Risk of death was 5.1 times higher in untreated patients versus patients treated with NULIBRY

未经治疗的患者死亡风险是NULIBRY治疗患者的5.1倍

Treatment also led to improvements in urinary biomarker levels and development outcomes

治疗还导致尿生物标志物水平和发育结果的改善

NULIBRY is the first therapy to reduce the risk of mortality in patients with known or presumed MoCD Type A

NULIBRY是第一种降低已知或推定的MoCD A型患者死亡风险的疗法

SOLANA BEACH, Calif., Sept. 7, 2023 /PRNewswire/ -- Sentynl Therapeutics, Inc. (Sentynl), a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases, announced that data evaluating NULIBRY® (fosdenopterin) for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A were presented at the 2023 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting on Aug.

位于美国的生物制药公司SOLANA BEACH，2023年9月7日/PRNewswire/-Sentynl Therapeutics，Inc。（Sentynl），专注于为患有罕见疾病的患者带来创新疗法，宣布8月在2023年先天性代谢错误研究学会（SSIEM）年会上发表了评估NULIBRY®（fosdenopterin）治疗A型钼辅因子缺乏症（MoCD）患者的数据。

30 in Jerusalem. NULIBRY is indicated to reduce the risk of mortality in patients with MoCD Type A, an ultra-rare, autosomal recessive, inborn error of metabolism causing sulfite-induced neurodegeneration and early death..

30在耶路撒冷。NULIBRY可降低A型MoCD患者的死亡风险，这是一种极为罕见的常染色体隐性先天性代谢错误，可导致亚硫酸盐诱导的神经变性和早期死亡。。

'Clinicians must consider MoCD in infants with encephalopathy or intractable seizures,' said Dr. Guenter Schwarz, Professor for Biochemistry at the Department of Chemistry & Center for Molecular Medicine, Cologne University, Germany. 'Early treatment with fosdenopterin (NULIBRY) improves survival and neurodevelopmental outcomes, reducing burden on patients and caregivers.'.

德国科隆大学化学与分子医学中心生物化学教授Guenter Schwarz博士说：“临床医生必须考虑患有脑病或顽固性癫痫发作的婴儿的MoCD。”用fosdenopterin（NULIBRY）早期治疗可改善生存率和神经发育结果，减轻患者和护理人员的负担。

In comparison of three non-randomized retrospective and prospective open-label studies versus a retrospective and prospective natural history study, the authors reported the following survival and clinical outcomes of patients treated with recombinant cPMP/NULIBRY:

通过比较三项非随机回顾性和前瞻性开放标签研究与回顾性和前瞻性自然史研究，作者报告了用重组cPMP/NULIBRY治疗的患者的以下生存率和临床结果：

Risk of death was 5.1 times higher in untreated MoCD Type A patients compared to those treated with rcPMP/NULIBRY (Cox proportional hazards [95% CI]=5.1 [1.32, 19.36], P=0.0144).

与使用rcPMP/NULIBRY治疗的患者相比，未经治疗的MoCD A型患者的死亡风险高5.1倍（Cox比例风险[95%CI]=5.1[1.32,19.36]，P=0.0144）。

Treatment with rcPMP/NULIBRY led to a normalization of MoCD Type A-associated urinary biomarker levels.

用rcPMP/NULIBRY治疗导致MoCD a型相关尿生物标志物水平正常化。

Treated patients were more likely than untreated patients to feed orally and meet growth and developmental milestones.

接受治疗的患者比未接受治疗的患者更有可能口服喂养并达到生长和发育里程碑。

'These results were pooled from a series of carefully designed studies and corroborate previous anecdotal findings. Early treatment of children with typical neonatal disease manifestation has a dramatic effect on their survival and overall development,' said Dr. Bernd C. Schwahn, Consultant in Paediatric Metabolic Medicine, Manchester Centre for Genomic Medicine, St.

'这些结果来自一系列精心设计的研究，并证实了之前的轶事发现。曼彻斯特基因组医学中心儿科代谢医学顾问Bernd C.Schwahn博士说，早期治疗具有典型新生儿疾病表现的儿童对其生存和整体发育具有显着影响。

Mary's Hospital, in Manchester, United Kingdom. 'Increased disease awareness and the use of new technologies, including improved biochemical testing and rapid whole genome sequencing, will help to shorten the diagnostic gap and allow timely access to effective treatment for a higher proportion of affected children.'.

玛丽医院，英国曼彻斯特。”提高疾病意识和使用新技术，包括改进生化检测和快速全基因组测序，将有助于缩短诊断差距，并为更高比例的受影响儿童及时获得有效治疗。

Based on these data, NULIBRY was approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health. To further evaluate the safety and efficacy of NULIBRY, a post-approval non-interventional study is being initiated in Europe.

根据这些数据，NULIBRY获得了美国食品和药物管理局，欧洲药品管理局和以色列卫生部的批准。为了进一步评估NULIBRY的安全性和有效性，欧洲正在开展批准后的非介入性研究。

'Given Sentynl's focus on meaningful treatments for serious rare diseases, we are grateful to the authors for presenting these data and increasing awareness of MoCD Type A in the medical community,' said Matt Heck, CEO of Sentynl. 'We thank the patients, their families and caregivers, and all investigators involved in this study.

“鉴于Sentynl专注于严重罕见疾病的有意义治疗，我们感谢作者提供这些数据并提高医学界对MoCD A型的认识，”Sentynl首席执行官Matt Heck说我们感谢患者，他们的家人和护理人员以及参与本研究的所有研究人员。

We remain focused on continued evaluation of NULIBRY to reduce the risk of mortality and progression of this devastating disease.'.

我们仍然专注于继续评估NULIBRY，以降低这种破坏性疾病的死亡率和进展风险。

Treatment with NULIBRY/rcPMP was generally well-tolerated in patients with MoCD Type A. Most patients experienced a treatment-emergent adverse event (TEAE), the majority of which were catheter-related or infections and were mild to moderate in severity. In the retrospective study, two serious TEAEs of death occurred, one from RSV pneumonia (unrelated to treatment), and one from necrotizing enterocolitis (possibly related to treatment)..

对于A型MoCD患者，使用NULIBRY/rcPMP治疗通常具有良好的耐受性。大多数患者经历了治疗紧急不良事件（TEAE），其中大多数是导管相关或感染，并且严重程度为轻度至中度。在回顾性研究中，发生了两例严重的TEAE死亡，一例来自RSV肺炎（与治疗无关），另一例来自坏死性小肠结肠炎（可能与治疗有关）。。

Please click here for full Prescribing Information of NULIBRY.

请点击此处获取NULIBRY的完整处方信息。

About Molybdenum Cofactor Deficiency (MoCD) Type AMoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.2.

关于钼辅因子缺乏症（MoCD）A型AMoCD是由钼辅因子合成1基因突变引起的常染色体隐性先天性代谢错误，其特征是钼辅因子产生不足，导致缺乏钼依赖性酶活性[1,2]。缺乏活性导致亚硫酸盐氧化酶活性降低，亚硫酸盐和次级代谢产物（如S-硫代半胱氨酸）在脑内积聚，导致不可逆的神经损伤。

MoCD Type A is an ultra-rare disease. The estimated prevalence of MoCD Type A in the European Union is 0.005 per 10,000. Based on these estimates, MoCD Type A is likely to be underdiagnosed.

A型MoCD是一种极为罕见的疾病。欧盟A型MoCD的估计患病率为0.005/10000。根据这些估计，A型MoCD可能未得到充分诊断。

The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment..

A型MoCD最常见的症状是癫痫发作，进食困难和脑病。在婴儿期以后存活的A型MoCD患者通常患有进行性脑损伤，其在磁共振成像（MRI）上以特征性模式呈现。这种损害导致严重的精神运动障碍，无法协调运动或与周围环境沟通。。

About NULIBRY® (fosdenopterin) for InjectionNULIBRY® (fosdenopterin) for Injection is a substrate replacement therapy that provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites.

关于用于注射的NULIBRY®（fosdenopterin）用于注射的NULIBRY®（fosdenopterin）是一种底物替代疗法，可提供外源性cPMP来源，可转化为钼喋呤。然后将钼蝶呤转化为钼辅因子，钼辅因子是激活钼依赖性酶（包括亚硫酸盐氧化酶）所必需的，亚硫酸盐氧化酶是一种降低神经毒性亚硫酸盐水平的酶。

NULIBRY is approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health for the treatment of patients with known or presumed MoCD Type A (discontinued if MoCD Type A is not confirmed), and it is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A.

NULIBRY获得美国食品和药物管理局，欧洲药品管理局和以色列卫生部的批准，用于治疗已知或推定的MoCD A型患者（如果未确认MoCD A型，则停止使用），这是第一个也是唯一一个FDA批准的治疗方法，用于降低MoCD A型患者的死亡风险。

Clinical trials have demonstrated that patients treated with NULIBRY or rcPMP had an improvement in overall survival compared to the untreated, genotype-matched, historical control group..

临床试验表明，与未治疗的，基因型匹配的历史对照组相比，接受NULIBRY或rcPMP治疗的患者的总生存期有所改善。。

References1 Mechler K et al. Genet Med. 2015;17(12):965-970.2 Schwarz G. Cur Op in Che Bio. 2016;31:179-187.

参考文献1.；Mechler K等人，Genet Med.2015；17（12）：965-970.2.；Schwarz G.Cur Op in Che Bio.2016；31:179-187。

About Sentynl TherapeuticsSentynl Therapeutics is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl's experienced management team has previously built multiple successful pharmaceutical companies.

关于Sentynl TherapeuticsSentynl Therapeutics是一家总部位于美国的生物制药公司，致力于为患有罕见疾病的患者带来创新疗法。该公司于2017年被Zydus集团收购。Sentynl经验丰富的管理团队此前已经建立了多家成功的制药公司。

With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines.

以商业化为重点，Sentynl寻求在广泛的治疗领域提供有效且差异化良好的产品，以满足未满足的需求。Sentynl致力于最高的道德标准并遵守所有适用的法律，法规和行业准则。

For more information, visit https://sentynl.com..

有关更多信息，请访问https://sentynl.com..

SOURCE Sentynl Therapeutics

来源Sentynl Therapeutics