Limb-Girdle Muscular Dystrophy, Type 2B

-- LGMD is a Rare Form of Muscular Dystrophy with No Approved Therapy -- Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, announced today that the European Commission (EC) has granted orphan drug designation for AB-1003 (also known as LION-101)* for the treatment of limb-girdle muscular dystrophy (LGMD). AB-1003 is a novel investigational recombinant adeno-associated virus (AAV) based gene therapy currently being developed as a one-time intravenous (IV) infusion for the treatment of patients with LGMD type 2I/R9 (LGMD2I/R9), a disease subtype affecting 4.5 people per million worldwide, including more than 5,000 people in the EU and US. The EC decision, dated February 15, 2023, follows a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) and was received through AskBio's EU-based subsidiary BrainVectis. AB-1003 is being investigated in the US in a Phase 1/2 multicenter study that will evaluate the safety, tolerability and efficacy of a single IV infusion of gene therapy in adult subjects with genotypically confirmed LGMD2I/R9. "The EC orphan drug designation for AB-1003 is an important recognition of the unmet medical need in LGMD, which has no approved therapy," said Sheila Mikhail, Co-Founder & CEO, AskBio. "The burden of this rare form of muscular dystrophy on patients and their families is significant, and this decision supports our efforts to potentially bring a new therapeutic option to people in the EU living with the 2I/R9 type of this devastating disease." The EC grants orphan drug designation for medicinal products intended to treat a life-threatening or chronically debilitating disease that affects no more than five people in 10,000 in the EU, provided there is no other satisfactory treatment option or the medicine can be of significant benefit to those affected by a specific condition. This designation will provide special incentives in the EU, including eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees. In addition, if the medicine is approved for marketing, this designation will provide 10 years of marketing exclusivity. About Limb-Girdle Muscular Dystrophy (LGMD) and Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) Limb-girdle muscular dystrophy (LGMD) is a term for a group of diseases that cause progressive weakness and wasting of the muscles in the arms and legs.1 The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area and thighs.1 The severity, age of onset, and features of LGMD vary among the many subtypes of the condition and are often inconsistent, even within the same family.1 Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.1 Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) is a form of LGMD and is caused by mutations in the FKRP gene.2 In LGMD2I/R9, signs and symptoms often develop in late childhood and may include difficulty running and walking.2 The symptoms gradually worsen over time toward significant disability, and affected people generally rely on a wheelchair for mobility approximately 23-26 years after onset.2 Currently, there is no treatment that modifies the disease progression, and management is based on the signs and symptoms present in each individual.2 Visit the National Institutes of Health Medline Plus website to learn more about LGMD and LGMD2I/R9. About AskBio Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, 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, Scotland, the company has generated hundreds of proprietary capsids and promoters, several of which have entered clinical testing. An early innovator in the gene therapy field, with over 800 employees in five countries, the company holds more than 750 patents in areas such as AAV production and chimeric and self-complementary capsids. Learn more at   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 . * European Commission orphan drug designation is for "adeno-associated viral vector serotype 9 expressing fukutin related protein." 1. National Institutes of Health – Medline Plus: Limb-Girdle Muscular Dystrophy – Description. Accessed February 17, 2021. Limb-girdle muscular dystrophy: MedlinePlus Genetics 2. National Institutes of Health — National Center of Advancing Translational Sciences: Genetic and Rare Diseases Information Center. Limb-Girdle Muscular Dystrophy Type 2I – Summary. Accessed February 17, 2021. Limb-girdle muscular dystrophy type 2I | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program (nih.gov) 内容来源于网络，如有侵权，请联系删除。

Research Triangle Park, NC – February 27, 2023 – Asklepios BioPharmaceutical , Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG,  announced today that the European Commission (EC) has granted orphan drug designation for AB-1003 (also known as LION-101)* for the treatment of limb-girdle muscular dystrophy (LGMD). AB-1003 is a novel investigational recombinant adeno-associated virus (AAV) based gene therapy currently being developed as a one-time intravenous (IV) infusion for the treatment of patients with LGMD type 2I/R9 (LGMD2I/R9), a disease subtype affecting 4.5 people per million worldwide, including more than 5,000 people in the EU and US. The EC decision, dated February 15, 2023, follows a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) and was received through AskBio’s EU-based subsidiary BrainVectis. AB-1003 is being investigated in the US in a Phase 1/2 multicenter study that will evaluate the safety, tolerability and efficacy of a single IV infusion of gene therapy in adult subjects with genotypically confirmed LGMD2I/R9. “The EC orphan drug designation for AB-1003 is an important recognition of the unmet medical need in LGMD, which has no approved therapy,” said Sheila Mikhail, Co-Founder & CEO, AskBio. “The burden of this rare form of muscular dystrophy on patients and their families is significant, and this decision supports our efforts to potentially bring a new therapeutic option to people in the EU living with the 2I/R9 type of this devastating disease.” The EC grants orphan drug designation for medicinal products intended to treat a life-threatening or chronically debilitating disease that affects no more than five people in 10,000 in the EU, provided there is no other satisfactory treatment option or the medicine can be of significant benefit to those affected by a specific condition. This designation will provide special incentives in the EU, including eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees. In addition, if the medicine is approved for marketing, this designation will provide 10 years of marketing exclusivity. About Limb-Girdle Muscular Dystrophy (LGMD) and Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) Limb-girdle muscular dystrophy (LGMD) is a term for a group of diseases that cause progressive weakness and wasting of the muscles in the arms and legs. 1 The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area and thighs. 1 The severity, age of onset, and features of LGMD vary among the many subtypes of the condition and are often inconsistent, even within the same family. 1 Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild. 1 Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) is a form of LGMD and is caused by mutations in the FKRP gene. 2 In LGMD2I/R9, signs and symptoms often develop in late childhood and may include difficulty running and walking. 2 The symptoms gradually worsen over time toward significant disability, and affected people generally rely on a wheelchair for mobility approximately 23-26 years after onset. 2 Currently, there is no treatment that modifies the disease progression, and treatment is based on the signs and symptoms present in each individual. 2 Visit the National Institutes of Health Medline Plus website to learn more about LGMD and LGMD2I/R9. About AskBio Asklepios BioPharmaceutical, Inc. (AskBio), a wholly owned and independently operated subsidiary of Bayer AG, 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, Scotland, the company has generated hundreds of proprietary capsids and promoters, several of which have entered clinical testing. An early innovator in the gene therapy field, with over 800 employees in five countries, 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 . AskBio Forward-Looking Statements This press release contains “forward-looking statements.” Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “will,” “intends,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding AskBio’s pipeline of development candidates, manufacturing technology and process. These forward-looking statements involve risks and uncertainties, many of which are beyond AskBio’s control. Known risks include, among others, AskBio may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, its reliance on third-parties, clinical development plans, manufacturing processes and plans, and bringing its product candidates to market due to a variety of reasons, including the ongoing COVID-19 pandemic, possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved in a timely manner, potential disagreements or other issues with our third-party collaborators and partners, and regulatory, court or agency feedback or decisions, such as feedback and decisions from the United States Food and Drug Administration or the United States Patent and Trademark Office. Any of the foregoing risks could materially and adversely affect AskBio’s business and results of operations. You should not place undue reliance on the forward-looking statements contained in this press release. AskBio does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof. * European Commission orphan drug designation is for "adeno-associated viral vector serotype 9 expressing fukutin related protein." 1. National Institutes of Health – Medline Plus: Limb-Girdle Muscular Dystrophy – Description. Accessed February 17, 2021. Limb-girdle muscular dystrophy: MedlinePlus Genetics 2. National Institutes of Health — National Center of Advancing Translational Sciences: Genetic and Rare Diseases Information Center. Limb-Girdle Muscular Dystrophy Type 2I – Summary. Accessed February 17, 2021. Limb-girdle muscular dystrophy type 2I | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program (nih.gov) Media Contact: Phil McNamara Vice President of Communications E: pmcnamara@askbio.com T: +1 984.389.1797

Therapies to target neuromuscular disorders affecting million of people worldwide are on the horizon thanks to research at the Montreal Clinical Research Institute of Montreal. Fusion of myoblasts, the stem cells responsible for the formation of skeletal muscles, could allow the repair of muscles damaged by diseases such as muscular dystrophy. Neuromuscular disorders affect millions of people worldwide. Now a discovery made at the Montreal Clinical Research Institute of Montreal (IRCM) opens the door to the development of targeted therapies. Published in the journal Nature Communications, the development caps several years of research by doctoral student Viviane Tran under the direction of Université de Montréal medical professor Dr. Jean-François Côté, the IRCM's president and scientific director, with international partners. The formation of muscles, a complex process, requires the action of specialized cells, the myoblasts. In order for skeletal muscle to develop and regenerate, myoblasts must align with each other, move towards each other, and touch each other until their membranes are joined. This is called the myoblast fusion stage and is the basis for the formation of muscle fibers. During embryogenesis, myoblast fusion is crucial, with mutations in certain genes resulting in the extremely rare clinical myopathy called Carey-Fineman-Ziter syndrome. In adults, an army of satellite cells is responsible for muscle growth and regeneration. In response to activation signals, satellite cells proliferate, differentiate and fuse to repair damaged myofibers. The proteins and signaling pathways that control this fusion are still being identified. 'We didn't think it possible' "Until recently, myoblast fusion was the subject of only basic research," said Dr. Côté. "We weren't interested in it in the context of disease; we didn't think it was possible to use this process to cure certain diseases. Yet, understanding in detail all the factors involved in this fusion could contribute to the development of targeted therapies." In what was a key experiment, the researchers created a mouse model in which a protein involved in fusion is expressed in its active form in the mammal. During muscle development and regeneration, an increase in myoblast fusion was observed. "We also observed that this mouse model, when crossed with a mouse modeling limb-girdle muscular dystrophy 2B, can improve disease phenotypes," said Tran. Direct evidence of usefulness The new data therefore provide direct evidence that the myoblast fusion process could be exploited for regenerative purposes and to improve the outcome of muscle diseases. In the long term, this research shows, increasing cell fusion could "repair" muscles in other types of muscular dystrophy, such as Duchenne (occurring in 1 in 4,000 boys) or other severe conditions, such as cachexia (secondary muscle breakdown due to various diseases and some forms of cancer). The potential to manipulate the myoblast fusion step will undoubtedly be the subject of future studies, said the researchers, who worked with colleagues at UdeM's Institute for Research in Immunology and Cancer) and the IRCM, in Montreal and internationally.