Utilizing RNA to intervene with a gene’s expression of disease-causing proteins is a validated therapeutic strategy, however to date, the merchandise on this drug class solely handle liver proteins. Lowering ranges of sure proteins within the central nervous system (CNS) might provide a brand new option 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 packages 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 packages 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 Prescription drugs’ Onpattro grew to become the primary 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 deliver 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 stated. One in every 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 stated. As a substitute, the startup’s medication make use of what she described as a divalent construction during 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 akin to efficiency and sturdiness.
“These molecules are very particular and have demonstrated the power to attain actually broad mind distribution in all areas, [and] importantly, deep mind penetration,” Secor stated.
Mello was notably thinking about creating therapies for Huntington’s illness, a uncommon neurological dysfunction that originates deep within the mind. UMass analysis revealed 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 a minimum of six months.
Quickly after the analysis was revealed, 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 Collection A financing, it additionally revealed R&D alliances with Biogen and Genentech. Secor acknowledged that it’s uncommon for a startup to land two huge pharma partnerships at such an early stage, however she stated the offers communicate to the business curiosity in bringing RNAi to the mind.
The alliances supplied Atalanta with non-dilutive capital that enabled the corporate to embark on extra preclinical analysis that additional de-risked its expertise platform, Secor stated. CNS targets of the Genentech partnership stay undisclosed. Huntington’s was a part of the Biogen alliance, however Secor stated that settlement is unwinding “for enterprise causes.” Atalanta now has full management of the Huntington’s packages, certainly one of which the startup goals to advance to human testing later this yr.
Different corporations are additional alongside in growth with Huntington’s drug candidates. Final month, Novartis agreed to pay $1 billion for rights to a PTC Therapeutics small molecule on observe for pivotal testing. Roche and Ionis Prescription drugs are companions within the growth of tominersen, an antisense oligonucleotide (ASO) that has weathered medical trial setbacks. Secor describes Atalanta’s expertise as a extra environment friendly method of selectively delivering a potent Huntington’s remedy into the mind.
“There isn’t a different oligonucleotide that has been in a position to obtain what we have now by way of knockdown and sturdiness,” Secor stated. “I feel most individuals would argue ASO chemistry is nice, however RNAi is the following technology.”
The opposite Atalanta program on observe to the clinic is a possible therapy 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 every day that aren’t treatable with current anti-seizure medication, Secor stated. 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 stated.
Evaluating security is the primary objective of the deliberate Section 1 take a look at of the KCNT1 remedy, however this research will even allow Atalanta to rapidly show its expertise can work in people. That’s as a result of seizure exercise will also be measured. Lowering seizures within the trial will present some medical proof of idea for the drug, and for Atalanta’s expertise, Secor stated.
Atalanta’s newest financing is a Collection B spherical co-led by EQT Life Sciences and Sanofi Ventures. Different members embody new buyers RiverVest Enterprise Companions, Novartis Enterprise Fund, funds managed by abrdn Inc, Pictet Different Advisors, Mirae Asset Monetary Group, and GHR Basis alongside earlier investor F-Prime Capital.
Moreover the Huntington’s and KCNT1 packages, 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 on the lookout for extra companions proper now, however Secor is leaving the door open.
“We’ve bought a reasonably highly effective platform that may principally knock down any transcript within the mind the place there’s genetic validation that it’s illness inflicting,” she stated. “There’s an entire universe of targets and we’re open to inbound curiosity. Proper now, we’re targeted on submitting our [investigational new drug applications]. However you recognize, we could be open [to partnerships] in 2025.”
Picture by Atalanta Therapeutics
