Leading Diversity & Discovery At Janssen

By Wayne Koberstein, Executive Editor, Life Science Leader
Follow Me On Twitter @WayneKoberstein

Anuk Das Champions Multicultural Networking In Immunology Research.

Diversity is not just a liberal ideal — it is a portal to discovery. To understand that statement in the context of the biopharmaceutical industry, the words at either end of the sentence must be taken at their largest meaning. Diversity of people and research resources leads to more productive discovery of human potential and new therapeutic entities. Diversity and discovery go hand in hand at Janssen Research & Development, where Anuk Das heads the Disease Integrative Biology, Immunology Research unit, and where she has helped make diversity a cultural priority at the company. (Janssen R&D is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.)

Of course, diversity includes people with a variety of backgrounds beyond the traditional preponderance of Caucasian males “at the top” and, for that matter, right down to the bottom of companies in the past. More females, more people of other ethnic groups and nationalities, and a generally freer mix reflecting the planet’s population are all first principles from which diversity in a greater sense grows. (See “Diversifying Leadership Teams With People Who Have The X-Factor” in our April 2015 issue.)

As it turns out, the mentality of inclusion offers other benefits when so much of the innovation involving large companies begins outside of those companies, amongst the amalgam of academics and mostly small enterprises loosely called biotech. Das has built a research network of players in that sector, as well as an internal team to integrate the external network with the company, based on a philosophy of opening doors to a wider mix of people and external research partners. And with significant evidence of positive results, she believes the new R&D operating model, aligned with the idea of diversity in discovery, may succeed where others have failed.

Das presents us with a case of theory turned to action. In parallel with her leadership of an immunology discovery team and collaborator network, she has championed diversity in employment in the scientific and engineering areas of the company through outreach to students pursuing education and careers in the STEM (science, technology, engineering, and math) fields — leading the creation of a postdoctoral program with the University of Michigan for underrepresented minorities that, Das says, “provides us with opportunities for access to innovative science and a diverse talent pipeline.”

A conversation with Das supplies some key insights into several areas at once: the evolution of discovery strategy and structure in a leading, though atypical, Big Pharma company; the ever greater understanding and alignment of drug mechanisms with disease mechanisms; and the overriding value of maximizing the variety of people, disciplines, and research nodes in a largely external discovery network.

Leader Origins

How And Why Did You Join This Industry And This Company?
DAS: Prior to joining the pharmaceutical industry, I was a postdoc in academia in the United Kingdom with a pharmacology background. I joined J&J’s pharmaceutical company Centocor in 2001, in the discovery group then called the Immunobiology department, moving there from my first pharmaceutical job, at DuPont Pharmaceuticals, which was also in the United States. In my postdoctoral years, I had done a sabbatical at a large pharmaceutical company, which opened my eyes to the impact pharmacologists in that setting can have on patients with disease. My basic reason for wanting to do pharmacology was to learn how drugs affect biological processes, and I realized that in the pharma world, I would have far more opportunities to apply that knowledge than in academia.

What Were The Major Steps That Led To Your Current Work?
For the first few years, I built up my experience in large molecule drug discovery. I was recruited for my research background in lung inflammation with respiratory diseases, and during my tenure in the discovery group, I essentially laid our foundation for respiratory disease research and progressed respiratory drugs into clinical trials. I also expanded our research and established a new area, in fibrotic diseases, building a portfolio for that as well. Then I was asked to take a role with a new function in Janssen R&D and the Immunology Therapeutic Area called “external innovation,” where we would invest in emerging areas of science. We have a commitment as a company to invest with a long-term view, because we believe investing in new areas of science will put us at the forefront of science and pay dividends as we build our external network of collaborators, expand our knowledge of the science, and strengthen our credibility by visibly applying that science to drug discovery.

How Does Your Group Fit Into The Larger Janssen R&D/J&J And Corporate Organizations, Both As A Team And As A Contributor To Drug Discovery?
Within J&J, we have separate divisions for consumer medicines, medical devices, diagnostics, and Janssen [pharmaceuticals]. And within Janssen, there are five therapeutic areas, the Immunology Therapeutic Area being one of them. My group resides within Research Immunology, and the diseases we focus on are priority disease areas within the Immunology Therapeutic Area. Through interrogation of disease data in our Network Pharmacology platform, we have quickly come to a point of validating our hypotheses and predictions derived from the platform. Novel gene connections predicted by the network have been validated, and small molecule targets have been identified. This is a new paradigm for discovering our next generation of therapeutic mechanisms and targets. In drug discovery, it’s all about impacting the disease biology with the correct therapeutic mechanism.

These Days, Mechanistic Drug Discovery Is Easy To Take For Granted, But In The Early 1990s, Paul Janssen Told Me He Thought Detailed Understanding Of Drug Mechanisms Lay Far In The Future.
It is so exciting that you bring that up, because my current role is focused precisely on making that happen. In the Immunology Therapeutic Area, we are now at a stage to make disease understanding a reality; and to understand how our drugs are working we also need to learn, in parallel, from examples of patients who have been treated with the drugs. In a large number of clinical trials we’ve conducted in immunology, together with trials in a range of immune-mediated diseases, we have been forward-looking in collecting samples as well. Those samples are now giving us insights into how the drugs work.

Your Focus Is On Discovery, But It Includes Some Integration With Clinical Development.
We encompass the entire bench-to-bedside-and-back approach in collaboration with other units in R&D. We have taken drugs we discovered at our benches and put them through the clinical trials, and now we are bringing that data back to learn from it and delineate our next generation of therapeutic mechanisms to address disease in new ways. We are focused on novel, differentiated drugs to address the remaining unmet medical needs, so understanding how drugs fail to work is also important.

What Is An Example Of A Particular Disease And Drug Target Your Platform Is Addressing?
For IBD [inflammatory bowel disease], we sought available technologies and potential drug targets where only the gut would have exposure to the drug, thus reducing systemic exposure. Of course, this approach has been used for a very long time in IBS [irritable bowel syndrome], but it is a new concept in IBD. There are quite a few companies pursuing the idea, as well as academic labs. One is the Icahn School of Medicine at Mt. Sinai, with which we have a large collaboration.

Are You The Only Ones Championing The Network Pharmacology Model?
There have been some high-impact journal publications on the model, but nothing has been done at the same scale or with the same strength of data as our platform, which offers a new way and much larger scale methodology for identifying our future targets, with human disease being the key.

Mapping Paths

How Would You Summarize The Essential Steps You Take From Understanding A Disease To More Effectively Targeting Drugs At The Condition?
The key to answering that question is in the name of my group: Disease Integrative Biology. The “disease biology” part is clear: Our mission and our focus is around disease biology. But the “integrative” piece is unique; what it really means is we are studying disease biology through interrogating many different kinds of human-disease data, with the ultimate goal to increase our understanding of the diseases.

There is an overwhelming mass of human-disease data, but we approach it in a unique way by using clinical-network pharmacology modeling platforms — or disease maps — that give us a visual way to interrogate the data in a more thorough and careful manner. The maps also allow us to make connections between different types of genes and interrogate the data in a highly efficient manner.

What Is The Technical Description Of How You Use The Network Pharmacology Platform To Map Disease Biology?
Our Systems Pharmacology and Biomarkers team construct probabilistic graphical models, or “Bayesian networks” — molecular maps for visualizing the molecular pathways in human disease — by integrating transcriptomics (RNAseq or microarray), gene co-expression, and cis-expression quantitative trait locus (eQTL) data. The cis-eQTL data identifies those genes that are most likely to regulate their neighbors in the network, thereby providing directionality to the network links.

The first network we focused on is constructed from molecular profiling data from IBD blood and tissue samples collected from Janssen clinical trials. My team of biologists interrogates the Bayesian network in silico — focusing on priority areas of biology important to our IBD disease area. We isolate connected subnetworks relevant to IBD from within the larger networks, identify the subnetworks’ key regulators, perform experimental confirmation of the Bayesian network predictions, and prioritize candidate targets to enter the drug-discovery portfolio.

How About A Description Of The Same Process For Laypeople?
Through mathematical modeling using genotype data, our platform can predict how different genes talk to each other or are connected to each other. In the models we use, there is also causality — some genes are regulator genes, with one gene affecting multiple others. We may have a modeled network that shows connections among what we call a “hairball” of 9,000 genes, and we single out areas of the network of importance to us from a biology perspective.

For example, we can ask the question, Is there a biological difference between thousands of samples taken from inflammation sites and sites with no inflammation? And what are the genes associated with those sites, and how are those genes talking to each other? To put it simply, that gets us into the realm of mechanism. So the network is all designed to produce mathematical predictions. Right now, in IBD, we’ve prioritized some of those genes and see whether the predictions of these genes talking to each other are true. We are testing the predictions in vitro, in primary human cell models, to see whether each gene identified as a regulator really knocks down or expresses all the other genes as predicted. We have already gained novel insights into new genes and their association with IBD no one had seen or published before.

What Is The End Goal Of The Network Pharmacology Platform From A Strategic Perspective?
For the past half-decade or so, we have read about how the pharmaceutical industry has not delivered the number of new drugs with the efficacy and safety as expected for the investments made. The majority of our targets in the past — and even in the present — have come from the literature, producing more failures than successes. But network pharmacology gives us a new approach — integrating a mass of human data to identify targets. We first need to invest in this approach to establish its validity, and if it works, we will be in a phenomenally strong position to deliver a sustainable pipeline for immunology.

Diversity — Outside & Inside

At What Point Does “Externalization” Of R&D Come Into Play In Your Group?
My career opportunities certainly broadened my appreciation for leveraging expertise outside of one’s own group. For example, we developed our microbiome strategy during my tenure in the innovation unit, and we made it happen by collaborating and seeking external advice. Building relationships with external experts has allowed us to build our internal knowledge of the microbiome area, and we anticipate embarking on additional collaborations. My group is small, and I wanted it to be small, because that forces us to go outside the group to leverage expertise and collaborate with other functions or outside the company to seek expertise anywhere in the world. In the IBD collaboration with Icahn, we will be leveraging our innovation center colleagues, our network of already existing academic collaborators, and perhaps new collaborators as well to help execute on validating our targets. We may even partner at a later point with other companies and experts on discovering new drugs aimed at those targets.

You Have Championed Diversity On Your Team, In The Company, In The Industry. How Does Diversity Impel Innovation?
Innovative ideas for new technologies and medical solutions arise from individuals or groups making connections between two or more supposedly unrelated ideas or existing concepts. That takes diversity in thinking by a diverse group of people working together to find the solution, bringing a wide range of perspectives to the table. Realization of the value of diversity came to me through key personal experiences. First was a diversity program we established jointly with the University of Michigan — a postdoctoral program recruiting minority doctoral and postdoctoral candidates. The power of this program is not only evident in the recruitment of diverse candidates, but also in the richness of the projects developed by the university scientists and our scientists working together in the program.

Then, as I recruited my team for disease integrative biology, I wanted it to be extremely diverse — not only in the obvious terms of gender, cultural background, countries represented, but also in background and experience. In our group of eight, we represent academic, small biotech, and large pharma backgrounds. We have a nice representation of genders as well as underrepresented minorities. I believe we are very strong because of our diversity.

So You Integrated Expertise, Along With Culture.
Our quest to make network pharmacology the new paradigm in target discovery within the Janssen Immunology Therapeutic Area required bringing together two very different kinds of experts: biologists, that’s my group; and computational biologists, statisticians and mathematicians who know everything about the in silico model of disease. Now we have a phenomenally strong team, completely integrated, and the communication is excellent — although even the languages we speak are very different. Again, that is a reflection of our diversity, not just in underrepresented minorities and women, but in different sets of expertise coming together to make something happen.

In What Ways Does Your Unit Interact With Janssen Business Partners To Apply Insights Of Patient, Customer, And Market Unmet Needs At The Level Of Discovery?
With the changes in the payer environment and the healthcare environment, there is a lot of awareness, going all the way through to discovery, of how the bar has been raised in drug efficacy. Psoriasis is a good example of a disease for which effective therapeutics already exist, and there are even more effective therapeutics now in pipelines, so the efficacy bar for psoriasis has risen much higher, and we are on the way to surmounting it. Of course, the next hurdle will be either cure or sustained remission.

Sharing This Market View All The Way To Discovery Implies Some Corporate Integration As Well.
In discovery, we certainly understand drug R&D will be conducted more and more through integrated groups with input from regulatory, market access, clinical development, and physician experience. Starting now, it will be about 15 years, if we’re lucky, before one of our drugs finally comes to market. So what will the market potentially look like in 15 years’ time? To be differentiated, an approved drug must not only be of value to patients and physicians, but also to the payers. We have these discussions early on in terms of mechanisms: For any given target, how is this different from drugs that we already know about and drugs that are on the market, and drugs that we are aware of in the pipeline, either in ours or competitive pipelines that have been disclosed?

Of course, we have a near-term pipeline that we need to support and move forward as well. It is a balance; there really is a commitment to focusing some of our resources on our emerging pipeline, as well as our future pipeline.