LAMA1

LAMA2-CMD is characterised by the absence of the LAMA2 protein, leading to severe, early-onset muscular dystrophy. Credit: Ines Nepo/Shutterstock. The US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to Modalis Therapeutics’ investigational therapy, MDL-101, aimed at treating congenital muscular dystrophy type 1A (LAMA2-CMD). An epigenetic editing therapy, MDL-101 includes a guide nucleotide targeting the LAMA1 gene — a close homolog of the disease-causing LAMA2 gene. It utilises an enzyme-null Cas9 (dCas9) fused with a trans-activating domain, driven by a muscle-specific promoter and delivered via a muscle-specific AAV [adeno-associated virus] vector. MDL-101 works by upregulating LAMA1 gene products in patients’ muscle tissue to compensate for loss of function resulting from LAMA2 mutations. This approach has the potential to offer a one-time, long-lasting treatment option for individuals with LAMA2-CMD. ODD status facilitates the development of treatments for conditions affecting fewer than 200,000 patients in the US. See Also: UAE’s clinical trials space matures with experience from Covid-19 FDA approves Iterum’s ORLYNVAH NDA for uUTI treatment Under the ODD status for MDL-101, Modalis will receive benefits including exemption from application fees on filing new drug applications, tax reductions for clinical development and preferential treatment for the development and promotion of the asset in the US. On receipt of regulatory approval, MDL-101 would also receive seven years of exclusive sales rights in the US market. The US regulator previously granted rare paediatric disease designation for gene therapy for patients with LAMA2-CMD. LAMA2-CMD is characterised by the absence of the LAMA2 protein, a critical component comprising more than 3,000 amino acids. This leads to severe, early-onset muscular dystrophy, and due to the protein’s size, conventional gene therapy approaches such as using an AAV vector are challenging. Modalis focuses on the development of precision genetic therapies leveraging its epigenome editing technology, CRISPR-GNDM. This technology enables modulation of gene expression without causing double-strand DNA breaks. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

近日，国家卫生健康委、财政部等部门公布，慢性阻塞性肺疾病（简称慢阻肺病）患者健康服务被纳入国家基本公共卫生服务项目，意味着更多的慢阻肺病患者将被及时发现和接受规范化治疗。同期，正大天晴下属企业南京顺欣制药传来喜讯，自主研发的创新生物药TQC2938注射液获得国家药品监督管理局药品审评中心（CDE）临床试验许可，处于国产治疗慢阻肺病同靶点新药研发的领先位置。 正大天晴作为一家专注于医药研发、生产和销售的企业，近年来将呼吸疾病作为企业的重点治疗领域之一，深耕细作、硕果累累。目前，正大天晴已上市天晴速畅、天晴速乐等治疗慢阻肺的主要药物，同时，TQC3721吸入混悬液/吸入粉雾剂、TQC3927吸入粉雾剂、TQC2938注射液等创新药研究正在稳步推进，致力于为患者提供更多样的治疗选择。 慢阻肺成国内第三大死因 TQC2938应对急性加重挑战 上下滑动观看漫画 目前，我国慢阻肺总患病人数约1亿，年死亡超100万人。慢阻肺已成为国内第三大死因，具有患病率高、死亡率高、经济负担高的特点[1]。虽然最高标准的三联（LABA+LAMA+ICS）吸入疗法可以降低慢阻肺急性加重风险，仍然有30%-40%的患者在接受三联治疗后出现中重度急性加重，其用药市场存在巨大未被满足的临床需求[2]。 当下，生物制剂的研发成为扭转慢阻肺治疗困境的关键。研究表明，患者血清中IL-33/ST2水平的高低与急性加重风险有关[3]。正大天晴自主研发的TQC2938注射液（抗ST2人源化单克隆抗体）通过靶向ST2受体，阻断IL-33/ST2信号通路，从而抑制慢阻肺病理过程中的炎症反应，减少气道高反应性和肺部组织损伤，为慢阻肺患者提供了新的治疗方案。 深耕细作呼吸领域 多款创新药引领慢阻肺治疗篇章 呼吸领域一直是正大天晴研发的重点领域，历经多年的自主研发与技术积淀，公司已构筑起吸入制剂完整的研发、生产及质控体系，并布局了多条针对慢阻肺治疗的创新药研发管线。 其中，TQC3721吸入混悬液正在开展II期临床研究，可用于中重度慢阻肺的维持治疗，是国内研发进度领先的PDE3/4双重抑制剂，同时该产品还开发了吸入粉雾剂剂型；TQC3927吸入粉雾剂兼具LABA/LAMA双靶点活性，有望成为慢阻肺双支扩的替代药物，已经进入Ib期中重度慢阻肺人群探索。 随着慢阻肺患者健康服务被纳入国家基本公共卫生服务项目，未来将有更多患者在疾病早期阶段被及时识别，这对正大天晴提出了更迫切的科研创新要求。正大天晴始终秉持以临床需求为核心导向的原则，以创新驱动发展，研发更多基于新机制、新靶点的创新药物，并开发更为便捷有效的新型制剂，以满足患者多样化的治疗需求。 参考文献： [1].全球慢阻肺病指数（COPD Index） [2].Sridhar S, et al.Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases[J]. Respir Res, 2019, 20(1): 14. [3].KEARLEYJ，et al.Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type Ⅰ interleukin-33-dependent response to infection[J].Immunology,2015,42(3):566-579. 声明： 1. 本新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。 2. 本公司不对任何药品和/或适应症作推荐。 3. 本新闻稿中涉及的信息仅供参考，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。 ● 正大天晴引进CD3/EpCAM双抗M701 将造福癌症胸腹水患者 ● 正大天晴安罗替尼闪耀2024 CSCO，彰显抗肿瘤巨大潜力 ● 主要终点PFS双重显著获益！正大天晴乳腺癌1类新药库莫西利亮相2024 CSCO ● 展现难治性疾病治疗潜力，正大天晴BCL-2抑制剂等四项创新药研究临床数据公布

LAMA2-CMD is an early onset congenital muscular dystrophy caused by the absence of the LAMA2 protein. Image credit: Shutterstock/ Dan76. Modalis Therapeutics has been awarded a rare paediatric disease designation by the US Food and Drug Administration (FDA) for its congenital muscular dystrophy type 1a (LAMA2-CMD) gene therapy. As per the designation, the Japan-based company will be eligible to receive a priority review voucher if the drug candidate, MDL-101, is approved by the FDA. Recipients can redeem priority review vouchers themselves for any chosen drug or instead sell them to other pharma companies. Having the ability to slash four months off FDA review time, vouchers can sell for about $100m. The designation comes after a period of uncertainty for the vouchers’ future, with the programme facing a tight deadline on sunset provisions. The US House of Representatives ultimately passed a bill last week to reauthorise the rare paediatric priority review voucher program through September 2029. Modalis said it also pursuing orphan drug status for its candidate, with the FDA currently reviewing the company’s application. Orphan drug status provides benefits such as tax credits for US-based clinical trials and market exclusivity. See Also: FDA approves PureTech’s KarXT to treat schizophrenia in adults FDA greenlights Regeneron’s Dupixent for the treatment of COPD LAMA2-CMD is an early-onset congenital muscular dystrophy caused by the absence of the LAMA2 protein. Affected infants can have severe muscle weakness, hypotonia, and joint deformities, amongst others. As those with the disease grow, spinal curvature and speech issues can also develop. There are no approved therapies to treat LAMA2-CMD. Gene therapies for LAMA2-CMD using an adeno-associated virus (AAV) vector are difficult to develop as LAMA2 is made up of 3,000 amino acids, meaning it cannot be loaded onto a vector, according to Modalis. The company is therefore using its clustered regularly interspaced short palindromic repeats (CRISPR)-based epigenome editing technology to develop the therapy. MDL-101 works by inducing the expression of the sister gene LAMA1 in muscle tissues, which compensates for the deficient function of LAMA2. Modalis’s CEO Haru Morita said: “We have received many requests for our efforts from children and families around the world suffering from this disease for which there is currently no treatment, and we feel a mission to respond to the expectations of patients who are eagerly awaiting the start of clinical trials as soon as possible.” Modalis expects to file an investigational new drug (IND) application in 2025, according to a Q2 2024 financial results press release.