Scribe Therapeutics shares are up 30% since it raised $125 million in its initial public offering Friday. The cash will fund three clinical trials testing whether Scribe's one-time treatments can halve the risk of heart attacks and strokes.
Scribe's therapies turn off the genetic instructions leading to high levels of damaging lipids, without having to cut a gene's DNA strands like other one-shot genetic treatments in the clinic. It employs the latest outgrowths from the Crispr-Cas editing technology that won a Nobel Prize for University of California at Berkeley professor Jennifer Doudna, a Scribe co-founder.
And while most genetic editing treatments target relatively rare ills, like sickle-cell disease, Scribe is targeting the blood fats -- or lipids -- blamed for 50% to 80% of cardiovascular disease: LDL cholesterol, lipoprotein (a), and triglycerides.
"The three are probably the top three lipid risks for [atherosclerotic cardiovascular disease] stacked on top of each other...a boxed set," says CEO and co-founder Ben Oakes. "You could have the ability to solve the leading cause of death globally."
The first Crispr therapies -- like the approved Casgevy treatment for sickle cell, developed by CRISPR Therapeutics and Vertex Pharmaceuticals -- home in on a troublesome gene and then slice its two strands of DNA to permanently inactivate it.
Second-generation Crispr approaches only nick one strand of DNA, using the base-editing technique that is in clinical trials by Beam Therapeutics and the Eli Lilly unit Verve Therapeutics, or using the prime-editing technique in trials by Prime Medicine.
Scribe's lead product doesn't cut a gene's DNA. Instead it edits the natural mechanisms that tell genes when to turn on and off. This "epigenetic" machinery consists of molecular markers that surround a cell's DNA to control when the gene sends out instructions for making the stuff of life -- and disease.
By putting down artificial epigenetic markers, the company's Crispr-Cas products can durably silence a problematic gene. Epigenetic controls are specific to a gene, so Scribe expects the approach to have fewer off-target effects than other Crispr techniques. Lab studies suggest that epigenetic edits might also be reversible, unlike Crispr DNA edits.
The company got the green light this year to start its first clinical trial in Australia, by infusing up to 64 people with an epigenetic editor that silences the gene for PCSK9, a protein that controls blood levels of LDL cholesterol. Initial data could appear in the first half of 2027.
Injectable drugs marketed by Amgen, Novartis and Regeneron Pharmaceuticals can silence the same gene for months at a time, by degrading the instructions for PCSK9 before they reach the liver cell's production machinery. Merck got approval this month for a daily pill that does the same.
In lab tests on primates, Scribe's epigenetic PCSK9 edits cut LDL cholesterol levels by more than 50%, and they have working for over two years. That means the gene-control alterations got passed down, when liver cells turn over. The hope is that the silencing from one infusion of an epigenetic editor could last a decade or more, before requiring the next infusion boost.
Scribe also edits DNA genes, and it expects to start clinical trials for lowering lipoprotein (a) and triglycerides in the next couple of years. Those studies will show how Scribe's gene-editing stacks up against the other gene-editing approaches now in clinical trials; including a Crispr DNA editing therapy from CRISPR Therapeutics, and a base-editing therapy from Lilly's Verve unit.
Lilly is teaming up with Scribe to investigate epigenetic editing treatments for neurological disorders. With 9% of Scribe's stock, Lilly is its second largest shareholder.
After jumping as high as 70% Friday from its IPO price of $15 before settling down later that day, Scribe stock slid 13% to $18.75 in Monday trading.
Like all gene-editing technologies, the epigenetic approach is better suited for some genetic targets than others. Fortunately, some of them are implicated in the world' deadliest disease.
"The universe exists in a certain way," says Oakes. "And it is asking us to fix [atherosclerotic cardiovascular disease]."
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