Julian Adams – widely regarded as one of the most innovative and dedicated leaders in the biotechnology industry – will be the first to admit that behind every success, there has been a failure. But, after nearly three decades in the industry, the synthetic organic chemist continues to follow his scientific curiosities, which have led him to new biology and therapies that have the potential to solve important disease problems and unmet needs.
Adams – who has made remarkable contributions to the development of targeted therapies and continues to have a major impact in this rapidly evolving field – has received multiple awards, holds over 40 patents, and has authored more than 100 papers and book chapters in peer-reviewed journals.
While he has worn several hats in industry – including at Merck, Boehringer Ingelheim and at Infinity Pharmaceuticals – Adams is now lending his expertise to Clal Biotechnology Industries (CBI) as chief science officer and president. Clal, Israel’s leading life sciences investment company, hired Adams in January 2017 to oversee the firm’s Cambridge, Mass. office, evaluate investment opportunities, and support portfolio companies.
In addition to his role at CBI, Adams was also elected to positions in two of CBI’s portfolio companies: Executive Chairman of Vedantra Pharmaceuticals, an immunotherapy company focused on developing products for cancer and infectious diseases; and Chairman of Gamida Cell, a world leader in cellular and immune therapies for the treatment of cancer and orphan genetic diseases.
I recently caught up with Adams, who shared his attraction to CBI’s diverse portfolio, his plans to help advance these innovative pipelines, as well as his attraction to unknown frontiers in chemistry.
Rich Soll: You have been branded as one of the finest medicinal chemists in the industry. How did your journey begin?
Julian Adams: My first industry job was at Merck Frost Labs in Montreal in the heyday of Merck in the 80s when Merck was America’s most admired company. Merck’s research labs were second to none in pharma. We were doing very innovative research in the field of leukotrienes; in fact, that was the lab that discovered SINGULAIR®, and after I left they also discovered VIOXX®. It was a very productive group. I learned the craft of medicinal chemistry while at Merck, and later when I moved to Boehringer Ingelheim, I led the chemistry group that discovered nevirapine (Viramune®), the first non-nucleoside reverse transcriptase inhibitor (NNRTI). Working on these first-in-class, groundbreaking therapeutics was, for me, very revealing about how the craft of chemistry could interrogate biology both looking at receptors and enzymes. I realized how impactful chemistry could be because the training in synthetic organic chemistry made me more and more fearless about tackling complicated chemistries, and ultimately embracing more complexity in the molecules and in stereochemistry, including multiple stereocenters.
Rich Soll: Were there particular factors that influenced or shaped your perspectives since you’ve had the opportunity to view the landscape through the lens of a medicinal chemist?
Julian Adams: I was fortunate to be at the right place at the right time to work on cutting edge biological problems that eventually led to drugs that went through clinical testing and were eventually approved. In parallel to the cutting edge biology were advances in technologies for medicinal chemists – computational chemistry and structural biology. So more and more I became enamored by these technologies and developed a strong affinity for directed chemistry based on the ability to see or model the biological target, especially when investigating protein surfaces, and trying to see if you can fit a small molecule into a cavity, or understanding the way an enzyme reaction works and trying to design a molecule that could interfere with that enzyme active site, or if available, an allosteric site. As long as synthetic chemistry was not limiting and we weren’t afraid of introducing complexity into the molecules, we could interrogate the biology with more and more exotic structures.
Rich Soll: How has the field of chemistry evolved?
Julian Adams: The tools of chemistry became ever more sophisticated – bond making, bond breaking, catalysis, synthesis became routine for chemists who trained in synthetic organic chemistry, both in methods and in natural products synthesis. I was of an era where the major breakthroughs in chemistry brought on new reactions to make bond-forming steps that were very complicated, and syntheses were very long and tedious. The breakthrough in chemistry was the ability to make complex molecules based on new agents, catalysis, and the ability to do really good process research, and engineer sophisticated molecules. So, the fear of the complexity of the molecule went away.
Rich Soll: Going back to this evolution of the medicinal chemist, do you think that there have been quantum leaps or do you think they have been incremental?
Julian Adams: The quantum leaps are in chemical catalysis, the ability to get protein structures, and the computational power of molecular modeling, which allow chemists to visualize and be able to do virtual screening and make calculations, rank order various molecules, and make training sets and build on those training sets. So I think it’s borrowing from three different areas – synthesis, structural biology, and computational power, combined with sophisticated graphics, which allow us in a much shorter time to visualize the problem and do better molecular design. These factors have influenced medicinal chemistry thinking, especially in light of what has developed over time in translational research when one administers a molecule – one doesn’t only look at the pharmacokinetic behavior of the molecule, but also the pharmacodynamic behavior of the molecule in that does it engage its target in vivo, does it elicit a biochemical response that can be measured, does it elicit a phenotype that can be measured, a biological response that can be measured, and that way we can have better predictions of the fitness of the molecule so we can determine the disease state.
Rich Soll: How did the discovery of Velcade play a role in this evolution?
Julian Adams: Velcade is a drug that I am pretty proud of. First of all, we interrogated a biological target, the proteasome, for the first time; nobody had thought that the proteasome was a legitimate target nor was it appreciated that the proteasome inhibition could be a medicine – that wasn’t well adopted, and was not, in fact, accepted by the pharma community at all. The active site of the proteasome was revealed through structural work by Robert Huber at the Max Planck Institute for Biochemistry, who solved the three-dimensional structure of the proteasome, revealing the first and only example of a threonine protease. Lastly, we borrowed from main group elements, namely, boronic acids to develop active site inhibitors. We had our tool in the form of PS-431, which eventually became Velcade. The whole program, from its initiation to drug approval, was accomplished in nine-and-a-half years including identification of a problem, use of the tool compound as the inhibitor of the proteasome, establishment of the link to cancer, and completion of an efficient clinical trial in a very underserved patient population, patients with multiple myeloma, a lethal blood cancer; I found all of that very gratifying. By paying attention to the data throughout the course of the program, we won over first the National Cancer Institute, then the individual clinicians who took the trouble to investigate our molecule, a novel cancer therapeutic, and ultimately, on a larger scale, the multiple myeloma cancer patient advocates who appreciated all this, and finally the FDA, who was swayed by the biological activity and efficacy using this approach.
Rich Soll: You serve on several boards. Do you have a particular philosophy in choosing board positions?
Julian Adams: Every company I interact with is doing cutting edge research in an area of unmet need. I have no interest in being the second, third and fourth generation anything. It’s not that I think there’s no place for that; it’s just that my scientific curiosities take me to different arenas where there’s an unmet need, a new biology being explored, a new modality to explore it, whether they are large or small molecules, whether they are even cell therapies or molecular therapies in an area that is solving a fundamental important disease problem, and interrogating new disease biology. I love this first-in-class type of problems because they make me think, they keep me humble. I’m not always successful, by the way. I’ve had many failed programs. Again, when I fail, when a program fails I want it to be a noble failure. I want it not to be a failure that fails because of technical reasons like we couldn’t get the drug absorbed or we couldn’t get the dose high enough, or that we picked the wrong patient population. I want it to be based on sound scientific preclinical evidence that we were going into interrogative biology, which is sometimes more complicated than we appreciate. Failure is not a defeat; failure is an acknowledgement that sometimes problems are harder than we think. If you think of diseases like Alzheimer’s and a whole host of neurological conditions and think of our understanding of neurobiology, of course we’re going to see failures and drugs that can’t meet their endpoints because we really haven’t defined the biological system with sufficient precision. It still makes the journey very interesting and very inspiring.
Rich Soll: You currently serve on the board of some great companies, some of which are Israeli, which brings me to Clal. How did you connect with Clal?
Julian Adams: It’s not a complete accident. I have both a sister and a brother who independently moved to Israel, and I thought, wouldn’t it be nice to see them once in a while on a more regular basis. I thought if I joined the board of an Israeli company I would have a professional excuse to go visit Israel. Contemporaneously I was asked to serve on the Blavatnik Center for Drug Discovery advisory board at Tel Aviv University, and then, eventually, the major investor in Gamida Cell saw me at the first board meeting and invited me to join their venture group. They have a portfolio of biotech companies, five of which are in the Boston area. So I became their president and chief scientific officer to oversee their portfolio of companies and be closer to their investments in the Boston-area companies.
Rich Soll: Let me ask you about the Boston-Israel connection. Is there a particular reason those companies are located in Boston?
Julian Adams: There were independent investments made in Boston-based companies; some were funded by Clal alone, with a history that made a connection to some academic finding that was attractive. And some of it does have an Israeli connection, as Israeli investigators are involved with some of the companies in the U.S. So in some cases, Clal was the sole investor and in other cases they are co-investors with other notable venture groups in the Boston area like Atlas and Third Rock Ventures. Boston is a natural habitat for biotechnology now, if not one of the epicenters of the world, and probably the largest concentration of biomedical life science research anywhere. And so is Israel. Israel also has a very high concentration of innovative life sciences investigations and in new companies, and so there’s a nice transatlantic, trans-Mediterranean access between the two environments.
Rich Soll: With respect to the capital markets, do you have any issues trying to raise capital or trans-border issues?
Julian Adams: Raising capital for an Israeli company abroad is necessarily more difficult; it probably requires the company to be more mature, be more of a clinical stage company. I think investments in early stage companies are pretty difficult. But even investments in Boston-based companies are not trivial. The limiting feature of making an investment is the investment in the managers, and that’s in short supply, both in Boston and even more so in Israel. Boston has had three decades to develop the talent for biotechnology, and Israel is still learning how to do that because it doesn’t have the graduates from pharma entering biotechnology, it doesn’t have nearly the density of biomedical research Boston has, but it’s certainly far more advanced than many other places. And then the sophistication of the capital market in the U.S. is second to none, and it just makes access to capital more feasible in the U.S. Although, that’s changing around the globe and we’re starting to see the Israeli markets respond as well. And the level of sophistication in Israel is starting to respond.
Rich Soll: Some of the companies you are working with are focused on neurological diseases, which are something a few years ago, many companies abandoned. It’s a tough area, so what are your plans?
Julian Adams: One of Clal’s investments in a neuroscience company is Cadent, which is partnered with Novartis. They just announced a milestone – Novartis took their NMDA receptor antagonist into Phase I trials. The NMDA receptor has been a much studied receptor, with a very rich history in biology. The company is exploring positive allosteric modulators to look at cognition deficits in schizophrenic patients. So, there are new data and new phenomena that had been covered, and that opens the door for medicinal chemistry to come in. The company is also pursuing a genetic condition of spinal cerebral ataxia which is a defect in an ion channel. The thought there is that a molecule might alter the biology of that signaling and the re-polarization of that ion channel, and help with the ataxia that is experienced by those patients. It even considers things like essential tremor, which is a complex set of diseases in elderly patients. There’s nothing like forging new frontiers; I like being in areas where it’s a frontier of science and chemistry.
Rich Soll: What’s your collective vision for the Israeli companies?
Julian Adams: What I’d like to see is that one or more of the Israeli companies become the next Biogen or Vertex and become a juggernaut and powerhouse in biotechnology. No company has really broken through that ‘Valley of Death,’ the requirement for both keeping a management team together and the continuous need for funding until they become a freestanding company and start to grow a pipeline. Often one sees companies that are single product companies, and you know from a business case model, it’s just not sustainable. Typically what happens is the molecule is licensed or sold. The question is, are there companies that have a research pipeline that can do it more than once? When you see such a company, as I do with Gamida Cell that has a whole suite of technologies to develop cell therapies, could that be the breakthrough company that was developed in Jerusalem and will become major industry participants?
Rich Soll: So what you’re saying is there is a certain level of risk mitigation and they have to have a stellar technology?
Julian Adams: I’m saying something more than risk mitigation. To have a successful and thriving business, beyond risk mitigation, you need to have a pipeline of products, and that’s what sustains a business. Every several years you can introduce a new product.
Rich Soll: Is there anything that keeps you up at night?
Julian Adams: A lot of things keep me up at night because my mind doesn’t shut off. There are all kinds of mundane issues like recruiting and retaining great talent, enrolling patients into a clinical trial, being able to find a drug in a preclinical setting that you can feel confident would be a good drug candidate and is worthy of taking into clinical trials. Frontiers of science that are not so clear, areas of disease where there is maybe a lot of competition with solutions to the same problem and you know you have to come out ahead, and some of those things are out of your control. All of these things keep me up at night.
Rich Soll: What advice would you give to young scientists or chemists today?
Julian Adams: I think if I had one piece of advice, particularly for younger people who are thinking about a career in science, it’s to cross-train – not only be good at the discipline in which you received your degree, but follow other areas of science that are relevant and pertinent and be able to weave broadly across scientific disciplines. You don’t have to be an expert at everything, but you have to understand and appreciate all of the multiple disciplines that go into scientific research if you want to make an impact in medicine.