Ceroid Lipofuscinosis, Neuronal, 2

Neurogene licensed a CLN5 gene therapy program from the University of North Carolina at Chapel Hill.\n Neurogene followed up a premarket setback to its Rett syndrome program Monday with a postmarket confirmation that development of another gene therapy has hit a wall.The postmarket update covered NGN-101, a gene therapy Neurogene was developing as a treatment for CLN5 Batten disease, and repeated what the biotech disclosed last week. Three months ago, the biotech said it planned to meet with the FDA and try to align with the agency on clinical requirements to support a streamlined registration pathway. Neurogene framed alignment on a streamlined pathway as critical for continued investment in the program.Talks with the FDA haven’t gone according to plan. Seeking a streamlined pathway, Neurogene submitted a Regenerative Medicine Advanced Therapy (RMAT) application to the FDA. The biotech said the filing met the standard of preliminary clinical evidence required to obtain an RMAT designation.However, the FDA denied the application. Neurogene responded by dropping plans to advance NGN-101. The decision reflects the rarity of CLN5 Batten disease, which led the biotech to conclude it would need to align with the FDA on a streamlined registrational pathway to support further investment in the asset. Neurogene said in a release that it is now evaluating options for the program. The biotech licensed the CLN5 gene therapy program from the University of North Carolina at Chapel Hill (UNC) back in 2019. The deal was small, with Neurogene agreeing to pay UNC up to $1.7 million in sales-related milestones and making five-figure payments tied to the progress of the program. UNC received $15,000 when the candidate secured orphan drug designation and $30,000 when phase 1 dosing began.The UNC deal led to Neurogene becoming the first company to test a gene therapy in people with CLN5 Batten disease. The biotech recently completed enrolling the six subjects in its phase 1/2 dose-escalation trial. Other organizations are working on treatments for CLN2 and CLN3 disease, but NGN-101 is the only CLN5 therapy listed on ClinicalTrials.gov.Neurogene’s stock plummeted after it disclosed the setback to the Rett gene therapy, closing down more than 40% at below $20.Editor’s Note: This article was updated at 11 am ET on Nov. 19 to say Neurogene previously disclosed the CLN5 update. 

Tern Therapeutics debuted on Tuesday with $15 million in funding and a pair of early-stage gene therapies designed to treat separate symptoms of the ceroid lipofuscinosis type 2 (CLN2) form of Batten disease, a rare neurodegenerative condition. Both candidates, as well as the biotech’s leadership team, can trace their roots to Regenxbio. The newco has global licences to TTX-381 and TTX-181 — formerly RGX-381 and RGX-181, respectively — from Regenxbio. The most advanced programme, TTX-381, is an adeno-associated viral (AAV) vector-based gene therapy engineered to deliver a copy of the TPP1 gene directly to the retina, with the aim of treating the vision loss associated with CLN2 disease. A Phase I/II dose-escalation study is underway in London. According to ClinicalTrials.gov, the trial will enrol up to 16 children between the ages of 1 and 12 and is expected to wrap in mid- to late 2025. The second asset, TTX-181, is meant to be delivered via AAV vector directly to the central nervous system (CNS) to prevent further neurodegeneration caused by the disease. Two years ago a child was given the experimental treatment at the Hospital de Clinicas in Porto Alegre, Brazil as part of a single-patient, investigator-initiated study. The gene therapy was well-tolerated, with no treatment-related serious adverse events as of December 2022.The financing, which was led by ATW Partners and Steve Oliveira, head of Nemean Asset Management, is expected to help move TTX-381 through its current trial and advance TTX-181.  Gene therapy experienceNot only does Tern’s pipeline hail from Regenxbio, but so do its founders. Chief executive Alex Bailey previously was the head of early program and portfolio development at the Maryland-based firm.The Tern team is “excited to continue the work we started at Regenxbio,” he commented. “No one knows these programmes better than the team we’ve assembled at Tern, and we deeply appreciate the confidence and trust that Regenxbio and the patient community have placed in us to lead the next phase of development of these promising investigational therapies,” Bailey added.He founded the biotech along with Christina Ohnsman and Matthew Rosini, who serve as Tern’s chief medical officer and chief financial and administrative officer, respectively. Ohnsman was executive director of clinical development at Regenxbio, where she oversaw the firm’s portfolio of ocular and CNS rare disease gene therapies. Prior to joining the drug developer, she was a medical consultant and provided advice on commercialisation initiatives for Luxturna (voretigene neparvovec-rzyl), the first-ever FDA-approved gene therapy. At Regenxbio, Rosini served as head of strategic initiatives; he previously was a partner at  the life sciences-focussed FoxKiser law firm.Amy Fenton Parker, president and CEO of the Batten Disease Support, Research, & Advocacy organisation, called the launch of Tern “incredibly encouraging for our CLN2 community.”“The transition of both gene therapy programs to the Tern Therapeutics team, who are already so familiar with the programs and connected to our CLN2 community, is invaluable for the seamless continuity and advancement of this clinical research,” she said.

The treatment is intended for children of all ages with CLN2 disease, irrespective of symptom status. Credit: Luis Molinero / Shutterstock. The US Food and Drug Administration (FDA) has expanded its approval of BioMarin Pharmaceutical’s supplemental biologics licence application (sBLA) for enzyme replacement therapy, BRINEURA (cerliponase alfa), to include children aged under three with neuronal ceroid lipofuscinosis type 2 (CLN2) disease. The move broadens the therapy’s previous indication to reduce the loss of ambulation, which was initially limited to symptomatic children aged three years and above with late infantile CLN2 disease The treatment is intended for children of all ages with CLN2, irrespective of symptom status. The sBLA for BRINEURA was supported by data from a Phase II trial known as Study 190-203 which indicated that the treatment slows the decline in motor function and delays disease onset, even in children younger than three. The open-label, multicentre trial analysed children aged one to six years at baseline over approximately three years. See Also: EC conditionally approves Pfizer’s haemophilia B gene therapy MHRA approves Pfizer-BioNTech’s Comirnaty JN.1 vaccine Results from Study 190-203 demonstrated that intraventricular-administered BRINEURA effectively slowed the progression of CLN2 disease. The safety profile of BRINEURA in children under three was consistent with the known safety data of the medicine. These findings also suggested that initiating treatment before the age of three could delay the onset of the disease. BioMarin pharmaceutical worldwide research and development president Hank Fuchs stated: “The approval represents a significant step forward in enabling children to be treated with BRINEURA as early as possible, when we can have the greatest impact in altering the natural course of disease. “We know that every day counts for families affected by serious genetic conditions such as CLN2 disease, which is characterised by a rapid onset of neurodegenerative symptoms. We have been working diligently since BRINEURA’s initial approval to support this expanded use in children of all ages, even before they begin to show symptoms.” In June 2023, BioMarin’s Roctavian received FDA approval as a one-time therapy in adults with severe haemophilia A.