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RNA revolutionized COVID-19 vaccines; local biotech company is betting that’s just the beginning

Replicate Bioscience scientific director Shigeki Miyake-Stoner visually inspects cells.
(Jarrod Valliere / The San Diego Union-Tribune)

Replicate Bioscience is developing RNA therapies against cancer, autoimmune diseases and other disorders.

Replicate Bioscience emerged from stealth mode this month with an ambitious vision for how RNA treatments can combat cancer, autoimmune disease and inflammatory disorders.

It’s a goal that seems more attainable after the success of Pfizer’s and Moderna’s COVID-19 vaccines, according to Nathaniel Wang, chief executive of Replicate, which is located at the BioLabs incubator just north of Scripps Memorial Hospital La Jolla. Both vaccines use RNA to teach the immune system to mount a response against the coronavirus and have been shown to be safe and effective in hundreds of millions of people.

“There was a lot of skepticism, to be honest, about a year and a half ago about RNA technologies,” Wang said. “There had been some pretty big failures and people were wondering, ‘Could it ever work?’

“It’s no longer a question of ‘Is this even feasible?’ So I think that’s been incredibly transformational.”

Wang is betting the transformation will extend well beyond vaccines. So is ATP, a New York venture capital firm that poured $40 million into Replicate during a Series A funding round.

The biotech has four drugs in development: two for breast and lung cancer, one for tumors that don’t respond to drugs that rev up the immune system, and one for autoimmune diseases and other disorders. Wang said he expects at least one of those drugs to enter clinical trials by the second half of 2022.

The candidate drugs all use a common strategy, delivering RNA molecules that make extra copies of themselves once inside a cell. If standard RNA therapies are an instruction manual that teaches cells how to make specific proteins, think of self-replicating RNA as a manual that comes with a photocopier.

The approach has a few potential advantages. Self-replicating RNA can be administered at low doses, which could reduce side effects while still generating strong, long-lasting responses as the molecule copies itself over time.

Typical RNA drugs last about two to three days, Wang said, while self-replicating molecules can churn out copies for up to about two months. He estimates that non-replicating RNAs have to be delivered at 600 to 2,000 times the dose of self-replicating molecules to match their effectiveness.

Other companies already are pursuing similar strategies, including San Diego biotech Arcturus Therapeutics and local manufacturer TriLink Biotechnologies. But Wang said Replicate’s drug design is a bit different from those companies and that there’s plenty of space in the RNA market.

“One of the things that people often ask is, ‘Are you trying to compete with existing therapies or are you trying to create completely new ones?’” he said. “And the answer is we’re trying to do both.”

The first-time CEO, 37, is an immunologist who earned his doctorate at Scripps Research in La Jolla in 2012. Before co-founding Replicate, he spent time developing RNA therapies at Johnson & Johnson and Synthetic Genomics. The latter was founded in 2005 by J. Craig Venter and Nobel laureate Dr. Hamilton Smith.

Replicate Bioscience has eight employees. Wang said the company will double in size within the next few months. ◆