Utilizing RNA to intrude with a gene’s expression of disease-causing proteins is a validated therapeutic strategy, however thus far, the merchandise on this drug class solely tackle liver proteins. Decreasing ranges of sure proteins within the central nervous system may supply a brand new strategy to deal with neurological issues. The problem dealing with drug builders is getting these therapies deep into the mind.

Atalanta Therapeutics has expertise that delivers RNA interference therapies into the CNS. The startup has spent the previous 4 years quietly engaged on its expertise and potential medication. On Tuesday, Atalanta revealed two lead applications for uncommon neurological issues that at present haven’t any FDA-approved therapies. The Boston-based startup additionally introduced $97 million in financing to advance these applications to the clinic and assist different CNS therapies in its pipeline.

An RNA interference (RNAi) remedy makes use of small items of non-coding RNA to dam how sure genes are expressed. In 2018, Alnylam Prescribed drugs’ Onpattro turned the first FDA-approved RNAi drug. This remedy is delivered inside a lipid nanoparticle, which preferentially goes to liver cells. Alnylam and others have been pursuing methods to convey RNAi to the CNS.

Atalanta, named for the legendary Greek huntress, makes its therapies with oligonucleotides, quick items of artificial RNA. Early efforts in oligo and RNAi medication couldn’t get past the outer layer of the mind, Atalanta CEO Alicia Secor mentioned. Considered one of Atalanta’s founders is Craig Mello, a professor within the RNA Therapeutics Institute on the College of Massachusetts Medical Faculty who was awarded the 2006 Nobel Prize in Physiology or Medication for his RNAi discoveries. Mello’s analysis contains methods to ship oligo therapies into the mind.

Atalanta doesn’t use lipid nanoparticles or different supply applied sciences, Secor mentioned. As a substitute, the startup’s medication make use of what she described as a divalent construction through which two small-interfering RNA (siRNA) duplexes are joined by a linker. This construction allow the remedy get into the CNS and it imbues the remedy with properties equivalent to efficiency and sturdiness.

“These molecules are very particular and have demonstrated the flexibility to realize actually broad mind distribution in all areas, [and] importantly, deep mind penetration,” Secor mentioned.

Mello was significantly occupied with growing therapies for Huntington’s illness, a uncommon neurological dysfunction that originates deep within the mind. UMass analysis printed in Nature Biotechnology in 2019 described mouse and monkey research that confirmed a single injection of divalent siRNA led to silencing of the gene that causes Huntington’s. This silencing lasted not less than six months.

Quickly after the analysis was printed, F-Prime Capital licensed the UMass expertise and shaped Atalanta with Secor as its first worker. When the startup emerged from stealth in 2021 with $110 million in Sequence A financing, it additionally revealed R&D alliances with Biogen and Genentech. Secor acknowledged that it’s uncommon for a startup to land two massive pharma partnerships at such an early stage, however she mentioned the offers communicate to the business curiosity in bringing RNAi to the mind.

The alliances offered Atalanta with non-dilutive capital that enabled the corporate to embark on extra preclinical analysis that additional de-risked its expertise platform, Secor mentioned. CNS targets of the Genentech partnership stay undisclosed. Huntington’s was a part of the Biogen alliance, however Secor mentioned that settlement is unwinding “for enterprise causes.” Atalanta now has full management of the Huntington’s applications, one in all which the startup goals to advance to human testing later this yr.

Different corporations are additional alongside in improvement with Huntington’s drug candidates. Final month, Novartis agreed to pay $1 billion for rights to a PTC Therapeutics small molecule on monitor for pivotal testing. Roche and Ionis Prescribed drugs are companions within the improvement of tominersen, an antisense oligonucleotide (ASO) that has weathered scientific trial setbacks. Secor describes Atalanta’s expertise as a extra environment friendly approach of selectively delivering a potent Huntington’s remedy into the mind.

“There is no such thing as a different oligonucleotide that has been in a position to obtain what we’ve when it comes to knockdown and sturdiness,” Secor mentioned. “I feel most individuals would argue ASO chemistry is sweet, however RNAi is the following technology.”

The opposite Atalanta program on monitor to the clinic is a possible remedy for a uncommon type of epilepsy pushed by gain-of-function variants within the KCNT1 gene. Sufferers who’ve this illness can expertise 50 to 100 seizures day by day that aren’t treatable with current anti-seizure medication, Secor mentioned. Atalanta’s remedy is designed to scale back ranges of KCNT1 protein. In mouse research, a 50% discount in protein led to a 70% discount in seizures, Secor mentioned.

Evaluating security is the primary purpose of the deliberate Part 1 take a look at of the KCNT1 remedy, however this examine may also allow Atalanta to rapidly display its expertise can work in people. That’s as a result of seizure exercise will also be measured. Decreasing seizures within the trial will present some scientific proof of idea for the drug, and for Atalanta’s expertise, Secor mentioned.

Atalanta’s newest financing is a Sequence B spherical co-led by EQT Life Sciences and Sanofi Ventures. Different individuals embody new traders RiverVest Enterprise Companions, Novartis Enterprise Fund, funds managed by abrdn Inc, Pictet Various Advisors, Mirae Asset Monetary Group, and GHR Basis alongside earlier investor F-Prime Capital.

Moreover the Huntington’s and KCNT1 applications, the Atalanta pipeline at present spans Alzheimer’s illness, ache, and unspecified CNS issues pushed by a number of undisclosed targets. Atalanta just isn’t actively in search of extra companions proper now, however Secor is leaving the door open.

“We’ve acquired a fairly highly effective platform that may mainly knock down any transcript within the mind the place there’s genetic validation that it’s illness inflicting,” she mentioned. “There’s a complete universe of targets and we’re open to inbound curiosity. Proper now, we’re targeted on submitting our [investigational new drug applications]. However , we may be open [to partnerships] in 2025.”

Picture by Atalanta Therapeutics