Company on track to dose first participant in multi-part, adaptive Phase 1, first-in-human study in healthy volunteers and Parkinson's Disease (PD) patients in the first quarter of 2024

公司将在2024年第一季度为健康志愿者和帕金森病（PD）患者的多部分，适应性阶段1，首次人体研究中的第一个参与者提供剂量

CTA comes as Nature Reviews Drug Discovery hails Mission's mitophagy approach as 'an appealing disease-modifying therapeutic strategy' for PD

CTA来自Nature Reviews Drug Discovery hails Mission的线粒体自噬方法被认为是PD的“一种有吸引力的疾病改善治疗策略”

CAMBRIDGE, England, Dec. 5, 2023 /PRNewswire/ -- Mission Therapeutics ('Mission' or the 'Company'), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, today announces that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted clinical trial authorisation (CTA) for Mission to commence its multi-part, adaptive Phase 1, first-in-human study evaluating the safety and tolerability of MTX325, intended for the treatment of Parkinson's Disease (PD)..

英国剑桥，2023年12月5日/PRNewswire/-Mission Therapeutics（'Mission'或'Company'），一家临床阶段生物技术公司，开发针对线粒体自噬的一流疗法，今天宣布英国药品和保健品监管机构（MHRA）已授予Mission临床试验许可（CTA），以开始其多部分适应性阶段1，用于治疗帕金森病（PD）的MTX325安全性和耐受性的首次人体研究。。

'The MHRA's authorisation marks a major step forward in our mission to develop MTX325 as a disease-modifying therapy for Parkinson's Disease,' said Anker Lundemose, Chief Executive Officer, Mission Therapeutics. 'Having recently published data[i] showing that MTX325 produced a similar beneficial effect to knockout of USP30 in a mouse model of PD, bringing MTX325 into the clinic — with its potential to preserve vital dopamine-producing neurons in the brain — demonstrates our commitment to pushing the boundaries of research in diseases with limited treatment options.

mission Therapeutics首席执行官Anker Lundemose说：“MHRA的授权标志着我们将MTX325开发为帕金森病的疾病缓解疗法的使命向前迈出了重要一步。”最近公布的数据[i]显示MTX325在PD小鼠模型中产生了与敲除USP30相似的有益效果，将MTX325带入临床-具有保护大脑中重要的多巴胺产生神经元的潜力-证明了我们的承诺推动治疗选择有限的疾病研究界限。

Following successful completion of the Phase 1 clinical study with our peripheral compound, MTX652, earlier this year, we now have two compounds targeting mitophagy in clinical phase testing, and this approval represents significant further validation of our unique approach to target unmet medical needs.'.

在今年早些时候成功完成了我们的外周化合物MTX652的1期临床研究后，我们现在有两种化合物在临床阶段测试中针对线粒体自噬，这一批准代表了我们针对未满足医疗需求的独特方法的重大进一步验证。

Dr Paul Thompson, Chief Scientific Officer, Mission Therapeutics, said: 'There are currently no approved treatments for Parkinson's Disease which modify the underlying pathology of this common and devastating degenerative condition. By enhancing mitophagy, MTX325 is designed to address the loss of dopamine-producing neurons resulting from the build-up of dysfunctional mitochondria in these brain cells.

Mission Therapeutics首席科学官Paul Thompson博士说：“目前还没有批准的帕金森病治疗方法可以改变这种常见和破坏性退行性疾病的潜在病理。通过增强线粒体，MTX325被设计为解决由于这些脑细胞中功能失调的线粒体的积累而导致的产生多巴胺的神经元的损失。

Mitophagy is the natural 'quality control system' cells use to clear out dysfunctional mitochondria, and we believe that increasing the removal of these dysfunctional mitochondria will improve the health of dopaminergic neurons and thereby slow the progression of PD.'.

线粒体自噬是用于清除功能失调的线粒体的天然“质量控制系统”细胞，我们认为增加这些功能失调的线粒体的去除将改善多巴胺能神经元的健康，从而减缓PD的进展。

Dr Suhail Nurbhai, Chief Medical Officer, Mission Therapeutics, commented 'We are delighted to have approval to start clinical testing with MTX325. This Phase 1 trial is intended to confirm the safety and tolerability of MTX325, in both healthy volunteers and patients with Parkinson's Disease, and help us determine appropriate doses for future efficacy testing.

Mission Therapeutics首席医疗官Suhail Nurbhai博士评论说：“我们很高兴批准开始使用MTX325进行临床测试。该1期试验旨在确认MTX325在健康志愿者和帕金森病患者中的安全性和耐受性，并帮助我们确定适当的剂量用于未来的功效测试。

We look forward to starting the trial in the coming months, and providing preliminary first-in-human data later in 2024.'.

我们期待在未来几个月开始试验，并在2024年晚些时候提供初步的首次人体数据。

Up to 160 adults, both healthy people and those with PD, will be recruited for the trial, which is planned to take place at sites across the UK.

将招募多达160名成年人，包括健康人和PD患者，进行试验，计划在英国各地进行。

The CTA comes as the journal Nature Reviews Drug Discovery identified Mission's recent work with scientists at Cambridge University and Harvard University investigating the potential of MTX325 in PD mouse models[i] — as a 'Research Highlight'. NRDD commented: 'Mitochondrial dysfunction and reduced mitophagy are strongly implicated in the pathogenesis of dopaminergic neurodegeneration in both sporadic and familial Parkinson's Disease (PD).

CTA作为期刊Nature Reviews药物发现确定了Mission最近与剑桥大学和哈佛大学科学家合作研究MTX325在PD小鼠模型中的潜力[i]-作为“研究亮点”。NRDD评论说：“线粒体功能障碍和线粒体自噬减少与散发性和家族性帕金森病（PD）中多巴胺能神经变性的发病机制密切相关。

Restoring mitophagy to accelerate the removal of damaged mitochondria is therefore an appealing disease-modifying therapeutic strategy.'[ii].

因此，恢复线粒体自噬以加速受损线粒体的去除是一种有吸引力的疾病改善治疗策略[ii]。

About MTX325 and USP30

关于MTX325和USP30

MTX325 is a potent selective central nervous system-penetrant compound designed to improve mitochondrial quality and function by enhancing mitophagy. MTX325 inhibits USP30, a deubiquitylating enzyme, localised to mitochondria, which is a negative regulator of mitophagy. Data from an in vivo model of Parkinson's, where USP30 was deleted through gene knockout, validate USP30 as a potential target in PD.

MTX325是一种有效的选择性中枢神经系统渗透化合物，旨在通过增强线粒体自噬来改善线粒体的质量和功能。MTX325抑制USP30，一种去泛素化酶，定位于线粒体，线粒体是线粒体自噬的负调节因子。来自帕金森氏症体内模型的数据，其中USP30通过基因敲除被删除，验证USP30作为PD中的潜在靶标。

Researchers found MTX325 produced a similar effect to gene knockout of USP30 in the same PD mouse model, further validating the approach of USP30 inhibition in PD. See the paper in Nature Communications here: https://www.nature.com/articles/s41467-023-42876-1.

研究人员发现MTX325在相同的PD小鼠模型中产生与USP30的基因敲除相似的效果，进一步验证了PD中USP30抑制的方法。参见Nature Communications中的论文：https://www.nature.com/articles/s41467-023-42876-1.

About Mission Therapeutics

关于Mission Therapeutics

Mission Therapeutics is a world leader in discovering and developing novel therapeutics, which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles, which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy.

Mission Therapeutics是发现和开发新疗法的世界领导者，这些疗法可促进线粒体功能障碍的清除，促进细胞健康和功能。线粒体是产生能量的细胞器，其需要通过称为线粒体自噬的遍在蛋白介导的清除机制进行终生质量控制。

In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's Disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's..

在某些情况下，例如细胞应激，细胞损伤和/或线粒体自噬过程的缺陷，线粒体可能变得功能失调并损害细胞，导致能量产生，氧化应激，炎症和潜在的细胞死亡减少。功能失调的线粒体是急性肾损伤（AKI），帕金森病（PD），心力衰竭，杜兴氏肌营养不良症，IPF，线粒体疾病和阿尔茨海默病的疾病病理生理学的重要驱动因素。。

USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on the clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria — consequently improving overall cellular health.

USP30是一种去泛素化酶，可不断从线粒体中去除泛素，为清除功能失调的线粒体提供潜在的制动作用。Mission目前正在开发两种小分子药物，MTX652（外周）和MTX325（靶向CNS），通过抑制线粒体DUB酶USP30，将促进功能失调的线粒体的清除-从而改善整体细胞健康。

Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction..

Mission的USP30抑制剂MTX652和MTX325可能用于治疗由线粒体功能障碍引起的任何疾病或病症。。

Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital.

Mission得到了包括辉瑞风险投资，Sofinnova合作伙伴，罗氏风险基金，SR One，IP Group和Rosetta Capital在内的蓝芯片投资者的支持。

[i] https://www.nature.com/articles/s41467-023-42876-1[ii] USP30 inhibition protects dopaminergic neurons (nature.com)

[i]https://www.nature.com/articles/s41467-023-42876-1[ii]USP30抑制作用可保护多巴胺能神经元（nature.com）

SOURCE Mission Therapeutics

源任务疗法