TOKYO, April 19, 2024 – Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that it concluded a license agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) for zilebesiran, an investigational RNAi therapeutic for hypertension created by Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) and currently under development by Roche and Alnylam.

东京，2024年4月19日–Chugai Pharmaceutical Co.，Ltd.（东京：4519）宣布，它与罗氏公司（SIX:RO，ROG；OTCQX:RHHBY）签订了zilebesiran的许可协议，zilebesiran是由Alnylam Pharmaceuticals，Inc.（纳斯达克：ALNY）创建的一种用于治疗高血压的RNAi研究药物，目前正在由罗氏公司和Alnylam开发中。

Under the license agreement between Roche and Chugai, Chugai obtained commercialization rights in Japan for zilebesiran. Roche will receive an upfront fee and milestone payments..

根据罗氏和中盖之间的许可协议，中盖获得了zilebesiran在日本的商业化权利。罗氏将收到预付费和里程碑付款。。

“Hypertension is a serious disease that can lead to the onset and recurrence of various cerebrovascular and cardiovascular events including myocardial infarction and stroke. However, up to 80%1 of patients with hypertension still show uncontrolled blood pressure and there remains a significant unmet need.

“高血压是一种严重的疾病，可导致包括心肌梗塞和中风在内的各种脑血管和心血管事件的发作和复发。然而，高达80%的高血压患者仍然表现出不受控制的血压，并且仍然存在大量未满足的需求。

Chugai will work closely with Roche and Alnylam to bring innovations through this new modality to patients with hypertension as soon as possible,” said Chugai’s President and CEO, Dr. Osamu Okuda..

Chugai将与Roche和Alnylam密切合作，通过这种新方式尽快为高血压患者带来创新，”Chugai总裁兼首席执行官OsamuOkuda博士说。。

Zilebesiran is an RNAi therapeutic targeting angiotensinogen (AGT) that reduces vasoconstrictor angiotensin II by inhibiting the synthesis of angiotensinogen in the liver. Alnylam conducted the global Phase II KARDIA-2 study of zilebesiran in patients with mild to moderate uncontrolled hypertension evaluating the efficacy and safety of a single subcutaneous dose of zilebesiran when added to one of three standard of care antihypertensives.

Zilebesiran是一种靶向血管紧张素原（AGT）的RNAi治疗剂，可通过抑制肝脏中血管紧张素原的合成来减少血管收缩剂血管紧张素II。Alnylam对轻度至中度不受控制的高血压患者进行了齐莱贝西兰的全球II期KARDIA-2研究，评估了单次皮下剂量齐莱贝西兰加入三种标准治疗抗高血压药物之一时的疗效和安全性。

The primary endpoint was the change from baseline mean systolic blood pressure (SBP) at month three, assessed by 24-hour ambulatory blood pressure monitoring (ABPM). The KARDIA-2 study met its primary endpoint, demonstrating clinically and statistically significant additive, placebo-adjusted SBP reductions.

主要终点是通过24小时动态血压监测（ABPM）评估的第三个月基线平均收缩压（SBP）的变化。KARDIA-2研究达到了其主要终点，证明了临床和统计学上显着的添加剂，安慰剂调整的SBP降低。

The global Phase II KARDIA-3 study was recently initiated in patients at high cardiovascular risk and uncontrolled hypertension to evaluate the efficacy of zilebesiran when added to two or more hypertensive medications..

全球II期KARDIA-3研究最近在心血管高危和高血压不受控制的患者中启动，以评估齐利贝西兰加入两种或多种高血压药物后的疗效。。

Chugai will continue to effectively utilize the research and development resources of the Roche Group to find innovative new drugs so as to satisfy unmet medical needs.

楚盖将继续有效利用罗氏集团的研发资源，寻找创新新药，以满足未满足的医疗需求。

About hypertension Hypertension is the leading cause of cardiovascular disease worldwide, and a major risk for premature mortality.1 Early effects of hypertension can include subtle target organ damage such as left-ventricular hypertrophy and cognitive dysfunction.2,3 Over time, uncontrolled hypertension can lead to cardiovascular disease including stroke (ischaemic and haemorrhagic), coronary artery disease, heart failure, peripheral artery disease, chronic kidney disease and end-stage renal disease, dementia, and Alzheimer’s disease.4,5,6,7 There remains a significant unmet medical need, as poor rates of adherence to daily medications can result in inconsistent blood pressure control and an increased risk for stroke, heart attack, and premature death.8 In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients at high cardiovascular risk.9.

关于高血压高血压高血压是世界范围内心血管疾病的主要原因，也是过早死亡的主要风险。高血压的早期影响可能包括微妙的靶器官损害，如左心室肥大和认知功能障碍。2,3随着时间的推移，不受控制的高血压可能导致心血管疾病，包括中风（缺血性和出血性）、冠状动脉疾病、心力衰竭、外周动脉疾病、慢性肾病和终末期肾病、痴呆和阿尔茨海默病。4,5,6,7仍然存在严重的未满足的医疗需求，因为坚持每日药物治疗的比率低可能导致血压控制不一致，并增加中风、心脏病发作和过早死亡的风险。8特别是，有许多高未满足的医疗需求T需要新的高血压治疗方法需要额外的发展重点，包括心血管高危患者。

About zilebesiran Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure regulation and its inhibition has well-established antihypertensive effects.

关于zilebesiran zilebesiran是一种针对血管紧张素原（AGT）的研究性皮下给药RNAi治疗剂，正在开发中，用于治疗高度未满足需求人群的高血压。AGT是肾素-血管紧张素-醛固酮系统（RAAS）中最上游的前体，RAAS是一种级联反应，在血压调节中具有明显的作用，其抑制作用具有公认的抗高血压作用。

Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilises Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran.

齐莱贝西仑抑制肝脏中AGT的合成，可能导致AGT蛋白的持续减少，最终导致血管收缩剂血管紧张素（Ang）II的持续减少。齐利贝西兰利用Alnylam的增强稳定化学加（ESC+）GalNAc缀合物技术，该技术可以实现不频繁的皮下给药，具有更高的选择性和实现强直性血压控制的潜力，在24小时内表现出持续和持久的血压降低，单剂量齐利贝西兰后持续长达六个月。

In 2023, Roche and Alnylam entered a global partnership to co-develop and co-commercialise the RNAi therapeutic zilebesiran. As a part of this agreement, Alnylam and Roche will co-commercialize zilebesiran in the U.S. Outside the U.S., Roche has exclusive commercialisation rights, Chugai has obtained commercial rights in Japan under its license agreement with Roche.

2023年，罗氏和Alnylam建立了全球合作伙伴关系，共同开发并共同商业化RNAi治疗剂zilebesiran。作为本协议的一部分，Alnylam和Roche将在美国以外的美国共同商业化zilebesiran。Roche拥有独家商业化权利，Chugai已根据其与Roche的许可协议在日本获得商业权利。

The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, PMDA or any other health authority..

FDA，PMDA或任何其他卫生当局尚未确定或评估齐莱贝西仑的安全性和有效性。。

About RNAi therapeutics RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine.

关于RNAi治疗学RNAi（RNA干扰）是一种基因沉默的自然细胞过程，代表了当今生物学和药物开发中最有前途和快速发展的前沿之一。它的发现获得了2006年诺贝尔生理学或医学奖的认可。

RNAi therapeutics is harnessed the natural biological process of RNAi occurring in our cells. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made..

RNAi治疗是利用我们细胞中发生的RNAi的自然生物学过程。小干扰RNA（siRNA）是介导RNAi并构成Alnylam RNAi治疗平台的分子，它通过有效沉默信使RNA（mRNA）（编码致病或疾病途径蛋白的遗传前体）而在当今药物的上游发挥作用，从而阻止了它们的产生。