CLN3

Researchers find that an easy-to-measure brain process may be a target or biomarker in measuring treatment outcomes in clinical trials in Batten disease. Early symptoms can be subtle. A child's personality and behavior may change, and clumsiness or stumbling develops between the ages of five and ten. Over time, cognitive impairment sets in, seizures emerge or worsen, vision loss begins, and motor skills decline. This is the course of Batten disease, a progressive inherited disorder of the nervous system that results from mutations to the CLN3 gene. "It is a devastating neurodegenerative disorder of childhood," said John Foxe, PhD, director of the Del Monte Institute for Neuroscience and co-director of the University of Rochester Intellectual and Developmental Disabilities Research Center (UR-IDDRC), "and while it is very rare, it is important to study and understand because it could inform what we know and how we treat it and other related rare diseases." A possible neuromarker In a new study, out today in theJournal of Neurodevelopmental Disorders, Foxe and a team of researchers from the University of Rochester Medical Center may be closer to that goal of understanding. The paper describes how they measured changes in brain function of participants with CLN3 disease, also known as 'juvenile-onset' Batten disease. Researchers found that the functioning of the auditory sensory memory system -- the brain system required for short-term memory recall -- appears to decrease as the disease progresses. They revealed this by utilizing electroencephalographic recordings (EEG) to measure the brain activity of participants with and without Batten disease as they passively listened to simple auditory beeps. The participants simultaneously watched a video of their favorite movie while the brain responses to these beeps were being measured. In the participants with Batten disease, the EEG revealed a decline in the response from the auditory sensory memory system as the disease progressed. There were no significant changes among the other participants. This finding suggests that this easy-to-measure brain process may be a target or biomarker in measuring treatment outcomes in clinical trials. "We needed to find a task that did not require explicit engagement or attention, and this is one of those kinds of tasks," Foxe said. "The brain produces the signal that we're looking at, regardless of whether the participant is paying attention to the beeps or not. It is an objective method that provides new insight into the brain function of a population with varying communication abilities." Leading Batten disease research & treatment There are 12 currently known childhood-onset forms of Batten disease, each genetically distinct from one another, and all significantly impact neurodevelopment. The University of Rochester Batten Center (URBC) is a recognized leader in research and treatment of this condition. URBC is designated a Center of Excellence by the Batten Disease Support and Research Association (BDSRA). The University is a designated Intellectual and Developmental Research Center (IDDRC), and its current principal project is aimed at neuromarker discovery in Batten disease. With several potential gene therapies for Batten disease currently in advanced stages of development, this recent finding continues the mission at URMC to identify biomarkers to evaluate the effectiveness of these experimental treatments. Progressing scientific findings Researchers in the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Lab, where Foxe is co-principal investigator with Edward Freedman, PhD, are using these findings to leverage a Batten disease mouse model. They aim to measure the impact pharmaceuticals have on the auditory perceptual system. Researchers are starting with treatments already on the market for other conditions. "We think this potential biomarker is key to the possibility for us to screen these treatments in the mouse models. The auditory sensory memory marker provides a sensitive measure," Foxe said. "We'll be able to tell you pretty quickly if a treatment is having an impact and know if it is actually changing dynamics -- i.e., whether the system in the brain is improving, what the speed of improvement is, etc. I think that is a big deal." Additional authors include first author Tufikameni Brima, PhD, Edward Freedman, PhD, Kevin Prinsloo, PhD, Heather Adams, PhD, Kuan Hong Wang, PhD, Luke Shaw, and Emma Mantel of the University of Rochester School of Medicine and Dentistry, Erika Augustine, MD, of the Kennedy Krieger Institute, and Jonathan Mink, MD, PhD. This research is supported by the Schmitt Program in Integrative Neuroscience (SPIN) through the Del Monte Institute for Neuroscience pilot program, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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 and AUSTIN, TX and CARDIFF, UK / ACCESSWIRE / February 21, 2023 / 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 pro 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 . 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 - Batten-1 - that slows the progression of the disease in Batten models. More information can be found at . 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). More information at Click and follow us on Twitter and Linkedln 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 29 April 2022 under number D. 22-0399, a copy of which is available on ) 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 SOURCE: Theranexus View source version on accesswire.com:

ImCheck Publishes Seminal Paper in Cell Reports Elucidating How Butyrophilins Activate Vγ9Vδ2 T cell Function Against Tumor Cells Marseille, France, July 13, 2021 – ImCheck Therapeutics today announced the publication of preclinical data elucidating the fundamental role of butyrophilins (BTNs) in the activation of V gamma 9 V delta 2 (Vγ9Vδ2) T cells leading to an anti-tumor immune response in the peer-reviewed journal, Cell Reports. The publication, titled “BTN2A1, An Immune-checkpoint Targeting Vγ9Vδ2 T Cell Cytotoxicity Against Malignant Cells” summarizes the findings of the interaction between specific BTN subtypes that efficiently activate Vγ9Vδ2 T cells, an important subset of cytotoxic γδ T cells. In addition, the publication demonstrates that an anti-BTN2A1-specific antibody is able to inhibit the cytotoxic function of the Vγ9Vδ2 T cells. The article was authored by ImCheck scientists in collaboration with the laboratory of Prof. Daniel Olive, Professor of Immunology and Director of the Oncology Research Programs at Aix Marseille University and the company’s scientific founder. “ImCheck was founded to advance fundamental discoveries on the role of the butyrophilin superfamily of immunomodulators in  T cell modulation, and bring a new class of antibody-based therapeutics to patients. Today’s publication provides convincing evidence that the interaction of butyrophilins plays a major role in the activation of these crucial cytotoxic T cells,” stated Loui Madakamutil, PhD, Chief Scientific Officer of ImCheck. “As our lead program ICT01, which targets BTN3A to selectively activate Vγ9Vδ2 T cells, continues to successfully advance in its clinical development and has now demonstrated biological activity to activate V9V2 T cells in tumor patients, we value the recognition from an important journal like Cell Reports of the ground-breaking science that supports our mission of developing new therapies to treat cancer.” Gamma-delta (γδ) T cells are an important component of the immune system and exhibit diverse functional attributes including the killing of cellular pathogens or abnormal or cancerous cells. BTNs represent a new super-family of immunoregulators present on the surface of several cell types, including cancer cells. The preclinical results published today provide key evidence that one specific BTN, BTN2A1, forms a complex with all the three isoforms of BTN3A (BTN3A1, BTN3A2, BTN3A3) to trigger the activation of Vγ9Vδ2 T cells. These findings advance the understanding of how BTNs activate Vγ9Vδ2 T cell function against tumor cells. In addition, the results validate ImCheck’s leadership in BTNs and the company’s development of a novel and disruptive pipeline of antibodies that target BTNs as potential therapies in oncology, autoimmune and infectious diseases. ** About IMCHECK THERAPEUTICS ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies positioned at the crossroads of two high-potential immunological fields: γ9δ2 T cells and butyrophilins (BTN), a novel super-family of checkpoint molecules. Due to their mechanism of action, and notably their ability to simultaneously modulate innate and adaptive immunity, ImCheck's “first-in-class” activating antibodies may be able to produce superior clinical results as compared to the first-generation of immune checkpoint inhibitors and when used in combination to overcome the resistance to this group of agents. In addition, preclinical experiments with ImCheck’s antagonist antibodies are being evaluated as potential treatments for autoimmune diseases. Co-founder of the Marseille Immunopole cluster, ImCheck benefits from support from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille Université), a worldwide leader in γδ T cells and butyrophilins research; from the experience of an expert management team; and from the commitment of leading US and European investors. For further information on ImCheck: and @ImCheckThx Press contacts US and EU Trophic CommunicationsGretchen Schweitzer +49 (0) 172 861 8540 imcheck@trophic.eu FranceATCG-PARTNERSCéline Voisin+33 (0)9 81 87 46 72 / +33 (0)6 62 12 53 39imcheck@atcg-partners.com Attachment