Converting Ideas to Products: Catalyst Pairs UCSF Scientists with Business to Improve Clinical Outcome for Patients

By Dan Fost

It’s great to have success, whether in science or in business, but sometimes failure is even better.

“The colossal failures are where I learn the most,” serial biotech entrepreneur Nathaniel “Ned” David, PhD, told the UCSF scientific community during his inspiring keynote prior to the Catalyst Report Out in June. The Catalyst program pairs the University’s researchers with industry experts, venture capitalists and others who can advise them on how to advance their ideas towards products eventually forming companies or licensing their technologies to established companies to bring their therapies, diagnostics devices and digital health solutions to market. 

With degrees from UC Berkeley and Harvard, David has founded five companies, raising $1.5 billion and employing 400 people in total. His latest venture is Unity Biotechnology, which designs therapeutics aimed at preventing, halting or reversing the diseases associated with aging. He’s had other successful companies, including Syrrx and Kythera Biopharmaceuticals, but he said he prefers to talk about the failures.

“We try to fail early, so we don’t waste our time and money later on projects that never should have made it out of the crib,” David said. 

As such, he advised scientists against taking their ideas out of the University before the concept has been rigorously tested. “Bringing something out of the academic setting too early is damaging to the science, damaging to the founders and damaging to the University,” he said. Watch video.

That concept fits neatly with one espoused by UCSF’s Harold E. “Barry” Selick, PhD, who re-joined the University in April as its first vice chancellor for business development, innovation and partnerships. Selick aims to start a fund, with philanthropic dollars, to keep innovations in-house at UCSF longer, so that when they are licensed, there’s a higher likelihood that they’ll work, and investors will pay UCSF more for the technology.

Selick was a daylong attendee at Catalyst’s Report Out, at which UCSF scientists told of their work with industry advisors in honing their ideas into something that could eventually go to market. Selick’s purview at UCSF includes Catalyst.

“Catalyst is actually the front end of a process to convert ideas to inventions, to licenses for companies,” Selick said. “It’s the front end at which inventors can meet with experienced drug developers as well as entrepreneurs and get guidance on how to build a development plan and defend a commercial strategy.”

New Skills for Scientists

Those skills aren’t always innate in scientists and clinicians. They didn’t take courses in entrepreneurship on their way to their PhD or MD. Scientists at the June event praised the program and their advisors for bringing them new skills.

“I've never done a pitch before,” said Karin Gaensler, MD, who is trying to come up with a next-generation autologous immunotherapy that could help fight leukemia. With the help of her advisor Sam Wu, MD, PhD, and with Catalyst’s program director for devices and therapeutics, Roopa Ramamoorthi, PhD, and program intern Terri Lee, Gaensler felt like she had “a tribe.” “They all jumped in with both feet,” she said.

“I didn't know what a target profile was,” Gaensler said. “I had no idea how to set up for any of this. They were all really helpful. It was an utterly positive experience.”

Gaensler was among several first-time participants in the Catalyst program, which is part of Selick’s new UCSF Innovation Ventures Organization.

“Sam was instructive, effective, and very patient,” Gaensler said. He taught her “how to tell the story. What the story needs to be. I was really learning a vocabulary that I didn't know.”

As a clinician, Gaensler’s story was more powerful than most. “I've said goodbye to far too many patients with leukemia,” she said. In her talk, she called the therapy she’s working on “an unmet need very near and dear to my heart.”

Her project, which she calls Trileukevax, is already showing promise in mice and in human leukemia cells. Her hope is to come up with a therapy that causes fewer adverse effects than current standard of care, that can be administered on an outpatient basis, would double the median survival rate, and would be cost-effective. “This gives us a really powerful new strategy for therapeutics for patients who have very few options,” she said, “and those options are very toxic.”

Her advisor Wu, a managing director at Acuris Partners, said he works with Catalyst in part because he loves to see cutting edge new technologies, but also because he views his work as “giving back.”

“It’s a way of helping potential entrepreneurs create a more thriving local ecosystem,” he said.

Nadav Ahituv, PhD, working with his postdoc Navneet Matharu, PhD, also presented in Catalyst’s Therapeutics track. Their idea: Use CRISPR activation (CRISPRa) along with adeno-associated virus (AAV) to combat autosomal dominant polycystic kidney disease (ADPKD), the most frequent hereditary kidney disorder, affecting 12.5 million people worldwide.

The promise of CRISPRa is such that, Matharu said, if their theory pans out, the therapy could be applicable to dozens of other diseases, including some forms of cancer.

“Researchers like us live in a bubble with our ideas and technology,” Matharu said. “Now thanks to Catalyst we can look forward.” 

“When the Catalyst team, heard about us, they said, ‘Why don’t you take this to the next level?’” she said. “The next level for us is getting many companies to invest in this technology, to try to amplify this idea and let it catch on in the market.”

“We as researchers are not trained as entrepreneurs, not at all,” she said. “It's not our training. Catalyst bridges that gap between researchers and business. San Francisco has benefited from a lot of bridges, like the Bay Bridge and the Golden Gate Bridge. I think the work of Catalyst is of immense importance, bridging the gap between skills and experience.”

New Advisors Bring Diverse Experience

Some advisors like Sam Wu have been with Catalyst almost since the program’s beginning (Wu started in 2012, two years after its founding) while other industry veterans marked their first Report Out event as advisors. Not all come from pure business backgrounds.

Isabel Elaine Allen, PhD, a professor of biostatistics and epidemiology and a mentor in QB3 at UCSF, as well as an emeritus professor of statistics and entrepreneurship at Babson College, consults in several industries. She advised two teams of UCSF scientists presenting digital health projects in June.

“I love seeing a person's idea move to a viable company idea,” Allen said.

She was particularly impressed with the variety of projects at Catalyst. “We had two projects, and they were both in digital health, and yet they were miles apart,” she said.

One was an effort by radiation oncologists Gilmer Valdes, PhD, and Timothy Salberg, PhD, to bring physician review to machine-learning algorithms, preventing high-risk decisions to be made solely by computers. The other, from dermatologist Maria Wei, MD, PhD, proposed using a predictive algorithm and neural networks to screen for melanoma, the most common and deadliest skin cancer. 

Valdes gushed enthusiastically about the value of working with Allen and investment professional Rick Beberman, MBA, MAcc. “When we started, we had no idea of our business model at all,” Valdes said. “Working with them, they defined our vision, validating all our operations. I had the idea in my head before going through this process. They really defined how we're going to keep going forward with this technology.”

“This has been great training for me,” Valdes said. “I would recommend this experience to anyone.”

Valdes presented his proposal on “Mediforests”. The concept is that machine-learning algorithms, while valuable, need to be interpretable by doctors to ensure accuracy. They described a case where a neural network that could not be interpreted was inadvertently labeling asthmatic patients as low risk for pneumonia, leading to premature discharge from hospitals with potentially dire consequences.  Mediforests could conceivably save not only lives, but could capture a portion of the more than $3 billion healthcare analytics market—still a fraction of what Valdes said the market is expected to hit-- $24.6 billion by 2021.

Other Tracks, Other Voices

In addition to Catalyst’s Digital Health track, in which Valdes presented, and the Therapeutics track, which included Gaensler’s and Ahituv’s presentations, Catalyst features tracks in Devices and Diagnostics.

Pamela Munster, MD, described her proposal to develop and commercialize an implantable device made of silastic-silicone for the sustained local delivery of an anti-estrogen to prevent breast cancer in women at high risk. Once Munster began working with advisors Chris Jones, MSE, Al Chin, MD, and Mika Nishimura, MBA, she was able to quantify that the device could help as many as 170,000 women, and could create a market as large as $2 billion. 

Thinking in terms of market size was a revelation. “We were all somewhat surprised that this market is this sizable,” she said. Not only that, but the cost savings could be enormous, as a low-cost device could replace long-term regimens of treatment and years of doctor visits.

Catalyst also runs a Diagnostics track. Terumi Kohwi-Shigematsu, PhD, working with her husband, Yoshinori Kohwi, PhD, a fellow professor of orofacial sciences, on the development of an antibody-based test that could detect which tumors would respond to chemotherapy and which ones won’t.  Many tumors don’t have metastatic potential, yet without the ability to identify them, many patients have unnecessary chemotherapy.

“What we really need is a powerful biomarker to identify individual tumor cells destined to metastasize,” Kohwi-Shigematsu said. “We want to provide a quick, inexpensive and effective front line assay.” 

Her advisors, Greg Yap, MBA, and Stan Naides, MD, not only brought business expertise, but they also had the scientific chops to help. “Stan actually gave me advice about a different way of making antibodies,” Kohwi-Shigematsu said. “Greg Yap also gave me the clinical utility and whether SATB wants to become a standalone or we should combine it with other therapies.”

“I don't put much time into thinking about potential translation,” Kohwi-Shigematsu said. “This gave me a really wonderful opportunity to explore the translational thinking.”

Click here for a complete list of Catalyst awardees.  

Interns Give Something, Gain Something

Many of the principal investigators (PIs) praised the participation of the Catalyst program’s interns, who proved invaluable in putting together presentations and conducting background research. The interns said the program provided plenty of benefits to them as well.

“I've been interested in investments and business development for awhile and trying to figure out what I want to do after a Ph.D,” said intern Terri Lee, a graduate student at UCSF. “Being here in Catalyst has been really helpful in getting me that exposure and experience.”

“I primarily came from a basic science background,” Lee said. “It's nice to see what ideas in academia seem translatable. Many times what seems cool doesn't really translate, which can be a little discouraging, but it is eye-opening.” 

Khyati Shah, a postdoc in the lab of Sourav Bandyopadhyay, PhD, applied for the internship when her principal investigator planned to apply for a Catalyst grant. She became intrigued with the program.

“I want to understand how drug development happens and what the business decisions are that go into it,” Shah said. “That was career-transforming for me.”

Watch video by Ned David, Founder of Unity Biotechnology, as he gives Catalyst keynote address "Dispatches From the Frontiers of Biotechnology.