April 22, 2019| By Hiroomi Tada, MD, PhD, Chief Medical Officer

Why I Joined Notable

“What’s next?” For me, the simple answer to this question is joining a life sciences tech startup to build and lead a clinical development organization. But the reasons behind my move from a successful and well-respected East Coast biotech (and a job I absolutely loved) is part of a much more complicated complex answer to this question.

A colleague recently attended a conference sponsored by a patient advocacy group. The purpose of the meeting was to bring together patients and their families with scientists, researchers, physicians, and nurses to learn more about a specific type of rare cancer they had been diagnosed with, see the latest research and clinical trials being conducted, and share their journeys with each other. My colleague was presenting a recent analysis of data from a clinical trial our company was conducting in this particular cancer. He related to me how awesome and inspiring it was to meet patients who approached him and said they were being treated on this clinical trial. They hugged him and thanked the team for all of the work we were doing to bring a new targeted medicine to patients with this rare cancer. He also met one or two patients who initially benefited from the therapy, but for whom the new drug was no longer working. These patients were extremely grateful nonetheless for the opportunity to be on the clinical trial. What struck my colleague as the most poignant and tough question was when they asked, “What’s next?”

When he shared this story with me, I knew exactly how he felt when he heard that question. I was a liver and pancreas cancer surgeon early in my career. I dreaded that question from patients and families because it meant that their cancer had recurred following what was all too often a short-lived success following surgery. On rare occasions, surgery could be performed again to try and achieve a “cure”, but usually, it was not a single recurrence in a single site that could be successfully removed. “What’s next” usually meant a referral to one of my medical oncology colleagues, a discussion of their case at our multidisciplinary tumor board, and an all too common recommendation for what was considered standard of care. On a rare occasion, a clinical trial was available, as these were the days before targeted and immunotherapies that brought what is now what we consider the era of precision oncology. “What’s next” was never good news.

I moved into pharmaceutical drug development in 2007 after an epiphany. As a cancer surgeon, one of the most technically demanding operations was the Whipple procedure for pancreas cancer. The debate those days was around who should be doing that operation with high volume surgeons and institutions arguing that only they should be doing those operations as they had the “best outcomes.” It was really just about “marketing,” as their own data said that surgeons doing 6 or more Whipples a year had the best outcomes–numbers that were matched by many university-based pancreas surgeons. What struck me as particularly odd about that was, as a medical community, we had not changed the 5 year survival rate in pancreas cancer in 30 or 40 years. What I came to realize was that we did not need better surgeons and surgery, we needed better medicines (as an aside, in the 12 years since I left academic surgery, the 5 year survival rate has doubled to 9% at 5 years – still not good enough, but a significant advance for patients).

Fast forward to where we are today. I’ve been fortunate enough to work on therapies targeting tumor vasculature and molecules that target specific gene mutations (i.e. precision oncology), as well as in immunotherapy. The entire field of cancer therapy has made tremendous progress, but we are still faced with the question from patients “What’s next?” That is because despite the progress, it’s not enough. Only a minority of patients benefit from the new immunotherapies and patients on targeted therapies eventually develop resistance and disease progression. The subsequent options are either conventional chemotherapies or possibly a clinical trial with a novel drug or combination. For the patients fortunate enough to be eligible for a clinical trial they often only have one shot to choose the “right” trial that gives them the best chance to respond to the therapy. There are no resources available to patients that can help them understand ahead of time if there is a chance they might benefit from the treatment, or only experience the toxicities. Precision oncology has promised the right drug for the right patient and we are making progress, but we are far from delivering when a patient’s disease progresses after that first or second precision medicine.

That’s precisely what brought me to Notable. Our CEO, Matt De Silva, shared with me his personal experience navigating the treatment landscape for his father who developed glioblastoma in 2013, and Matt’s all too common frustration with the current state of clinical trials and drug development. How do you choose the right clinical trial when there are many being conducted and no good reason why one would be better for you than another? In oncology, we quote statistics of response rates and the likelihood that patients will survive 5 years, but when it comes down to the patient sitting in front of you, we don’t have specific answers.

To his credit, what Matt sought to build was borne from that frustration, that researchers should be able to do something to tip the advantage to the patient by choosing the right treatment and clinical trial based on a platform testing their own cancer. This concept is not new, it has been around in one form or another for several decades. For me, what makes where I am now different, is the breadth of backgrounds and expertise that you just don’t see in traditional pharma and biotech. We have biomedical, microfluidic, and software engineers, chemists, immunologists, molecular and computational biologists, business people, lawyers, and even a former Capitol Hill healthcare staffer, all working together to develop a system that can predict what drugs or combinations a patient’s blood cancer will respond. This kind of platform has the ability to change the way we make treatment decisions for patients. But more importantly, it has the possibility of helping select the right patients for the right clinical trials, speeding drug development and decreasing costs, leading to approval of drugs that benefit specific patients — true precision oncology. Who wouldn’t want to work on something that actually has an answer to “What’s next” for patients?