Genentech and Biogen roll the dice on an upstart biotech with a new siRNA approach — going deep into the brain for targets in neurodegeneration
Atalanta isn’t your average stealth biotech making a debut. They have some history and deals to sketch out in rough outlines.
The founding execs date the silent launch all the way back to mid-2019, with the publication of a seminal study looking at a new siRNA strategy for neurodegeneration. And instead of scouting for their first partners, the fledgling biotech can already count 2 prominent players as allies in the extensive preclinical work that’s been done to establish the platform.
Just because they’ve been assembling the pieces for well over a year doesn’t mean they’re ready to spill all the tech beans they’re working with. But enough is on display to arouse plenty of additional interest in what happens from here.
“What was observed in the preclinical research that was done in the lab of our founder Anastasia Khvorova and published in 2019 was the ability of this unique branched siRNA structure now to overcome that barrier and get access to the deep brain regions,” says Aimee Jackson, who worked on RNAi oligonucleotide therapies at miRagen and has stepped in as CSO at the startup. “So we think now we finally have the opportunity to unlock these areas and now actually approach solutions to neurodegenerative indications driven by degeneration in those deeper brain structures.”
Khvorova, who runs an eponymously named lab at UMass Medical School, noted in her abstract that gene silencing, RNAi’s big promise, had never been achieved in the brain using small interfering RNA, or siRNA. Her team, however, had created an architecture that had a “robust” affect in the brain, achieving “sustained gene silencing in the central nervous system of mice and nonhuman primates following a single injection into the cerebrospinal fluid.”
Using two linked siRNAs, the “branched” tech Atalanta boasts of, the researchers “induced the potent silencing of huntingtin, the causative gene in Huntington’s disease, reducing messenger RNA and protein throughout the brain. Silencing persisted for at least 6 months, with the degree of gene silencing correlating to levels of guide strand tissue accumulation. In cynomolgus macaques, a bolus injection of di-siRNA showed substantial distribution and robust silencing throughout the brain and spinal cord without detectable toxicity and with minimal off-target effects. This siRNA design may enable RNA interference-based gene silencing in the CNS for the treatment of neurological disorders.”
You can learn more about her work on the UMass website on inventions, illustrating how the tech involving “branched oligonucleotide structure improves the level of tissue retention in brain by more than 100 fold compared to non-branched compounds of identical chemical composition. The invention discloses branched oligonucleotides, specifically di-branched assymetric fully modified siRNAs, exhibiting great uniform distribution throughout the CNS and other target tissues, enhanced cellular uptake, minimal immune response and off-target effects, without formulation.”
Khvorova is a key scientific founder of this new biotech, along with Craig Mello, her famous colleague at UMass who won the Nobel Prize for his foundational work in RNAi and Neil Aronin, an expert in Huntington’s disease.
That last expert adviser puts the spotlight on one of the leading programs at Atalanta. Biogen signed up to partner on that target, while Genentech aligned itself with the biotech on Parkinson’s and the Big Kahuna of neurodegeneration: Alzheimer’s.
F-Prime has been footing the bill on the early work — all by itself — with Stephen Knight joining the board. Knight and the old Fidelity team that joined together in F-Prime have a long history in Alzheimer’s investment — none of it successful. They backed Deborah Dunsire on her work at Forum, which went belly up before they all went their separate directions.
F-Prime and the startup’s 2 big partners have put up the first $110 million to get the company rolling, but the founders — led by Juniper vet Alicia Secor as CEO and employee #1 at Atalanta — aren’t telling me who did what.
Are there milestones attached? Yes. We can imagine the numbers are large, but the CEO won’t say how large.
According to Secor, it was Stacie Weninger, a neuro expert who heads up the F-Prime Biomedical Research Initiative, who first came across the tech. She’s the one who brought in Knight, whose ambitions in the field have widened considerably from the initial focus on Alzheimer’s.
There are a number of startups that have come along to take a new crack at these big neurodegenerative targets, driven in part by the widespread carnage in the clinic for everything that came earlier. Now we can add Atalanta, at a time some of the majors are lining themselves up for the second, or third waves.