OSAKA, Japan--(BUSINESS WIRE)--Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter 'Shionogi') announced the U.S. Food and Drug Administration (FDA) has granted Tetra Therapeutics Inc. (hereafter 'Tetra'), a Shionogi Group Company, Rare Pediatric Disease Designation for zatolmilast (BPN14770), an investigational treatment being studied for Fragile X syndrome (FXS), a leading cause of inherited intellectual disability and autism..

日本大阪-（商业电线）-Shionogi＆Co.，Ltd。（总部：日本大阪；首席执行官：Isao Teshirogi，博士；以下简称“Shionogi”）宣布美国食品和药物管理局（FDA）已授予四联疗法公司（以下简称“Tetra”），一家Shionogi集团公司，罕见儿科疾病名称为zatolmilast（BPN14770），正在研究脆性X综合征（FXS）的研究性治疗，FXS是遗传性智力障碍和自闭症的主要原因。。

FDA grants Rare Pediatric Disease Designation (RPD) for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. The RPD designation allows Tetra to request a priority review voucher from FDA which, if granted, may be used for a subsequent human drug application.

FDA为主要影响18岁以下儿童和美国不到20万人的严重和危及生命的疾病授予罕见儿科疾病名称（RPD）。RPD名称允许Tetra向FDA申请优先审查凭证，如果获得批准，可用于随后的人类药物申请。

Zatolmilast was also awarded Orphan Drug Designation by the FDA in 2018..

Zatolmilast也于2018年被FDA授予孤儿药称号。。

“We are committed to advancing a potential medicine for people with Fragile X syndrome, a rare genetic disorder which affects all aspects of life for individuals and families. While symptoms vary among individuals, intellectual disability is one of the most prevalent neuropsychiatric hallmarks of the disorder,” said Chad Coberly, JD, Chief Executive Officer, Tetra Therapeutics.

“我们致力于为脆性X综合征患者提供一种潜在的药物，脆性X综合征是一种罕见的遗传性疾病，会影响个人和家庭的各个方面。虽然症状因人而异，但智力残疾是该疾病最普遍的神经精神病学标志之一。”Tetra Therapeutics首席执行官Chad Coberly说。

“A treatment that has the potential to improve cognition could lead to enhanced memory formation as well as improved vocabulary and reading skills. Overall gains in these domains may help people with Fragile X syndrome, their families and caregivers.”.

“有可能改善认知能力的治疗方法可以增强记忆形成，提高词汇和阅读技能，这些领域的总体收益可能会帮助患有脆性X综合征的人，他们的家人和护理人员。”。

Shionogi acquired Tetra in 2020 as part of its mission to develop medications for unmet medical needs and thereby contribute meaningfully to society. Tetra’s clinical programs, which focus on addressing cognitive function in FXS and other disorders, align strategically with Shionogi’s global vision.

Shionogi于2020年收购了Tetra，作为其为未满足的医疗需求开发药物的使命的一部分，从而为社会做出有意义的贡献。Tetra的临床计划专注于解决FXS和其他疾病的认知功能，从战略上与Shionogi的全球视野保持一致。

Shionogi is advancing the zatolmilast development program with the intent, if it is approved, to offer people living with FXS the first cognitive treatment developed specifically for this rare genetic disorder..

Shionogi正在推进zatolmilast开发计划，目的是（如果获得批准）为患有FXS的人提供专门针对这种罕见遗传疾病开发的第一种认知疗法。。

Zatolmilast Clinical Program

Zatolmilast临床计划

Zatolmilast is an investigational drug that is believed to work by modulating a signaling molecule called cyclic AMP (cAMP), which may promote the maturation of connections between neurons that are impaired in individuals with FXS.

Zatolmilast是一种被认为通过调节称为环AMP（cAMP）的信号分子起作用的研究药物，其可以促进FXS个体中受损的神经元之间的连接的成熟。

In a randomized, double-blind, placebo-controlled two-way crossover Phase 2 trial that included 30 adult males with FXS, the primary endpoint of this study was safety. An exploratory analysis of the efficacy of zatolmilast showed improvement in cognition, specifically in language domains including picture vocabulary and oral reading recognition.1 Clinically meaningful improvements in daily functioning were also observed.1 The most commonly reported adverse events were vomiting and upper respiratory tract infections, however rates were similar between the active and placebo arms.

在一项随机，双盲，安慰剂对照的双向交叉2期临床试验中，包括30名FXS成年男性，本研究的主要终点是安全性。对zatolmilast疗效的探索性分析显示认知能力有所改善，特别是在语言领域，包括图片词汇和口头阅读识别.1还观察到日常功能的临床意义改善.1最常见的不良事件是呕吐和上呼吸道感染，然而，积极和安慰剂组之间的比率相似。

No participants discontinued the study due to adverse events..

没有参与者由于不良事件而停止研究。。

Zatolmilast is currently being evaluated in a pivotal Phase 2b/3 program, which includes two randomized, double-blind, placebo-controlled studies of 150 participants each. The first, Study 204 (NCT05163808), includes adolescent males ages 9-17. The second, Study 301 (NCT05358886), includes adult males ages 18-45.

Zatolmilast目前正在关键阶段2b/3计划中进行评估，该计划包括两项随机，双盲，安慰剂对照研究，每组150名参与者。第一项研究204（NCT05163808）包括9-17岁的青少年男性。第二项研究301（NCT05358886）包括18-45岁的成年男性。

The zatolmilast clinical program also includes Study 302 (NCT05367960), an open-label extension study available to participants after completing Study 204 or Study 301..

zatolmilast临床计划还包括研究302（NCT05367960），这是一项在完成研究204或研究301后可供参与者使用的开放标签扩展研究。。

Primary endpoints for the studies include a cognitive assessment of the efficacy of zatolmilast, as measured by the cognition crystallized composite score of the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB), a calculated score from a series of tests to assess the subjects’ change from baseline of the Picture Vocabulary and Oral Reading domains of the NIH-TCB, as well as determinations of the drug’s safety and tolerability.

这些研究的主要终点包括对扎托米司特疗效的认知评估，通过美国国立卫生研究院工具箱认知电池（NIH-TCB）的认知结晶综合评分来衡量，这是一系列测试的计算得分，用于评估受试者的NIH-TCB图片词汇和口头阅读领域的基线变化，以及确定药物的安全性和耐受性。

Secondary endpoints include assessments of daily living, caregiver and clinician improvement scales and other domains from the NIH-TCB..

次要终点包括NIH-TCB对日常生活，护理人员和临床医生改善量表以及其他领域的评估。。

About Fragile X Syndrome (FXS)

关于脆性X综合征（FXS）

FXS is a leading genetic cause of inherited intellectual disability and the most common known cause of autism in the U.S.2 FXS is known to have a greater effect on males than females because the mutation of the FMR1 gene is carried on the X chromosome.3 The most important clinical abnormality associated with FXS is global developmental delay and intellectual disability.4 The IQ of males with full mutation varies, with a mean value of 40–51.4 Other common symptoms of FXS include aggressiveness, attention problems and anxiety.2 FXS can cause challenges across many aspects of daily life, such as impacting individuals’ ability to care for themselves and communicate with others.3.

FXS是遗传性智力障碍的主要遗传原因，也是美国最常见的自闭症原因.2由于FMR1基因的突变携带在X染色体上，FXS已知对男性的影响大于女性.3与FXS相关的最重要的临床异常是全球发育迟缓和智力障碍.4男性智商充分突变各不相同，平均值为40-51.4 FXS的其他常见症状包括攻击性，注意力问题和焦虑.2 FXS可能在日常生活的许多方面带来挑战，例如影响个人照顾自己和与他人沟通的能力0.3。

About Tetra Therapeutics

关于四疗法

Tetra Therapeutics, a Shionogi Group Company, is a clinical stage biotechnology company focused on developing a portfolio of therapeutic products to address unmet needs in central nervous system diseases and disorders. In addition to advancing the zatolmilast clinical program, Tetra also has a PDE4B Inhibitor in pre-clinical development.

Shionogi集团公司Tetra Therapeutics是一家临床阶段的生物技术公司，致力于开发一系列治疗产品，以满足中枢神经系统疾病和疾病的未满足需求。除了推进zatolmilast临床计划外，Tetra还在临床前开发中使用PDE4B抑制剂。

Tetra Therapeutics is headquartered in Grand Rapids, Michigan. For more information, visit tetratherapeutics.com..

Tetra Therapeutics总部设在密歇根州大急流城。欲了解更多信息，请访问tetratherapeutics.com。。

About Shionogi

关于Shionogi

Shionogi & Co., Ltd. is a leading global research-driven pharmaceutical company dedicated to bringing benefits to patients based on its corporate philosophy of 'supplying the best possible medicine to protect the health and well-being of the patients we serve.' Shionogi has discovered and developed novel antibiotics, medicines for HIV and influenza and currently markets medicines for infectious diseases and central nervous system disorders.

Shionogi＆Co.，Ltd。是一家领先的全球研究驱动型制药公司，致力于根据其“提供尽可能好的药物以保护我们服务的患者的健康和福祉”的企业理念为患者带来益处Shionogi发现并开发了新型抗生素，用于艾滋病毒和流感的药物，目前销售用于传染病和中枢神经系统疾病的药物。

Shionogi’s global pipeline includes research programs in infectious disease, pain/CNS, metabolic disorders, oncology and stroke. For more information, visit https://www.shionogi.com/global/en/..

Shionogi的全球渠道包括传染病，疼痛/中枢神经系统，代谢紊乱，肿瘤学和中风等研究项目。欲了解更多信息，请访问https://www.shionogi.com/global/en/..

Forward-Looking Statements

前瞻性声明

This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate.

本公告包含前瞻性声明。这些陈述基于预期根据目前可用的信息，可能导致实际结果与这些陈述大不相同的风险和不确定性假设。风险和不确定性包括一般国内和国际经济状况，如一般工业和市场状况，以及利率和货币汇率的变化。

These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations.

这些风险和不确定性特别适用于与产品相关的前瞻性陈述。产品风险和不确定性包括但不限于完成和终止临床试验；获得监管部门批准；对产品安全性和有效性的要求和担忧；技术进步；重要诉讼的不良后果；国内外医疗改革与法律法规的变化。

Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise..

同样对于现有产品，存在制造和营销风险，其中包括但不限于无法建立满足需求的生产能力，缺乏原材料和进入竞争产品。无论是由于新信息，未来事件还是其他原因，本公司均不承担更新或修改任何前瞻性声明的任何意图或义务。。

1 Berry-Kravis, E.M., Harnett, M.D., Reines, S.A. et al. Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat Med 27, 862–870 (2021). https://doi.org/10.1038/s41591-021-01321-w.

1 Berry-Kravis，E.M.，Harnett，M.D.，Reines，S.A。等。抑制脆性X综合征成人中的磷酸二酯酶-4D：一项随机，安慰剂对照的2期临床试验。Nat Med 27862-870（2021）。https://doi.org/10.1038/s41591-021-01321-w.

2 Cleveland Clinic. (2021, May 18). Fragile X Syndrome: Diagnosis, Symptoms & Treatment. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome

2克利夫兰诊所。（2021年5月18日）。脆性X综合征：诊断，症状和治疗。克利夫兰诊所。https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome

3 Centers for Disease Control and Prevention. What is Fragile X Syndrome? CDC. https://www.cdc.gov/ncbddd/fxs/facts.html

3疾病预防控制中心。什么是脆性X综合征？疾病预防控制中心。https://www.cdc.gov/ncbddd/fxs/facts.html

4 Ciaccio, C., Fontana, L., Milani, D., et al. Fragile X syndrome: A review of clinical and molecular diagnoses. Italian Journal of Pediatrics. (2017, April 19). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395755/

4 Ciaccio，C.，Fontana，L.，Milani，D.，et al。脆性X综合征：临床和分子诊断综述。意大利儿科杂志。（2017年4月19日）。https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395755/