Life sciences venture firm TP on Wednesday announced the launch of Replicate Bioscience in a bid to replicating the success RNA technology has had in responding to the COVID-19 pandemic but with self-replicating RNAs to go after cancers and autoimmune disorders at lower doses. The biotech will use $40 million in committed Series A funding from ATP to promote multiple novel sRNA programs into clinical development.
“Next-generation srRNA agents are taking RNA therapeutics into many more areas of disease treatment, and what Replicate is doing is to define and expand this field is completely new and exciting,” said Michael Ehlers, M.D., Ph.D., Chief Scientific Officer of ATP and a venture partner at the company.
“ATP is investing in Replicate because we see the company’s technology as a quantum leap in RNA therapeutics.”
Conventional, non-replicating mRNA technology offers an instructional manual to cells on how to produce proteins. But that instructional manual degenerates after a few days.
“Imagine there’s a bunch of toddlers running around the cell and spilling stuff all over that manual,” explained Nathaniel Wang, Ph.D., Replicate CEO and co-founder, in an interview. Self-replicating RNAs, or srRNAs, on the other hand, deliver an instruction manual and a copier to the cell, which enables the production of multiple copies of the manual and creation of “a lot more protein” that lasts longer and at lower doses, the CEO said.
That explains why Replicate Biosciences, founded in February 2020 was unveiled to the public for the first time Wednesday. The srRNA technology is designed to inhibit or destroy drug-resistant cancer mutations through “synthetic immune lethality” and is also being put into tests in autoimmune and inflammatory disorders. SrRNAs works by imitating themselves inside the body cells and instructing the cells to produce and keep making, therapeutic proteins.
Replicate uses original molecular design principles, synthetic biology and a diverse, proprietary repertoire of virally derived vectors to ensure the production of custom srRNAs that offer unique advantages relative to other RNA or srRNA therapeutic approaches. These advantages include reduced dosing levels by several orders of magnitude; higher duration of therapeutic effect; and selectively programmed ability to either activate or deactivate the immune system.
The biotech has two programs focused on breast and lung cancers, another aimed at immunotherapy resistance in solid tumors and a fourth program aimed at inflammation related to autoimmune disorders that goes after “downstream mediators of the inflammasome,” Wang added.
Current RNA technologies bring about adverse events at a level “right up against the edge of what would be acceptable for most clinical indications, and almost every other therapeutic indication would require higher doses,” Wang disclosed. That implies that the types of indications these products can aim after is limited to ones that require “a very small amount of protein for a very short amount of time.”
SrRNAs generally can lower the required dosing by about tenfold, Wang stated. At its current stage, the biotech believes it can reduce the dose a thousandfold. Most importantly, the firm believes it can further the technology to reduce dosing a million – or 10 millionfold as against what’s obtainable in current technologies.
“We started Replicate to build a best-in-class srRNA platform from scratch – to pursue our vision of a better way to make srRNAs that we are convinced can solve life-threatening medical problems, from drug resistance in cancer to autoimmune, inflammatory disorders and more. We are thrilled to partner with ATP to accelerate our progress towards realizing that vision for patients.” Wang said.