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Cathy Tralau-Stewart: Creating the Secret Sauce for Translational Science

With 25-plus years of drug discovery experience spanning both industry and academia, Cathy Tralau-Stewart could write a book about the meticulous work required for a drug compound to progress through the pipeline. In her role at UCSF’s Catalyst Program, she unites various collaborators to keep breakthrough science in motion.

“I wanted to bring the orchestrated drug discovery effort that one finds in industry into academic settings,” says SLAS Board Member Cathy Tralau-Stewart, Ph.D. “How you blend academia, industry and other funders together makes great science move forward – it’s the secret sauce.”

In her 20 years with GlaxoSmithKline (GSK), Tralau-Stewart worked with and witnessed more drug development projects than most people see in a lifetime. She immersed herself in research development and built her acumen in the commercialization process because of experiences she had during her Ph.D. program at the University College London.

“I was fortunate coming out of graduate school to secure a position in which I could work and pursue my Ph.D.,” she explains. “The mix of working in the hospital lab environment, caring for patients in the clinic and seeing their struggle drove me to pursue science that improved patient outcomes.”

During this program, Tralau-Stewart worked with a cancer drug that successfully reduced large tumors and led her to an important realization, “that the drug wouldn’t progress into wider patient populations because the data was published prior to patenting. A patent would therefore not be securable,” she says. “To get funding to progress, a drug discovery project will probably require the protection of a filed or approved provisional patent application for investors or partners to be interested to take it forward. No patent, no funding. No funding, no progress.”

This realization led her from academia into the pharma industry, specifically to GSK, “where I learned what it takes to develop a drug and get it to patients,” she says. “GSK was a tremendous learning ground for me and it was there that I learned my trade in the drug discovery and commercialization process.”

One of the drug discovery teams she worked with developed the corticosteroid nasal spray Flonase. “I was a very junior person at that point,” recalls Tralau-Stewart, “and seeing chemists, medicinal chemists, pharmacokineticists and biologists with different skill sets working on a united goal to deliver this drug to patients made a tremendous impact on me. I now try to re-create these multi-disciplinary teams as a key part of the academic-industry alliances we are developing.”

Drug Discovery in Academic Settings

Since moving from GSK into academia 11 years ago, Tralau-Stewart’s talents helped build two successful initiatives – a drug discovery center at Imperial College London and her current post in the Catalyst program, a research accelerator housed at University of California, San Francisco’s (UCSF), UCSF Innovation Ventures group. The Catalyst program fosters academic and industry collaborations as well as enhances education in early translational research and entrepreneurship to increase the speed and success of translating research into products with clinical impact through funding, mentorship and identification of resources.

The UCSF Catalyst program enjoys the contributed talents of a wealth of local industry people “who are happy to give their time to support the development of academic projects. They all come to us as volunteers and this is what makes the difference. We’re lucky to have an excellent advisory panel,” Tralau-Stewart says.

“On the whole, most of the expertise required to take a drug target from an early lab position to a clinical trial is sitting in industry in contract research organizations (CROs), biotechs and pharma. Catalyst brings in this outside industry expertise and focuses it on the problems of advancing a particular academic project,” she continues. “Collaboration plays a major role in enabling academic projects to get funded as well as to achieve access to expertise and capabilities from an industry point of view, which is very different from how an academic may look at science.”

Some of Catalyst's success stories include facilitating licensing agreements such as one announced in March 2017 between Vanda Pharmaceuticals Inc. and UCSF researchers to develop and commercialize a portfolio of cystic fibrosis transmembrane conductance regulator (CFTR) activators and inhibitors. Vanda will pay $1 million, and as much as $46 million in potential development, regulatory and sales milestones as well as royalties on net sales should a product be commercialized from the UCSF portfolio of compounds. Created in the laboratory of Alan S. Verkman, M.D., Ph.D., the compounds are at a pre-investigational new drug (IND) stage where in addition to ongoing chemistry optimization work, several lead compounds have been identified which are ready for further IND-enabling work.

Another success story is that of Scott Baraban, Ph.D., a professor of neurological surgery whose work with the efficacy of testing certain drugs in zebrafish led to success in a clinical trial. In that trial, children with Dravet syndrome, a rare and devastating genetic form of epilepsy that can cause hundreds of seizures per day, responded to the same medication that tested well in zebrafish.

Catalyst has even offered guidance and support in the start up of biotechnology companies, such as ViewPoint Therapeutics. Established in 2014 by UCSF’s Jason E. Gestwicki, Ph.D., and his former student Leah Makley, Ph.D., ViewPoint is expanding the UCSF team's scientific discovery that transformed into a promising treatment for presbyopia and cataracts, leading causes of vision loss and blindness worldwide.

“My absolute intention is to be involved with more compounds that turn into drugs that help patients,” says Tralau-Stewart, who describes these successes as the most exciting part of her role in Catalyst. “It is definitely my inspiration.”

But, she says there is more to be done. To bolster efforts and share resources for all of UC’s five medical center campuses — Davis, Irvine, Los Angeles, San Diego and San Francisco – Tralau-Stewart is Principal Investigator in the newly created University of California Drug Discovery Consortium, a plan to work together to speed and increase development of a range of drugs to help patients.

“This is the first time that all five UC medical centers have come together in this type of effort,” says Tralau-Stewart, who is the principal investigator on a $2.0 million, three-year grant from UC’s Multicampus Research Programs and Initiatives. The grant to the Drug, Device, Discovery and Development workgroup of UC Biomedical Research Acceleration, Integration and Development (BRAID) is helping to get the consortium off the ground. “Similar to what we do within Catalyst at UCSF, the consortium will bring in industry and funding to drive early projects from throughout the state, answer key questions and develop new drugs to benefit patients sooner,” she says.

The Hard Work of Commercializing Science

Her work at Catalyst must also address issues that negatively impact or even kill projects, which doesn’t often happen in academia. “We tell our researchers if their work doesn’t look like a development project. It’s challenging sometimes to do that, but it’s an important part of it,” says Tralau-Stewart.

Part of what kills projects, as she noted earlier, is the issue of patenting. “An awful lot of innovative science never gets commercialized. It gets trapped in publications because it hasn’t been protected beforehand. That stops the progression of a particular asset,” she continues.

“The key is for researchers to discuss their work with their technology transfer office prior to any public disclosures, presentations or publications. Their technology transfer office can help to decide if patents should be filed to protect intellectual property that includes compound structures, assay protocols, prototype design, etc.”

The Catalyst program ensures that any part of a project that’s patentable is protected. “We secure this protection before it’s published or before the academic shares information during a conference,” Tralau-Stewart says. “You can’t inhibit academics from presenting their achievements at conferences and in publications because that’s what their end-point metrics are.

“However, there is a tremendous naiveté regarding patents in academia,” she continues. “Some researchers can’t imagine that giving a presentation at a scientific conference or having a small open discussion about their research can stop them from being able to patent their discoveries. It’s a fundamental issue and often bypasses academics who haven’t worked within the industry space before.”

What is certain is that translational science requires different, innovative approaches. “If one aspect of research doesn’t work, then change it and find another way around that obstacle,” Tralau-Stewart continues. “It is about having a passion to achieve something useful for society.”

She describes how teams of researchers during her time at GSK navigated obstacles to achieve success. “We created this drug, mepolizumab, the anti-interleukin-5 monoclonal antibody for asthma to reduce eosinophils, but it failed in a clinical trial because it didn’t actually help the patients’ symptoms. It was put to bed for a couple of years,” Tralau-Stewart says. “Then another GSK team worked on it, and it’s now marketed to people with eosinophilic esophagitis, a chronic allergic/immune condition in which a person has inflammation of the esophagus. The mechanism piece was still quite helpful to other diseases, so it was repurposed and marketed in a new space.

“Life sciences research and discovery are not very efficient at repurposing drug candidates, but we keep trying,” Tralau-Stewart observes. “I think there is huge potential for repurposed compounds. The challenge is that your patents are not very strong when they are repurposed for other indications. You can get use patents, but they are weaker, making it hard to get investor’s interest to raise money to move it forward.”

She adds that these patents are more based around use in a new indication. “It is possible to get market exclusivity for the product in the particular use; however this is limited to three years versus five years for a New Chemical Entity. If is repurposed for an orphan indication, one can get a seven-year market exclusivity in the U.S.,” Tralau-Stewart explains. “Clearly, these do still offer protection but it is easier for competitors to find ways around them. The strongest intellectual property (IP) position is related to Composition of Matter IP where the actual structure of the drug is protected by a patent. Most pharma companies would rather make a different molecule for the molecular target which has been revealed by the repurposed drug to be important in a new indication. They learn from that molecule, but then they make a different molecule so that they can patent the new molecule and space around it more broadly and not specifically for that indication alone.”

Passion and persistence frequently emerge as topics when Tralau-Stewart discusses her career, which spans therapeutic areas that include oncology, inflammation, respiratory, allergy, cardiovascular and infection.

“I’m very much someone who followed my passion for science. My excitement about what could be achieved was kindled by great teachers,” says Tralau Stewart, who remembers an early chemistry teacher who inspired her in high school. “I think that’s the main goal to succeeding in this profession: seek out great professors, mentors and collaborators. They provide the inspiration you need to sustain your persistence.”

Time to Connect

A move to the U.S. five years ago from her native England launched Tralau-Stewart into what she calls “the work-focused California lifestyle,” which suits her ambitions and those of her husband, Craig Stewart, who is vice president, product, of a software integration company. The only downside is that their two adult children are still in the U.K., one studying philosophy of law at Oxford, the other working as a junior doctor in the National Health Service (NHS). “They are working hard and we get together when we can,” she says, adding “They definitely inspire my work; I’m a very proud mother.”

Her other loves include exploring the beautiful, sweeping California beaches and reading. The amateur British historian enjoys books about medieval British history, the formation of crown and country and how it shapes the politics of the day.

As expected, her reading list also includes a lot of science, and she highly recommends Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions, a book by Richard Harris, a veteran science correspondent for National Public Radio and a moderator for the SLAS2017 panel discussion, Whose Responsibility is Research Reproducibility?”

“Harris’ book provides a great description of the challenges life sciences researchers face. Reproducibility is an important issue in trying to drive projects forward,” Tralau-Stewart says. “The biggest problem with academic and other research failing when you try to develop it is that you just can’t reproduce the data. It’s a big issue.”

Moving into the second year of her three-year term on the SLAS Board of Directors, Tralau-Stewart anticipates expanding the role of academia in the Society thanks to forward-thinking programs such as SLAS Ignite, a series that fosters scientific innovation through collaboration. As SLAS2018, the SLAS Ignite Academic Theater premiers in the new Exhibition Theater, allowing academic researchers to showcase their capabilities and latest research before a diverse audience of prospective collaborative partners with the goal of formalizing research partnerships.

“I would hope that initiatives such as SLAS Ignite assure academics that SLAS is a good home for technology development,” Tralau-Stewart says. “When one attends the SLAS International Conference and Exhibition, for example, it’s quite clear that it offers a much broader spectrum than just the technology around high-throughput screening,” Tralau-Stewart notes. “We need academia to see that SLAS is a place to interact with industry.”

December 11, 2017