By Dan Fost
To develop a new drug, or create a new diagnostic test or medical device, a scientist often needs a catalyst – something to spark the innovative idea that has the potential to change the way a disease is treated and improve patient outcomes.
In addition to a catalyst, the scientists themselves may need some synergistic sparks and help to get their discoveries out of the lab and into real products that can help patients. The Catalyst Awards program at UC San Francisco (UCSF) provides that boost, teaming scientists with advisors from industry who can help refine the experimental process and provide the expertise required to bring a product to market.
Now in its seventh year, the program showcased some of its most promising current projects in late January 2017 in Genentech Hall, including novel therapeutics that attack the problem of hearing loss, a device that could serve as a bio-artificial pancreas, a diagnostic tool to detect pathogens that are resistant to antimicrobials, and a digital application that could help elderly patients prepare for surgery, improving their chances of having a successful operation.
Each one of these and other projects owed its success to date on several factors: ambitious and creative UCSF scientists, clinicians and students looking to solve some vexing problems; Catalyst advisors from industry with the invaluable experience of having seen similar projects succeed and fail; and Catalyst funding that helped the project get off the ground and test its early hypotheses.
The key, participants say, is the network of experienced industry advisors: More than 200 people who generously give their time to help nurture promising projects.
Charles “Chaz” Langelier, MD, PhD, and his colleague Emily Crawford, PhD, presented their work on an antimicrobial-resistant diagnostic test. Langelier said advisors Greg Yap, MBA, a biotech entrepreneur, and Terry Wright, MD, who works in drug development for Genentech, proved invaluable.
“The meetings really made me realize the potential for how working with an industry partner could take an idea and translate it to improving patient care,” Langelier said. “I had not appreciated that at the same level before. That was exciting to really see our project progress in that direction.”
Langelier was grateful for the advisors’ time and expertise.
“I was really impressed by their dedication and their responsiveness to emails, and by the number of ideas that they would present in meetings,” he said. “What was most helpful was their ability to really find the key concepts that we needed to work on to translate our scientific methods into a viable diagnostic product.”
The advisors returned the compliment. “They are good learners. They took things on board,” Wright said. “It was a total delight working with them. They're smart, they're committed, and they're applying novel technology to a very important question. They’re running into some challenges for sure, but I think they're going in the right direction.”
Wright was especially helpful in having seen similar projects go awry.
“I have some relevant experience in how things have not been done well in the past, which serves as a guide to how you differentiate, how you are going to show clinical utility, what's a very good pathway, and what's commercialization,” she said.
Leadership Change
That’s exactly the sort of fruitful collaboration June Lee, MD, had in mind when she assumed the leadership of the program six years ago.
Lee had served in a fellowship at UCSF upon her graduation from medical school and then spent several years at Genentech, leading early clinical development efforts in attacking cardiovascular disease, respiratory ailments, infectious diseases, and other health problems. She sought to bring that industry expertise back to the academic setting.
“The idea behind this program was, we live in this incredibly rich life sciences ecosystem of the Bay Area that we weren't yet fully leveraging,” Lee said. “To do translational research in a meaningful way takes a multidisciplinary team effort. Some of those disciplines don't necessarily live in academic institutions. So the idea is to really bring what's missing here in from the outside, because they're all around us.”
Lee started by reaching out to her personal and professional contacts. She posed a question: “Can you help advise the projects that we think are good on what they need to do exactly to be considered fully translated?”
Nearly everyone she asked said yes, signing confidential disclosure agreements and promising to work pro bono. People were not just generous; they saw a chance to make an impact, and support the mission of UCSF.
From three dozen advisors that first year to more than 200 today, the program is ready to enter a new phase. Lee is now returning to industry as chief operating officer of South San Francisco’s MyoKardia, a clinical stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases.
Lee’s deputy and experienced drug discovery pharmacologist, Cathy Tralau-Stewart, PhD, associate director and head of the Catalyst program’s therapeutics track, has taken the reins as Catalyst’s interim director.
“June had a vision for building something, and she's achieved it,” Tralau-Stewart said. “She's built a mechanism that clearly supports early drug discoveries – and devices, and diagnostic and digital health tools – and moves them from predominantly NIH-funded labs to where they need to be from an industry and patient point of view.”
Tralau-Stewart said the program needs to increase its funding, and double down on the effort to make sure the scientists’ work bears fruit for patients. “In an academic environment, you will require funds for this translation of projects to patients.” Industrial expertise and mentorship is essential for these projects. However, potential partners and mentors frequently identify further required data and grant funding rarely covers this.”
But industry needs the innovation from academia to help fuel its product pipelines, and the two sides are working together better than ever.
“We are moving towards developing the required academic-industry partnerships to effectively move projects and products forward,” she said. “UCSF is gearing up to be a model of how to unite both groups and translate things. We need to get more of the groundbreaking science to a point where it changes our ability to improve patient lives. Catalyst is a really good foundation for this.”
Grateful Scientists
Sometimes scientists can be overly ambitious. Ian Seiple, PhD, an assistant professor of pharmacy, had ideas for combating what he said is becoming “the most imminent threat to human health right now”—antibacterial-resistant infections. He thought he could study several classes of antibiotics as a way to get started attacking the problem—and then he consulted his advisors, Sarah Lively, PhD, executive director, Site Head ChemPartner South San Francisco, and Gary Patou, MD, PhD, managing director at MPM Capital.
“They told me, correctly, that was way too broad of a scope, especially considering the one year timeline of the Catalyst Award,” Seiple said. So he scaled back his plans, honed his presentation, and showed tremendous progress. “They see drug development from a perspective that I have never seen before,” Seiple said.
Lively said the concept is relatively simple, even if the science is complex. “Often there are a lot of big ideas and academics are very enthusiastic about being able to do everything, and Ian in particular has a very broad platform,” she said. “When you look at translational research and think about bringing things to patients, you've really got to have a very targeted path forward and concentrate your efforts on the path of least resistance and the path of most success.”
Lively loved being able to help. “This is my first time” participating in Catalyst, she said. “I've only been very recently introduced to this program, and it's such a great opportunity to be exposed to lots of new science, lots of really exciting discoveries, and PIs (principal investigators) at UCSF who are really at the forefront of science.”
She counts Seiple high among those. “Ian was pretty awesome,” she said. “He doesn't need much guidance. He's very enthusiastic. He's incredibly ambitious. It's so great to have a small part in being able to help him.”
Al Chin, MD, a legend in the biotech arena who earned his medical degree at UCSF and has gone on to start five companies and develop products generating more than $3.2 billion in revenue, was part of the first group of industry players to sign on to Catalyst. “I started at the beginning of the program. It's just the idea of being able to help these students and professors get their ideas to market,” he said. “I'm constantly helping students get their way through designing medical devices and get things on the market, so they can really help the populace.”
Chin and Chris Jones, MSE, who consults with early stage medical device companies, advised a team of Elaine Tseng, MD, and Liang Ge, PhD, on their development of a removable and replaceable transcatheter aortic valve. “Chris and Al were phenomenal,” Tseng said. “They helped us break down a very ambitious product to smaller sections. That change was very pivotal for us.”
Like all of the Catalyst scientists, Tseng is trying to solve a serious health issue, even if it doesn’t show up in front page headlines. She said aortic stenosis affects 1.5 million people in the U.S., and its effects are severe for 300,000 of them. Half of those will die within three years.
The standard treatment has been a surgical aortic valve, or SAVR, but that’s being replaced by a transcatheter aortic valve, or TAVR, which doesn’t last as long as the SAVR. A SAVR can last 18-22 years, while half of TAVRs wear out in eight years, she said. “Our solution is a TAVR replacement,” she said.
While Tseng and Ge initially thought about coming up with a new device, Jones and Chin persuaded them to repurpose products already in existence. They narrowed their plans and came up with something they see as superior to both SAVR and current TAVRs. It won’t require open-heart surgery, as SAVR does, and it won’t create risks of coronary obstruction, as TAVR does.
“They were incredibly responsive to our advice and our feedback,” Jones said. “They modified their goals, allowing us to make suggestions and think about a hybrid approach that can get them in front of VCs and get people excited about the technology.”
Seeing a direct impact is one of the reasons Jones stays involved with Catalyst.
“We come in with the scar tissue of knowing what they want to see,” he said. “We can help fill in some of the gaps that go beyond the clinical science or the specific details of a design or a project, and help them communicate a glimpse of their idea. They get excited by filling in other pieces that eventually strategic acquirers are going to want to see.”
Jones can remember when he started, and he’s glad to provide his perspective to others who crave the advice.
“I have a network now,” he said. “I've been doing this for 25 years. It's fun to be able to integrate people into that network and share those contacts and see the excitement that comes from bringing these early ideas on farther downstream.”
The Catalyst program has also helped shape the career of Megan Sullivan, BSN, RN, a student pursuing a masters of translational medicine, a joint degree at UCSF and UC Berkeley. Sullivan is serving as a Catalyst Awards intern.
“I came into the program with so many interests,” Sullivan said. “I liked so many things, and I still do, but I narrowed it to really enjoying seeing the commercialization of early stage products. I'm in the digital health track. It really helps people go into the conversations they need to have, getting the scientists from Point A to Point B, getting them from an idea to a real product to actually help patients.”
She got so much out of the program. “It solidified my interest in innovation. How to get strategic partnerships, and learn what it takes to really understand your product, market it, and see where you go wrong, and learn how to innovate.”
Fall 2016 Catalyst Award winners
Dena Dubal, MD, PhD Brain Resilience: A New Approach to Treating Neurodegenerative Disease
Richard Fidler, RN, PhD, CRNA & Xiao Hu, PhD Develop SuperAlarm Front-End Clinical User Interface
Kim Kirkwood, MD & Charles, Craik, PhD Development of Fluorogenic Substrates for the Diagnosis of Pancreatic Cysts
Chaz Langelier, MD, PhD & Emily Crawford, PhD Precision Detection of Antimicrobial Resistant Respiratory Pathogens via Next Generation Sequencing
Hanmin Lee, MD SmartDerm Algorithm for Ulcer Risk Assessment (AURA): A Pressure Ulcer Risk Stratification Tool
Shuvo Roy, PhD An Intervascular Ultrafiltration-based Bioartificial Pancreas
Ian Seiple, PhD A Platform for the Synthesis of Antibiotics that Target Bacterial Ribosomes
Elliott Sherr, MD, PhD & Dylan Chan, MD, PhD A Novel Approach to the Treatment of Hearing Loss
Jeoung-Sook Shin, PhD Identification of a Small Molecule Inhibitor for Treatment of Asthma
Elaine Tseng, MD & Liang, Ge, PhD Development of a Removable and Replaceable Transcatheter Aortic Valve