News

One company’s failed drug is this company’s ‘jewel’

Dr. Thomas Bock, CEO of Notable, is helping the company develop a ‘new class’ of predictive precision medicines in oncology.

Meagan Parrish, Lead Editor
PharmaVoice

Published May 2, 2022 – Many pharma execs find that a personal experience with a patient serves as a catalyst to enter the field. For Dr. Thomas Bock, CEO of the precision oncology medicine company Notable, that brush with a disease has hit especially close to home.

In fact, Bock says his entire life has been centered around advancing medical oncology. When Bock was young, his 6-year-old sister died from brain cancer. After seeing how she experienced the “toxicity [of her cancer treatment] without the benefit,” he embarked on a quest in medical school to develop better treatment options.

As his career in pharma later blossomed, Bock accrued a lengthy list of accomplishments that harkened back to those early life goals, including the development of six blockbuster medications while working for Celgene, Alexian, Novartis and others.

Then, about 10 years ago, Bock’s wife began her battle with breast cancer. As it would turn out, one of the treatments she was given was Femara — a blockbuster Bock had helped bring into existence. Talk about seeing the impact of your work up close.

“I’m particularly proud of Femara because my own wife was treated with this. And so that hits quite deeply,” Bock explains.

Bock’s wife survived her cancer diagnosis. And studying the difference in her experience versus his young sister made Bock an even stronger believer in the need to develop oncology drugs that are more effective with fewer toxic side effects.

Today, that sharp focus is guiding Bock’s leadership at Notable, which specializes in a “new class” of predictive precision drugs for various cancers. The company’s approach is to identify existing treatments that are less attractive to other drugmakers due to their lower efficacy, and then, using a proprietary platform, Notable “bio-simulates a patient’s cancer cells” to identify a patient population that is more likely to respond.

In other words, the company uses its platform to match oncology diamonds in the rough with the right patients.

Notable currently has two candidates in phase 2 trials for acute myeloid leukemia, and two in phase 1 for pediatric leukemia and solid tumors. According to Bock, early studies have shown that its platform is over 90% accurate at identifying clinical responders. The approach also helps patients and their doctors answer what Bock says is the important question in someone’s journey with a disease.

“In the end, it comes down to one thing I believe matters most to the patient: Will this drug work for me?” he says.

Here, Bock talks about his storied history in pharma, the business advantages of the company’s approach, and how Notable has turned the pandemic into an opportunity to be more efficient and innovative than ever before.

This interview has been edited for length and clarity.

PharmaVoice: What attracted you to Notable?

Thomas Bock: When I got connected with Notable, its founders and its team, we had exactly the right passion because we had this personal experience, very high ambitions and a high bar. We said if we want to move forward to serve our family members and our patients, we have to do two things: We have to develop drugs with compelling medical benefits. But the second piece is we have to make sure that each treated patient also has that dramatic benefit, and it’s not just one out of three [patients who] get benefits.

We now develop treatments by combining tech and life sciences that work in more treated patients, and that’s huge. So that’s what attracted me immediately and what resonated.

In your career, you’ve played a hand in developing six blockbuster medications. Tell me about some of the highlights in that journey.

There are three that really changed the paradigm of how we treat patients. One was Gleevec, [which was developed] when I was the global medical head at Novartis Oncology. It was the first cancer precision medicine and a designed molecule for a genetic mutation of a biological pathway. With Gleevec, you treat the patient and find out whether she or he responds, and it was just game changing. You replace bone marrow transplantation in this field and 99% of the patients responded, and it extended the lifespan by many years.

The second one was Revlimid at Celgene. Everyone wanted to treat and kill cancer cells and treatments were very toxic and we said, ‘Let’s modulate the immune system and get cancer under control.’ And so, Revlimid was much more tolerable and again, extended life spans by five to seven years.

Then there was Soliris, from when I was global head of medical affairs at Alexion. It’s a company that really intrigued me because they said, ‘No patient should be left behind. Even the smallest populations, (which we defined as 5,000 patients or less worldwide), deserve progress.’ It wasn’t the business model at the time and people thought you couldn’t create that, but we delivered. If you create momentum for innovation and drug development on these patient populations, and if you create that life-transforming impact, you can also create a business model around it that’s viable and sustainable. That’s been my experience.

Tell me more about the medication you helped develop that your wife used to treat her cancer. What was it like to see a medication you helped create being used by a patient in your own home?

It made me very humble, honestly. And you can see that even great therapies sometimes have side effects because you’re now so close to the patient, and it makes you doubly cautious and diligent when you set the bar for any new drug that you develop.

How did those experiences impact your approach to developing medications at Notable?

When I met the founder and the team of the company for the first time, they had developed this predictive platform mostly for diagnostic purposes. We give it to a doctor and then they can predict which target they should give to a patient and whether they’ll respond or not. I saw this and thought, ‘Wow, that’s an amazing thing.’ But imagine if we could develop drugs where that is not even necessary because they’re only developed for clinical responders?

So we’re using our platform to develop treatments selectively for responders who will have a compelling benefit. And also, in an ideal scenario, every single patient who is treated is going to respond. We call that a predictive precision medicine.

What’s unique about your platform?

The platform was developed for drug classes where we can find and match to the right patient populations. In our paradigm, we take drugs that have a compelling efficacy, but maybe for only 10% to 20% of the population, and we licensed them from other companies. So it’s a drug the other company doesn’t want to continue developing because it doesn’t have a financially rewarding clinical profile — it may not even get through the FDA with a 10% to 20% response rate. But it’s still a jewel. And so we take that drug, we bring it on our platform, we identify the clinical responders, and then we develop that drug exclusively in clinical responders.

How does the underlying technology of the platform work?

We take a sample of cancer cells from the patient, we process it with a drug, and then we measure directly how well the cancer cell responds. We monitor 100,000 data points per sample, and then we have an AI algorithm that’s correlated to behavior on our platform, with the actual patient response later on.

There was a clinical trial at Stanford University, which showed if our platform says this patient is a predictive responder, it’s 92% accurate. It’s still not perfect, but with more data, we hope to get as close to 100% as possible.

What are the drug development benefits of this approach?

We call it triple de-risked: We know it’s efficacious, we know it’s safe, and we can match it to the right population. Then we bring it to the FDA for clinical trials.

Now, because you have such a high response rate, we need about 75% fewer patients, because if you have a big difference to the current standard of care, you can have a smaller trial. And because we have the platform combined with a treatment, we trigger a brand-new patent life, which gives us essentially 20 years of patent protection, versus the average industry average of seven or eight years. So it’s extremely valuable for patients because everyone gets the compelling benefit. But it’s also very valuable for drug development because it’s developed at a higher speed, there’s a higher likelihood of success, and it’s a higher return on investment.

How well will a treatment option like this compete with other options on the market such as CAR-T cell therapies?

I worked with cell therapies and it’s a very promising, very innovative new approach. But unfortunately, CAR-T cell therapies can also be very toxic, and it doesn’t work in every patient.

As a treating physician, the critical thing I want to know is: Does this patient respond? What is that outcome? If I knew this patient would respond with a 92% likelihood to the drug, that’s what I would do first, regardless of what the mechanism of action is.

We are starting with hematological cancers because we have a wealth of experience in this area and that’s where the innovation will go very, very fast. Yes, there are other treatments approved. But, for instance, for relapsed refractory acute myeloid leukemia, a 15% to 20% response rate is the standard of care. But we could come with a proposition that 92% have responded. So that’s where we can change the standard of care.

What is your style of leadership and what lessons are you learning in the CEO role?

We are a very fast-growing company and changing from a research company to a clinical and commercial company. Also, we are all going through a once-in-a-century pandemic, and that affects all of us personally and professionally. But we said, ‘We have to make this happen anyway, so let’s actually not see this as a challenge, let’s think about what we could learn to create an even better, more productive environment.’ So we have built a workflow model that we continuously monitor for improvements.

Workers in the lab, for instance, often need to be at the bench, so they are in the office. But engineers or coders sometimes work best if they have their headphones on in a dark room. So it’s a very tailored model where either being together and working alone or working on Zoom is continuously being optimized. We measure this productivity through questionnaires or surveys. And that’s a very deliberate way of thinking through it.

With a combination of being face to face and at home, we are creating a more unique work model that makes us more productive, more innovative, and faster.

Contact

Caroline Bone

Notable Labs
communications@notablelabs.com
415-851-2410