic colorectal cancer (mCRC). We recently published our findings in the Journal of Clinical Oncology, which outlines our work with onvansertib in combination with chemotherapy and bevacizumab for KRAS-mutant CRC. This publication Ahn, D., et al. 2024. J Clin Oncol., provides insight into the clinical rationale and progress in this area.
This work directly aligns with my expertise, as I’ve specialized in cancer signaling for the past 20 years—one of the main reasons I was drawn to this company.
What are the current trends you’re seeing in cancer research and how do you see cancer drug development evolving over the next 5-10 yrs?
As I’ve reflected on my career, I see how the field of oncology has evolved in remarkable ways. When I started about 25 years ago, we were still in the discovery phase—piecing together what causes cancer, the factors that lead to its progression in patients, and how to design therapies that might intervene. Then, around 10 to 15 years ago, we shifted into a phase where we had a clearer understanding and began developing drugs with meaningful clinical activity. These initial drugs weren’t perfect, but they laid the groundwork for optimizing later generation drugs, leading to more precise and effective treatments based on what we were learning in the clinic. This is what we call the “precision medicine” phase, where therapies are tailored to the specifics of a patient’s cancer biology.
If you think back 30 years, cancer treatment options were largely limited to surgery followed by chemotherapy—a broad approach that wasn’t specific to the molecular changes specific to a patient’s particular cancer. Chemotherapy, while somewhat effective, was often a “sledgehammer” with significant side effects on normal cells and tissues. Then we progressed to targeted therapies. Targeted therapies, which I’ve been working on for the past 25 years, are designed to act on altered targets or pathways specific to tumor cells, ushering in a more targeted approach to treatment with improved efficacy and safety.
I believe we’re now transitioning from precision medicine to what I’d call “individualized medicine”. Cancer is an incredibly complex disease, and each patient’s case is unique due to specific mutations and other cellular changes. Where we’re headed in the next 10 to 20 years will be transformative. In the past, a diagnosis relied on biopsy and pathology, followed by a recommendation of a standard treatment regimen approved for that indication. With the rise of molecular biology, we started sequencing tumor DNA to identify mutations and match them with targeted therapies.
Now, as technology advances, we’re seeing tools that allow us to analyze a patient’s cancer in real-time. In the future, patients may visit their doctor, undergo detailed DNA sequencing and molecular profiling of their cancer, and receive a precise list of recommended therapies that address the specific events driving their disease.
This shift toward highly individualized care will likely be supported by advancements in technology and data analytics. AI, still in its early days, could become a powerful tool for sorting through the enormous amounts of data that diagnostic platforms will soon produce, guiding the next generation of physicians in making real-time therapeutic decisions with the best available drugs.
What advice would you give to young scientists and those aspiring to become leaders in the biotech industry?
I think everyone has their own path, and ultimately, you have to synthesize what you learn from others to figure out what works best for you. With that in mind, what worked well for me was pursuing things I was passionate about, areas where I could see a clear direction by listening to field experts, and where there was a good fit with my abilities.
For example, like many scientists, I’m more of an introvert, so I had to learn a lot about public speaking and becoming more comfortable in extroverted roles as I moved up the leadership ladder. But the key elements were passion, excitement, vision, and fit—finding roles that aligned with my strengths. Having a realistic assessment of my strengths and weaknesses and a plan to improve areas needed for success have been essential to developing my career.
