MUSC News Center
Innovative drug discovery model aims to accelerate cures
Dawn Brazell | MUSC News Center | April 27, 2015
|Karen Lackey, director of the S.C. Center for Therapeutic Discovery and Development, is trying out a new model to find faster methods of drug discovery and is excited that early signs show it's working.|
When you have a disease with no good treatment, the next logical question is: What is the next experimental procedure or drug in the pipeline that might help?
That’s certainly the question that preys on the mind of Karen Lackey, who was recruited to the Medical University of South Carolina in 2014 to head up MUSC’s South Carolina Center for Therapeutic Discovery and Development. The recruitment already is paying off with the recent announcement that Aeterna Zentaris, Inc., of Canada has agreed to transfer its drug discovery library of about 100,000 unique compounds valued from $5 to $15 million to the center.
Another major contract with an industry partner is expected to be announced soon. Lackey smiles, savoring the moment. It’s a sign that what MUSC set out to do is working and that she’s on track with the driving call in her life.
“My mission is to increase the success rate of drug discovery. The reason I am here is that I believe there is a better way to do drug discovery. I spent most of my career in the pharmaceutical industry, and I know exactly what they are doing - all too well,” said Lackey, who comes to MUSC as an accomplished pharmaceutical research and development executive who has served in top positions at Hoffman La Roche and GlaxoSmithKline.
“And then you come to a university and you see tons and tons of potential, and people really don't know how to do drug discovery. My entire mission is to say if we could take the best of both of these worlds and integrate them - that's all I care about. There’s not even a brain cell in my head that thinks about royalties.”
That’s not to say Lackey is naïve. She knows research takes money and that governmental funding is limited. Her goal is to find new funding streams. “You can’t go knocking on the door of government all the time.”
Before she took on her MUSC position, she talked to multiple colleagues who were setting up drug discovery centers at a variety of academic centers and found most were using mini-pharma models. She knew when she arrived, she wasn’t interested in doing what had been done before. She wanted to create a new model that would work within the culture of an academic medical research center that would appeal to its scientists and clinicians and also to potential industry partners.
“Our model is unproven, untested, and innovative, and most people wonder how we will do it, but now we have two alliances, and so clearly something we are doing is working. I believe in this adaptive learning process where every time we have a potential partner come, we listen to every piece of feedback and take action.”
Generally, drug discovery takes anywhere from 11 to 24 years, but that’s not the scariest part. Ninety percent of novel medicines fail in the clinic for efficacy. In other words, the right target is not being used in the right patient population, she said.
“We've been doing drug discovery for 50 to 60 years, and we are stuck. Instead of going on this linear path of taking 11 to 24 years to validate a concept, I just really think we have to try something new.”
Take patients who have lupus, for example. “The patients who don't have a drug, i.e., lupus, they have nothing. I want to work on lupus. Knowing that 90 percent of what you put into clinical trial will fail due to efficacy is criminal.”
There’s no way to short circuit the arduous process, both involving time and money, of getting compounds proven to be on target and safe. The goal is not to shorten the process as much as it is to improve the success rate. That means better collaboration. “If you changed the 90 percent failure to 80 percent, that is huge.”
Her dream: To have the best minds and expertise delivering effective medicines so that business administrators can sit around the table figuring out what the royalties are because they have something that works rather than energy being expended on a process that keeps failing.
Her idea is a push-pull model that capitalizes on the trending medical movement of team science that aims to break down silos and use expertise from a wide range of areas. One way to support this within MUSC is the establishment of a virtual huddle - a private, online virtual space where clinicians and researchers can log project ideas with the goal of generating discussions and potential research collaborations.
There will be components in that huddle space designated for the aspects needed to make a project successful. Projects with more of those spaces filled in will rise to the top as potential candidates to pitch to pharmaceutical companies, based on their interests. MUSC faculty also can proceed on their own through traditional channels. It can be a powerful springboard for younger faculty to jumpstart their research projects, as well, she said.
“The idea is that we have this portfolio of project opportunities - pieces that come together in a perfect collaboration for a drug discovery opportunity.”
Interestingly, there now are National Institutes of Health grants that encourage industrial-academic partnerships, opening another stream of possible funding. Academic researchers also have the pull of industry to give them more momentum for their projects.
“With a strategic alliance, in addition to having the push with the researchers with their ideas, you have the pull from the company side that wants to commercialize the product. That push-pull feels like you have the continuum that goes all the way from basic research to the clinic that is often missing.”
Take the recent agreement with Aeterna Zentaris, she said. It represents the beginning of an exciting long-term relationship.
The company is transferring ownership of its compound library entirely to MUSC to form a strategic alliance with special emphasis in potential treatments in the areas of oncology, neurology, endocrinology and women’s health. MUSC, as one of its goals, is to provide Aeterna with at least 10 development candidates over 10 years starting in 2018. Aeterna will have the right of first refusal to license any of those candidates. MUSC will own any therapeutic compounds it discovers outside of the company’s areas of interest.
The agreement includes royalty payments for any ideas that are commercialized, depending on the role each one plays in the development process and what areas of therapeutic interest may be involved. The deal lets each entity focus on its strengths, Lackey said.
"Aeterna Zentaris gives us an awesome asset because lots of the compounds in the collection are drug-like and patentable. Most of the compounds that universities typically have access to are commercially available, so there are rarely IP (intellectual property) protections.”
Yuri Peterson, Ph.D., an expert in computational chemistry and data management and an assistant professor of Drug Discovery & Biomedical Sciences who will be overseeing the compound library, said the alliance is a huge step forward in solidifying the S.C. Center for Therapeutic Discovery and Development and realizing modern drug discovery at MUSC. Read his Q & A here.
“We now have a large, extremely high-quality and diverse set of propriety compounds and Aeterna Zentaris’ proven expertise in the field of drug development,” he said. “This puts MUSC scientists on a direct path to developing therapeutics for oncology, endocrinology and women's health for use in the clinic. This will truly facilitate our mission of bench to bedside or translational medicine.”
Lackey said Aeterna Zentaris can scale back on its in-house research-and-development program, and MUSC health professionals, who have a front row seat in working with patients and doing innovative research, get access to a high-quality compound collection that will significantly increase opportunities to find new medicines.
“Where MUSC excels is in its ongoing research in basic, translational, and clinical sciences and in its focus on understanding disease processes.”
It’s a win-win agreement, said Lackey.
There’s also an economic benefit. Aeterna announced last year that it would establish its North American business and global commercial hub in the Charleston region and part of that decision was based on MUSC, she said. The company’s local operation is based in the new S.C. Research Authority building in Summerville.
“This is something that Charleston as a community should be paying attention to because MUSC has amazing opportunities in making an impact in patient care, whether in devices or in therapeutic agents.”
Calling drug discovery a very tricky business, Lackey said the hardest part is pulling the components together because the groups need to focus on the target they want to modulate and the way they want to modulate it so that it works and is safe in a patient population. She has high hopes for the model being developed at MUSC and looks forward to many other industry partnerships to expedite the process.
“Think about it. You take a pill, you swallow it, and you expect that pill to ignore everything else and go exactly where it needs to go and work its business and then get out cleanly without touching anything on its way out. There are a lot of factors involved to prove that you can do that,” she said.
“That's why I think that it's the partnership with pharma and all their platforms and ability to push projects through that has to happen, but you really need that deep understanding of the pathology at each and every point and that's what we bring.”