更新于：2024-05-01

FASN

脂肪酸合成酶

更新于：2024-05-01

基本信息

别名

脂肪酸合成酶、[Acyl-carrier-protein] S-acetyltransferase、[Acyl-carrier-protein] S-malonyltransferase

+ [11]

简介

Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication.

关联

项与 FASN 相关的药物

Isoniazid/Pyrazinamide/Rifampin

异烟肼/吡嗪酰胺/利福平

靶点

FASN x RNAP

作用机制

FAS抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1994-05-31

Pyrazinamide

吡嗪酰胺

靶点

FASN

作用机制

FAS抑制剂

在研机构

哈尔滨国康药业有限公司 [+2]

原研机构

Alfresa Pharma Corp.

在研适应症

结核

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1956-09-20

Denifanstat

地尼法司他

靶点

FASN

作用机制

FAS抑制剂

在研机构

Sagimet Biosciences, Inc. [+4]

原研机构

Sagimet Biosciences, Inc.

在研适应症

寻常痤疮 [+12]

非在研适应症

肝炎 [+1]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

127

项与 FASN 相关的临床试验

NCT06253715 / Not yet recruiting临床3期IIT

Shortened Regimen for Drug-susceptible TB in Children

While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

开始日期2024-09-30

申办/合作机构

The Johns Hopkins University

NCT06248008 / Not yet recruiting临床3期

An Open, Multicenter, Phase III Extension Clinical Trial to Evaluate the Long-term Safety of ASC40 (Denifanstat) Tablets in Patients With Moderate to Severe Acne Vulgaris

This is a multicenter, open-label study designed to determine the long-term safety of ASC40 (Denifanstat) tablets in patients with moderate to severe acne vulgaris enrolled in the ASC40-303 Phase III study. All subjects are eligible for study eligibility screening after enrollment in ASC40-303 Phase III study, and all eligible subjects with moderate to severe acne vulgaris will receive ASC40 (Denifanstat) tablets after signing informed consent. The investigational drug will be administered orally once daily (QD) for up to 40 weeks. There will be a total of 7 visits for screening and follow-up. The tests required by the program included routine blood tests, blood biochemistry, lipid profile, pregnancy test and urine routine, etc.

开始日期2024-04-24

申办/合作机构

歌礼药业（浙江）有限公司

NCT05917340 / Not yet recruiting临床3期IIT

Comparative Evaluation of Intensified Short Course Regimen and Standard Regimen for Adults TB Meningitis : an Open-label Randomized Controlled Trial

Tuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups

开始日期2024-03-01

申办/合作机构

Indian Council of Medical Research

[+3]

100 项与 FASN 相关的临床结果

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100 项与 FASN 相关的转化医学

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0 项与 FASN 相关的专利（医药）

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7,488

项与 FASN 相关的文献（医药）

2024-03-01·Molecular medicine reports

Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease.

Article

作者: Yaowei Bai ; Kequan Chen ; Jiacheng Liu ; Yingliang Wang ; Chaoyang Wang ; Shuguang Ju ; Chen Zhou ; Wei Yao ; Bin Xiong ; Chuansheng Zheng

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is an increasingly significant global health burden for which there is currently no effective treatment. The present study aimed to explore the underlying mechanisms and investigate the effects of donafenib and atorvastatin in MASLD. The effects of donafenib and atorvastatin on the activity and lipid metabolism of HepG2 cells were analyzed in vitro. A rat model of MASLD was established induced by a high‑fat diet in vivo. H&E and Oil red O staining were used to observe the improvement in MASLD, western blotting analysis was used to detect the expression of proteins related to fat metabolism and immunofluorescence was used to detect reactive oxygen species (ROS) levels. In vitro, donafenib and atorvastatin inhibited lipid accumulation in HepG2 cells. In vivo, donafenib and atorvastatin activated the AMP‑activated protein kinase (AMPK) pathway, downregulated the expressions of proteins related to fatty acid synthesis (sterol regulatory element‑binding protein‑1, 3‑hydroxy‑3‑methylglutaryl‑CoA reductase and fatty acid synthase) and upregulated the expression of proteins related to fatty acid β‑oxidation (carnitine palmitoyl‑transferase 1C and acyl‑CoA oxidase). The levels of free fatty acids, cholesterol and triglycerides in the liver and serum decreased in all three treatment groups. Additionally, donafenib and atorvastatin reduced oxidative stress in the liver tissue and decreased ROS levels. Low‑dose donafenib combined with atorvastatin improved MASLD by regulating fatty acid metabolism and reducing oxidative stress through activation of the AMPK signaling pathway.

2024-03-01·Molecular medicine reports

Excess phosphate promotes SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation via the SCAP‑SREBP2 signaling pathway.

Article

作者: Mi-Hua Liu ; Xiao-Long Lin ; Le-Le Xiao

Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS‑CoV‑2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). The expression levels of SARS‑CoV‑2 N protein, SREBP cleavage‑activating protein (SCAP), mature N‑terminal SREBP2, NLRP3, procaspase‑1, cleaved caspase‑1, IL‑1β and IL‑18 were examined by western blotting. The expression levels of SREBP2, HMG‑CoA reductase, HMGCS1, low density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), SREBP1c, fatty acid synthase, stearyl coenzyme A desaturase 1, acetyl‑CoA carboxylase α and ATP‑citrate lyase were determined by reverse transcription‑quantitative PCR. The translocation of SCAP or NLRP3 from the endoplasmic reticulum to the Golgi was detected by confocal microscopy. The results showed that excess PI promoted SCAP‑SREBP and NLRP3 complex translocation to the Golgi, potentially leading to NLRP3 inflammasome activation and lipogenic gene expression. Furthermore, PI amplified SARS‑CoV‑2 N protein‑induced inflammation via the SCAP‑SREBP pathway, which facilitates NLRP3 inﬂammasome assembly and activation. Inhibition of phosphate uptake with phosphonoformate sodium alleviated NLRP3 inflammasome activation and reduced SREBP‑mediated lipogenic gene expression in VSMCs stimulated with PI and with SARS‑CoV‑2 N protein overexpression. Inhibition of SREBP2 or small interfering RNA‑induced silencing of SREBP2 effectively suppressed the effect of PI and SARS‑CoV‑2 N protein on NLRP3 inflammasome activation and lipogenic gene expression. In conclusion, the present study identified that PI amplified SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation and lipogenic gene expression via the SCAP‑SREBP signaling pathway.

2024-03-01·International journal of oncology

Targeting endogenous fatty acid synthesis stimulates the migration of ovarian cancer cells to adipocytes and promotes the transport of fatty acids from adipocytes to cancer cells.

Article

作者: Thomas W Grunt ; Renate Wagner ; Alexander Ries ; Anna S Berghoff ; Matthias Preusser ; Michael Grusch ; Peter Valent

Despite significant advances in oncology, 1 of 108 female patients succumb to ovarian cancer (OC) each year. Improved novel treatments against this aggressive disease would be a major improvement. The growth of OC cells has been demonstrated to be highly dependent on lipids. OC cells are abundantly present in the abdominal cavity and omentum, the main sites of OC expansion. Accordingly, it has been attempted not only to block the hyperactive synthesis of fatty acids (FAs) in cancer cells, but also to disrupt lipid supply. While either strategy has yielded promising results as monotherapy, the induction of resistance pathways diminishing the anticancer effects is yet conceivable. The endogenous regulation of lipid biosynthesis in OC has been extensively studied. However, the role of stromal cells in the modulation of the effects of anti‑lipogenic drugs has not yet been well documented. The present study thus examined the interaction between OC cells and associated stromal cells, when de novo FA synthesis was blocked. It has recently been revealed by the authors that when FA are provided to OC cells in monoculture, the lipid deficiency induced by pharmacological inhibition of FA synthase (FASN), the key enzyme of endogenous FA synthesis, cannot be compensated through an increased FA uptake by OC cells. In the present study, OC cells were co‑cultured with adipocytes preloaded with fluorescent FA and the effects of FASN‑inhibition on OC homing to adipocytes and the transcellular delivery of fluorescent FA from adipocytes to OC cells were examined. The FASN inhibitors, G28UCM and Fasnall, stimulated the spontaneous migration of A2780 OC cells in a concentration‑dependent manner and stimulated the transfer of FA from adipocytes to OC cells. Similar effects were observed with all types of adipocytes tested. The models applied in the present study demonstrated that co‑cultured cancer‑associated adipocytes may attenuate the anticancer effects of FASN inhibitors by attracting tumor cells and by supplying the cells with FA. This lipid‑mediated dependency may provide a rationale for the design of new treatment approaches for the treatment of OC.

140

项与 FASN 相关的新闻（医药）

2024-04-04

·药事纵横

歌礼制药：砍管线，加注NASH赛道

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。“从原计划试验中节约的资金将用于加速推进ASC41和ASC40的NASH适应症临床研究及研发全球首创或同类最佳候选药物。”歌里制药近日在公告里表示。今年3月首款NASH新药获FDA批准上市，百亿美元空间已打开。在内卷加剧、行业融资困难的大背景下，主动放弃竞争优势不足的管线，聚焦更有价值和前景的资产，也不失为一种明智之举。4月3日晚，歌礼制药-B （01672）发布公告，宣布有关法尼醇X受体(FXR)激动剂ASC42的战略决定：对ASC42治疗原发性胆汁性胆管炎(PBC)的II期临床试验(ClinicalT rials.gov ：NCT05190523)数据进行全面分析后，公司做出了不再继续开展ASC42治疗PBC临床试验的战略决定。该决定基于12周II期研究的疗效和安全性数据，该研究包括三个ASC42活性治疗组（5毫克、10毫克和15毫克，每日一次）和一个安慰剂对照组。结果表明，与目前处于开发和注册阶段的新型PBC候选药物相比，ASC42未显示出竞争优势。此外，公司也决定不再继续开展FXR激动剂ASC42联用治疗非酒精性脂肪性肝炎(NASH)的临床研究(ASC43F)，以及ASC42治疗乙肝的临床研究。截至2023年12月31日，公司的现金及现金等价物以及定期存款约为23亿人民币。这些战略决定是公司继续评估和优化研发管线，为提高效率和保存现金的努力的一部分。从原计划试验中节约的资金将用于加速推进ASC41和ASC40的NASH适应症临床研究及研发全球首创或同类最佳候选药物。ASC41在经肝穿活检证实的NASH患者中进行的II期临床试验取得了积极期中结果，表明ASC41有望成为同类最佳的甲状腺激素受体β(THRβ)激动剂。作为同类首创FASN抑制剂，ASC40（地尼法司他）为期52周治疗经肝穿活检证实的纤维化2期或3期NASH患者的IIb期临床试验显示，ASC40在NASH缓解和纤维化改善方面均取得了统计学显著性结果。业绩及管线情况2023年报显示：歌礼制药实现营业收入约5660万元，同比增加4.6%，由于利托那韦产品产生的收入增加约4940万元，但大部分被推广服务收入减少约4040万元所抵销，原因为集团终止向上海罗氏制药有限公司提供派罗欣在中国的推广服务。2023年研发成本由2022年度的约2.671亿元减少18.8%至2023年度的约2.168亿元，主要由于临床及临床前项目研发效率提高;及无形资产的折旧及摊销成本减少。截至2023年12月31日，现金及现金等价物约为22.746亿元，预计足以支持其直至2028年的研发活动及营运。目前公司已建立12项关键临床阶段资产专注于病毒性疾病、NASH及肿瘤的全面管线。2024年的策略及展望1.完成ASC41用于NASH的II期临床试验患者入组;2.开始与国家药监局就ASC40治疗中、重度纤维化(F2或F3期)NASH患者的注册试验展开讨论;3.完成ASC40用于痤疮的III期临床试验患者入组;4.完成用于rGBM的ASC40III期注册研究预设的期中分析;5.加快全球同类首创或同类最佳候选药物的自主研发，增强集团的全球竞争力;6.持续探索各种临床前及临床阶段资产的对外授权机会;7.继续评估及优化研发管线，以提高效率及保留现金。总结从公司研发战略调整可以看出：歌礼制药是想将资源集中在NASH领域自己最可能成功的管线上。据全球肝脏研究所预计，2030年全球将有3.57亿人的生活受到MASH影响。而弗若斯特沙利文的数据显示，预计在2025年全球MASH药物市场规模达107亿美元，到2030年将增长至322亿美元。当下，NASH是业界研发的热点之一，其市场空间巨大，但也是有名的研发难点。直到今年3月，FDA才批准了首款NASH疗法——Madrigal公司的创新药resmetirom，联合饮食和运动用于治疗患有中重度肝纤维化（F2至F3期）的非肝硬化NASH成人患者。值得一提的是resmetirom的靶点与歌礼制药的ASC41相同。对于MASH领域而言，由于致病机理尚未完全摸清，现阶段包括FXR、FGF21、GLP-1R、PPAR、ASK1、THR-β等靶点百花齐放。除歌礼制药外，国内布局NASH疗法的公司还有信达生物、中国生物制药、海思科、众生药业等。资料来源：歌礼制药药融云数据库

临床2期ASCO会议临床3期临床结果临床1期

2024-04-04

·医药魔方

歌礼孤注一掷NASH

因竞争优势不足而及时作出终止开发的战略决策，不失为一种明智之选。但是当这种场景屡次发生在同一家药企身上，似乎便成为了一种不能承受之重。4月3日，歌礼制药发布一则公告，宣布有关法尼醇X受体（FXR）激动剂ASC42的战略决定。核心内容是，歌礼制药将终止ASC42用于原发性胆汁性胆管炎（PBC）、联合治疗非酒精性脂肪性肝炎（NASH）以及治疗乙肝这3大方向的临床研究。ASC42的开发之路似乎走到了尽头。在歌礼制药官网最新的产品管线图中，ASC42的身影已消失不见。值得注意的是，歌礼制药此前还放弃了治疗肝癌的候选药物ASC06和HIV新药ASC09，其与罗氏就肝炎药派罗欣的合作也已画上终止符。目前，歌礼制药的股价已下跌至1.350港元/股，总市值13.67亿港元。留给歌礼制药的弹药越来越珍贵。绝地求生下，歌礼制药将削减管线节流而来的资金加注到NASH赛道。THR-β激动剂ASC41和FASN抑制剂ASC40承载着歌礼制药未来的希望。FXR激动剂的折戟在2023年11月，歌礼制药发布了一则发表ASC42 I期数据的公告。在公告中，歌礼制药将ASC42描述为一款自主研发、拥有全球知识产权、有望成为同类最佳（best-in-class）的新型高效选择性非甾类FXR激动剂。I期研究表明，在健康受试者中，ASC42在给药单次剂量高达100毫克以及14天多次日剂量高达15毫克的情况下，总体上是安全的，耐受性良好。此外，成纤维细胞生长因子19（FGF19）和7α-羟基-4-胆甾烯-3-酮（C4）呈剂量依赖性的升高和降低，显示出ASC42有效的FXR靶标作用。这项研究结果为继续研究ASC42在非酒精性脂肪肝病（NAFLD）/NASH/PBC患者中的应用提供了支持。然而时间过去不到半年，情况便完全不同了。在歌礼制药近日发布的公告中，其表示对ASC42治疗PBC的II期临床试验（NCT05190523）数据进行全面分析后，公司做出了不再继续开展ASC42治疗PBC临床试验的战略决定。该决定基于12周II期研究的疗效和安全性数据，该研究包括三个ASC42活性治疗组（5mg、10mg和15mg，每日一次）和一个安慰剂对照组。结果表明，与目前处于开发和注册阶段的新型PBC候选药物相比，ASC42未显示出竞争优势。PBC是一种自身免疫性肝病，最终可进展为肝硬化和肝功能衰竭。一项流行病学研究显示，中国的PBC患者人数约为65.6万，其中40岁以上女性患者人数为44万[1]。熊去氧胆酸是目前中国唯一获批的治疗PBC的药物。作为首款FXR激动剂，奥贝胆酸是美国唯一获批用于治疗对熊去氧胆酸不耐受或应答不足的PBC患者的药物，但并未在中国获批。今年2月，正大天晴开发的奥贝胆酸已申报上市，有望拿下首仿。此外，歌礼制药也决定不再继续开展ASC42联用治疗NASH的临床研究（ASC43F），以及ASC42治疗乙肝的临床研究。这也不难理解，同靶点竞品奥贝胆酸用于治疗NASH引起的肝硬化前期伴有肝纤维化患者的新适应症申请已于2023年6月被FDA拒绝。基于此，奥贝胆酸的开发者Intercept先是决定停止所有NASH相关投资，之后更是彻底宣布以8亿美金卖身给意大利制药公司Alfasigma。先驱者的悲惨际遇，对于歌礼制药也是一种警示。歌礼制药的过去与未来事实上，ASC42并不是歌礼制药削减的第一项管线。2023年6月，歌礼制药宣布终止治疗肝癌的候选药物ASC06和HIV新药ASC09的开发。歌礼制药曾对ASC06寄予厚望，希望将其打造成使用RNA干扰递送技术治疗肝癌的首个系统性递送治疗药物。但是，随着RNA干扰递送技术研究进展，ASC06采用的RNA干扰递送技术成为早期技术且已过时。因此，ASC06可能无法展现如歌礼制药先前预测的市场竞争优势。所以，歌礼制药表示已经在2020年决定不再继续进行ASC06的研发。同样在竞争中逐渐失去优势的还有ASC09，它是一种HIV蛋白酶抑制剂候选药物，拟开发用于治疗HIV 1型感染。然而，治疗相同适应症的替代产品（如HIV融合抑制剂药物）已在中国获批上市，已成为治疗HIV 1型感染的主流药物，并相较于蛋白酶抑制剂类表现出更佳的疗效、安全性及耐药性。歌礼制药遭遇的变故还不止于此。2022年，歌礼制药与罗氏分手，终止向后者提供肝炎药派罗欣的推广服务。派罗欣是一种经由对人体内自然产生的抵抗病毒的蛋白质进行修饰的长效干扰素。该药物分别在2003年和2005年在中国获批，用于慢性乙型肝炎和丙型肝炎的治疗。基于罗氏对派罗欣在中国大陆地区市场策略的调整，歌礼制药与罗氏已达成一致，自2022年12月31日起双方不再继续派罗欣在中国大陆地区市场的推广合作关系。而歌礼制药过往的营收很大程度上依赖于派罗欣。昔日辉煌已不再。歌礼制药也深知其困境，正在试图扭转局势。换种角度而言，这些战略决定也是歌礼制药继续评估和优化研发管线，为提高效率和保存现金的努力的一部分。截至2023年12月31日，歌礼制药的现金及现金等价物以及定期存款约为23亿人民币。未来，歌礼制药重点将宝押注在NASH赛道。从原计划临床试验中节约的资金将用于加速推进ASC41和ASC40的NASH适应症临床开发，及研发全球首创或同类最佳候选药物。ASC41治疗经肝穿活检证实的NASH患者的II期临床试验取得了积极结果。12周时，高剂量ASC41组患者的肝脏脂肪含量较基线的相对降幅平均值高达68.2%，而安慰剂组的降幅为13.1%。歌礼制药表示，ASC41有望成为同类最佳的甲状腺激素受体-β（THR-β）激动剂。THR-β激动剂治疗NASH的路已经走通。今年3月，Madrigal Pharmaceuticals开发的Resmetirom获加速批准上市，成为FDA批准的首个治疗NASH的创新药物。在NASH赛道，歌礼制药还布局了一款重磅管线——潜在同类首创FASN抑制剂ASC40（地尼法司他）。为期52周治疗经肝穿活检证实的纤维化2期或3期NASH患者的IIb期临床试验显示，ASC40在NASH缓解和纤维化改善方面均取得了统计学显著性结果。至于歌礼制药能否真正穿越NASH这一研发死亡谷，我们拭目以待。[1]中华医学会风湿病学分会, 原发性胆汁性胆管炎诊疗规范(2021)[J]. 中华内科杂志, 2021, 60(8): 709-15. DOI: 10.3760/cma.j.cn112138-20210520-00360.Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床1期临床2期临床结果

2024-04-03

·FierceBiotech

Ascletis pulls FXR agonist from pipeline over phase 2 primary biliary cholangitis data

Ascletis’ most advanced candidate is ASC22, an injected PD-L1 antibody in phase 2 development as a functional cure for chronic hepatitis B and HIV. China’s Ascletis has been developing the farnesoid X receptor (FXR) agonist ASC42 in a raft of conditions ranging from primary biliary cholangitis (PBC) to metabolic-associated steatohepatitis (MASH). But the company announced this morning that work is being halted on the drug after getting a glimpse of data from a phase 2 trial of three different doses of ASC42 to treat PBC. The results “indicated that ASC42 did not show competitiveness to new PBC drug candidates currently in development and registrational stages,” the company explained in an April 4 release. Based on this failure, Ascletis has also decided to drop other programs involving the drug. These include testing the therapy for hepatitis B virus (HBV) as well as part of a combo treatment for MASH. The biotech, which entered the year with cash and equivalents of 2.4 billion Chinese Yuan ($330 million), attributed today’s decision to “efforts to continue to evaluate and optimize its research and development pipeline to increase efficiency and preserve cash.” With ASC42 thrown on the discard pile, Ascletis still has more promising options to treat MASH, a fatty liver disease that has previously been known as non-alcoholic steatohepatitis (NASH). At the start of the year, the company’s subsidiary Gannex Pharma linked a THRβ agonist, dubbed ASC41, to significant reductions in liver fat and pointed to findings that it sees providing an edge over Madrigal Pharmaceuticals and Viking Therapeutics. Viking has previously accused Ascletis of stealing trade secrets to support the development of a drug candidate to rival its MASH prospect VK2809. That dispute rumbled on throughout last year, during which time Gannex continued to work toward midphase data on the molecule at the center of the row. Ascletis’ most advanced candidate is ASC22, an injected PD-L1-targeted antibody in phase 2 development as a functional cure for chronic hepatitis B and HIV. The company's clinical-stage pipeline also includes a FASN inhibitor called ASC40 that’s being assessed as a treatment for both MASH and acne, as well as a PD-L1 small molecule inhibitor called ASC61 in early-stage trials for solid tumors. Part of the savings from discontinuing the various ASC42 programs will be funneled into the continued clinical development of ASC41 and ASC40 for MASH, the biotech explained in today’s release.