Beyond Batten Disease Foundation is proud to share a major milestone for families, clinicians, and researchers working to improve care for individuals affected by CLN3 juvenile Batten disease: the publication of the first comprehensive international guidelines for the diagnosis and management of CLN3 disease. Published in Orphanet Journal of Rare Diseases, the article provides an evidence- and consensus-based tool designed for healthcare professionals involved in CLN3 disease care and notes that, until now, no comprehensive clinical recommendations existed for CLN3 disease.

This achievement is especially meaningful because BBDF helped make it possible from the project’s early development through completion. In September 2021, BBDF announced a formal sponsorship agreement with Care Beyond Diagnosis to establish internationally validated clinical management guidelines for CLN3 disease. At the time, BBDF recognized that methodically and transparently developed guidelines could help establish and improve standards of care, support access to effective management, and help families and clinicians navigate medical necessity.

BBDF’s investment was about more than funding a publication. It was about closing a critical gap for the CLN3 community. Care Beyond Diagnosis noted that BBDF’s financial commitment was important to keep the program moving forward and that BBDF would also be instrumental in helping get the completed guidelines into the hands of families and caregivers. Today, that commitment has reached the finish line: the guidelines are published, accessible, and available to support care conversations around the world. Read the guidelines here.

The completed publication brought together 39 international experts from eight specialties, including the perspective of patient advocacy, and resulted in 53 recommendation statements across 11 care domains. These domains include diagnostics, clinical recommendations and management, assessments, social considerations, ocular management, epilepsy and seizures, nutrition, respiratory health, sleep and rest, and end-of-life care.

The recommendations also reflect the kind of practical, multidisciplinary support families need throughout the course of CLN3 disease. Diagnostic delay and misdiagnosis remain major challenges, especially when vision loss—the most common early sign—is mistaken for more common eye conditions. The publication emphasizes early recognition, holistic management, and coordinated care, including support for families navigating CLN3 disease outside of specialist centers.

Importantly, BBDF’s support helped make the work possible while preserving the independence of the clinical recommendation process. The program was run separately by Care Beyond Diagnosis, that sponsors were not invited to participate in statement development, voting rounds, or manuscript preparation, and that sponsors were updated only on task completion.

This project is a powerful example of BBDF’s mission in action. Since its founding in 2008, BBDF has worked to eradicate juvenile Batten disease by raising awareness and funds to accelerate research for a treatment or cure. The foundation’s approach includes funding high-impact projects, filling gaps in juvenile Batten disease research, and working with scientists and project managers to identify, develop, coordinate, and monitor efforts that move the field forward.

For families, these recommendations offer a framework to help guide discussions with clinicians, advocate for care aligned with international standards, and support shared decision-making across the lifespan. For clinicians, they provide a practical reference for earlier diagnosis and more consistent, multidisciplinary management. For BBDF and our community of donors, families, advocates, and partners, they represent donor-powered impact from start to finish.

We are grateful to Care Beyond Diagnosis, the international experts and clinicians who contributed to this work, the patient advocates whose lived experience shaped the recommendations, and BBDF Principal Scientific Consultant Ineka Whiteman, PhD, who co-authored the publication. BBDF is proud to have supported this project through funding and in-kind support, helping turn a recognized community need into a completed, published resource for the global CLN3 community.

Read the full recommendations in Orphanet Journal of Rare Diseases.

Lyon, France – Austin, Texas, United States – Mai 13, 2025 – 6.00 pm CET –Theranexus, a

biopharmaceutical company developing drug candidates for rare neurological diseases and the Beyond

Batten Disease Foundation (BBDF), today announced new real-world data strongly supporting the efficacy of

Batten-1 (miglustat) as a treatment for CLN3 disease, also known as juvenile Batten disease.

The analysis evaluated visual acuity outcomes in CLN3 patients treated with Batten-1 (miglustat, n=11),

versus untreated patients (n=22), using real-world data collected from natural history studies, family

interviews, published reports, and prescribers’ personal communications. This analysis focused on patients

with measurable visual acuity at baseline (visual acuity score ≤ 1.9 LogMAR) and compared the progression

of visual function between groups over a 12-month period. To ensure an appropriate comparison between the

treated and untreated groups, a propensity score methodology was applied.

The analysis demonstrated a statistically significant and clinically meaningful difference in favor of

Batten-1 treatment on visual function with a notable preservation of visual acuity in treated patients

compared to untreated patients. The notable preservation of visual acuity in treated patients compared to

untreated patients add to the positive results from the Phase 1/2 study of Batten-11 and underscore the

potential of miglustat to address critical unmet needs in Batten disease. The visual acuity endpoint used in

the real-world analysis is the same as that selected for the planned pivotal Phase 3 clinical trial of Batten-1,

a design endorsed by the U.S. Food and Drug Administration (FDA)2 and the European Medicines Agency

(EMA)3.

“We are deeply grateful to the patients, their families, and the healthcare providers who made this important

analysis possible by agreeing to share their experiences and those unique clinical data. This collaboration has

been essential in demonstrating Batten-1 potential to change the course of CLN3 disease” explains Craig

Benson, Chairman of the Beyond Batten Disease Foundation.

“Achieving near stabilization of visual acuity over 12 months in CLN3 patients is truly remarkable and

unprecedented. In this population, we would typically expect a relentless decline in vision. These results offer

real hope for altering the natural progression of the disease,” commented Dr. Gary Clark, MD, Chief of

Neurology and Developmental Neuroscience at Baylor College of Medicine, Houston, Texas.

“These results have been observed using the primary efficacy endpoint defined in our Phase 3 trial, this is

highly reassuring. These findings strongly support our development strategy and reinforce the relevance of our

endpoint in demonstrating Batten-1 potential efficacy” concluded Marie Sebille, Chief Medical Officer at

Theranexus.

Lyon, France – Austin, Texas, United States – November 19, 2024 – 6 PM CET – Theranexus, a biopharmaceutical

company innovating in the treatment of rare neurological diseases, and the Beyond Batten Disease Foundation

(BBDF) presented the final and positive results of the Phase I/II trial to evaluate Batten-1 in 6 young adult patients

with CLN3 Batten’s disease after 18 months of treatment, at the Child Neurology Society Annual Meeting in San

Diego, 11 to 14th November.

This presentation highlights the strong safety profile of miglustat in CLN3 Batten disease patients and underscores

the positive efficacy data gathered during this trial. The findings demonstrate clear target engagement, a

biological effect, and are suggestive of a stabilization of disease progression over the treatment period. All trial

participants chose to continue receiving miglustat through the BBDF’s early access program, with no safety

concerns reported after two years of ongoing treatment.

Lyon, France – Austin, Texas, United States – 6 June 2024 – 7:30am CT – Theranexus, a biopharmaceutical company innovating in the treatment of rare neurological diseases, and the Beyond Batten Disease Foundation (BBDF), confirm positive results in their Phase I/II trial to evaluate Batten-1 in Batten disease (CLN3) after 18 months of treatment. The results indicate a decline in serum neurofilament light chain (NfL), a biomarker of neuronal death, and confirm the therapeutic potential of the Batten-1 drug candidate in juvenile (CLN3) Batten disease.

Measurements of the concentration of neurofilament light chains (NfL), a recognized biomarker of neurodegeneration, after 18 months of treatment confirm the 12-month results presented at the International NCL2023 Congress in September 2023. This biomarker, measured in the serum of patients compliant to protocol, decreased by an average of 33% after 18 months of treatment (as a reminder, 32% after 12 months of treatment) compared to pre-treatment level.

Theranexus Announces Positive Data on Efficacy and Safety in the Phase I/II Trial of Batten-1

Stabilization of motor symptom progression in young adult patients suffering from juvenile Batten disease (CLN3) after 18 months of treatment

Lyon, France – Austin, Texas, United States – 17 April 2024 – 3pm CET – Theranexus, a biopharmaceutical company innovating in the treatment of rare neurological diseases and the Beyond Batten Disease Foundation (BBDF), today announce final positive data on efficacy and safety in the Phase I/II trial of its drug candidate Batten-1 in juvenile Batten disease (CLN3) after 18 months of treatment.

The 18-month safety and efficacy data confirm the 12-month results announced in September 2023. Batten-1 presented a good safety profile. On average, in the 6 young adult patients, treated with Batten-1, progression of motor symptoms was considerably slowed down and appeared stable compared to progression in untreated patients, as evaluated by the modified UBDRS Physical Assessment score. The mean change from baseline was +1,83 for the six subjects treated over 18 months vs +6,04 in untreated subjects from the natural history study conducted by the University of Rochester (n=46).

For Professor Gary Clark, the trial’s principal investigator and Chief of Child Neurology at Texas Children’s Hospital in Houston, “The data collected after 18 months of treatment with Batten-1 further reinforce its highly promising potential. We currently no longer observe a marked progression of motor symptoms in the 6 patients treated. These results support the prospect of a major benefit of Batten-1 for the children with this very severe disease and for their families”.

For Theranexus’ CEO, Mathieu Charvériat: “These positive results on efficacy and safety of Batten-1 are highly encouraging for the patients and their families. Together with BBDF and the investigators we are initiating an Expanded Access Program (EAP) to enable the 6 patients previously in the trial to continue receiving the treatment, considering its favorable risk-benefit profile. These results highlight the strong therapeutic potential Batten-1 on the clinical course of the disease. In this context, we are exploring different funding options to ensure we have the adequate resources to launch a phase 3 pivotal trial, which design has already received positive opinions by the FDA and the EMA”.

As a reminder, the Phase I/II trial conducted by Theranexus and BBDF to evaluate their drug candidate, Batten-1, included six patients with juvenile Batten disease (CLN3) aged 17 years and over. The patients were treated for 18 months. Following their participation in the trial, all patients are offered the possibility to continue receiving the treatment through a compassionate use program. 

About Batten-1
Batten-1 is a novel and exclusive proprietary drug containing the active ingredient miglustat. The mechanism of action of this substance blocks the accumulation of glycosphingolipids and neuroinflammation, thus significantly reducing neuronal death that contributes to a progressive loss of function in patients. For patients over 17 years of age in the Phase I/II trial, the product is administered in solid form. In the Phase III trial, it will be administered in a liquid form better suited to pediatric patients.

Phase I/II trial design: this is an open-label trial involving 6 patients over 17 years of age with CLN3 Batten disease, treated with miglustat up to 600 mg/day for an 18-month period. The primary endpoint is patient safety and tolerability, assessed using reports of adverse effects, biological tests and ECG, as well as the pharmacokinetics of miglustat. The secondary endpoints include biomarkers (NfL, glycosphingolipds), efficacy monitoring: Unified Batten Disease Rating Scale, visual acuity, measurement of brain volumes by MRI and measurement of the thickness of the neuronal layer of the retina by optical coherence tomography scans. Administration of Batten-1 in escalating doses with a maximum of 600 mg/day was well tolerated, with no severe side effects observed causing treatment discontinuation. The most commonly reported adverse events are reversible gastrointestinal effects of often light to moderate severity, thus demonstrating the good tolerability profile of Batten-1 in this population. Further information about the trial is available on https://clinicaltrials.gov/ct2/show/NCT05174039.

About Batten disease
Juvenile Batten disease, also known as Spielmeyer-Vogt or CLN3 disease, is a rare, fatal, inherited disorder of the nervous system for which there is no treatment or cure. Juvenile Batten disease belongs to a group of disorders referred to as neuronal ceroid lipofuscinoses (NCLs). Over 400 different errors in 13 genes have been attributed to various forms of NCL, which differ from one another primarily by when symptoms first appear. The first symptom in the juvenile form, progressive vision loss, appears between the ages of 4 and 6 and is followed by cognitive disorders, behavioral disorders, and motor disorders. Seizures commonly appear within 2-4 years of the onset of disease. Over time, patients continue to decline mentally and physically. Eventually, those affected become wheelchair-bound, are bedridden, and die prematurely.

Juvenile Batten disease is always fatal; usually by the late teens to early 20s. In the United States and Europe, the juvenile form is the most common of the NCLs, which together, affect nearly 2,000 patients[1]. In pathophysiological terms, interactions between neurons and glial cells play key roles in the emergence and progression of all the NCLs.

About Beyond Batten Disease Foundation
Beyond Batten Disease Foundation (BBDF) is the world’s largest nonprofit organization dedicated to funding research for a treatment and cure for juvenile (CLN3) Batten disease. Since its inception in 2008, over $35 million has been invested in research by leveraging donations, co-funding and strategic partnerships. BBDF is spearheading a unique, cohesive strategy, incorporating independent scientific resources and collaboration with related organizations to drive research in juvenile Batten Disease. Today there is a treatment in sight. BBDF funded research has discovered a drug – Batten-1 – that slows the progression of the disease in Batten models. More information can be found at www.beyondbatten.org.

About Theranexus
Theranexus is an innovative biopharmaceutical company that emerged from the French Alternative Energies and Atomic Energy Commission (CEA). The company has a unique platform for the identification and characterization of advanced therapy drug candidates targeting rare neurological disorders and an initial drug candidate in clinical development for Batten disease.

Theranexus is listed on the Euronext Growth market in Paris (FR0013286259- ALTHX).

[1] National Organization for Rare Disorders (NORD)/Orphanet