'Like a kid in a candy shop': Michael Ehlers gets behind RNA 'copy machine' tech
Nathaniel Wang and Andrew Geall spent years working on self-replicating RNAs at Synthetic Genomics and Novartis Vaccines, respectively, before they realized they were coming at it the wrong way.
“For years and years, we thought that the technology was essentially plug and play,” Wang said. “It turns out … the vector itself, the protein that you’re putting into that vector, and the fat droplet you use to formulate it before you inject it into a person are all independent variables.”
They decided to start from scratch, along with Duke University professors Herbert Kim Lyerly and Zachary Hartman — and right away, their work piqued the interest of ex-Biogen R&D chief and current ATP CSO Michael Ehlers. On Wednesday, ATP unveiled a $40 million Series A round for the company they launched together, dubbed Replicate Bioscience.
“I think one of the things, from my perspective, that’s really nice about this technology is, it was really in a good situation where it was ripe with a lot of low hanging fruit,” Ehlers told Endpoints News.
The company currently has four disclosed programs — related to something they call “synthetic immune lethality” in breast in lung cancers, immunotherapy resistance in solid tumors and autoimmune and inflammatory diseases, said Wang, who’s helming the company as CEO.
If RNA is an instruction manual that teaches a cell how to create a given protein, srRNA is the copy machine. The problem with RNA is that it tends to degrade after a couple days.
“Imagine having a little toddler at home … constantly spilling everything on any document you have lying around the house,” Wang said.
With srRNA, you’re essentially delivering a copy machine along with the instruction manual, giving you more protein produced over a longer period of time. Replicate thinks this approach will allow it to reduce dosing levels by “several orders of magnitude” compared to other RNA therapeutics.
They’re currently testing an idea fleshed out at Duke for srRNA tech that can prevent or remove drug-resistant cancer mutations. With targeted therapies, like a small molecule or an antibody, you run the risk of a patients’ cancer cells developing a resistance mutation.
“What we’re doing is for the patients who are on something like that hormone therapy. We’re educating the immune system to recognize those mutations that confer resistance to it. And so in the process, you create a forceful linkage between the two,” Wang said.
“What we’re not talking about here is a run-of-the-mill neoantigen or some sort of private mutation or just any old neoantigen,” Ehlers said. “We know that those have run into problems … and that’s all because they can’t do what Nathaniel just showed. They can all escape the immune system.”
Replicate is putting together technology they believe can be used to target many of those mutations and drivers all at the same time, he added. The team expects to be in the clinic in the second half of next year.
“It’s like a kid in a candy shop with the kind of things you can do and the patient impact that you can have,” Ehlers said.