BV CYP01

RESEARCH TRIANGLE PARK, N.C. and PARIS, Aug. 23, 2022 /PRNewswire/ -- Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, has received clearance to conduct a Phase I/II trial for its novel Huntington's Disease (HD) gene therapy, BV-101, in France through its subsidiary BrainVectis. This authorization, provided by the National Agency for Safety of Medicines and Health Products (ANSM), the country's governing drug authority, along with the approval of the trial protocol by the Ethics Committee in charge, enables the company to begin recruiting participants. BV-101 is a novel, exclusively designed adeno-associated virus (AAV) gene therapy vector that simultaneously addresses the metabolic dysfunction of diseased neurons as well as contributes to the clearance of the mutant huntingtin protein. BV-101 is administered through MRI-guided neurosurgical techniques directed to target tissues in the basal structures of the brain. In preclinical studies in mice, BV-101 demonstrated the ability to repair the essential cholesterol pathway, provide neuroprotection, and restore physical performance by delivering CYP46A1, a crucial enzyme in the brain which is reduced in people with Huntington's Disease. BV-101 was granted orphan drug designation in the European Union in 2019 by the European Medicines Agency. "Unlike other attempts to treat Huntington's Disease, BV-101 aims to restore cholesterol metabolism, reduce mutant huntingtin and to improve neuronal function. Importantly, BV-101 does not affect the levels of normal huntingtin protein in cells," said Nathalie Cartier-Lacave, MD, founder of BrainVectis and now Vice President, Sector Lead Neurobiology, at AskBio. "If this proves successful, we have the potential to change the course of a devastating disease that causes severe functional and cognitive decline." Currently, there are no approved disease modifying therapies for HD, a rare inherited neurodegenerative disease that, based on information from the Committee for Orphan Medicinal Products (COMP), affects approximately 62,000 people in the European Union. The disease is caused by anomalous repeating mutations in the huntingtin gene leading to abnormal protein aggregates in nerve cells. This results in a range of progressive symptoms, leading to complete physical and mental deterioration, with symptoms usually beginning in adults ages 30 to 50, but which can also occur at an earlier age. "The approval of this trial in France marks a major milestone to potentially treat one of the world's most devastating genetic diseases," added Sheila Mikhail, JD, MBA, CEO and Co-Founder of AskBio. "If successful, this novel approach for treating Huntington's Disease may impact how we treat many other neurodegenerative diseases in the future." About the BV-101 Clinical Trial The BV-101 clinical trial will be an open-label, dose-escalation study to assess the safety, tolerability, and preliminary efficacy of administration of BV-101 in adult subjects with early-stage Huntington's Disease (HD). The trial will include 12-18 participants and is expected to begin in Paris in Q4, 2022. The trial will be led by principal investigator, Alexandra Durr, MD, PhD, Professor Genetics, Reference Centre for Rare diseases-Neurogenetics. For more information about the BV-101 Huntington's Disease clinical trial, contact [email protected] or visit askbio.com. About AskBio Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG acquired in 2020, is a fully integrated gene therapy company dedicated to developing life-saving medicines and changing lives. The company maintains a portfolio of clinical programs across a range of neuromuscular, central nervous system, cardiovascular and metabolic disease indications with a clinical-stage pipeline that includes therapeutics for Pompe disease, Parkinson's disease, and congestive heart failure. AskBio's gene therapy platform includes Pro10™, an industry-leading proprietary cell line manufacturing process, and an extensive capsid and promoter library. With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, UK, the company has generated hundreds of proprietary capsids and promoters, several of which have entered clinical testing. Founded in 2001 and an early innovator in the gene therapy field, the company holds more than 750 patents in areas such as AAV production and chimeric and self-complementary capsids. Learn more at www.askbio.com or follow us on LinkedIn. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability, and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, visit www.bayer.com.

BrainVectis, a subsidiary of Bayer-owned Asklepios BioPharmaceutical, Inc. (AskBio) will begin assessing a gene therapy for Huntington’s disease in France after receiving clearance from health authorities there to conduct a Phase I/II study. The trial will assess BV-101, a novel adeno-associated virus (AAV) gene therapy vector designed to simultaneously address the metabolic dysfunction of diseased neurons and clear the mutant huntingtin protein. Huntington’s disease is a progressive brain disorder that ultimately causes changes in the brain that affect movement, mood and critical thinking skills. There are medications to treat the symptoms, but nothing is currently on the market that will arrest the progression of the disease. The BrainVectis gene therapy is delivered to the patient through MRI-guided neurosurgical techniques directed to target tissues in the basal structures of the brain. In preclinical mice studies, BV-101 successfully delivered CYP46A1, a crucial enzyme in the brain which is reduced in people with Huntington's disease, into mouse models. The gene therapy was able to repair the essential cholesterol pathway, provide neuroprotection and restore physical performance in the mice, the company reported. Nathalie Cartier-Lacave, the founder of BrainVectis who is also sector lead in neurobiology at AskBio, said BV-101 aims to restore cholesterol metabolism, reduce mutant huntingtin and improve neuronal function. She noted that the gene therapy does not affect the levels of normal huntingtin protein in cells. “If this proves successful, we have the potential to change the course of a devastating disease that causes severe functional and cognitive decline,” Cartier-Lacave said in a statement. Huntington’s disease affects approximately 62,000 people in the European Union. It tends to appear in adults over the age of 30 but can also manifest in younger patients. BV-101 has been granted orphan drug designation in the EU. Sheila Mikhail, the co-founder of AskBio, said the approval of the Phase I/II study in France marks a major milestone in efforts to potentially treat the disease. She added that if this trial is successful, it could impact how other neurodegenerative diseases are treated in the future. The dose escalation study will assess the safety and tolerability of BV-101 in adult patients with early-stage Huntington’s disease. The trial will enroll between 12 and 18 participants and is expected to begin in the fourth quarter of this year. Alexandra Durr, a professor of genetics at the Reference Centre for Rare diseases-Neurogenetics, will be the principal investigator on the study. Life sciences giant Bayer acquired AskBio for up to $4 billion in 2020 as the company expanded its gene therapy programs. AskBio’s Pro10 AAV manufacturing process has become something of a standard across the industry. The platform is used by multiple companies, including Pfizer, Takeda and Viralgen Vector Core SA. Novartis subsidiary Avexis also used the AskBio platform in the development of its gene therapy for spinal muscular atrophy Zolgensma, which was approved in 2019.