Sperogenix(Shanghai) Med Tech Co.,Ltd

Pratteln, Switzerland, June 10, 2024 – Santhera Pharmaceuticals (SIX: SANN) announces that its partner Sperogenix Therapeutics has launched a paid-for Early Access Program (EAP) for AGAMREE® (vamorolone) in China for patients with Duchenne muscular dystrophy (DMD). In April 2024, the Hainan Medical Products Administration (HMPA) authorized the EAP for AGAMREE based on local policies, AGAMREE’s existing overseas approvals (U.S., EU, UK) and its demonstrated ability to address urgent clinical needs in DMD, where approved treatments are currently unavailable in China. The EAP has started in the Bo’ao Lecheng Pilot Zone, located in Hainan Province, in mid-May, when the first patients were treated with AGAMREE. In March 2024, the National Medical Products Administration (NMPA) accepted the new drug application (NDA) filing for AGAMREE in DMD for patients aged 4 years and older, incorporating it into both the Priority Review Program and the Breakthrough Therapy Program. Subject to a positive review outcome, approval could be obtained by Q1-2025. Duchenne muscular dystrophy is a rare neuromuscular disease affecting about 70,000 patients in China. Currently, there is no approved drug to treat DMD in China, leaving a high unmet medical need and therapeutic gap, especially considering the increasing diagnosis rates that enable more patients to access specialized treatment centers. According to the license agreement between the companies, first announced in January 2022, Sperogenix holds exclusive development and commercialization rights to AGAMREE in DMD and all other rare disease indications for China. Santhera is supplying treatment medication to Sperogenix for the EAP as well as for commercialization. Sperogenix will pay Santhera double-digit percentage royalties on net product sales (including for the EAP) and additional revenue-dependent milestones on commercial sales. About AGAMREE® (vamorolone) AGAMREE is a novel drug with a mode of action based on binding to the same receptor as glucocorticoids but modifying its downstream activity. Moreover, it is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes that may be responsible for local drug amplification and corticosteroid-associated toxicity in local tissues [1-4]. This mechanism has shown the potential to ‘dissociate’ efficacy from steroid safety concerns and therefore AGAMREE is positioned as a dissociative anti-inflammatory drug and an alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD [1-4]. In the pivotal VISION-DMD study, AGAMREE met the primary endpoint Time to Stand (TTSTAND) velocity versus placebo (p=0.002) at 24 weeks of treatment and showed a good safety and tolerability profile [1, 4]. The most commonly reported side effects were cushingoid features, vomiting, weight increase and irritability. Side effects were generally of mild to moderate severity. Currently available data show that AGAMREE, unlike corticosteroids, has no restriction of growth [5] and no negative effects on bone metabolism as demonstrated by normal bone formation and bone resorption serum markers [6]. AGAMREE (vamorolone), an orphan medicinal product, is approved for use in the United States (Prescribing Information), the European Union (Summary of Product Characteristics) and the United Kingdom. References:[1] Dang UJ et al. (2024) Neurology 2024;102:e208112. doi.org/10.1212/WNL.0000000000208112. Link.[2] Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link.[3] Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293[4] Heier CR et al (2019). Life Science Alliance DOI: 10.26508[5] Ward et al., WMS 2022, FP.27 - Poster 71. Link.[6] Hasham et al., MDA 2022 Poster presentation. Link. About Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males. DMD is characterized by inflammation which is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure. Corticosteroids are the current standard of care for the treatment of DMD. About SperogenixSperogenix Therapeutics is a platform company dedicated to developing and commercializing rare disease therapeutics in China. With prioritized therapeutic areas such as neuromuscular diseases and inherited metabolic diseases, Sperogenix is dedicated to establishing an innovative commercial model tailored to the China rare disease field, in order to provide affordable and reliable products and services to Chinese physicians and patients. Sperogenix was founded in 2019 and is backed by biopharma industry blue chip investors including Lilly Asia Ventures, Morningside Ventures and Prosperico Ventures. www.sperogenix.com. About SantheraSanthera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. The Company has an exclusive license from ReveraGen for all indications worldwide to AGAMREE® (vamorolone), a dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with Duchenne muscular dystrophy (DMD) as an alternative to standard corticosteroids. AGAMREE for the treatment of DMD is approved in the U.S. by the Food and Drug Administration (FDA), in the EU by the European Medicines Agency (EMA), and in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA). Santhera has out-licensed rights to AGAMREE for North America to Catalyst Pharmaceuticals, Inc. and for China to Sperogenix Therapeutics. For further information, please visit www.santhera.com. AGAMREE® is a trademark of Santhera Pharmaceuticals. For further information please contact: public-relations@santhera.com orEva Kalias, Head Investor Relations & CommunicationsPhone: +41 79 875 27 80eva.kalias@santhera.com Disclaimer / Forward-looking statements This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements. # # # Attachment 2024 06 10_EAP-China_e_final

来源：药渡撰文：幻目     编辑：哦呼前言DMD（杜氏肌营养不良症）的发病机理是由于患者体内编码抗肌萎缩蛋白(dystrophin)的基因发生变异，导致抗肌萎缩蛋白的缺失或功能缺陷。在临床表现上，患者会出现全身肌肉渐进式退化和运动功能减退，同时也会影响心脏功能与呼吸系统，多数患者在十几岁时会失去行走能力，发病后期其心肺功能也会逐渐衰竭，并最终死亡。有统计数据显示，在全球范围内，每3500-5000例男婴中就有1例DMD患者。中国则是杜氏肌营养不良症患病人数最高的国家之一，每年有400～500例患儿出生，累计患者达7-8万人。近日，美国食品和药物管理局（FDA）批准了ITF Therapeutics公司的Duvyzat（吉维诺他），Duvyzat是首个获准用于所有基因变异患者的非甾体类药物。也是自去年6月以来杜氏肌营养不良症的第三种新疗法。本文将对三种治疗杜氏肌营养不良症的疗法进行总结。     Duvyzat（Givinostat吉维诺他）图1.Givinostat hydrochloride monohydrate结构式（图片来源：药渡数据）生产商：ITF Therapeutics注册情况：2020年10月，FDA授予了Givinostat治疗DMD的罕见儿科疾病资格（RPDD）。早些时候，FDA和EMA还授予了Givinostat治疗DMD的孤儿药资格（ODD）、治疗DMD的快速通道资格（FTD）。2023年7月获得FDA优先审评，最终于2024年3月批准上市，口服治疗六岁及以上杜氏肌营养不良（DMD）患者。药物机制：在DMD患者的肌肉组织中，组蛋白去乙酰化酶（HDAC）活性异常升高，这种升高的HDAC活性可能促使肌肉再生受损，并妨碍肌肉超细纤维适应收缩的能力。Givinostat旨在通过抑制DMD患者中异常升高的HDAC活性，缓解肌肉组织的损害，保护肌肉超细纤维的功能，从而为此类患者提供一种全新的治疗策略。临床疗效：Givinostat此次获批是基于一项随机双盲、安慰剂对照、多中心III期临床试验的积极结果。该试验的对象为已接受类固醇治疗至少6个月的179名平均年龄为9岁的具有行走能力的男性患者。患者以2：1的比例随机分配，接受口服Givinostat或安慰剂治疗18个月。每日两次，同时继续他们的皮质类固醇治疗方案。治疗主要终点是使用爬4级楼梯来测量运动功能从基线到第18个月的变化。研究结果显示，DMD患儿在接受18个月的Givinostat治疗后，计时运动功能有所改善，接受Givinostat治疗的患者从基线到第18个月爬4级楼梯的平均时间变化为1.25秒，而安慰剂组患者则为3.03秒。此外，试验还达成了各项次要终点，包括NorthStar门诊评估量表（NSAA）得分、起立时间、肌肉力量分析以及磁共振脂肪浸润评估。与安慰剂相比，接受Duvyzat治疗的患者18个月后NSAA评分恶化较少。在安全性上，最常见的副作用是腹泻、腹痛、血小板减少、恶心/呕吐、甘油三酯增加和发烧。     Elevidys图2.Delandistrogene moxeparvovec的作用机制（图片来源：药渡数据）生产商：Sarepta Therapeutics注册情况：2021年12月，FDA授予孤儿药资格（ODD），2022年6月获得治疗DMD的罕见儿科疾病资格（RPDD）。2022年11月获得FDA优先审评，最终于2023年6月加速批准上市。适应症为4-5岁患有杜氏肌营养不良症(DMD)且已确认DMD基因发生突变的门诊儿童患者。药物机制：基因疗法Elevidys是一种基于腺病毒(AAV rh74)的重组基因疗法，将表达抗肌萎缩蛋白（micro-dystrophin）的转基因包装在AAV病毒载体中，从而向肌肉细胞传递抗肌萎缩蛋白，以弥补患者缺乏的正常蛋白，该疗法可以对所有类型的DMD患者有效，且Elevidys仅需单次静脉输注给药。临床疗效：加速批准的主要依据是多中心NCT03769116和NCT04626674的疗效和安全性数据。试验包括两部分，其中第1部分的患者接受Elevidys或安慰剂治疗，并随访48周。而在试验第2部分，让第1部分接受安慰剂治疗的患者接受Elevidys治疗，而在第1部分接受Elevidys治疗的患者转为使用安慰剂，并对所有试验参与者进行额外随访48周。此随机临床试验的数据证实接受Elevidys治疗的4-5岁DMD患者体内存有Elevidys微抗肌萎缩蛋白的表达。FDA最终认为，根据所递交的数据，Elevidys微抗肌萎缩蛋白表达（替代终点）的增加，可合理地用以预测4-5岁DMD患者的临床获益。此外，Elevidys还在进行SRP-9001-301试验，这是一项全球性、随机双盲、安慰剂为对照的III期临床试验，在126名4-7岁的DMD患者中进行。FDA可能根据此试验数据考虑扩大Elevidys的使用范围，使其能够被用于6-7岁DMD患者的治疗。此外，Sarepta亦计划开展Elevidys在8岁以上患者的临床试验。最常见的不良反应报告为呕吐、恶心、肝功能检查结果升高、发热和血小板减少。此外，在临床试验中观察到免疫介导的肌炎和急性严重心肌炎以及肌钙蛋白-I升高。     Agamree (vamorolone)图3.Vamorolone结构式（图片来源：药渡数据）生产商：Santhera Pharmaceuticals & ReveraGen BioPharma注册情况：2023年10月FDA批准Agamree用于治疗2岁及以上患者的杜氏肌营养不良症(DMD)，此前也曾获得FDA罕见儿科疾病及孤儿药的资格认定。2023年欧盟批准上市。曙方（上海）医药科技有限公司目前正在中国进行上市申请。药物机制：AGAMREE（Vamorolone）是一种全新的药物，它与普通类固醇药物的区别在于，能够有选择性地激活类固醇的某些信号通路。在DMD患者中，类固醇药物的抗炎症效果是介导药物疗效的主要机制，但是类固醇的其它活性会带来影响患者生活质量的副作用。Vamorolone能够在保持类固醇对DMD疗效的同时减少副作用的产生，Vamorolone被定位为现有皮质类固醇的替代品，为DMD患者提供更为安全和有效的治疗选择。临床疗效：该批准基于随机、双盲、安慰剂和活性对照2b期VISION-DMD研究(NCT03439670)的数据，该研究评估了vamorolone对4岁至7岁患有DMD的能走动的男孩的疗效和安全性，总治疗期长达30个月。结果表明：24周时从初始到站立测试(TTSTAND)速度，6分钟步行测试(6MWT)，以及跑步或步行10米的时间(TTRW) 均优于安慰剂。此外，接受Vamorolone治疗的患者在生长方面表现出与安慰剂治疗相似的效果，而相较之下，接受泼尼松治疗的患者则呈现生长迟缓。此外，从泼尼松转为Vamorolone的患者在研究的剩余时间内成功恢复了身高增长。最常见的不良反应是库欣样特征、精神疾病、呕吐、体重增加和维生素D缺乏。总结DMD管线也充满了新的候选药物，包括辉瑞的迷你抗肌萎缩蛋白基因疗法fordadistrogene movaparvovec，预计将于2024年下半年获得III期数据，以及REGENXBIO的一次性基因疗法。未来，随着更多创新疗法上市，有望为全球范围内的DMD患者提供更为个体化和创新的治疗方案。END*声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！Wegovy日本热卖，诺和诺德为何将亚洲首站设在此地？2024FDA新药风云榜，获批拒绝结果汇总MNC巨资追逐核药创新，国内企业加速抢滩点击蓝字关注我们

Pratteln, Switzerland, March 27, 2024 – Santhera Pharmaceuticals (SIX: SANN) announces that the China National Medical Products Administration (NMPA) has accepted for priority review the new drug application (NDA) for vamorolone in Duchenne muscular dystrophy (DMD) which was submitted by Sperogenix Therapeutics, Santhera's specialized rare disease partner for China. The Center for Drug Evaluation (CDE) of the Chinese drug authority NMPA accepted the filing and granted priority review for vamorolone in DMD for patients aged 4 years and older which could, subject to a positive outcome, lead to approval by Q1 2025. Previously, the CDE included vamorolone for the treatment of DMD in the Breakthrough Therapy Program, which addresses serious diseases lacking effective treatments and includes drugs offering clear clinical advantages over existing treatments. Duchenne muscular dystrophy is a rare neuromuscular disease affecting about 70,000 patients in China. Currently, there is no approved drug to treat DMD in China, leaving a high unmet medical need and therapeutic gap, especially considering the increasing diagnosis rates that enable more patients to access specialized treatment centers. The NDA in China is supported by an extensive data package which led to approval of vamorolone in the U.S., EU and UK in late 2023/early 2024. Evidence for clinical efficacy and safety was based on data from the positive pivotal VISION-DMD study, showing superiority of vamorolone compared with placebo, and three open-label studies in which vamorolone was administered at doses between 2 and 6 mg/kg/day for a total treatment period of up to 30 months. In addition, the filing included data from three open-label studies in which vamorolone was administered at doses between 2 and 6 mg/kg/day for a total treatment period of up to 30 months [1-4]. The submission is further supported by a study which investigated the pharmacokinetic parameters of vamorolone in healthy adult Chinese volunteers. According to the license agreement between the companies, first announced in January 2022, Sperogenix Therapeutics holds exclusive development and commercialization rights to vamorolone in DMD and all other rare disease indications for China. Upon commercialization, Sperogenix will pay Santhera sales-based milestones and double-digit percentage royalties on net sales. About AGAMREE® (vamorolone) AGAMREE is a novel drug with a mode of action based on binding to the same receptor as glucocorticoids but modifying its downstream activity. Moreover, it is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes that may be responsible for local drug amplification and corticosteroid-associated toxicity in local tissues [1-4]. This mechanism has shown the potential to ‘dissociate’ efficacy from steroid safety concerns and therefore AGAMREE is positioned as a dissociative anti-inflammatory drug and an alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD [1-4]. In the pivotal VISION-DMD study, AGAMREE met the primary endpoint Time to Stand (TTSTAND) velocity versus placebo (p=0.002) at 24 weeks of treatment and showed a good safety and tolerability profile [1, 4]. The most commonly reported side effects were cushingoid features, vomiting, weight increase and irritability. Side effects were generally of mild to moderate severity. Currently available data show that AGAMREE, unlike corticosteroids, has no restriction of growth [5] and no negative effects on bone metabolism as demonstrated by normal bone formation and bone resorption serum markers [6]. AGAMREE (vamorolone), an orphan medicinal product, is approved for use in the United States (Prescribing Information), the European Union (Summary of Product Characteristics) and the United Kingdom. References: [1] Dang UJ et al. (2024) Neurology 2024;102:e208112. doi.org/10.1212/WNL.0000000000208112. Link. [2] Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link. [3] Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293 [4] Heier CR et al (2019). Life Science Alliance DOI: 10.26508 [5] Ward et al., WMS 2022, FP.27 - Poster 71. Link. [6] Hasham et al., MDA 2022 Poster presentation. Link. About Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males. DMD is characterized by inflammation which is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure. Corticosteroids are the current standard of care for the treatment of DMD. About Sperogenix Sperogenix Therapeutics is a platform company dedicated to developing and commercializing rare disease therapeutics in China. With prioritized therapeutic areas, such as neuromuscular diseases and inherited metabolic diseases, Sperogenix is dedicated to establishing an innovative commercial model tailored to the China rare disease field, in order to provide affordable and reliable products and services to Chinese physicians and patients. Sperogenix was founded in 2019 and is backed by biopharma industry blue chip investors including Lilly Asia Ventures, Morningside Ventures and Properico Ventures. About Santhera Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. The Company has an exclusive license from ReveraGen for all indications worldwide to AGAMREE® (vamorolone), a dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with Duchenne muscular dystrophy (DMD) as an alternative to standard corticosteroids. AGAMREE for the treatment of DMD is approved in the U.S. by the Food and Drug Administration (FDA), in the EU by the European Medicines Agency (EMA), and in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA). Santhera has out-licensed rights to AGAMREE for North America to Catalyst Pharmaceuticals, Inc. and for China to Sperogenix Therapeutics. The clinical stage pipeline also includes lonodelestat to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases. For further information, please visit . AGAMREE® is a trademark of Santhera Pharmaceuticals. Disclaimer / Forward-looking statements This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements. # # # Attachment 2024 03 27_NDA-China_e_final