Utilizing RNA to intrude with a gene’s expression of disease-causing proteins is a validated therapeutic method, however to this point, the merchandise on this drug class solely handle liver proteins. Lowering ranges of sure proteins within the central nervous system might supply a brand new method to deal with neurological problems. The problem going through 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 problems that presently don’t have 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 Prescribed drugs’ Onpattro grew to become 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 carry 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. One in all Atalanta’s founders is Craig Mello, a professor within the RNA Therapeutics Institute on the College of Massachusetts Medical College 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 an alternative, 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 corresponding 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 mentioned.
Mello was significantly all in favour of 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 at the least 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 mentioned the offers converse 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 further 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 packages, one among which the startup goals to advance to human testing later this yr.
Different firms 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 Prescribed 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 any different oligonucleotide that has been capable of obtain what we now have when it comes to knockdown and sturdiness,” Secor mentioned. “I believe most individuals would argue ASO chemistry is nice, however RNAi is the subsequent era.”
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 each 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 check of the KCNT1 remedy, however this examine can even allow Atalanta to rapidly reveal its expertise can work in people. That’s as a result of seizure exercise may also be measured. Lowering seizures within the trial will present some medical proof of idea for the drug, and for Atalanta’s expertise, Secor mentioned.
Atalanta’s newest financing is a Collection B spherical co-led by EQT Life Sciences and Sanofi Ventures. Different individuals embrace new buyers 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.
In addition to the Huntington’s and KCNT1 packages, the Atalanta pipeline presently spans Alzheimer’s illness, ache, and unspecified CNS problems pushed by a number of undisclosed targets. Atalanta will not be actively searching 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 mentioned. “There’s a complete universe of targets and we’re open to inbound curiosity. Proper now, we’re centered on submitting our [investigational new drug applications]. However you already know, we is perhaps open [to partnerships] in 2025.”
Picture by Atalanta Therapeutics