A new startup wants to take antisense and siRNA one step further, and build more potent drugs than Ionis and Alnylam
Drugging RNA has become a hot biopharma topic in recent years, particularly after the massive successes of the Covid-19 vaccines. But one biotech is aiming to take things a step further, utilizing the single-stranded molecules before they even become RNA.
Ceptur Therapeutics launched Wednesday morning with a $75 million Series A, the company announced. The goal is to push forward a slate of oligonucleotide-based therapies that can control gene expression, and even silence some targeted genes, at the “pre-mRNA level,” co-founder and CEO Peter Ghoroghchian told Endpoints News.
The biotech has recruited a blue-chip syndicate as well, with venBio and Qiming Ventures co-leading the round. In addition, Ceptur received new support from Perceptive Xontogeny Venture Fund, Bristol Myers Squibb and Janus Henderson Investors.
Ceptur’s main idea centers around a protein complex known as the U1 snRNP (pronounced SNURP), which Ghoroghchian said serves as a biological gatekeeper when DNA is transcribed into RNA and RNA into proteins. When cells go through this process, they’re constantly splicing genetic sequences in and out, with some left out of the final mRNA.
“The splicing machinery that helps mRNA to mature is recruited by the U1 snRNP, and the U1 snRNP also helps to turn off and control the level of transcripts, so how much of a given mRNA is made,” Ghoroghchian said. “It does this for every single gene in the body, so it has this very central role in biology.”
To take advantage of these gateways and create drugs, researchers led by Rutgers professor Sam Gunderson, another Ceptur co-founder, developed bivalent oligonucleotides called U1 Adaptors. The adaptors target specific genetic sequences and recruit the U1 snRNP to destroy the desired pre-mRNA, essentially controlling which genes make it into the final proteins.
It’s an approach similar to antisense oligonucleotides and siRNA therapies, Ghoroghchian said, only Ceptur aims to drug the RNA at a much more granular level. And because the U1 snRNP is so ubiquitous throughout the body — Ghoroghchian says there are more than one million copies in every cell — Ceptur believes different cell types and genes won’t impede the company’s progress.
Colin Walsh, a partner at Qiming Ventures, noted the RNA drugging field has boomed in recent years, ever since the idea took off in the early days of Ionis and Alnylam. But he believes Ceptur represents a big step forward in how such approaches will shape the space in the future, particularly once it moves past the gene silencing application.
“There is a large appetite for ways to control protein function at the RNA level,” Walsh said. “The U1 Adaptor protein complex is really a master regulator of the transcriptome, it’s splicing and other things. Though knockdown is the first place where you can take this, we see this as a really broad potential platform for modulating RNA using oligo-based therapeutics.”
For its in-house pipeline, Ceptur isn’t revealing much just yet. Ghoroghchian said the team has a few candidates that could hit IND-enabling studies sometime in 2023, including oncology programs targeting KRAS and MYC in cancer, as well as one for Huntington’s disease. Past that, though, everything remains in the discovery phase.
And though the biotech is trying to control genetic sequencing, Ghoroghchian believes Ceptur’s drugs will prove far safer than gene therapies that sometimes continue editing DNA beyond the therapeutic use. Because Ceptur isn’t engaging in DNA or base editing, its drugs will only work as long as the adaptor is in the patient’s system.
Ceptur’s oligonucleotides are extremely small, Ghoroghchian said, and “every nucleotide is chemically modified. And we can use a lot of existing and validated chemistries to dial in how long it lasts, either to how long they can knock the gene down, or how quickly it can be degraded, in order to dial in the safety aspect.”
On top of the new investors, Ceptur also received Series A support from existing seed investors Affinity Asset Advisors, Boxer Capital and LifeSci Venture Partners.