Rett Syndrome

Study site selection and finalization of clinical trial agreement final step toward initiation of RVL-001 proof-of-concept clinical studies early next year BOSTON, Oct. 24, 2024 /PRNewswire/ -- Unravel Biosciences, Inc., ("Unravel"), an AI-enabled therapeutics company established to advance drugs for complex diseases, and the clinical research unit of the PECET of the University of Antioquia, certified in Good Clinical Practices by the Colombian Health Regulatory Authority ("INVIMA") and located in in Medellín, Colombia, today announced the finalization of a clinical trial agreement enabling PECET to be the designated study site for Unravel's RVL-001 proof of concept clinical trials for Rett syndrome (RTT) and Pitt Hopkins syndrome (PTHS). Unravel's proprietary BioNAV™ drug discovery platform identified RVL-001 as a potentially promising therapeutic drug for Rett Syndrome and PTHS. Building on previously announced initiatives by Unravel to initiate a proof-of-concept clinical trials of RVL-001 in Colombia for RTT as well as a collaboration by the Pitt Hopkins Research Foundation (PTHF) to conduct an extension study of RVL-001 in PTHS, today's agreement with PECET in Colombia formally establishes the clinical infrastructure for Unravel to rapidly evaluate BioNAV™ identified drugs in patients. "We are excited to collaborate with the highly skilled PECET team to accelerate therapeutics development for rare disease patients," said Richard Novak, Ph.D., Unravel Co-Founder and CEO. "By conducting multiple clinical trials in parallel at a single clinical trial site enables faster and less costly drug development to support more patients with unmet needs." RTT and PTHS are both rare neurogenetic disorders starting in early childhood that lead to debilitating cognitive, motor and autonomic disability. Despite one approved treatment for RTT, there remains a significant unmet need for novel treatments having meaningful efficacy and acceptable safety and tolerability. There are no known treatments for PTHS. In addition to Unravel's RVL-001 program for RTT and PTHS, the company has also initiated development work on RVL-002, a first-in-class novel molecule for Rett syndrome. Initiation of patient dosing for the RVL-001 trial in RTT and extension trial in PTHS are both anticipated in early 2025, with study startup activities including clinical trial material manufacturing and patient recruitment initiated earlier this year as previously announced. "We are pleased to be the designated clinical trial center for Unravel, it is a great challenge that we will take on with great enthusiasm to contribute to the search for solutions for this type of disease," said Iván Darío Vélez, Professor Emeritus of the University of Antioquia and founder of PECET. "PECET has extensive expertise conducting clinical studies with international biopharma sponsors including US to support worldwide registration and approval and we look forward to supporting Unravel in their development efforts". About Unravel Biosciences Unravel Biosciences revolutionizes drug development, uncovering disease-modifying targets from patient data powered by AI systems biology computation, rapid in vivo screening, and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ foundational model of human health combining target and drug discovery, preclinical screening and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical programs. Unravel's platform developed RVL001, a novel formulation to treat neurodevelopmental disorders, RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics using existing drugs as a key stepping stone to validating novel targets and mechanisms in real patient populations. and SOURCE Unravel Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Data from an analysis of five NHP studies showed lumbar IT administration led to widespread and consistent biodistribution of AAV9 gene therapy vectors across brain and spinal cord regions IT and ICM administration achieved comparable biodistribution across brain and spinal cord regions in NHPs Findings from the analysis reaffirm the clinical potential of IT administration as an effective, safe and minimally invasive approach to deliver AAV-based gene therapies designed to treat CNS diseases in both children and adults DALLAS, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announced that it will present biodistribution data from an analysis of 28 non-human primates (NHP) evaluating the delivery of AAV9 gene therapy vectors across five different studies using intrathecal (IT) delivery by lumbar puncture (four studies) or intra-cisterna magna (ICM) injection (one study). The data will be presented during a poster presentation at the upcoming 31st Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), taking place in Rome, Italy from October 22-25, 2024. These findings reinforce Taysha’s clinical development approach utilizing IT administration to deliver AAV-based gene therapies designed to treat the genetic root cause of CNS diseases, including the TSHA-102 program in clinical evaluation for children, adolescents and adults living with Rett syndrome. “Findings from an analysis across five NHP studies showed that both IT and ICM administration led to comparable, consistent and widespread biodistribution of AAV9 vector throughout the brain and spinal cord regions,” said Sukumar Nagendran, M.D., President and Head of Research & Development at Taysha. “Importantly, these findings further support the clinical potential of IT administration as an effective, safe and minimally invasive delivery approach for broad targeting of the CNS that has potential for outpatient use in both children and adults. We believe the NHP biodistribution data, together with our additional preclinical data, reaffirm our clinical development strategy utilizing IT administration and provide translational support for the broad clinical effect reported following treatment with TSHA-102 in both our REVEAL adolescent/adult trial and REVEAL pediatric trial." Poster presentation details are as follows: Title: Broad CNS Biodistribution of AAV9-based Gene Therapies Delivered by Intrathecal Lumbar Puncture in Non-Human Primates Presenters: Nino Devidze, MS, Ph.D., Clinical Development Lead and Emdadul Haque, Ph.D., Senior Director, Translational Sciences at Taysha Gene Therapies Date and Time: Wednesday October 23, 2024, from 13:30 to 15:00 CEST Poster Session: CNS & Sensory Diseases Poster Number: P0284 Additional details on the meeting can be found at the 31st Annual ESGCT Congress website. About TSHA-102TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the CNS. TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Regenerative Medicine Advanced Therapy, Fast Track and Orphan Drug and Rare Pediatric Disease designations from the FDA, Orphan Drug designation from the European Commission and Innovative Licensing and Access Pathway designation from the Medicines and Healthcare products Regulatory Agency. About Rett SyndromeRett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain. The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration. Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. Rett syndrome caused by a pathogenic/likely pathogenic MECP2 mutation is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K. About Taysha Gene TherapiesTaysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit www.tayshagtx.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” “plans,” and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include, but are not limited to, statements concerning the potential of TSHA-102 and Taysha’s other product candidates to positively impact quality of life and alter the course of disease in the patients Taysha seeks to treat, its research, development and regulatory plans for its product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed and the potential market opportunity for Taysha’s product candidates. Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding Taysha’s business are described in detail in its SEC filings, including in Taysha’s Annual Report on Form 10-K for the full-year ended December 31, 2023 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, which are available on the SEC’s website at www.sec.gov. Additional information will be made available in other filings that Taysha makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Taysha disclaims any obligation to update these statements except as may be required by law. Company Contact:Hayleigh Collins Director, Head of Corporate Communications and Investor RelationsTaysha Gene Therapies, Inc.hcollins@tayshagtx.com Media Contact:Carolyn HawleyInizio EvokeCarolyn.hawley@inizioevoke.com

Part A of the placebo-controlled Phase 2 study has been completed ANAVEX®3-71 demonstrates a dose-dependent pharmacodynamic effect on objective EEG biomarkers of schizophrenia Patients are currently being dosed in Part B of the Phase 2 study which will investigate a longer treatment duration Oct. 17, 2024 -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) diseases, today announced encouraging preliminary electroencephalography (EEG) biomarker results from the Part A of the ongoing placebo-controlled Phase 2 clinical study of ANAVEX®3-71 for the treatment of schizophrenia. Part A of the Phase 2 study ANAVEX®3-71-SZ-001 (NCT06245213), was a multiple ascending dose study in 16 participants treated with either oral placebo, oral ANAVEX®3-71 90 mg daily, or oral ANAVEX®3-71 180 mg daily for 10 days. Preliminary results demonstrated a dose-dependent effect of ANAVEX®3-71 on two key EEG biomarkers in patients with schizophrenia. Treatment with ANAVEX®3-71 compared to placebo resulted in improvements in 40 Hz Auditory Steady-State Response (ASSR) Inter Trial Coherence (ITC) and Resting State Alpha Power, both of which were increased. These effects were most pronounced in the higher dose group demonstrating a dose-dependent pharmacodynamic effect. These results provide evidence of CNS target engagement and potential therapeutic effects of ANAVEX®3-71 in schizophrenia. The observed changes reversed known EEG and ERP biomarker abnormalities associated with schizophrenia1. These EEG biomarkers correlate with positive, negative, and cognitive symptoms of schizophrenia. Individuals with schizophrenia typically have reduced neural synchrony as measured by 40 Hz ASSR ITC. Improvements in 40 Hz ASSR ITC indicate enhanced neural synchronization, potentially leading to reduced auditory hallucinations (positive symptom), improved executive function, and working memory (cognitive symptoms).2 Individuals with schizophrenia also typically have decreased resting state alpha power correlating with sensory and behavioral problems. Increases in Resting State Alpha Power reflect improvements in thalamocortical circuits and sensory gating, potentially resulting in reduced irritability and anxiety (negative symptoms).3 “We are pleased to see an initial effect of biomarkers changing in people with schizophrenia treated with our oral M1/SIGMAR1 therapy ANAVEX®3-71, which could eventually help patients address both positive, negative, and cognitive symptoms of schizophrenia,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “The results are encouraging for further development of ANAVEX®3-71 for people with schizophrenia.” ANAVEX®3-71 was well tolerated, with no serious adverse events reported. Oral ANAVEX®3-71 is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects. This novel mechanism of action offers the potential to treat all symptom domains of schizophrenia without the side effects of standard of care antipsychotics. ANAVEX®3-71 has previously demonstrated long-lasting, pro-cognitive effects and behavioral improvements in animal models of neurodegenerative diseases4,5, an ability to prevent cognitive decline in animal models6,7, and has shown robust safety signals in healthy volunteers at single doses ranging from 5 to 200 mg once daily.8,9 Recent research into the genetic underpinnings of schizophrenia has revealed links between this psychiatric disorder and neurodegenerative disease, suggesting the disorders may share certain mechanisms.10 Oral ANAVEX®3-71, in addition to the M1 muscarinic receptor activity, the combined SIGMAR1 receptor activity might offer a novel mechanism of action that may address multiple symptom domains without the motor side effects associated with traditional antipsychotics. The currently ongoing Part B of the placebo-controlled Phase 2 study, which includes more participants and a longer treatment duration, will provide more comprehensive data on the efficacy and safety of ANAVEX®3-71 in schizophrenia. Anavex expects data from Part B of the placebo-controlled Phase 2 study in the first half of 2025. Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 34% of people do not respond to therapy, 11 with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.12 Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn. 1 Cecchi M, Adachi M, Basile A, et al. Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers. Schizophr Res. 2023;254:178-189. doi:10.1016/j.schres.2023.02.018 2 Parker DA, Hamm JP, McDowell JE, et al. Auditory steady-state EEG response across the schizo-bipolar spectrum. Schizophr Res. 2019;209:218-226. doi:10.1016/j.schres.2019.04.014 3 Newson JJ, Thiagarajan TC. EEG Frequency Bands in Psychiatric Disorders: A Review of Resting State Studies. Front Hum Neurosci. 2019;12:521. Published 2019 Jan 9. doi:10.3389/fnhum.2018.00521 4 Fisher A, Bezprozvanny I, Wu L, et al. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neurodegener Dis. 2016;16(1-2):95-110. doi:10.1159/000440864 5 Hall H, Iulita MF, Gubert P, et al. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease. Alzheimers Dement. 2018;14(6):811-823. doi:10.1016/j.jalz.2017.11.009 6 https://www.anavex.com/post/anavex-life-sciences-reports-new-publication-in-scientific-journal-demonstrating-the-potential-of 7 Orciani C, Do Carmo S, Foret MK, et al. Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology [published online ahead of print, 2023 Sep 26]. Neurobiol Aging. 2023;132:220-232. doi:10.1016/j.neurobiolaging.2023.09.010 8 Fadiran EO, Hammond E, Tran J, et al. Concentration-QTc Relationship from a Single Ascending Dose Study of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for the Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease. Clin Pharmacol Drug Dev. 2023;12(9):888-901. doi:10.1002/cpdd.1303 9 Fadiran EO, Hammond E, Tran J, Missling CU, Ette E. Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease. Clin Pharmacol Drug Dev. 2024;13(1):21-31. doi:10.1002/cpdd.1323 10 Guo P, Meng C, Zhang S, et al. Network-based analysis on the genes and their interactions reveals link between schizophrenia and Alzheimer's disease. Neuropharmacology. 2024;244:109802. doi:10.1016/j.neuropharm.2023.109802 11 Potkin SG, Kane JM, Correll CU, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6(1):1. Published 2020 Jan 7. doi:10.1038/s41537-019-0090-z 12 Nucifora FC Jr, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131:104257. doi:10.1016/j.nbd.2018.08.016 The content above comes from the network. if any infringement, please contact us to modify.