Sixth patent together with growing clinical evidence of the safety and effectiveness of VALTOCO reinforce clinical and commercial potential

第六项专利以及VALTOCO安全性和有效性的越来越多的临床证据加强了临床和商业潜力

SAN DIEGO, Nov. 27, 2023 /PRNewswire/ -- Neurelis, Inc., a neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need, announced that it has secured the issuance of United States Patent No.

圣地亚哥，2023年11月27日/PRNewswire/-Neurelis，Inc。是一家神经科学公司，专注于开发和商业化治疗癫痫和孤儿神经系统疾病的治疗药物，其特点是医疗需求未得到满足，宣布已获得美国专利号的发布。

11,793,786 (the '786 Patent). The '786 Patent covers VALTOCO® and other pharmaceutical solutions for nasal administration consisting of diazepam or a pharmaceutically acceptable salt thereof in combination with specific ranges of one or more natural or synthetic tocopherols or tocotrienols, benzyl alcohol, and n-dodecyl beta-D-maltoside..

11793786（'786专利）。'786专利涵盖了用于鼻腔给药的VALTOCO®和其他药物溶液，其由地西泮或其药学上可接受的盐与特定范围的一种或多种天然或合成生育酚或生育三烯酚，苯甲醇和正十二烷基β-D-麦芽糖苷。。

The '786 Patent is listed in the U.S. Food and Drug Administration (FDA) publication Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book, as it relates to VALTOCO®, and is solely owned by Neurelis.

'786专利在美国食品和药物管理局（FDA）出版物批准的具有治疗等效性评估的药物产品中列出，通常称为橙皮书，因为它涉及VALTOCO®，并且仅由Neurelis拥有。

'We are pleased by our continued progress with the United States Patent and Trademark Office and the repeated recognition of the inventive nature of our VALTOCO franchise,' said Craig Chambliss, President and Chief Executive Officer of Neurelis. 'We will continue to expand our intellectual property, memorializing the scientific innovation that drives Neurelis' commitment to improving patient outcomes.

Neurelis总裁兼首席执行官Craig Chambliss说：“我们对美国专利商标局的持续进步以及对VALTOCO特许经营的创造性的反复认可感到高兴。”我们将继续扩大我们的知识产权，纪念推动Neurelis致力于改善患者结果的科学创新。

This innovation drives our expectations and efforts to extend VALTOCO's exclusivity even further.'.

这一创新推动了我们的期望和努力，进一步扩大了VALTOCO的排他性。

The '786 Patent, with an expiry date of March 2029, joins five other Orange Book listed patents that currently provide exclusivity to the VALTOCO franchise through 2029. As an immediate treatment for frequent seizure activity for patients with epilepsy six years of age or older, VALTOCO empowers patients and care partners to take a proactive role in managing their disease and improve their health outcomes..

'786专利于2029年3月到期，加入其他五项橙皮书上市专利，目前在2029年之前为VALTOCO特许经营提供专有权。作为六岁或以上癫痫患者频繁发作的直接治疗方法，VALTOCO使患者和护理伙伴能够在管理疾病和改善健康状况方面发挥积极作用。。

About Neurelis

关于Neurelis

Neurelis, Inc., is a neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need. In 2020, the FDA approved Neurelis' VALTOCO® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual's usual seizure pattern in adult and pediatric patients 6 years of age and older.

Neurelis，Inc。是一家神经科学公司，致力于开发和商业化治疗癫痫和孤儿神经系统疾病的治疗药物，其特点是高度未满足的医疗需求。2020年，FDA批准Neurelis'VALTOCO®（地西泮鼻腔喷雾剂）作为急性治疗间歇性，刻板发作的频繁癫痫发作（即癫痫发作簇，急性重复性癫痫发作），与成人和6岁及以上儿童患者的常见癫痫发作模式不同。

VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL®. Intravail's transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In its approval of VALTOCO, the U.S. Food and Drug Administration also granted Neurelis Orphan Drug Exclusivity and recognized VALTOCO's intranasal route of administration as a clinically superior contribution to patient care over the previously approved standard-of-care treatment (a rectal gel formulation of diazepam).

VALTOCO是地西泮的专有配方，结合了INTRAVAIL®的科学。Intravail的跨粘膜吸收增强技术可实现多种蛋白质，多肽和小分子药物的无创递送。在VALTOCO的批准中，美国食品和药物管理局还授予Neurelis孤儿药专有权，并认可VALTOCO的鼻内给药途径在临床上优于先前批准的标准护理治疗（地西泮的直肠凝胶制剂）对患者护理的贡献。

For more information on VALTOCO, please visit www.valtoco.com. In addition, Neurelis is developing NRL-1049 (previously known as BA-1049), an investigational, Phase I stage small molecule Rho kinase (ROCK) inhibitor, for the treatment of cerebral cavernous malformations (CCMS), a rare disorder of the central nervous system (CNS).

有关VALTOCO的更多信息，请访问www.VALTOCO.com。此外，Neurelis正在开发NRL-1049（以前称为BA-1049），这是一种研究性的I期小分子Rho激酶（ROCK）抑制剂，用于治疗脑海绵状血管畸形（CCMS），这是一种罕见的中枢神经系统（CNS）疾病。

For more information on Neurelis, please visit www.neurelis.com. For the latest scientific information on VALTOCO, please visit http://www.neurelismedicalaffairs.com/..

有关Neurelis的更多信息，请访问www.Neurelis.com。有关VALTOCO的最新科学信息，请访问http://www.neurelismedicalaffairs.com/..

Important Safety Information about VALTOCO:

关于VALTOCO的重要安全信息：

Indication

指示

VALTOCO® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.

VALTOCO®（地西泮鼻喷雾剂）适用于急性治疗6岁及以上癫痫患者常见癫痫发作模式不同的频繁癫痫发作活动（即癫痫发作簇，急性重复性癫痫发作）的间歇性，刻板性发作。

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS

警告：伴随使用阿片类药物的风险；滥用，滥用和成瘾；和依赖和撤退反应

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation..

伴随使用苯二氮卓类药物和阿片类药物可能会导致严重的镇静，呼吸抑制，昏迷和死亡。为替代治疗方案不足的患者保留这些药物的同时处方。将剂量和持续时间限制在所需的最低限度。跟踪患者呼吸抑制和镇静的体征和症状。。

The use of benzodiazepines, including VALTOCO, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes.

苯二氮卓类药物（包括VALTOCO）的使用使使用者面临滥用，滥用和成瘾的风险，这可能导致过量或死亡。滥用和滥用苯二氮卓类药物通常涉及同时使用其他药物，酒精和/或非法物质，这与严重不良后果的频率增加有关。

Before prescribing VALTOCO and throughout treatment, assess each patient's risk for abuse, misuse, and addiction..

在处方VALTOCO和整个治疗之前，评估每位患者滥用，滥用和成瘾的风险。。

The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although VALTOCO is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of VALTOCO may precipitate acute withdrawal reactions, which can be life-threatening.

继续使用苯二氮卓类药物可能导致临床上显着的身体依赖性。依赖和戒断的风险随着治疗时间的延长和日剂量的增加而增加。虽然VALTOCO仅适用于间歇使用，但如果使用频率高于推荐值，VALTOCO的突然停药或快速剂量减少可能会导致急性戒断反应，这可能会危及生命。

For patients using VALTOCO more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALTOCO..

对于比推荐更频繁使用VALTOCO的患者，为了降低戒断反应的风险，请逐渐减量停用VALTOCO。。

Contraindications: VALTOCO is contraindicated in patients with:

禁忌症：VALTOCO禁用于以下患者：

Hypersensitivity to diazepam

对地西泮过敏

Acute narrow-angle glaucoma

急性窄角型青光眼

Central Nervous System (CNS) DepressionBenzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits..

中枢神经系统（CNS）抑郁症苯二氮卓类药物，包括VALTOCO，可能会产生CNS抑郁症。警告患者不要从事需要精神警觉的危险活动，例如操作机械，驾驶机动车或骑自行车，直到药物的影响（如嗜睡）消退，并且随着他们的医疗状况允许。。

The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.

当VALTOCO与酒精或其他中枢神经系统抑制剂一起使用时，必须考虑协同中枢神经系统抑制作用的可能性，并向患者和/或护理伙伴提出适当的建议。

Suicidal Behavior and IdeationAntiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior..

自杀行为和观念抗癫痫药（AEDs），包括VALTOCO，会增加自杀意念和行为的风险。应监测接受任何AED治疗任何适应症的患者抑郁，自杀念头或行为的出现或恶化，和/或情绪或行为的异常变化。。

GlaucomaBenzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

包括VALTOCO在内的GlaucomaBenzodiazepines可以增加青光眼患者的眼压。VALTOCO只能用于开角型青光眼患者，只要他们正在接受适当的治疗。VALTOCO禁用于窄角型青光眼患者。

Neonatal Sedation and Withdrawal SyndromeUse of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly..

妊娠晚期VALTOCO的新生儿镇静和戒断综合征可导致新生儿镇静（呼吸抑制，嗜睡，肌张力低下）和/或戒断症状（反射亢进，烦躁不安，烦躁不安，震颤，哭闹不安，喂养困难）。监测怀孕期间暴露于VALTOCO的新生儿或分娩时镇静的迹象，并监测怀孕期间暴露于VALTOCO的新生儿是否有戒断迹象；相应地管理这些新生儿。。

Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol PreservativeVALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including 'gasping syndrome,' can occur in neonates and low-birth-weight infants treated with benzyl alcohol–preserved drugs, including VALTOCO.

由于苄醇保存量Valtoco导致婴儿严重不良反应的风险未被批准用于新生儿或婴儿。严重和致命的不良反应，包括“喘息综合征”，可能发生在新生儿和低出生体重婴儿用苯甲醇保存的药物，包括VALTOCO治疗。

The 'gasping syndrome' is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known..

“喘息综合征”的特征是中枢神经系统抑制，代谢性酸中毒和喘息呼吸。可能发生严重不良反应的苄醇的最小量尚不清楚。。

Adverse ReactionsThe most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.

不良反应最常见的不良反应（至少4%）是嗜睡，头痛和鼻部不适。

Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance.

地西泮是VALTOCO中的活性成分，是附表IV控制物质。

To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

要报告疑似不良反应，请致电1-866-696-3873联系Neurelis，Inc。或致电1-800-FDA-1088联系FDA（www.FDA.gov/medwatch）。

Please read full Prescribing Information, including Boxed Warning.

请阅读完整的处方信息，包括盒装警告。

Contacts:

联络：

Neurelis:Brittany Bradrick, Chief Operating Officer and Chief Financial Officer, +1 858 251 2135

Neurelis:Brittany Bradrick，首席运营官兼首席财务官，+1 858 251 2135

Media:Glenn Silver, FINN Partners, +1 646 871 8485

媒体：Glenn Silver，FINN Partners，+16468718485

SOURCE Neurelis, Inc.

资料来源：Neurelis公司。