November 11, 2021
SPARK Taiwan held its annual Translational Medicine Symposium late last month, at which SPARK founder and co-director Daria Mochly-Rosen and SPARK scholars and advisors shared their stories.
This year’s theme was COVID-19 vaccine efforts of SPARK GLOBAL and beyond. SPARK Asia Director Jane Tseng kicked off the symposium introducing the topic and speakers.
Dr. Mochly-Rosen spoke about SPARK in the time of COVID-19. She first gave an overview of SPARK – what the program is and why – which is to address the huge challenge academicians face of how to translate good ideas to solutions for patients, and overcoming the gaps between academic and industry. She then discussed the creation of SPARK Taiwan and SPARK GLOBAL to better address global health threats.
Dr. Mochly-Rosen then told a story representing SPARK’s response to the COVID-19 pandemic: Michael Wallach’s idea to use chicken-based IgY antibodies as a passive vaccine, via lozenges or nasal drops, to protect against COVID-19. Dr. Wallach (SPARK Oceania Regional Director) had already explored the use of IgY antibodies, and when he described his idea to her, she thought the idea had “many of the elements that we like: fast, cheap, logical, easy to do.” Dr. Mochly-Rosen brought the project to Stanford, and along with over 40 volunteer experts, developed the IgY antibody-based nasal drops. The project is ready to move to efficacy studies after studies in rats and a Phase I safety study in human volunteers. Beyond COVID-19, Dr. Mochly-Rosen said, the treatment can be quickly formulated to protect against other viruses to fight the next viral pandemic.
Dr. Mochly-Rosen answered questions from the audience, including how SPARK encourages students and postdocs to start a company on their work. She said, “all we have to do is bring them into the room,” and when they hear others discuss successful projects “and they see the potential to actually be impactful,” they are immediately inspired. Students are most excited to start new companies, she added, whereas faculty are more risk-adverse.
She also noted the speed with which the IgY-based nasal drops have been developed. “It shows the strength of the network: we gained advice from so many experts worldwide.”
Next, Mark Backer, SPARK advisor and longtime biotech executive and consultant, discussed the technical development of flu vaccines, particularly the nasal spray FluMist. Dr. Backer began by praising the value of the SPARK experience, “I’ve always felt like I’ve learned much more than I’ve contributed.”
Flu vaccines are unique from other vaccines, they have particular challenges, Dr. Backer said. Beyond the regulatory and commercial environment challenges that vaccines face, flu vaccines must be rapidly designed and manufactured against a new strain every year. Dr. Backer described the flu vaccine strain selection for the U.S. market each year and current vaccine production methods.
With these challenges in mind, Dr. Backer described how he helped get FluMist out of late-stage development and into the market. Just like Dr. Mochly-Rosen’s IgY-based passive vaccine, FluMist is produced in eggs and delivered via the nose. Dr. Backer explained how he and Aviron (later MedImmune) developed FluMist prior to its approval in 2005, including the many production and manufacturing challenges his team faced along the way. He explained the rationale for creating FluMist: potentially obtaining better immune response from a replicating live virus and exposure to the nasal membrane to generate cell-mediated and antibody-mediated protection, and a nasal spray would be more popular than an injection, increasing the overall vaccination rate. “Our thinking was if we can just sort of paint the inside of the nose with this vaccine, then replication can occur in the nose.”
Next, former SPARK scholar Che-Hong Chen spoke on precision oral cancer prevention. Dr. Chen brought the idea of a SPARK program to Taiwan in 2009 and has been a longtime advocate of the program. Dr. Chen described his work addressing the unmet medical need of aerodigestive track cancer in Taiwan, the 6th most common cancer in men with the highest death rate. Risk factors include smoking, alcohol and the aldehyde dehydrogenase (ALDH2) mutation, an Asian-specific missense mutation that affects 8% of the world’s population. The mutation renders ALDH2 inactive, leading to accumulation of the carcinogen acetaldehyde.
Dr. Chen developed a two-pronged solution of ALDH activators as therapeutics and chemoprevention and a precision oral cancer screening and prevention program to address this unmet need. With Dr. Mochly-Rosen, Dr. Chen had earlier developed therapeutics for ALDH2 deficiency and small molecule ALDH activators at Stanford and founded a startup company. Dr. Chen’s precision screening and prevention program, which he is advocating the Taiwanese government to expand, involves a risk score assessment of a questionnaire and non-invasive rapid genetic testing for genotyping for tailored screening and follow-up. Dr. Chen is currently initiating the community screening program at three hospitals in Taiwan.
Dr. Chen spoke about the need for community involvement and advocacy to raise awareness of the problem: He and Dr. Mochly-Rosen founded the International ALDH2 STAR Research Consortium in 2015, and in 2017 Dr. Chen founded the non-profit Taiwan Alcohol Intolerance Education Society (TAIES) in Taiwan.
Finally, longtime SPARK advisor Lyn Frumkin talked about assessing the attractiveness of biotechnology opportunities, speaking from his point of view as an industry clinical scientist. “One of the things that surprised me when I entered industry as a clinical scientist was the importance of evaluating internal and external technology… because the companies I was at were trying to bring things to the pipeline.”
“No matter how successful your programs are, partnering is usually necessary,” he said. Dr. Frumkin dug into the mindset of the biopharmaceutical industry, a ‘behind-the-scenes’ view at what the industry looks for in drug development and how it evaluates biotechnology. R&D is a complex, expensive, and risky business, he said: it takes an average of 10 years to develop a drug or biologic, and costs an average of $2.6 billion, good opportunities are rare, and licensing of new opportunities is essential. Current trends are moving from primary care to specialty care like targeted therapies, a shift to innovation and discovery for rare diseases with unmet medical needs and regulatory incentives, and more targeted strategic goals. Dr. Frumkin listed factors that are important to him, as an industry clinical scientist, in evaluating risk, or the probability of success – starting first with the scientific rationale.
Listening to Dr. Frumkin makes one realize just how many factors an investigator must consider when developing a drug compound. The SPARK program and SPARK advisors introduce all of these factors to SPARKees, and make sure they’re all considered. Academia historically has been a massive contributor of early discoveries, and “SPARK has been an incredible contributor” translating that science to products that benefit patients, said Dr. Frumkin. The relationship between SPARK Taiwan and the strong bioindustrial clusters in Taiwan “is a very large asset,” Dr. Frumkin added.