GlaxoSmithKline (GSK), like so many other pharmaceutical and biotechnology companies, is looking to boost its pipeline. Pearl Huang, Ph.D., vice president and global head of GSK’s Discovery Partnerships with Academia (DPAc), is taking direct aim at the drug discovery concept stage to take up the challenge.
During a discussion at BIO 2014 in San Diego, Huang speaks quietly but openly, and starts many of her sentences with the word “so,” as if to ensure the listener understands the reason for the next lies within the cause of the former. “The last two and a half years,” she says, “we have reviewed over 1,300 opportunities, and started 14 programs, so our hit rate is about 1 in 100. So when 99 percent of your time is spent on something that ends up not as productive as you would like, you have to find a new way to do it.”
One new way at GSK of reviewing opportunities for pipeline bolstering is via a contest for academia-based scientists, called Discovery Fast Track. It is located organizationally under DPAc, but can and does draw on GSK expertise from anywhere within the company.
Everybody Loves A Contest
When the prize is assistance in moving concept-stage drug discovery projects through initial screening programs, maybe nobody likes a contest more than academia-based researchers. According to Huang, “the point is to get through that first half of drug discovery where you have new targets, and that entails doing HTS (high throughput screening). A major part of the prize is getting access to our entire chemical collection and all of our HTS technologies. We provide free advice and consulting from GSK scientists, who, by the way, are really excited about doing this.”
Huang says the number one feature when picking a winning program for Discovery Fast Track is the therapeutic hypothesis. “If there are some data that actually establish a casual relationship between the target and the human disease, that is our biggest driver,” she explains. “And then we factor in tractability, the personality of the academic, and whether or not we feel we can actually bring something to the table to solve the problem.”
The inaugural contest was held in 2013. “We did it in the U.S. and Canada first, because we understood contest law here better than anywhere else,” Huang says with a smile. This year’s contest – the application window has now closed – added the U.K. and Europe. Otherwise, Huang points out, “We are geography agnostic and disease area agnostic in our approach.”
I challenge Huang on whether GSK will select programs in therapeutic areas the company is not particularly interested. “Yes, we already have,” she replies. “How do you define “not interested”? Does GSK already have a sales staff selling a drug in this indication? It does not matter. It takes us 10 years to create a product, and any commercial analysis you do today will change, the environment will change. We have great flexibility.” Huang adds, “You know we just sold our oncology business to Novartis. But we are still doing some cancer drug discovery. Because if we could sell it to Novartis today, we can sell it to somebody else in ten years, right? So the real key is to create value.”
Huang attributes a bit more than the usual flexibility at GSK to the fact that her group (DPAc) is in a larger department called Alternative Discovery and Development. “We really are not restricted,” she emphasizes. “The philosophy is nobody wanted an iPhone until they made an iPhone. In this early space we have to have this kind of openness. I have a team of 22 seasoned scientists all of whom have been successful in drug discovery. They are biologists, medicinal chemists and pharmacologists. Everybody has complimentary skills and experience in different therapeutic areas, and really come at problem solving in very different ways.”
And The Winners Are
Huang’s team received about 140 initial, non-confidential applications in 2013. About a third of these made it through a review process that included an internal two-day, face-to-face roundtable discussion at GSK. Nineteen of the applicants were then invited to submit a more detailed, confidential submission and to spend a day at GSK. Finally, eight new projects were declared winners and taken on by GSK.
These initial winners have been announced and are published on the web (with the exception of one who decided to stay anonymous). Six of the eight initial screens have already been completed, and GSK is reviewing the results to determine whether to move any of these to a longer-term collaboration, which could last from three to five years, says Huang. (Note: We’ll learn more about what comes after the initial screening results in Part 2 of our interview with Huang.)
Picking winners in any contest is not easy. Huang says vital to Discovery Fast Track are the 50 or so scientists at GSK who evaluate all of the opportunities in “a blinded fashion so prior influence cannot be exerted.”
“We actually designed software to do this, and designed a program by which we evaluate each submission with a numerical metric,” Huang says. “We use dropdown menus to assign scores to different facets of the program. We don’t know yet whether this is any better than more qualitative measures, but we are doing everything possible to make this a pure analysis. We think combining the qualitative and quantitative is a work in progress, but it is getting us to an important unbiased approach.”
What program would Huang select to exemplify how Discovery Fast Track works?
“The great thing with DPAc overall is that we can get others from around the company to join in,” she starts. “For example, we have an academic who brought in a very intractable problem that involved a transcription factor, but we thought the program rationale was very strong. As we started to move this along, GSK’s nuclear receptor group at Research Triangle Park caught wind of it. They said it looks similar to what they were doing and wanted to take a look.” As a result, says Huang, “these world-class experts in nuclear hormone receptors applied their knowledge to this novel transcription factor and have done some incredible work with the academic investigator. Because we really are a transparent organization, this group at GSK actually found us, we didn’t ask them. Overall, I cannot think of a single negative interaction that has occurred.”
On the contestant side, 2013 winner Sarah Ades, Ph.D., associate professor of biochemistry and molecular biology at Pennsylvania State University, whose program is a novel approach for an anti-microbial agent class of antibiotic for gram negative bacteria, sums up her experience with Discovery Fast Track this way:
“The competition pushed me to think about my research in a different light. The experience made me think more and harder about incorporating approaches and answering questions that are more relevant to translational research. These approaches will enhance my basic science and help me move along the path from the lab to the clinic."
The expanded contest in 2014 has brought in nearly 500 applications. “We are pretty excited, we think there are some nuggets – some gems – in there,” says Huang. “What we will do over the next few months is pick and meet the finalists and figure out who we can take on.”
The Contest Leader
Huang started her career in 1990 at Merck as a senior research scientist. She then ran oncology discovery at GSK from 2001 to 2006, but got recruited back to Merck to do early oncology development, an area she didn’t know but wanted to learn. She then left pharma to cofound a company with three other people in Beijing (called BeiGene).
What did GSK say to bring her back to head this new idea to work with academia? “The enticement line I got was, ‘You can do anything you want with anyone you want anyway you want.’” She adds with a smile, “and my immediate response was there is no such subset.” Nonetheless, Huang says she understood the value and real willingness to approach academia to develop early discovery ideas, and took on the challenge. “The one great piece of advice I got in the beginning was ‘don’t align yourself with anyone, because you will never get anything done,’” she says. “To have this freedom, combined with great resources, is what a scientist needs to innovate. What more could you ask for?”
Editor’s Note: In Part 2 of our discussion with Pearl Huang, Ph.D., vice president and global head of GSK’s Discovery Partnerships with Academia (DPAc), we will indeed learn more about how GSK is working innovatively with academia.