Pilocarpine Hydrochloride

Primary endpoint was met with 74% of participants dosed with LNZ100 achieving three-lines or greater improvement at 3 hours post treatment，and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). The difference in efficacy was statistically significant in the LNZ100 treatment group compared to the vehicle group (p<0.0001) Rapid onset and long duration shown with 69% of participants achieving three-lines or greater improvement at 30 minutes and 30% at 10 hours 91% of participants indicated they noticed an improvement in their near vision LNZ100 could potentially be the best-in-class non-invasive treatment for presbyopia SHANGHAI, China and SAN DIEGO, Oct. 27, 2024 (GLOBE NEWSWIRE) -- Corxel Pharmaceuticals (CORXEL) and LENZ Therapeutics (Nasdaq: LENZ) today announced positive topline data from the Phase 3 JX07001 clinical trial of LNZ100 in patients with presbyopia in China. CORXEL is a leading biotech company committed to bringing innovative science and medicines to underserved patients with serious and life-threatening diseases. LENZ Therapeutics is a pre-commercial biopharmaceutical company focused on developing the first and only aceclidine-based eye drop to improve near vision in people with presbyopia. In this China Phase 3 safety and efficacy trial, LNZ100 (1.75% aceclidine HCl) achieved the primary endpoint and key secondary endpoints, with statistically significant three-lines or greater improvement in Best Corrected Distance Visual Acuity (BCDVA) at near, and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). More results showed (all p<0.0001): Rapid onset: 84% and 69% achieved two-lines and three-lines or greater improvement at 30 minutes respectively.3 hours post treatment: 88% and 74% achieved two-lines and three-lines or greater improvement at 3 hours respectively，and maintained their optimal distance visual acuity (i.e., not losing 5 or more letters).Long duration: 61% and 30% achieved two-lines and three-lines or greater improvement at 10 hours respectively. LNZ100 was well-tolerated with no serious treatment-related adverse events observed in the trial. The study was a Phase 3, multicenter, randomized, double-blind, vehicle-controlled study, including a 4-week efficacy study followed by a 5-month extension safety study, designed to evaluate the efficacy and safety of LNZ100 (an aceclidine-based ophthalmic solution) in participants with presbyopia. The objectives were to assess the potential of LNZ100 to improve near vision among Chinese presbyopia patients and to evaluate the efficacy and safety profiles.  The trial has enrolled 300 participants, with a broad enrollment criteria of between 45 and 75 years of age with a refractive range of -4.0D SE to +1.0D SE, including those who had undergone laser-assisted cornea refractive surgery/monofocal IOL implantation. Professor Jia Qu, Principal Investigator and Co-Principal Investigator，Vice Chairman of Ophthalmology Branch, Chinese Medical Association, Director of optometry department, Wenzhou Medical University said: “we are very pleased with the results of the LNZ100 trial, particularly the significant efficacy and favorable safety profile of LNZ100 in patients with presbyopia, demonstrating an important advance in the field of presbyopia treatment in China. Currently, patients mainly rely on wearing eyeglasses as treatment for presbyopia. There is a large unmet need for non-invasive and reversible treatments. We expect that LNZ100 will fill this vacuum and become an innovative force in the treatment of presbyopia in China, providing more patients with the hope of clear vision." Professor Fan Lyu, Principal Investigator and Co-Principal Investigator，Head of optometry working-group under Ophthalmology Branch, Chinese Medical Association, Director of National Clinical Medical Research Centre for Eye Diseases said: "The main active ingredient of LNZ100, aceclidine, causes temporary pupil constriction, resulting in an optical effect that significantly extends the depth of focus and improves the quality of vision. The statistically significant data and clinically meaningful outcomes observed in the trials provide strong support for the efficacy and safety of LNZ100. We anticipate that LNZ100 will be a practical treatment option for a wide spectrum of patients and will have a favorable impact on paradigm shift of helping improve near-vision in the Chinese presbyopia population. “We are especially grateful to all the hard-working and dedicated researchers, partner organizations and all the volunteers who participated in the study,” Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL, said. “The common goal is to benefit hundreds of millions of people around the world, to set an international leading research benchmark, and to introduce novel treatment concepts and potentially optimal products to China first, providing a safe and convenient treatment option for the vast number of presbyopia patients. Looking ahead, we will actively communicate and cooperate with drug regulatory authorities to expedite the submission and approval of LNZ100. We believe that LNZ100 will not only significantly improve patients' vision and quality of life, but will also have a profound impact on the field of presbyopia treatment and research in China.” “We would like to first congratulate the team at CORXEL for their effort in their Phase 3 clinical study in China. We are pleased with the impressive and consistent performance demonstrated by LNZ100 in our collective studies, further validating the vision of targeting an ‘all eyes, all day’ solution,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “With this data, we believe LNZ100 has further enhanced its potential as a global therapy and is further on its path towards providing access to the estimated 400 million people with presbyopia in China. This data signifies a tremendous joint effort between the CORXEL and LENZ teams and comes in rapid succession to the recent FDA acceptance of our New Drug Application for LNZ100 in the United States.” About PresbyopiaPresbyopia is a physiological phenomenon associated with aging that results in a progressively worsening ability to see nearby objects clearly. It is caused by the gradual hardening of the lens. This results in a decline of the eye's adjustment function, and the inability to focus the image of nearby objects on the retina, leading to a decline in near vision. Studies have shown that the onset of presbyopia typically occurs around the age of 38, reaching a prevalence rate of nearly 100 percent at the age of 52 in China. It is estimated that more than 400 million people in China suffer from presbyopia.  Currently, the treatment options for presbyopia are very limited. Wearing glasses requires frequent removal and insertion, causing many inconveniences in work and life. Surgery, as an irreversible invasive operation, has a very limited acceptance. There are no approved drugs for the treatment of presbyopia in China and the medical need for non-invasive, safe, efficient and reversible treatments for presbyopia remains unsolved.  About LNZ100LNZ100 (aceclidine) eye drops are being developed by LENZ Therapeutics and CORXEL acquired the Greater China rights for the development and commercialization in April 2022. LNZ100 is formulated with aceclidine, a miotic, and designed to achieve optimal pupil diameter without impacting distance vision, a key limitation of other miotics. Miotics are compounds that cause pupil constriction, or miosis, creating a pinhole effect that enables better focus of incoming light from near objects onto the retina. Research has shown that a pupil diameter below two millimeters (2 mm) is optimal for presbyopia treatment and results in clinically meaningful improvement in near vision. Unlike other miotics such as pilocarpine and carbachol, aceclidine’s mechanism of action is pupil-selective, meaning it can activate the iris sphincter muscle and cause miosis of the pupil to a diameter below 2 mm without overstimulating the ciliary muscles that can cause a myopic shift and impair distance vision. As a result, aceclidine does not require any remaining accommodation to improve near vision, broadening its benefits to older presbyopes whose lens has lost this capacity. Therefore, we expect that users may be able to benefit from treatment even as they age from mid-40s to well into their mid-70s and across a broad range of refractive errors, as demonstrated in clinical testing to date. About CORXELCORXEL, formerly named Ji Xing Pharmaceuticals, is a leading biotech company headquartered in US and China committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic diseases. Backed by RTW Investments, CORXEL was founded in 2019 to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in diseases. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to deliver a meaningful and lasting impact on patients. The full portfolio of CORXEL consists of 2 assets with global rights and 4 assets with Greater China rights in late-stage clinical development. The portfolio with global rights are JX09 for hypertension and JX10 for acute ischemic stroke (AIS), while the portfolio with Greater China rights include aficamten, etripamil, varenicline solution nasal spray/US brand name TYRVAYA®, and LNZ100. For further information about CORXEL, please visit www.corxelbio.com.   About LENZ TherapeuticsLENZ Therapeutics is a pre-commercial biopharmaceutical company focused on the development and commercialization of the first and only aceclidine-based eye drop to improve near vision in patients with presbyopia. LENZ’s product candidate, LNZ100 is a preservative-free, single-use, once-daily eye drop containing aceclidine. LNZ100 was evaluated in the registration-enabling Phase 3 CLARITY study as a potential therapy for the treatment of presbyopia, a condition impacting an estimated 1.8 billion people globally and 128 million people in the United States. The U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025 for LNZ100. LENZ is committed to commercializing an ideal pharmaceutical presbyopia solution that enhances vision for “all eyes, all day”. LENZ is headquartered in San Diego, California. For more information, visit: LENZ-Tx.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of United States federal securities laws. You can identify forward-looking statements by words such as “may,” “will,” “could,” “can,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “poised,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, but not all forward-looking statements will contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the potential of LNZ100 to have best-in-class performance and LNZ100 as a global therapy; the size of the addressable population for LNZ100; expectations regarding the commercial opportunity and beneficial characteristics of LNZ100; and plans and expectations regarding commercialization of LNZ100, if approved. These statements are based on numerous assumptions concerning the development of LENZ’s products and target markets and involve substantial risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievement to be materially different from the information expressed or implied by these forward-looking statements, including those risk factors described in the section titled “Risk Factors” in LENZ’s Quarterly Report on Form 10-Q filed for the quarter ended June 30, 2024 and in LENZ’s subsequent filings with the SEC. LENZ cannot assure you that the forward-looking statements in this press release or the assumptions upon which they are based will prove to be accurate. The forward-looking statements in this press release are as of the date of this press release. Except as otherwise required by applicable law, LENZ disclaims any duty to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. LENZ Therapeutics Contact: Dan Chevallard IR@LENZ-Tx.com

▎药明康德内容团队编辑 LENZ Therapeutics今天宣布，美国FDA已接受其醋克立定（1.75% aceclidine）眼药水配方LNZ100用于治疗老花眼的新药申请（NDA）。根据之前所公布的3期试验结果，在不影响患者远视力（distance vision）的情形下，患者的近视力（near vision）可在使用LNZ100眼药水后30分钟内达成显著的改善，且疗效可维持10个小时！这表示患者只要在早上滴几滴眼药水，几乎整个白天的近视力都得到提高！该申请的PDUFA的目标日期为2025年8月8日。 老花眼是随着年龄的增长而出现的常见视力衰退，影响全球近20亿人。我们眼睛中的晶状体像是照相机中调节焦距的镜片，改变它的形状可以将图像聚焦在视网膜上，让我们清晰地看到外面的世界。然而，随着年龄的增长，我们眼睛中晶状体的弹性变差，控制晶状体形状的睫状体肌肉的收缩能力也逐渐下降，这些综合因素让晶状体的聚焦能力随之下降，这让近处的图像难以聚焦在视网膜上。老花眼通常在40岁之后出现，目前大多数治疗方法是佩戴老花镜，但是对很多人来说并不方便。 目前开发的老花眼药物疗法大多数采用的策略是缩小瞳孔。缩小瞳孔产生的针孔效应（pinhole effect）可以增加景深，让穿过瞳孔的光能够聚焦在视网膜上。 ▲缩小瞳孔改善老花眼患者视力的科学基础（图片来源：参考资料[3]） 这次NDA的提交主要基于关键3期CLARITY试验积极数据的支持。CLARITY是一项LNZ100和LNZ101治疗老花眼的3期多中心、双盲、随机的疗效和安全性研究。它由两项为期六周的疗效试验CLARITY 1和2以及一项为期六个月的安全性试验CLARITY 3组成。 分析显示，LNZ100达成试验主要终点和关键次要终点，即在近视力测量上，表现出视力表上3行（15个字母）以上的阅读改善，同时并不失去1行（5个字母）的远视力。在溶剂对照的CLARITY 2试验中，试验第1天结果显示LNZ100展现以下效果： ▲LNZ100达成试验主要终点（图片来源：参考资料[2]） 快速起效：71%患者在30分钟内实现视力表上三行或更大的改善（p<0.0001）。 达主要终点：71%的患者在3小时内取得视力表上三行或更多的改善（p<0.0001）。 持续时间长：40％的患者在10小时内实现了视力表上三行或更多的改善（p<0.0001）。 在为期四周的研究期间，CLARITY 1和2试验中所显示患者的近视力改善具有可重复性与一致性。 LNZ100耐受性良好，在三项CLARITY试验中未观察到严重的治疗相关不良事件。 ▲LNZ100展现良好的耐受性（图片来源：参考资料[2]） LNZ100是一种不含防腐剂、每日使用一次的眼药水，其中主要有效成分为醋克利定。醋克立定是一种小分子乙酰胆碱受体激动剂，可引起瞳孔收缩，产生针孔效应，从而改善近视力。但与其它胆碱受体激动剂相比，它对控制瞳孔大小的虹膜肌肉的作用更具有特异性，从而在缩小瞳孔的同时减少睫状体肌肉的收缩，降低晶状体的屈光变化，进而避免影响患者的远视力。 图片来源：123RF 近年来多家医药公司投入治疗老花眼的眼药水疗法开发。艾伯维（AbbVie）旗下艾尔建（Allergan）公司的Vuity（1.25%毛果芸香碱滴眼液）在2021年10月获得美国FDA批准用于治疗老花眼。毛果芸香碱是一种成熟的眼部护理治疗药物，它的主要作用机制是收缩瞳孔，从而增强景深，改善近视力和中距视力。试验结果显示，与安慰剂相比，接受Vuity治疗的患者检验近视力的指标获得显著改善，同时这一眼药水不会影响患者的远视力。它最快在滴入15分钟后生效，疗效可持续6个小时。新闻稿指出，这是FDA批准的首款用于治疗老花眼的眼药水疗法。去年10月，Orasis Pharmaceuticals所开发的Qlosi（0.4%毛果芸香碱滴眼液）获得FDA批准上市，用于治疗成人老花眼。受试者最早在接受治疗20分钟后就可获得视力改善，并且疗效可持续长达8个小时。而由Eyenovia开发，同样以毛果芸香碱为主要配方的MicroLine眼药水也在3期临床试验当中获得积极结果，上市申请正在准备中。MicroLine的给药方式与众不同。传统的给药方式是用药瓶滴眼药水，一滴药水的体积大约是40微升。而MicroLine配方使用一种喷雾器的方式向眼睛里喷出细小的毛果芸香碱液滴，这种给药方式每次只递送大约8微升的药物。降低给药剂量可以减少和药物或药水中防腐剂相关的副作用。 而由Visus Therapeutics公司所开发的Brimochol PF也在去年4月于3期试验当中获得积极结果。Brimochol PF包含了固定剂量的卡巴胆碱（carbachol）和溴莫尼定（brimonidine）两种获批药物。与其成分中的卡巴胆碱或溴莫尼定单药相比，该疗法在多个时间点均显著改善患者的近、远视力，并且瞳孔收缩效果可长达10小时。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] LENZ Therapeutics Announces FDA Acceptance of New Drug Application for LNZ100 for the Treatment of Presbyopia. Retrieved October 22, 2024 from https://www.globenewswire.com/news-release/2024/10/21/2966144/0/en/LENZ-Therapeutics-Announces-FDA-Acceptance-of-New-Drug-Application-for-LNZ100-for-the-Treatment-of-Presbyopia.html [2] Topline CLARITY Results. Retrieved April 3, 2024 https://d1io3yog0oux5.cloudfront.net/_1b75a0055e0f2e21ec4f05c07a9d694b/lenztx/db/2266/21446/presentation/Clarity+Topline+Presentation+Slides+04022024+final+locked.pdf [3] LENZ Therapeutics Corporate Presentation. Retrieved November 1, 2021, from https://lenz-tx.com/wp-content/uploads/2021/10/LENZ_corporate_presentation_for_website.pdf [4] Eyenovia Reports First Quarter 2023 Financial Results and Provides Business Update. Retrieved October 22, 2024 from https://www.sec.gov/Archives/edgar/data/1682639/000110465923059164/tm2315261d1_ex99-1.htm 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新