Collaboration. Overused buzzword or key to the universe? Knowing its true impact likely lies somewhere in between, panelists in the SLAS2013 special session – "HTS and Early Drug Discovery in Industry and Academia. Collaboration: Is the Sum Greater Than the Two Parts?" – intend to ignite free-flowing debate about this important topic.
"Large pharma pioneered high-throughput screening (HTS) in the early ‘90s. The 2000s saw a rapid increase in investment in HTS as well as in corporate compound collection size, with many companies developing collections of 2-5 million entities. Driven by a desire to seek out novel tool molecules for neglected diseases and cutting-edge research, academic institutions developed their own HTS infrastructure in the early to mid 2000s and started to accumulate and screen their own libraries. In the latter half of the decade, the National Institutes of Health (NIH) initiated a significant translational research effort across multiple academic and federal institutes, in which HTS played a significant role."
- SLAS2013 Conference Program
Four panelists, two from academia and two from industry, or corporate laboratories, will share perspective and lead discussion at this special session at SLAS2013. They are:
Martyn Banks, Ph.D., Bristol-Myers Squibb, Wallingford, CT
Peter Hodder, Ph.D., Scripps Research Institute, Jupiter, FL
Ricardo Macarron, Ph.D., GlaxoSmithKline, Collegeville, PA
Barbara Slusher, Ph.D., Johns Hopkins University, Baltimore, MD
With 78 years of combined experience and with different perspectives on early drug discovery, the panelists seem to agree that effective collaboration must be optimized to reach the ultimate goal – discovering drugs that help patients worldwide. Panelists invite SLAS2013 participants to weigh in on this issue during the two-hour session, Monday, January 14, beginning at 3:00 p.m. ET.
For those unable to attend SLAS2013, January 12-16 in Orlando, "HTS and Early Drug Discovery in Industry and Academia. Collaboration: Is the Sum Greater Than the Two Parts?" will be broadcast online live with free access for SLAS members worldwide. Simply access the SLAS2013 website at 3:00 p.m. ET and follow the instructions. Also, panelists will accept questions via Twitter, time permitting. Be sure #SLAS2013 is in your tweet.
Following the January conference, the recorded broadcast is available free to SLAS members via SLAS On-Demand.
Banks is executive director Bristol-Myers Squibb (BMS) Research, Wallingford, CT, and has spent his entire 25-year career tackling early drug discovery, both in therapeutic areas as well as promoting lead discovery. Before joining BMS, he spent 12 years at GlaxoSmithKline. Banks' BMS role encompasses directing teams for compound management; cellular assay design, both building cell lines and cellular assays; lead discovery, mainly assay design, HTS and case assessment; lead profiling which is high-throughput ADME (absorption, distribution, metabolism and excretion) tox screening; and he manages a specialist team of laboratory automation experts.
He believes that the group assembled at SLAS2013 for this session can make a large leap in promoting increased collaboration between corporations and academia in HTS and early drug discovery.
"I've been to other sessions or conferences where everybody can come up with 500 reasons why we can't work together," he states. "What we are trying to achieve at SLAS2013 is to understand how we can work together – both in screening and early drug discovery to benefit everybody. I call this the ecology of drug discovery – where you have a partnership between pharma, biotech, government and academia all working together. We need to work through the challenges and issues of developing this complex network."
Among the challenges are paying attention to each collaborator's individual business model, ensuring that the legal framework is properly in place, respecting academic freedom and protecting innovative ideas, navigating how to share the risk and, of course, understanding the cultural aspects of each workplace.
"Over the years, I believe we have made great strides in overcoming trust and intellectual arrogance issues," he notes. "In the early days there were some very staid opinions. Academia saw pharma companies as cash cows to provide open grants that complemented their NIH grants. Pharma thought academia was not really interested in drugs to meet unmet medical needs; rather they were interested in publications and building their personal academic careers. What I'm seeing today is a lot more willingness to collaborate in early drug discovery."
Banks explains that the SLAS2013 special session does not just feature him, Hodder, Macarron and Slusher. Audience members will be encouraged to offer opinions and voice their thoughts on the different strengths corporate and academic scientists bring to partnerships, and on their understanding of the concept of pre-competitive space.
"It will be interesting to get SLAS2013 participant perspectives," Banks adds. "For example, pre-competitive space is sort of a nebulous term that varies from institution to institution. Some companies may consider a compound collection as pre-competitive, while others will say ‘we've put a lot of time, money and more importantly, intellectual energy into creating a compound collection that supports our drug discovery.' But maybe there are aspects that everybody agrees are pre-competitive and that's something we can work together on very quickly."
At the end of the session, Banks will summarize the ideas presented by the panelists and audience participants. The goal is to take big steps toward a better understanding of how to enter into productive partnerships.
"The idea is to provoke people to go back to their various institutions and discuss this with their peers so that they can then start working together. People are looking for, and want, good partnerships," he concludes.
Hodder, senior scientific director at The Scripps Research Institute, Jupiter, FL, is one of the SLAS2013 special session panelists who has worked in both corporate laboratories and academia. After obtaining his doctorate in chemistry from the University of Washington, he started as a laboratory scientist at Merck Research Laboratories, advancing to manager of robotics before Scripps recruited him to its Florida campus.
"I loved my tenure at Merck, but the Scripps position was new and offered more responsibility," Hodder explains. "Translational research was a buzzword back in 2005, and Scripps took the initiative to set up a translational research institute that combined the strengths of academia and industry-trained researchers. For my part, I acquired equipment, hired staff and set up the facilities to do assay development, high-throughput screening and post-HTS lead identification, and it's where I've been the last seven years."
The move allowed Hodder to be in on the ground floor of the nation's growing interest in combining the best resources from corporations and academia.
"NIH Director Elias A. Zerhouni supported the concept of translational research and created a new initiative, the Molecular Libraries Program (MLP), to catalyze discoveries that happen in academic labs across the nation," Hodder says. "The MLP has been successful in enabling scientists to discover molecules that pharmacologically modulate the activity of various biological pathways and targets, and develop these molecules further into clinically relevant compounds."
"This gets me excited, and Scripps is on the forefront of this sort of endeavor," he continues. "It has been a fantastic experience. The MLP made a lot of opportunities available to academic researchers to help them translate their discoveries – from developing assays and screening compound libraries, to getting access to medicinal chemistry, pharmacology and clinical or pre-clinical related processes. Most likely a result of the MLP, things have really changed significantly from a decade ago. Then you could probably count on two hands the number of academic drug discovery centers doing translational research. Now there are over a hundred of these around the world. Not coincidentally, several of these academic centers now have ongoing collaborative translational research efforts with biotechs and pharmaceutical companies."
For Hodder, the MLP is not over as it was for some when NIH undertook its evaluation of the program last year.
"Scripps was rated number one in that review for its productivity and impact of its translational research on human health," he shares. "The MLP is a termed program but that doesn't mean NIH-sponsored translational research is at an end. Quite the opposite. With the recent formation of the National Center for the Advancing Translational Sciences (NCATS), there are plenty of new opportunities made available through the NIH."
"Several of the probe molecules that have been discovered through the MLP (and the associated chemical and biological data), and now publicly available on PubChem, may provide the basis for novel therapeutics for major diseases, and for over 6,000 known rare and neglected diseases," noted G. Sitta Sittampalam, Ph.D., senior science officer of the NIH Therapeutics for Rare and Neglected Diseases (TRND) program in a story in SLAS Electronic Laboratory Neighborhood earlier this year. "The question is how to take this to the next level? This process requires expensive pre-clinical testing to translate these molecular probes into useful clinical candidates. There is no easy answer to this question."
Finding ways to take MLP to the next level is one of the reasons the SLAS2013 collaboration session is so timely.
"The MLP has been fantastic from my point of view for catalyzing an understanding of early drug discovery in academia," Hodder notes. "If you would have asked an academic researcher what a screen was 10 years ago, they might think it was something you watch TV on. But now, academics understand more fully and are savvy to how access to screening facilities can potentially provide them with a positive control for their in vitro experiments, or maybe even with a little luck and perseverance, develop compounds that are drug-like and can be tested in vivo.'"
In his SLAS2013 presentation, Hodder intends to highlight a few Scripps collaboration success stories.
• A Scripps patent with a compound derived from an MLP screening hit, was credited by Receptos, who announced in October 2012 "its selective sphingosine?1? phosphate receptor 1 (S1P1) modulator, RPC1063, has been administered to the first patient in a Phase 2/3 study. RPC01-201, a Phase 2/3 placebo-controlled (Phase 2) and active comparator-controlled (Phase 3) trial, is the first of two planned pivotal studies for RPC1063 in the indication of relapsing multiple sclerosis (RMS)."
• An HTS Instrumentation spinoff invented at Scripps, licensed to and now marketed by the Brooks Life Science Systems division of Brooks Automation.
"For me, collaborations between industry and academia have always been there," Hodder says. "At Merck, we would access the expertise of academia through healthy collaborations with academic labs. However, with the technologies academia now has, corporations are actually engaging us on a broader variety of research topics, including proof-of-concept experiments, screening campaigns or development of novel technologies. These activities would historically be done in-house, but they are just as happy to work collaboratively now.
"I never saw it as going over to the dark side when someone moved to academia to industry or vice-versa," he continues. "They both have something to offer. Take advantage of what your partner brings to the table and make sure things happen.
"It's all good," Hodder summarizes. "I'm very positive about this. I feel there is a great renaissance in drug discovery, and both academia and industry will benefit. Academia will benefit from the discipline and know-how of industry and industry will be able to more fully participate in the development of new ideas coming out of academia."
Also representing corporate laboratories is Macarron, vice president of worldwide sample management technologies, GlaxoSmithKline Research and Development, Collegeville, PA. Macarron has worked in pharmaceutical research with GSK since 1992, in drug discovery functional areas including natural product screening, lab automation, high-throughput screening, assay development and sample management.
"Collaboration between industry and academia is definitely an area of growing activity, and we have a lot of academic groups entering drug discovery and a lot of interest from pharma and biotech to cooperate with those groups," says Macarron. "I think we are still in the early days of clarifying the best model. We need to explore how to best make use of the strengths of different groups within this complex world of drug discovery."
During the SLAS2013 session, Macarron intends to help debunk some of the "urban myths" sometimes put forth by representatives of pharma or academia about the other by focusing on complementary strengths. For example, academia is well positioned to advance basic HTS science and disease biology, while pharma companies take the lead in commercial drug discovery and development. He'll cite published materials based on data, not opinions. For example in a Nature Reviews Drug Discovery 2011 manuscript, "U.S. Academic Drug Discovery," drug discovery scientists from academia recognize medicinal chemistry as a corporate strength and disease expertise as an academic strength as it relates to early-stage drug discovery.
Macarron also will reference the 2008 report from the Center for Medical Progress Manhattan Institute report, The Truth About Drug Innovation: Thirty-Five Summary Case Histories On Private Sector Contributions To Pharmaceutical Science, which explores the untested premise that "most of the scientific advances that yield new and improved medicines are the fruit of research financed or conducted by public agencies, the National Institutes of Health (NIH) foremost among them, rather than the pharmaceutical companies that produce and market them."
According to the report, "We find that, for the discovery and/or development of all or virtually all of the thirty-two drug classes discussed in Section III, the scientific contributions of the private sector were crucial; and the same is true for three drugs—Taxol, Epogen, and Gleevec—that have received widespread attention, as discussed in Section IV. All or almost all the drugs discussed below would not have been developed—or, at best, would have been delayed significantly—in the absence of private-sector scientific discoveries.
"This study does not dispute the importance of publicly funded research. Both NIH-sponsored and private-sector research are crucial for the advance of pharmaceutical science and the development of new and improved medicines. Research conducted at universities and government laboratories, often funded by the NIH or other government agencies, has been an indispensable component of the advance of pharmaceutical science and the development of new medicines."
Macarron agrees that many drugs on the market are the result of great collaborations between corporate laboratories and academia.
"The goal of this SLAS2013 session is to look for those nuggets of real opportunity for collaboration and invite richer dialog to develop the best framework for collaborative efforts moving forward," he says. "We are all trained in the same places, and we are all trying to help patients in the end. We can and should work together from both sides to make that happen in a more effective way."
To help identify key gaps in reaching optimum collaboration, Macarron will share some examples from industrial labs in this arena and invite the audience to share their experiences. He'll also encourage SLAS2013 participants to help set the right expectations with respect to drug discovery.
"Setting appropriate expectations is another area of learning for all. It is good to be optimistic but the ‘I'm smarter than the world and therefore my endeavor will be successful' must be stopped completely," he cautions. "You have to look at the stats. The slow process of drug discovery is not because people are stupid, but because it is a hard job to find drugs that work."
Slusher is an associate professor of neurology and psychiatry and the director of the Brain Science Institute (BSI) NeuroTranslational Drug Discovery Program at Johns Hopkins University, Baltimore, MD. Like Hodder, her career began in corporate laboratories.
"I have spent most of my career in pharma at various levels up to senior vice president of research and translational development working at both large and small companies including ICI Pharmaceuticals, Zeneca (now Astra-Zeneca), Guilford Pharmaceuticals, MGI Pharma and Eisai," Slusher explains. "In 2010 about the time Eisai acquired MGI Pharma and decided to move the research employees to Boston, Hopkins was initiating the Brain Science Institute and wanted to bring in a translational group that could help take the discoveries at Hopkins and turn them into drugs and therapeutics."
When hired by Hopkins for this new position, she was able to move 20 folks from corporate laboratories to her new team at Hopkins.
"I now run an academic team focused on drug discovery and it includes people with expertise in medicinal chemistry, animal pharmacology/toxicology, drug metabolism, pharmacokinetics, assay development – basically the same discovery team you'd have in industry," she explains. "We have already licensed out one of our programs, and we are in the midst of licensing out our second."
Having worked both in corporate and academic environments, she is excited about being part of the SLAS2013 special session to help to energize participants – and be energized by them – regarding this changing landscape in early drug discovery.
"I am going to hit on new ways of doing HTS that are collaborative between academia and pharma and will share an example from Hopkins," she says. "We recently signed an agreement with Eisai, where we will bring novel targets to them. They will screen using the chemical library at their company and then give the hits they identify through the HTS back, and we will do the chemistry and drug discovery to identify a clinical candidate. Eisai will have first rights to the project. I think this is an example of the way of the future. It takes advantage of what academia does well – identify new targets – and of what pharma does well – screening with their proprietary drug collection which is much larger and more diverse than what we have available to us in academia."
Slusher notes another change in drug discovery that is also fueling more early work being done in academic centers. She says that big pharma is decreasing its work on early drug discovery, especially in high-risk areas.
"Our group works in the central nervous system," she shares. "You have companies that have gotten completely out of this area internally and are searching for external collaborations and projects. The ecosystem is changing, and I am excited by how much interest there has been to collaborate with us."
And, of course, it is not just Johns Hopkins experiencing this explosion within early drug discovery. Slusher, along with four other academic center founders, have formed the Academic Drug Discovery Consortium whose mission "is to facilitate collaboration and exchange of knowledge amongst academic drug discovery scientists in order to accelerate the development of new therapeutics to enhance the lives of patients." The new ADD Consortium website will be going live in early 2013.
The consortium's objectives are to:
• Establish a network of academic drug discovery scientists and programs from around U.S.
• Exchange know how and expertise related to - drug discovery programs, technologies, faculty engagement, industry partnerships, contractual arrangements
• Create a central repository website of drug discovery center information
• Provide education and training for students and for universities interested in establishing centers
• Advocate/Advisory to NIH and other funding agencies
• Establish (bi)annual meeting and programs
"Over the last 10 years, we've gone from about a half dozen academic drug discovery centers to more than 100 centers in the United States," she says. "What we are doing here at Hopkins – academic drug discovery – is definitely on the rise. We are responsible for translating the basic science discoveries at Hopkins into new drug therapies. Most of the drug discovery steps – the synthesizing drugs, the testing, assay development, metabolic stability, pharmacokinetics – all of that drug discovery happens internally. But the professor whose project it is is involved all along the way. It is a very collaborative process."
Banks, Hodder, Macarron and Slusher all believe that the SLAS2013 special session on Monday, January 14, at 3:00 p.m. ET, is the right place to discuss corporate laboratory and academic collaboration in high-throughput screening in early drug discovery. With SLAS's rich and diverse membership and its proven track record of working together, the panelists feel the conversation generated at the session will fuel ongoing progress to find the very best framework to maximize ultimate success and ensure this difference is noticed by patients counting on research.
As Macarron so simply states, "we are all trying to help patients in the end."
December 21, 2012