How Psychiatry Graduate Dr Tadimeti S Rao Career

He grew up in a working-class family in southern India, earning a Master's Degree in Pharmacy at Andhra University, northeast of Chennai, in the early 1980s.

1 January 2019

He grew up in a working-class family in southern India, earning a Master's Degree in Pharmacy at Andhra University, northeast of Chennai, in the early 1980s.

In 1987, with a bit of financial help, he moved to far-off Edmonton, where he completed a PhD in Neuroscience in the Department of Psychiatry / Faculty of Pharmacy at the University of Alberta.

Today, he leads a team of scientists at one of the world's biggest pharmaceutical companies, in beautiful San Diego, Calif.

It almost sounds like a Hollywood movie script.

But it's the real-life story of Dr. Tadimeti S. Rao, Scientific Director & Fellow, In Vivo Pharmacology - Immunology, at Janssen Pharmaceutical's Research & Development unit.

That's where Dr. Rao and his team evaluate new preclinical drug compounds that they hope will one day be used in the treatment of inflammation, pain, autoimmune disease, metabolic disease and various forms of cancer.

On a chilly Tuesday in January, Dr. Rao returned to his alma mater in Edmonton, delivering a lecture on Therapeutic Targeting in Multiple Sclerosis at the Li Ka Shing Centre for Health Research Innovation, attended by medical students, Department of Psychiatry Graduate students, Residents and Faculty members.

During a pre-lecture interview, Dr. Rao discussed the long and winding road that led to his current post at Janssen - a subsidiary of multinational U.S. corporate giant Johnson & Johnson - as well as the challenges and opportunities of bringing new drug therapies to market.

It's a topic he is very passionate about, after spending more than 30 years working for such major industry players as Ciba-Geigy (which later merged with Sandoz to form pharmaceutical giant Novartis AG); Pfizer Inc.; Sibia Neurosciences (acquired by Merck & Co. in 1999); Kalypsis Inc. (a private San Diego-based drug developer); and now, Janssen.

"The drug discovery process is very complex and requires many talents coming together to create a shared vision. Over the years I've worked in multiple therapeutic areas including Neuroscience, Immunology, Metabolic Disease and Oncology. The core competencies that allowed me to work in these areas came from the training in Pharmacology and strong mentorship I received from Drs. Baker in Psychiatry and Ronald Coutts in Pharmacy, that I received right here at the University of Alberta," he says.

"One of the unique features of the PhD program at the University of Alberta was the multidisciplinary approach. That's one of the best things that could have happened to me. As a student I was exposed not only to basic science but also clinical science. So the scientific issues I had to deal with and the skill sets I developed were very applicable as I made the decision to pursue a career in the pharmaceutical industry."

Janssen, founded in Beerse, Belgium in 1953 by famed Belgian Pharmacologist and drug researcher Dr. Paul Janssen, was acquired in 1961 by Johnson & Johnson. In 2010, all of Johnson & Johnson's far-flung global pharmaceutical operations were amalgamated under the Janssen umbrella.

Today, Janssen employs more than 40,000 people in dozens of countries around the world. The company focuses on six key therapeutic areas, including: Cardiovascular & Metabolism; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

"Our San Diego site has about 250 employees; our site in Spring House, Penn. has about 2,000 employees; and we have a major research centre in Beerse, Belgium (Johnson & Johnson's largest operation outside the U.S.) that also has a manufacturing plant," Dr. Rao explains.

"There are probably about 7,000 employees there, so it's an enormous site. Overall Janssen has about 10,000 people with varied skill sets working in Research & Development, if you include all the various functions."

Dr. Rao works in Janssen Immunology Discovery and leads the Pharmacology team within that area, which provides all of the preclinical models that are used to evaluate various drugs.

"In our area, in any given year, I'd say we develop three to five new molecular entities - or new drug candidates - that are ready to be tested in humans. In Phase I, these molecules will first undergo enabling toxicology studies, safety evaluation, scale up and manufacturing. Once they complete the first human clinical trials - mostly looking at safety and tolerability, not efficacy - you move to Phase II," he explains.

"That's where selected doses will be tested in a control group of patients to get clearer preliminary evidence of efficacy and safety. Then, based on the data from Phase II, we may proceed to a full-blown Phase III trial, the results of which form the basis for any New Drug Application (NDA) that is filed with the drug regulatory agencies."

It's an expensive, risky, and time-consuming process. On average, it costs somewhere between $1.5 billion (US) to $2 billion (US) to develop a new drug, from initial concept to the commercial marketplace. The average timeline: 10 to 15 years, says Dr. Rao.

"There is also a very significant attrition rate when you are developing new drugs. Often, new drugs won't work the way you expected it to work when you go from animals to human subjects. There are always surprises. So part of the Discovery Team's goal is to minimize those unpleasant surprises and build confidence that the drug will work the way you expect it to work."

Aside from the scientific challenges, developing new drugs entails other challenges as well. Sometimes there are personality clashes, and successful people with healthy egos don't always agree on the best path forward.

"A sports analogy is a good way to think about it. It's not the individual but the team that defines success. You may be very good at what you do, but at the end of the day there is only one common goal, so leaving your ego at the door is important. In a drug discovery program there is no room for prima donnas. But a good manager or project team leader will identify any rough edges and deal with them before they become bigger problems."

Since many promising compounds fail in clinical trials, some research scientists will go through their entire career without seeing one of their compounds succeed in the commercial marketplace. That's not the case for Dr. Rao, who participated in the advancement of several new drugs into the clinic, including Pfizer's Celebrex, which has been used by millions of patients to treat such as conditions as Acute Pain, Osteoarthritis and Rheumatoid Arthritis.

"I've been fortunate in my career to work on multiple programs that have entered the clinic in Phase I or Phase II. In every therapeutic area in which I've had an opportunity to work I feel fortunate to have been part of a team that was successful in taking a concept into the clinic. That doesn't mean it gets into the market, of course. But the Cyclooxygenase Inhibitor (Cox-2) is an example of a project that went all the way to the market."

So what is Dr. Rao and his team working on today?

"Our research focus now is on Autoimmunity so we're developing novel therapies for Rheumatology, Gastroenterology and Psoriasis, where there is a significant unmet need. There are a lot of drugs out there today and patients clearly have options compared to 10 or 15 years ago, but not all patients respond to existing therapies, so there is a need for much more effective therapies," he says.

As for his long-term career plans, they remain unchanged. After working for more than 30 years in the pharmaceutical industry, he says he is as engaged and excited about discovering new, more effective drug compounds as he was when he started.

"My passion remains in drug discovery, and the chance to learn something new. I feel very fortunate that the organization trusts scientists like me to tap into their creativity and work on a problem. There is no easy way to describe how satisfying that is. If you have a good day solving a problem, it is worth the weeks of frustration you sometimes experience. For me, a failed experiment is as important as a successful experiment, because it tells me where I should focus my energies for the next study."