Denifanstat

Denifanstat met all primary and secondary endpoints versus placebo Denifanstat was well tolerated Oral FASN inhibitors offer a novel mechanism of action for the potential treatment of moderate to severe acne Sagimet initiated first-in-human Phase 1 clinical trial of a second FASN inhibitor, TVB-3567, that is planned to be developed for acne in the U.S. SAN MATEO, Calif., June 04, 2025 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today reported denifanstat met all primary and secondary endpoints in a Phase 3 clinical trial for the treatment of moderate to severe acne vulgaris conducted by Sagimet’s license partner Ascletis Bioscience Co. Ltd. (Ascletis) in China. Denifanstat is a once-daily oral small molecule fatty acid synthase (FASN) inhibitor being developed by Ascletis as ASC40 for acne in China and by Sagimet for MASH in the rest of world. Additionally, Sagimet recently initiated a Phase 1 first-in-human clinical trial with a second FASN inhibitor, TVB-3567, that is planned to be developed for acne in the US. “We are highly encouraged by the positive results from Ascletis’ Phase 3 acne trial in China,” said David Happel, Chief Executive Officer of Sagimet. “FASN inhibition represents a novel potential approach to treat moderate to severe acne vulgaris, a widespread condition impacting more than 640 million people worldwide. These positive data support the rationale for our development of our FASN inhibitor TVB-3567 for moderate-to-severe acne and add to the body of evidence of the broad consequences of unchecked overactivity of FASN.” “It is very exciting to see this novel oral acne product candidate progressing through development in light of the limited innovation within the acne space over the past 40 years,” said Dr. Neal Bhatia, Director of Clinical Dermatology at Therapeutics Clinical Research in San Diego and a past Vice President of the American Academy of Dermatology. “These data demonstrate the significant clinical response that a FASN inhibitor can achieve for moderate to severe acne patients by addressing the overproduction of sebum and the inflammatory cascade, two of the primary pathways of acne, and most importantly through a novel mechanism of action. With currently available treatments either showing limited efficacy, high potential for irritation, or risks of antibiotic resistance, control of acne through new modes of action is more critical now than ever.” Over 50 million people suffer from acne in the US, making it one of the most prevalent skin diseases that physicians address annually. Patients with acne vulgaris have increased sebum production compared to non-acne populations which contributes to the pathogenesis of the disease. Increased sebum production is due to increased de novo lipogenesis (DNL) locally in the sebocytes. FASN is the last committed step in the DNL pathway which produces the majority (>80%) of key sebum lipids such as palmitate and sapienic acid in acne, and FASN also contributes to inflammatory pathways. Inhibition of FASN is therefore an attractive therapeutic approach to address acne. In two separate denifanstat Phase 1 clinical trials, Sagimet collected sebum as a non-invasive approach to assess FASN pharmacodynamic activity and showed that use of denifanstat led to significant reductions in sapienic acid, a sebum fatty acid produced only by de novo lipogenesis, confirming FASN inhibition. These results provided mechanistic proof of concept for FASN inhibition in sebum and provided a basis for Ascletis’ successful Phase 2 and 3 clinical trials of denifanstat in acne in China. Clinical Results The Phase 3 clinical trial (NCT06192264) was a randomized, double-blind, placebo-controlled, multicenter clinical trial in China to evaluate the safety and efficacy of denifanstat for the treatment of patients with moderate to severe acne. The 480 enrolled patients were randomized 1:1 into two treatment arms to receive denifanstat 50mg or placebo, once daily for 12 weeks. Primary endpoints included the percentage of treatment success (defined as an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease from baseline), the percentage change in total lesion count, and the percentage change in inflammatory lesion count. Ascletis reported that denifanstat met all the primary and secondary endpoints. Efficacy results are summarized in Table 1 below. Table 1: Efficacy data from Phase 3 trial of Denifanstat (ASC40) in acne vulgaris Source: Ascletis Press Release issued June 3rd, 2025 Ascletis reported that denifanstat was generally well-tolerated. Following 12 weeks of once-daily oral administration at 50 mg, the incidence rates of treatment-emergent adverse events (TEAE) were comparable between denifanstat and placebo. No incidence rate of TEAEs in any category exceeded 10%. Only two categories of TEAEs had an incidence rate of more than 5% (dry skin and dry eye reported in 6.3% and 5.9 % of denifanstat-treated subjects versus 2.9% and 3.8% in placebo-treated subjects, respectively). All denifanstat-related adverse events (AEs) were mild or moderate. There were no denifanstat-related grade 3 or 4 AEs and no denifanstat-related serious AEs (SAEs). No deaths were reported. These Phase 3 results confirm that FASN inhibition represents a potential therapeutic approach within acne. Ascletis has indicated that it plans to submit denifanstat for approval to the China National Medical Products Administration. Building on Ascletis’ positive Phase 3 results, Sagimet has recently initiated a Phase 1 first-in-human clinical trial with a second oral FASN inhibitor drug candidate, TVB-3567, that is planned to be developed for acne in the U.S. About Sagimet Biosciences Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic and fibrotic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of metabolic dysfunction associated steatohepatitis (MASH). FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. Denifanstat has been granted Breakthrough Therapy designation by the FDA for the treatment of non-cirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), and end-of-Phase 2 interactions with the FDA have been successfully completed, supporting the advancement of denifanstat into further development. Sagimet has recently initiated a Phase 1 first-in-human clinical trial with a second oral FASN inhibitor drug candidate, TVB-3567, that is planned to be developed for acne in the US. For additional information about Sagimet, please visit www.sagimet.com. About Acne There are 5.1 million acne patients in the U.S. who are treated by dermatologists annually, and a total U.S. acne market of over 50 million people. 1,2 There is no cure for acne; and due to its pathology, most patients require chronic management and multiple courses of treatment for flare control annually. Additionally, adherence to topical therapies is lower than with oral agents, with an estimated 30% to 40% of patients not adhering to their topical treatments. 3 Forward-Looking Statements This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding: the expected timing of the presentation of data from ongoing clinical trials, Sagimet’s clinical development plans and related anticipated development milestones, Sagimet’s cash and financial resources and expected cash runway. These statements involve known and unknown risks, uncertainties and other important factors that may cause Sagimet’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, these statements can be identified by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. Sagimet has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that Sagimet believes may affect its business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Sagimet’s control, including, among others: the clinical development and therapeutic potential of denifanstat or any other drug candidates Sagimet may develop; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines; Sagimet’s relationship with Ascletis, and the success of its development efforts for denifanstat; the accuracy of Sagimet’s estimates regarding its capital requirements; and Sagimet’s ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of Sagimet’s most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in these forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, Sagimet operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Sagimet may face. Except as required by applicable law, Sagimet does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Investor Contact: Joyce Allaire LifeSci Advisors JAllaire@LifeSciAdvisors.com Media Contact: Michael Fitzhugh LifeSci Advisors mfitzhugh@lifescicomms.com Source: Sagimet Biosciences Inc.

- 与安慰剂相比，每日一次口服脂肪酸合成酶（FASN）抑制剂地尼法司他（ASC40）在所有主要、关键次要及次要终点上均实现了高度具有统计学意义且临床意义显著的改善- 地尼法司他显示出良好的安全性和耐受性特征- 就经安慰剂校准后的治疗成功百分比而言，地尼法司他（18.6%）的疗效比美国食品药品监督管理局（FDA）批准的沙瑞环素（sarecycline，9.4%）和多西环素（doxycycline，6.7%）分别高98%和178%- 就经安慰剂校准后的治疗成功百分比而言，地尼法司他（18.6%）的疗效比FDA批准的柯拉特龙（clascoterone）乳膏（11.6%）高60%- 地尼法司他在III期试验中表现出了优越的疗效以及良好的安全性特征，有望实现痤疮治疗的重大突破香港，2025年6月4日--歌礼制药有限公司（香港联交所代码：1672，“歌礼”）今日宣布，同类首创（first-in-class）、每日一次口服小分子脂肪酸合成酶（FASN）抑制剂地尼法司他（ASC40）治疗中重度寻常性痤疮的III期临床试验（NCT06192264）达到所有主要、关键次要及次要终点。该项III期临床试验是一项在中国开展的随机、双盲、安慰剂对照、多中心的临床试验，旨在评估地尼法司他每日一次口服片在480例中重度寻常性痤疮患者中的安全性和疗效。患者被按照1:1的比例随机分至一个活性药物组和一个安慰剂对照组，接受每日一次50毫克地尼法司他口服片或匹配的安慰剂治疗，为期12周。地尼法司他组和安慰剂组基线特征均衡。表1概述了部分基线特征。主要、关键次要及次要终点可见表2。主要终点包括治疗成功百分比（治疗成功的定义为在第12周时，研究者总体评估（Investigator's Global Assessment，IGA）评分较基线下降至少2分，且IGA分级为0分（光洁）或1分（几乎光洁））、总皮损计数相对基线百分比下降，以及炎性皮损计数相对基线百分比下降。第12周时，地尼法司他治疗组治疗成功百分比为33.2%，而安慰剂组为14.6%，p<0.0001；地尼法司他治疗组总皮损计数相对基线百分比下降是57.4%，而安慰剂组为35.4%，p<0.0001；以及，地尼法司他治疗组炎性皮损计数相对基线百分比下降是63.5%，而安慰剂组为43.2%，p<0.0001。第12周时，非炎性皮损计数相对基线百分比下降（关键次要终点），地尼法司他治疗组为51.9%，而安慰剂组为28.9%，p<0.0001。每日一次口服50毫克地尼法司他，为期12周的安全性和耐受性特征良好。地尼法司他和安慰剂的治疗期间发生的不良事件（treatment-emergent adverse events，TEAE）发生率相当。任何类别的与试验药物相关的TEAE发生率均不超过10%。仅两类TEAE的发生率超过5%（皮肤干燥在地尼法司他治疗组和安慰剂组的发生率分别为6.3%和2.9%，干眼症在地尼法司他治疗组和安慰剂组的发生率分别为5.9%和3.8%）。所有与地尼法司他相关的不良事件（AE）均为轻度或中度。没有与地尼法司他相关的3级和4级不良事件，且没有与地尼法司他相关的严重不良事件（SAE）。无死亡病例发生。地尼法司他治疗痤疮的机制是：（1）通过抑制人皮脂细胞的脂肪酸从头合成（DNL），直接抑制面部皮脂生成；和（2）通过减少细胞因子分泌和Th17分化来抑制炎症。皮脂分泌过剩是导致痤疮的主要诱因之一，地尼法司他独特的作用机制可直接减少皮脂分泌过剩，这使得地尼法司他独树一帜，而其他大多数痤疮治疗药物并不针对痤疮的根本原因。歌礼创始人、董事会主席兼首席执行官吴劲梓博士表示：我们对III期试验顶线数据非常满意。地尼法司他片在治疗成功方面表现出色，且总皮损、炎性皮损和非炎性皮损均显著下降。很快我们将向中国国家药品监督管理局（NMPA）递交这一令人振奋的创新疗法。  地尼法司他与其它常用口服和外用痤疮药物对比（非头对头比较），显示出更优越的疗效，详见表3。对比沙瑞环素（sarecycline）、多西环素（doxycycline）和柯拉特龙（clascoterone）乳膏，地尼法司他的多个关键指标显示出优越的疗效。就经安慰剂校准的治疗成功百分比和经安慰剂校准的炎性皮损计数相对基线下降百分比而言，地尼法司他的疗效比沙瑞环素分别高98%和30%，比多西环素分别高178%和178%，以及比柯拉特龙乳膏分别高60%和59%。就经安慰剂校准的总皮损计数相对基线下降百分比而言，地尼法司他的疗效比多西环素和柯拉特龙乳膏分别高189%和85%。就经安慰剂校准的非炎性皮损计数相对基线下降百分比而言，地尼法司他的疗效比沙瑞环素和柯拉特龙乳膏分别高411%和102%。地尼法司他有望成为集疗效显著、患者依从性高、安全性和耐受性特征良好等优点于一体的同类首创、每日一次口服的痤疮药物。与其他口服痤疮药物相比，地尼法司他疗效显著且安全性高。无抗生素耐药性风险或脱靶效应（常见于四环素类药物），且未有报告地尼法司他相关的严重的不良事件，如肝毒性、听力障碍和抑郁症（这些见于异维A酸）。与外用药物相比，地尼法司他的患者依从性应当更高：据估计，约有30%至40%的患者不能遵医嘱完成外用治疗[1]。歌礼已从Sagimet Biosciences Inc.（纳斯达克股票代码：SGMT）获得地尼法司他的大中华区独家授权。复旦大学附属华山医院皮肤科主任医师、复旦大学皮肤病学研究所常务副所长、中国医师协会皮肤科医师分会副会长及地尼法司他中重度痤疮III期临床试验主要研究者项蕾红教授表示：地尼法司他的III期临床试验结果令人鼓舞，数据显示其针对中重度痤疮患者的治疗目标实现了统计学显著改善，33.2%的受试者实现治疗成功，总皮损、炎性皮损、非炎性皮损相比基线分别下降57.4%，63.5%和51.9%，且安全性和耐受性良好。地尼法司他通过独特的作用机制——抑制脂肪酸合成酶，靶向痤疮发病机制的关键通路，成为治疗痤疮具有该作用机制的全球首创。  [1] Purvis CG, Balogh EA, Feldman SR. Clascoterone: How the Novel Androgen Receptor Inhibitor Fits Into the Acne Treatment Paradigm. Ann Pharmacother. 2021;55(10):1297-1299. doi:10.1177/1060028021992055.表1. 地尼法司他III期试验基线特征表2. 口服、每日一次50毫克地尼法司他第12周时对比安慰剂的疗效终点（意向治疗集（ITT）分析）注释：（1）所有疗效终点均为最小二乘均值。（2）治疗成功的定义为在第12周时，研究者总体评估（Investigator's Global Assessment，IGA）评分较基线下降至少2分，且IGA分级为0分（光洁）或1分（几乎光洁）。表3. 地尼法司他与其它常用痤疮药物对比（非头对头比较）注释：（1）沙瑞环素数据为两个III期临床试验数据平均值。数据来自Moore, A., et al., J Drugs Dermatol 2018 Vol. 17 Issue 9 Pages 987-996。非炎性皮损的数据来自FDA(https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209521Orig1s000MultidisciplineR.pdf)。（2）多西环素16周数据来自Moore, A., et al., J Drugs Dermatol 2015 Vol. 14 Issue 6 Pages 581-6。 （3）柯拉特龙乳膏(1%) 数据为两个III期临床试验数据平均值。数据来自Hebert. A, et al., JAMA Dermatology 2020 Vol. 156 Issue 6, DOI: 10.1001/jamadermatol.2020.0465。关于歌礼制药有限公司歌礼是一家在香港证券交易所上市（1672.HK）的创新研发驱动型生物科技公司，涵盖了从新药研发至GMP生产的完整价值链。歌礼的管理团队具备深厚的专业知识及优秀的过往成就，在团队的带领下，歌礼聚焦代谢性疾病，致力于解决尚未满足的医疗需求，并以全球化的视野进行布局。歌礼的代谢疾病管线拥有多款临床阶段在研药物。欲了解更多信息，敬请登录网站：www.ascletis.com。关于该临床试验（NCT06192264），可点击“阅读原文”查看详细信息！