CARLSBAD, Calif., May 16, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive topline data from the HALOS Phase 1/2a open-label study of ION582 in Angelman syndrome. ION582 was safe and well tolerated in the study and showed encouraging and consistent benefits in individuals living with Angelman syndrome, with the most robust improvements observed in key areas of functioning including cognition, communication and motor function..

加利福尼亚州卡尔斯巴德，2024年5月16日/PRNewswire/--Ionis Pharmaceuticals，Inc.（Nasdaq:IONS）今天宣布，来自Angelman综合征中ION582的HALOS 1/2a期开放标签研究的正面数据。ION582在该研究中是安全且耐受性良好的，并且在患有Angelman综合征的个体中显示出令人鼓舞且持续的益处，在认知，沟通和运动功能等关键功能领域观察到了最有力的改善。。

Ionis also announced that it will independently advance ION582 as part of Ionis' leading portfolio of potentially transformational medicines for serious neurological diseases. Ionis plans to review the ION582 Phase 1/2a results with regulatory authorities to align on the design of the pivotal program.

Ionis还宣布，它将独立推进ION582，作为Ionis领先的针对严重神经系统疾病的潜在转化药物组合的一部分。Ionis计划与监管机构一起审查ION582 1/2a阶段的结果，以调整关键计划的设计。

Biogen has elected not to exercise its option to license ION582..

Biogen已选择不行使其许可ION582的选择权。。

'There are currently no approved treatments for Angelman syndrome, which causes developmental delays, cognitive impairment and severe communications challenges, with most individuals unable to speak or live independently,' said Lynne Bird, M.D., professor of clinical pediatrics at UC San Diego and HALOS study investigator.

加州大学圣地亚哥分校临床儿科教授、HALOS研究调查员林恩·伯德（LynneBird）医学博士说：“目前还没有批准的治疗安格曼综合征的方法，该综合征会导致发育迟缓、认知障碍和严重的沟通挑战，大多数人无法独立说话或生活。”。

'We are encouraged by the positive and consistent improvements seen in the HALOS study across multiple measures, as these functional improvements could have a transformative impact in the lives of people living with Angelman syndrome and their caregivers. We are also encouraged by the favorable safety and tolerability profile observed in the study, which is particularly important when treating children.

“我们对HALOS研究在多项措施中取得的积极和持续的改进感到鼓舞，因为这些功能改进可能会对患有Angelman综合征的人及其护理人员的生活产生变革性影响。我们还对研究中观察到的良好安全性和耐受性感到鼓舞，这在治疗儿童时尤为重要。

We very much look forward to further evaluation of ION582 in a pivotal program.'.

我们非常期待在关键项目中对ION582进行进一步评估。”。

Angelman syndrome is caused by a loss of function in the maternal UBE3A gene. ION582 is designed to unsilence the paternal UBE3A allele in order to increase production of the UBE3A protein in the brain. Angelman syndrome affects an estimated one in 12,000 to 20,000 people globally.1 It presents as profound and severe developmental delays in motor, language and cognitive functioning, seizures and ataxia.

Angelman综合征是由母体UBE3A基因功能丧失引起的。ION582旨在解除父系UBE3A等位基因的沉默，以增加大脑中UBE3A蛋白的产生。据估计，全球每12000至20000人中就有一人患有Angelman综合征。1它表现为运动，语言和认知功能，癫痫发作和共济失调的严重而严重的发育迟缓。

It is a serious neurodevelopmental disorder that presents in early childhood, resulting in complete dependence on a caregiver..

这是一种严重的神经发育障碍，出现在儿童早期，导致完全依赖照顾者。。

'We are encouraged by the data from the HALOS study and pleased to add this promising medicine to our growing independent pipeline of neurology medicines,' said Brett Monia, Ph.D., chief executive officer of Ionis. 'We look forward to sharing detailed data at the upcoming Angelman Syndrome Foundation meeting and to advancing ION582 into a pivotal study.

Ionis首席执行官布雷特·莫尼亚（BrettMonia）博士说：“我们对HALOS研究的数据感到鼓舞，并很高兴将这种有前途的药物添加到我们不断增长的独立神经病学药物管道中。”我们期待在即将举行的Angelman综合征基金会会议上分享详细数据，并将ION582推进关键研究。

Individuals with Angelman syndrome face significant neuro-developmental challenges and have no approved therapies today. We are committed to working closely with the community, investigators and regulators to advance this promising investigational medicine.'.

患有Angelman综合征的个体面临着重大的神经发育挑战，目前尚无批准的治疗方法。我们致力于与社区，调查人员和监管机构密切合作，以推进这种有前途的研究药物。”。

Part 1 of the HALOS trial was a three-month, multiple-ascending dose (MAD) study in 51 patients aged 2-50, which evaluated three doses of ION582. All eligible patients transitioned into the Part 2 long-term extension (LTE) portion of the study, which is evaluating the two higher doses of ION582 for an additional 12 months.

HALOS试验的第一部分是对51名2-50岁患者进行的为期三个月的多次递增剂量（MAD）研究，该研究评估了三剂ION582。所有符合条件的患者都进入了该研究的第二部分长期延长（LTE）部分，该部分正在评估另外12个月的两种更高剂量的ION582。

Part 3 of the study will evaluate eligible patients for an additional three years. Topline results were available for all patients at four months (one month after last MAD dose), and six months, and were consistent with preliminary findings reported at the Foundation for Angelman Syndrome Therapeutics (FAST) meeting in November 2023.

该研究的第3部分将对符合条件的患者进行另外三年的评估。所有患者在四个月（最后一次MAD剂量后一个月）和六个月时均可获得Topline结果，并且与2023年11月Angelman综合征治疗基金会（FAST）会议上报告的初步结果一致。

Topline data included:.

包含的Topline数据：。

Safety assessment was the primary objective of the trial and ION582 was safe and well tolerated at all dose levels. Adverse events in the trial were consistent with patient medical histories, Angelman syndrome diagnosis or related to intrathecal administration.

安全性评估是该试验的主要目标，ION582在所有剂量水平下都是安全且耐受性良好的。试验中的不良事件与患者病史，Angelman综合征诊断或鞘内给药有关。

ION582 showed consistent effects across multiple objective and subjective measures used to assess functioning in individuals living with Angelman syndrome. These include the Bayley-4, an objective physician assessment of clinical functioning, Angelman Syndrome Clinical Global Improvement Change (SAS-CGI-C) scale, which evaluates clinicians' impressions, and the Vineland-3 and Observer-Reported Communication Ability (ORCA) measures, which are parent-reported assessment tools.

ION582在用于评估患有Angelman综合征的个体的功能的多种客观和主观测量中显示出一致的效果。这些包括Bayley-4，一种客观的医生临床功能评估，Angelman综合征临床整体改善变化（SAS-CGI-C）量表，用于评估临床医生的印象，以及Vineland-3和观察者报告的沟通能力（ORCA）措施，这是父母报告的评估工具。

These positive results correlated with positive changes in EEG activity including a reduction in slow wave delta activity..

这些积极的结果与脑电图活动的积极变化相关，包括慢波δ活动的减少。。

At six months, approximately 65% of patients achieved an improvement in cognition on the Bayley-4. While no direct comparisons should be made, these improvements exceeded improvements seen in natural history studies over the same time period.

在六个月时，大约65%的患者对Bayley-4的认知有所改善。虽然不应该进行直接比较，但这些改进超过了同一时期自然史研究中的改进。

At six months, approximately 70% of patients showed improvement on Bayley-4 measures of receptive and/or expressive communication. While no direct comparisons should be made, these changes exceeded improvements seen in natural history studies over the same time period.

在六个月时，大约70%的患者在接受和/或表达沟通的Bayley-4测量中表现出改善。虽然不应该进行直接比较，但这些变化超过了同一时期自然史研究中的改进。

At six months, approximately 65% of patients showed improvements in Bayley-4 measures of fine and gross motor skills. While no direct comparisons should be made, these changes exceeded improvements seen in natural history studies over the same time period.

在六个月时，大约65%的患者表现出Bayley-4精细和粗大运动技能的改善。虽然不应该进行直接比较，但这些变化超过了同一时期自然史研究中的改进。

Ionis expects to report detailed results from the HALOS study at the Angelman Syndrome Foundation meeting in July. ION582 has received Orphan Drug designation in the U.S. The HALOS Phase 1/2a open-label trial is evaluating safety, tolerability, pharmacokinetics and pharmacodynamics in addition to certain clinical outcomes measures.

Ionis预计将在7月的Angelman综合征基金会会议上报告HALOS研究的详细结果。ION582在美国被指定为孤儿药。S、 HALOS 1/2a期开放标签试验除了某些临床结果测量外，还评估安全性，耐受性，药代动力学和药效学。

ION582 is administered intrathecally into the cerebral spinal fluid with a lumbar puncture. For more information on the HALOS Study (NCT05127226), visit clinicaltrials.gov..

ION582通过腰椎穿刺鞘内注射到脑脊液中。有关HALOS研究（NCT05127226）的更多信息，请访问clinicaltrials.gov。。

About Ionis' Neurology Franchise

关于Ionis的神经病学特许经营权

Ionis' neurology franchise addresses all major brain regions and central nervous system cell types and currently has three Phase 3 studies ongoing with 11 therapies in clinical development, several of which Ionis plans to commercialize directly. Ionis is discovering and developing potential treatments for many neurological diseases for which there are few or no disease modifying treatments, including common diseases like Alzheimer's and Parkinson's as well as rare diseases such as amyotrophic lateral sclerosis (ALS) and Alexander disease.

Ionis的神经学特许经营权涉及所有主要的大脑区域和中枢神经系统细胞类型，目前正在进行三期3研究，临床开发中有11种疗法，其中一些Ionis计划直接商业化。Ionis正在发现和开发许多神经系统疾病的潜在治疗方法，这些疾病很少或根本没有改善疾病的治疗方法，包括阿尔茨海默氏症和帕金森氏症等常见疾病以及肌萎缩侧索硬化症（ALS）和亚历山大病等罕见疾病。

Ionis has discovered and developed three commercially available neurological disease medicines, including SPINRAZA® (nusinersen), the first approved treatment for spinal muscular atrophy, WAINUATM (eplontersen), a medicine to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and QALSODY® (tofersen) for SOD1-ALS..

Ionis已经发现并开发了三种市售的神经系统疾病药物，包括SPINRAZA®（nusinersen），第一种被批准用于治疗脊髓性肌萎缩症的药物，WAINUATM（eplontersen），一种治疗遗传性甲状腺素转运蛋白介导的淀粉样多发性神经病（ATTRv PN）的药物，以及用于SOD1-ALS的QALSODY®（tofersen）。。

About Ionis Pharmaceuticals, Inc.

关于Ionis Pharmaceuticals，Inc。

For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing.

三十年来，伊奥尼斯发明的药物为患有严重疾病的人带来了更好的未来。Ionis目前拥有五种上市药物，并在神经病学、心脏病学和其他患者需求较高的领域拥有领先的渠道。作为RNA靶向药物的先驱，Ionis除了推进基因编辑的新方法外，还继续推动RNA疗法的创新。

A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients..

对疾病生物学和业界领先技术的深入了解推动了我们的工作，同时也激发了我们为患者带来改变生活的进步的热情和紧迫感。。