Genetic-medicines-focused Scribe Therapeutics is racing toward the clinic on the heels of a preclinical data drop for three programs, all of which were able to reduce cardiovascular risk factors in animal models.
The star of Scribe’s presentations at the American Heart Association Scientific Sessions in New Orleans was gene silencer STX-1150, which lowered levels of low-density lipoprotein cholesterol (LDL-C)—also called "bad cholesterol"—by more than 50% in primates for more than 515 days after one dose, Scribe said in a Nov. 17 release.
Two gene editors, STX-1200 and STX-1400, similarly slashed levels of lipoprotein(a) and APOC3 in mice and macaques, respectively.
“The three lipids we're targeting together make up the gas in the tank for ASCVD,” Scribe co-founder and CEO Benjamin Oakes, Ph.D., told Fierce Biotech. “If you don't have cholesterol, you can't advance atherosclerosis.”
Scribe is now “moving very quickly to bring these into the clinic,” Oakes added, but did not share further timeline details.
Scribe emerged in 2020 with $20 million, a Biogen partnership and the backing of Jennifer Doudna, Ph.D., the CRISPR pioneer who won a Nobel Prize the very next day. Oakes had joined Doudna’s lab to engineer new CRISPR molecules, eventually starting his own lab at the University of California, Berkeley before transitioning his research into the startup Scribe.
The biotech’s goal is to bring genetic medicines out of the realm of rare diseases and into broader patient populations, Oakes explained. Doing so requires gene editing enzymes that are safer and more potent.
To that end, Scribe has modified an enzyme called CasX, a variant of the better known Cas9, to greatly improve its editing efficiency.
“It is, to my knowledge, the only non-Cas9 molecule to demonstrate greater than 75% editing in a non-human primate,” Oakes said.
But while CRISPR technology is best known for gene editing, Scribe’s lead program STX-1150 is instead a gene silencer. Rather than altering the genome, the compound adds methyl groups and tweaks the structure of DNA at the targeted gene, turning off gene expression. Scribe is using STX-1150 to shut down the PCSK9 gene, a known cardiovascular target that is inhibited by existing cholesterol-lowering medicines Repatha (evolocumab) and Leqvio (inclisiran).
Oakes thinks of STX-1150 as the “end state” of RNA interference-style therapies, which includes Leqvio. While Leqvio is taken every six months, the Scribe CEO is hopeful that his company’s candidate could require a booster once every decade or two.
Enlicitide, a new daily oral PCSK9 inhibitor from Merck, may debut soon after clearing two phase 3 trials, with Leerink Partners analysts saying the asset has a “significant advantage” over injected biologics. But Oakes isn’t worried about growing competition in the field.
“These are the most effective drugs for LDL-C lowering,” Oakes said of PCSK9 inhibitors, yet they have hardly reached the huge number of patients who could benefit from them. “As someone with a high cardiovascular risk myself, the more people realize that statins are not the end all be all, but that lower is better for LDL-C and for these lipids, I think we can all be hugely successful.”
Scribe is also pursuing other therapeutic areas in big-name partnerships with Sanofi and Eli Lilly, deals inked after the company secured a $100 million fundraise in 2021. The Bay Area biotech’s clinical push began in earnest in January, with a 20% layoff that followed an earlier preclinical data drop.