Newsroom Archives: Research

From 22 to 26 February 2023 in Orlando, Florida 

▪ Presentation of preclinical data demonstrating how Batten-1 drastically reduces the buildup of toxic glycosphingolipids in Batten disease and a poster describing for the first time the burden of Batten disease. 

Lyon, France – Austin, Texas, United States – Cardiff, UK – 20 February 2023 – 6pm CET – Theranexus, a biopharmaceutical company innovating in the treatment of neurological diseases and pioneer in the development of drug candidates modulating the interaction between neurons and glial cells, and its partners Beyond Batten Disease Foundation (BBDF) and Cardiff University, today announced several presentations at WORLDSymposium 2023, an international scientific event focused on lysosomal diseases (22 to 26 February in Orlando, Florida – United States). 

At the conference, the research conducted by Cardiff University, Theranexus and BBDF will be showcased in five presentations, including one oral presentation. 

• • An oral session entitled “The Batten disease associated protein CLN3 is required for the efflux of lysosomal potassium“, presented by Dr. Hannah Best of Cardiff University, will feature her research on the CLN3 protein in Batten disease on Wednesday 22 February at 9am. Dr. Best will receive the Young Investigator Award for her outstanding research. 
• • The session will be followed by a poster session presenting our novel therapeutic strategy that uses Batten-1 to treat Batten disease by reducing toxic glycosphingolipids in neurons (Poster 229, Glycosphingolipid reduction with miglustat as a therapeutic strategy for CLN3 and other neuronal ceroid lipofuscinoses, Dr. Emyr Lloyd-Evans, Cardiff University). 
• • A broader presentation of the effects of Batten-1 active ingredient, miglustat, will also be given on the same day (Poster 230, Deciphering the various mechanisms of action of miglustat in the lysosomal disorders, Drs Emyr Lloyd-Evans and Charles Evans, Cardiff University). 
• • Lastly, a new series of studies will be presented, highlighting for the first time the burden of the disease as experienced by patients and their families (Poster 185, Understanding the functional burden of CLN3 through the eyes of patients and families, Skyler Jackson, Engage Health, BBDF, Theranexus). 

Theranexus CEO, Mathieu Charvériat explains: “These different presentations by internationally recognized teams confirm the solid scientific and clinical rationale underpinning the development of our asset Batten-1 in juvenile Batten disease, for which there are significant unmet medical needs representing a considerable burden for families. To our knowledge, Batten-1 is the only candidate in active clinical development to tackle the major medical challenges of this disease. In this context, we are currently preparing the Phase III trial which should begin during 2023.” 

For Dr. Emyr Lloyd-Evans, an expert in lysosomal disease indications from Cardiff University, “We are delighted to present our innovative research on CLN3 and miglustat to our peers, underlining a solid rationale for the use of Batten-1 in juvenile Batten disease. In this disease, as in the other two similar indications for which miglustat is registered and efficacious in patients, the drug blocks the toxic buildup of glycosphingolipids. Our scientific data and in-depth knowledge of miglustat therefore converge towards a potential efficacy of this drug candidate in Batten disease and we are excited for it to be tested in the Phase III trial to be conducted by Theranexus and BBDF.” 

“We present initial research quantifying the significant burden suffered by patients, families and caregivers, which justifies the absolute need to develop novel therapeutic approaches. The research also highlights, as regularly observed in our discussions with patients’ families and advocacy organizations, the wish of families to take part in clinical developments such as those led with Theranexus,” concludes Craig Benson, Chair of Beyond Batten Disease Foundation. 

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. 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 a 2-year 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 efficacy monitoring: Unified Batten Disease Rating Scale, visual acuity, and brain MRI and 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. Batten-1 will continue to be assessed in these patients treated over a 24-month period. 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 which is followed by personality changes, behavioral problems, and slowed learning. 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. Psychiatric symptoms or psychosis can appear at any time. 

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 3,000 patients1. In pathophysiological terms, interactions between neurons and glial cells play key roles in the emergence and progression of all the NCLs. 

1 National Organization for Rare Disorders (NORD)/Orphanet 

2 Settembre et al, TFEB links autophagy to lysosomal biogenesis, Science 2011 

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 Disease2. 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). It specializes in the treatment of central nervous system disorders and is a pioneer in the development of drug candidates targeting both neurons and glial cells. 

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. 

Lyon, France – Austin, Texas, United States – 6 September 2022 – 6 pm CEST – Theranexus, a biopharmaceutical company innovating in the treatment of neurological diseases and pioneer in the development of drug candidates modulating the interaction between neurons and glial cells, and the Beyond Batten Disease Foundation (BBDF), have today announced finalization of recruitment of the last patient for the Phase I/II clinical trial to evaluate the tolerability, pharmacokinetics of the Batten-1 drug candidate in juvenile (CLN3) Batten disease.

A total of six patients with juvenile Batten disease aged 17 and over are enrolled in the Phase I/II clinical trial. The Batten-1 drug candidate containing the active ingredient miglustat is administered in escalating doses. The initial tolerability and pharmacokinetic data for miglustat obtained after the first 9 weeks of treatment in this population will serve to initiate Phase III, and Phase I/II patients are being treated and evaluated over a 24-month period.

Franck Mouthon, Chairman of Theranexus, said: “Finalization of recruitment for our Phase I/II trial is an important milestone in the development of Batten-1, a drug candidate that aims to significantly slow progression of juvenile Batten disease for which there is currently no available treatment. Our goal for the next stages in the development process is to launch an international pivotal Phase II/III trial in 2023.”

Craig Benson, Chair of the Beyond Batten Disease Foundation, added: “As parents and representatives of patients with juvenile Batten disease and their families, we are delighted with the enrollment of the last patient in the Phase I/II trial. This new Batten-1 treatment offers tremendous hope for our children affected by the disease.”

The Phase I/II trial is being conducted by referral centers for Batten disease in the United States, with Dr. Gary Clark, Chief of Child Neurology at Texas Children’s Hospital in Houston, as principal investigator.

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 to prevent brain cell death. In the Phase I/II trial, Batten-1 is administered to patients over 17 years of age in solid form, and in Phase III it will be administered in a liquid form better suited to children.

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 which is followed by personality changes, behavioral problems, and slowed learning. 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. Psychiatric symptoms or psychosis can appear at any time.

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 3,000 patients. 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). It specializes in the treatment of central nervous system disorders and is a pioneer in the development of drug candidates targeting both neurons and glial cells.

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).

Next financial publication:
Tuesday 27 September 2022: First half 2022 financial results

More information at http://www.theranexus.com

Contacts
THERANEXUS
Thierry Lambert
Chief Financial Officer
contact@theranexus.com

NEWCAP
Théo Martin/Pierre Laurent
Investor Relations
+33 (0)1 44 71 94 97
theranexus@newcap.eu

FP2COM
Florence Portejoie
Media Relations
+ 33 (0)6 07 76 82 83
fportejoie@fp2com.fr

Disclaimer
This press release contains certain forward-looking statements concerning Theranexus and its business, including its prospects and product candidate development. Such forward-looking statements are based on assumptions that Theranexus considers to be reasonable. However, there can be no assurance that the estimates contained in such forward-looking statements will be verified, which estimates are subject to numerous risks including the risks set forth in the universal registration document of Theranexus filed with the AMF on 28 April 2021 under number D.21-0379 (a copy of which is available on www.theranexus.com) and to the development of economic conditions, financial markets and the markets in which Theranexus operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Theranexus or not currently considered material by Theranexus. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Theranexus to be materially different from such forward-looking statements. Theranexus expressly declines any obligation to update such forward-looking statements.

[1] National Organization for Rare Disorders (NORD)/Orphanet
[2] Settembre et al, TFEB links autophagy to lysosomal biogenesis, Science 2011

Lyon, France – Austin, TX, USA – 3 February 2022 – Theranexus, a biopharmaceutical company innovating in the treatment of neurological diseases and pioneer in the development of drug candidates modulating the interaction between neurons and glial cells, and the Beyond Batten Disease Foundation (BBDF), are starting recruitment for Phase I/II clinical trial to evaluate BBDF-101 in Batten disease.

Franck Mouthon, Chairman of Theranexus, said: “The launch of recruitment is a key step in the development of our drug candidate BBDF-101. This trial will be conducted with BBDF and in collaboration with leading North American referral centers for Batten Disease, a rare, fatal, genetic disorder of the nervous system. Our ambition is to demonstrate the full potential of BBDF-101 in this disease for which there are currently no therapeutic options for patients.”

Following on from the award of Investigational New Drug (IND) approval from the Food and Drug Administration (FDA) for its BBDF-101 program in 2021, Theranexus is now actively recruiting patients for its Phase I/II clinical trial. During the 2-year trial, six patients 17-year-old or older will receive BBDF-101 in escalating doses during the first 4.5 months to establish tolerability and pharmacokinetics of trehalose, miglustat and a combination of trehalose/miglustat. The results of the titration phase will be available at the start of the second half of 2022.

After consulting with the FDA, at the end of 2022 Theranexus plans to start a pivotal Phase III trial involving a pediatric cohort of 30 patients with regular measurements to assess disease progression and safety. The aim will be to compare the development of various signs and symptoms in these patients, as rated on the Unified Batten Disease Rating Scale (UBDRS, neurological and behavioral symptoms, activities of daily living, etc.), over a period of two years, to data from a study of disease progression in a cohort of untreated patients followed for many years at the University of Rochester.

This Phase III trial will be conducted in collaboration with the leading referral centers for Batten disease in the United States which include the Texas Children’s Hospital in Houston, TX, the fourth largest pediatric hospital in the United States, the National Institutes of Health, and the University of Rochester Batten Center in Rochester, NY.

“It is with great gratitude for our patients’ families and donors that we now see the launch of the BBDF-101 clinical program which aims to offer a therapeutic solution for patients suffering from this very rare genetic disease. Achieving this major milestone for the Foundation, in collaboration with Theranexus, is an exciting culmination of almost 12 years of research,” concludes Craig Benson, Chair of the BBDF Board of Directors. 

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 which is followed by personality changes, behavioral problems, and slowed learning. 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. Psychiatric symptoms or psychosis can appear at any time. 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 3,000 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[2]. Today there is a treatment in sight. BBDF funded research has discovered a drug that slows the progression of the disease in Batten models. More information can be found at www.beyondbatten.org

About development of BBDF-101 for Batten disease and the partnership between BBDF and Theranexus

The research funded by BBDF and conducted by academics specializing in lysosomal storage disorders (particularly Baylor College of Medicine) led to the discovery of the drug candidate BBDF-101. Following a partnership agreement between BBDF and Theranexus concluded in late 2019 (see below), Theranexus supplemented preclinical development of BBDF-101 with research to establish product safety. Thanks to the research findings, BBDF-101 will now be able to enter the clinical phase following the grant of IND status by the FDA in September 2021.

The clinical development pathway includes:

• Phase I/II for which recruitment began today,
• Phase III due to start by the end of 2022 and to include 30 patients with the aim of achieving final results in the second half of 2025,

The development of BBDF-101 is the result of a partnership concluded between BBDF and Theranexus in late 2019. The exclusive, global license agreement between BBDF and Theranexus covers the clinical development of drug candidate BBDF-101 pending approval and its commercial use. Theranexus also plans to continue its research on the NeuroLead platform of drug candidates targeting neurological forms of other lysosomal disorders.

In consideration for this license, the agreement provides for Theranexus to pay BBDF fixed sums on signing, approval, and achievement of commercial objectives post-approval. Moreover, the agreement provides for payment of royalties calculated based on net sales of BBDF-101 once it is marketed by Theranexus

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

[2] Settembre et al, TFEB links autophagy to lysosomal biogenesis, Science 2011

Austin, Texas, March 2, 2021

Beyond Batten Disease Foundation (BBDF) is pleased to announce an agreement with Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson, to provide Zavesca® (miglustat) for the development of BBDF-101, a proprietary combination of miglustat and trehalose to treat juvenile Batten disease (CLN3). Janssen will provide drug supply for the clinical trials and Extended Access Program, and right of reference to data within the Zavesca New Drug Application (NDA) to support the development of BBDF-101.

We are excited to announce the following major milestone for BBDF!

The FDA has awarded Orphan Drug and Rare Pediatric Disease designations to Beyond Batten Disease Foundation for BBDF-101. The aim of the program is to facilitate the development of new drugs and biological products for the prevention and treatment of rare pediatric diseases. These designations provide accelerated review for approval, support with the FDA regulatory process and at least seven years of post-approval protection, as well as exemption from filing fees that normally have to be paid to the FDA. These designations do not impact the clinical trial, but are beneficial once the therapy receives New Drug Approval. We are grateful to Theranexus for their continued partnership and commitment to initiating a clinical trial for BBDF-101 as quickly as possible.

THERANEXUS AND BBDF OBTAIN ORPHAN DRUG DESIGNATION (ODD) AND RARE PEDIATRIC DISEASE DESIGNATION (RPDD) FROM THE FOOD AND DRUG ADMINISTRATION (FDA) FOR BBDF-101 FOR BATTEN DISEASE

• Orphan Drug Designation (ODD) is a status that provides seven years of additional post-approval protection and exemption from filing fees
• Rare Pediatric Disease Designation (RPDD) qualifies the sponsor at the time of registration for a salable, transferable priority review voucher which can be used to speed up the approval process for another drug candidate

Lyon, August 28, 2020 – Theranexus, a biopharmaceutical company innovating in the treatment of neurological diseases, and Beyond Batten Disease Foundation (BBDF) today announced the decision by the Food and Drug Administration (FDA) to award Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) to the drug candidate BBDF-101 for Batten disease, a rare, fatal, genetic disorder of the nervous system for which there is no treatment.