UCSF Researchers Win Awards to Bring Treatments Out of Lab
By Dan Fost
Promising early stage research highlighted at Catalyst Awards Fall 2015 cycle final report out event.
It’s the sort of event that has become commonplace in Silicon Valley: Speaker after speaker gave the audience a 15-minute presentation, describing an innovation they’re working on and the unmet need they could help to address.
The speakers, however, were doctors and researchers from UC San Francisco (UCSF), many of them faculty looking to solve pernicious problems in medicine, from alcoholism to heart failure, from strokes to depression, from dry eye syndrome to kidney failure.
At the UCSF Catalyst Awards program’s report-out in Genentech Hall in late January, scientists from the Fall 2015 cycle showed their enthusiasm for finding insights in their labs and then turning those insights into innovations for patients, sometimes with the help of industry or venture capitalists.
Those industry experts were among the attendees at the ceremony. They have served as advisors to the scientists, hoping to find a solution not only effective at helping people lead healthier lives, but one that could also become a commercially viable product.
Take the idea of “an intelligent dipstick” developed in the lab of Michael Shlipak, MD, MPH, for instance. Shlipak, a professor of medicine, said 26 million Americans have kidney disease, at a cost of $50 billion a year to Medicare. “We really need to detect kidney disease earlier, while it is still reversible,” Shlipak told the audience. “Kidney diagnostics have not changed in 50 years. It’s an embarrassment.”
The device, which he is developing with Carmen Peralta, MD, MAS, associate professor of medicine, would work much like a pregnancy test, dipping a simple disposable plastic strip into a urine sample. The dipstick would look for biomarkers that appear in urine at the very onset of the disease. Shlipak proposes a prototype for HIV patients first, who often use a medication which can be kidney-toxic in some people. The dipstick could identify those people early on, allowing them to switch to a safer, albeit significantly more expensive, drug. This approach Shlipak noted, could save payers $20,000 in medication costs alone per patient per year – to say nothing of the health benefits.
Another technology, from the laboratory of Kamran Atabai, MD, assistant professor of medicine, and presented by Donald McCarthy, PhD, a postdoctoral fellow, was a therapeutic approach to treat malabsorption conditions, such as short bowel syndrome (SBS), via an orally delivered protein found in milk fat globules. SBS is a rare but devastating condition, affecting 15,000 patients worldwide. How impactful would an oral therapy be on quality of life when the standard of care is intravenous feeding, with high morbidity and mortality, and costs of $500,000 per year per patient? In addition to asking questions about promising preclinical data, the industry experts asked about the scientists’ intellectual property position, their manufacturing plans, and the design of clinical trials to ensure that the idea would translate into therapy.
The questions highlighted one of the strengths of the Catalyst Awards program: the involvement of industry advisors, who come from academia, private industry, law, and venture capital. The program has more than 200 people on its advisory panel, according to June Lee, MD, director of Catalyst at the UCSF Clinical and Translational Science Institute (CTSI), so it is able to pair advisors with projects that fit their area of expertise. Lee said Catalyst, now in its fifth year, has supported more than 100 projects, with mentorship and funding, and brought a 11-fold return on investment in ‘follow-on funding” to the program’s participants.
The awards are funded by CTSI’s grant from the National Center for Advancing Translational Science (NIH-NCATS) and by donations and collaborations with industry partners, said Cathy Tralau-Stewart, PhD, associate director and head of the Catalyst program’s therapeutics track. “Our experts help us choose promising projects and advance them as efficiently as possible by directly mentoring the teams,” she said. “We are using the life sciences and technology ecosystem of Silicon Valley to build products people need.”
Many investors jump at the chance to get involved, in the hopes that they might uncover the next big thing. “I get excited about this stage of science,” said Cameron Wheeler, PhD, a principal with Deerfield, a health care investing firm focused on advancing healthcare through investment information and philanthropy. “This is like a buffet of some of the best things that come out of UCSF and creates the opportunity to really advance healthcare.”
The event opened with an inspirational keynote from KR Sridhar, the co-founder and CEO of Bloom Energy, which develops power generation systems with fuel cell technology rooted in NASA’s Mars program. Although it may seem unconventional to have a clean energy entrepreneur addressing people in health sciences, Lee noted Sridhar has achieved the dream of many Catalyst participants – making an impact on the world we live in – but in Sridhar’s case, by choosing to make the leap from academia to become a successful entrepreneur. [Watch on Youtube]
“In my case, I felt I could make bigger impact outside of academia,” he said, so he took the big risk and started Bloom. “If I didn’t do it, I would regret it when I was older. You may come to a different answer than I did. There is no right or wrong one.”
The awards highlight innovations in four areas: therapeutics, diagnostics, devices and digital health. With the Shlipak’s dipstick serving as an example of a diagnostic technology, examples of the others include:
Therapeutics: Alan Verkman, MD, PhD, professor of medicine, worked with two of the finalists, ophthalmologist Marc Levin, MD, PhD, and research specialist Onur Cil, MD, PhD. Levin and Cil are seeking solutions to vastly different problems by developing therapeutics with similar mechanisms – Levin is focused on dry eyes, while Cil takes aim at constipation. Yet both involve the protein CFTR, mutations in which most famously cause cystic fibrosis, but which is also involved in fluid secretion in many tissues in its normal form. Both scientists tested different small-molecule CFTR activators in mice and showed promising results: Levin observes increased tear volume that alleviates dry eye pathology in mice treated with the agents and Cil sees increased intestinal fluid secretion in models of constipation.
“It is one of the great unmet needs in eye therapeutics,” Levin said of dry eye disorders, including Sjögren’s syndrome. Over-the-counter eye drops are a “band-aid,” he said. “No one has addressed the underlying cause. Our strategy is unique as it more directly targeting the problem of dessication. All of that is borne out of work I did as a UCSF graduate student. Now that I am in a position as faculty to develop a therapeutics program, and with support from Catalyst, it has taken off.” Levin has received a Catalyst award in the past, which allowed him to generate lead molecules and do preliminary proof-of-concept studies.
Cil, meanwhile, said constipation affects 42 million Americans, with $7 billion in health care costs, primarily on laxatives. “Despite the variety of treatment options, there is limited efficacy of approved drugs,” he said. Together, Verkman, Levin,and Cil filed three patent applications in December and are planning follow-on studies.
Devices: Insoo Suh, MD, assistant professor of surgery, together with surgery resident Isabelle Chumfong, MD, and Sachin Rangarajan, staff engineer, showed a device inspired by an obscure sea creature, the lamprey. The team cited their mentor, Orlo Clark, MD, professor emeritus of surgery, for the original concept. Instead of pinching organs and cancerous tumors, as the common tools now do, this tissue-grasping device would use suction for a more gentle grasp, leading to far fewer accidents involving tissue damage or tumor spillage in laparoscopic surgery. “It’s important to surgeons that the grasper can move from one tissue type to another and push things out of its way without causing tissue trauma,” Chumfong said. The team brought a prototype that people could touch, and many attendees tried their hand at the lamprey after the presentation.
Digital Health: The prevalence of smart phones and tablets has inspired several groups to develop apps that could have a major impact on how certain conditions are managed, from depression to premature baby care. Digital health products also could help health professionals. MissionControl Stroke, developed by Anthony Kim, MD, MPH, MS, takes aim at the millions of brain cells lost every second once a patient has a stroke. A dashboard that every responder has access to – nurses, pharmacists, lab techs and doctors – could make sure everyone is on the same page and has up-to-date information about the patient’s status without having to call or page multiple stakeholders, Kim said. “We get ‘time to burger’ information in a fast food restaurant that’s more sophisticated than ‘time to treatment’ for a stroke victim,” Kim pointed out. Saving 30 minutes in door-to-treatment time, he said, would result in significantly better outcomes for patients, and save millions of dollars in long-term health care.
At the reception following the presentations, both the presenters and industry advisors agreed: Catalyst represents an exciting and effective way to translate basic academic research into products with real patient benefit and commercial viability.