Sienna Biopharmaceuticals, Inc.

革新医学治疗模式的里程碑研究固然令人欢欣鼓舞，但更多时候需要面对创新药的研发失败，这可能预示着一场竞逐落幕、一条赛道的终结甚至是企业的一场灭顶之灾。当然，我们也可以从失败研究中积累不少有用的经验。近日，Fierce Biotech盘点了2023年的十大失败临床试验。在此，医药魔方进行了翻译和汇总，供大家参考。1. 预防HIV感染的III期研究2023年1月18日，强生旗下杨森制药与全球合作伙伴联盟宣布了对包含基于马赛克的腺病毒血清型26载体 (Ad26.Mos4.HIV) 研究性疫苗方案的III期Mosaico研究（也称为HPX3002/HVTN706）独立、定期审查结果。数据显示，与研究参与者的安慰剂相比，该方案在预防HIV感染方面无效。强生将根据独立数据和安全监测委员会 (DSMB）的决定，停止Mosaico临床试验。Mosaico研究于2019年开始，在阿根廷、巴西、意大利、墨西哥、秘鲁、波兰、波多黎各、西班牙和美国的50多个试验点进行，包括大约3900名易感染艾滋病毒人群，受试者于2022年10月完成疫苗接种。Mosaico DSMB分析基于迄今为止的有效数据，表明该方案不能预防HIV，预计该研究不会达到其主要终点。同时，强生表示，DSMB的决定也是在对IIb期Imbokodo研究的初步分析之后做出的，该研究于2021年8月宣布，发现类似的研究性HIV疫苗方案未能为撒哈拉以南的非洲年轻女性提供足够的HIV保护。Mosaico研究宣告失败的几周后，强生改革其传染病研发部门，裁员并完全减少HIV疫苗的研发工作。到8月，传染病药物的研发已经停止，但上市的HIV产品的工作在公司内部的其他部门继续进行。2. IL-2疗法针对系统性红斑狼疮的II期ISLAND研究2月23日，Nektar Therapeutics宣布，偏向性IL-2疗法Rezpegaldesleukin（NKTR-358）治疗系统性红斑狼疮（SLE）的II期ISLAND研究没有达到主要终点，这已经是Nektar在IL-2疗法上的第10次失利了。合作方礼来决定不再推进该适应症至III期临床。NKTR-358是Nektar通过高聚物偶联技术设计的第2款新型IL-2偶联物。传统IL-2半衰期只有1-2个小时，而NKTR-358半衰期显著延长，每个月只需注射1-2次。ISLAND研究共纳入了291例中度至重度SLE患者，旨在评估低中高三个剂量NKTR-358对SLE患者的治疗效果。研究的主要终点为SLEDAI-2K评分降低≥4分的患者比例。结果显示，与安慰剂组相比，三个剂量组SLEDAI-2K评分降低≥4分的患者比例均无显著性差异。在三个剂量组中，中剂量组数据上的改善最为明显，但仍未达到显著性水平。此前，Nektar与BMS联合开发的治疗肿瘤的IL-2疗法NKTR-214已经失败，包括黑色素瘤、肾细胞癌和膀胱癌等。在终止NKTR-214项目的临床开发后，Nektar削减了70%的团队，首席医疗官和首席商务官也在裁员名单内。NKTR-358在SLE适应症上的遇挫对Nektar来说无疑是雪上加霜，同时也重创了IL-2领域。4月，Nektar在SEC文件中披露礼来已决定退回NKTR-358的全部开发权益。3. 泛Trk抑制剂治疗特应性皮炎IIa期研究4月5日，BenevolentAI宣布BEN-2293的IIa期研究结果，它虽然达到了安全性主要终点，但是错过了减少瘙痒和炎症的次要疗效终点。BEN-2293是三种原肌球蛋白相关激酶（Trk）受体（TrkA、TrkB和TrkC）的选择性抑制剂。Trk是最广为人知的是癌症药物的靶标，但BenevolentAI的人工智能平台将这些靶点确定为特应性皮炎（最常见的湿疹形式）中诱导瘙痒和炎症的介质。BenevolentAI认为，BEN-2293具有治疗轻中度特应性皮炎症状的潜力，且与现有药物相比其副作用更少。BEN-2293作用机制此项随机、双盲、安慰剂对照的研究的主要终点是安全性，次要终点包括湿疹面积及严重程度指数（EASI）改善的患者比例和瘙痒症数字评分表（NRS）改善的患者比例。在这项研究中，91例特应性皮炎患者随机接受每日两次的BEN-2293（n=49）或安慰剂（n=42）治疗。BEN-2293的安全性和耐受性良好，但在整个意向治疗人群中没有显示出对NRS或EASI终点的统计学意义改善。虽然BenevolentAI对于Trk药物治疗特应性皮炎的兴趣源自其人工智能平台，但它并不是第一家开启探索的公司。现已停业的Creabilis早在十多年前就提出了这个设想，并对其TrkA抑制剂开展了特应性皮炎的II期研究……4. 西曲替尼治疗NSCLC的III期研究5月24日，Mirati Therapeutics宣布西曲替尼（sitravatinib）联合纳武利尤单抗治疗非小细胞肺癌（NSCLC）的III期SAPPHIRE研究在最终分析中未达到显著改善患者总生存期（OS）的主要终点。西曲替尼是一种广谱选择性小分子多激酶抑制剂，可有效抑制受体酪氨酸激酶（RTK），包括TAM家族受体（TYRO3，Axl，Mer），分裂家族受体（VEGFR2，KIT）和RET。西曲替尼作用机制（来源：Mirati官网）SAPPHIRE研究是一项多中心、随机、开放标签、阳性对照的III期研究，共纳入532例患者，旨在评估西曲替尼联合纳武利尤单抗对比多西他赛二线治疗既往接受铂类化疗和免疫检查点抑制剂治疗后进展的晚期非鳞状NSCLC（NSQ-NSCLC）患者的有效性和安全性。虽然该研究未达到主要终点，但是Mirati当时表示，主要研究者（PI）可以选择继续治疗有临床获益并希望继续接受治疗的患者。SAPPHIRE研究为西曲替尼第一项注册性III期临床试验，西曲替尼另有两项III期临床试验正在进行中，包括1）：SAFFRON-301研究（N=420）：西曲替尼联合替雷利珠单抗 vs. 多西他赛二线治疗NSCLC；2）：BGB-A317-Sitravatinib-303研究（N=684）：西曲替尼联合替雷利珠单抗治疗肝细胞癌。2018年1月，百济神州与Mirati达成协议，以1.33亿美元的总交易额获得该产品在亚洲（除了日本）、澳大利亚、新西兰的开发、生产和商业化权益。5. 视网膜血管疾病疗法的III期研究7月24日，Kodiak Sciences宣布了在研抗体偶联生物聚合物（antibody biopolymer conjugate，ABC）tarcocimab tedromer（KSI-301）用于治疗视网膜血管疾病的3项III期研究的顶线结果。然而，2项研究结果表明接受KSI-301治疗的患者白内障发病率增加，Kodiak决定终止该药物的临床开发计划。受此消息影响，该公司股价当日大跌60.15%。KSI-301是基于ABC平台开发的一款超长效抗VEGF药物，旨在延长药物在眼部组织的作用时间，从而改善视网膜血管疾病患者的预后，并为糖尿病眼病患者提供早期治疗和预防视力丧失的方案。ABC平台作用机制（来源：Kodiak官网）本次公布的是III期DAYLIGHT研究、GLEAM研究和GLIMMER研究的顶线结果。DAYLIGHT是一项随机、双盲、阳性对照的III期研究，旨在评估高频次KSI-301给药对比阿柏西普在既往未接受过治疗的湿性年龄相关性黄斑变性（AMD）患者中的疗效与安全性。DAYLIGHT研究达到了主要终点，在3个月治疗后，与阿柏西普治疗相比，接受KSI-301治疗患者的最佳矫正视力（BCVA）评分改善更明显。此外，KSI-301的安全性及耐受性良好，同时眼内炎症发生率较低。GLEAM和GLIMMER研究是两项设计相同、随机、双盲、阳性对照的III期研究，旨在评估KSI-301对比阿柏西普在既往未接受过治疗的糖尿病性黄斑水肿（DME）患者中的疗效与安全性。结果显示，这2项研究没有达到主要终点，即与接受阿柏西普治疗相比，接受KSI-301治疗的患者没有表现出明显的视力改善。然而，随着时间的推移，研究人员在GLEAM和GLIMMER研究KSI-301治疗组的部分患者中观察到了白内障的发生。不过在为期一年的DAYLIGHT研究期间，接受KSI-301或阿柏西普治疗的湿性AMD患者中均未观察到白内障的发生。尽管KSI-301显示出了治疗潜力，但Kodiak还是决定终止该药物的进一步临床开发计划。Kodiak首席执行官Victor Perlroth博士表示：“目前尚不清楚是什么原因导致DME患者在接受KSI-301治疗后白内障发病率增加。但鉴于这些发现和结果，我们将停止该项目的临床开发。”6. Izokibep治疗中重度化脓性汗腺炎IIb/III期研究9月11日，Acelyrin宣布IL-17融合蛋白拮抗剂Izokibep治疗中重度化脓性汗腺炎（HS）的IIb/III期研究B部分没有达到HiSCR75（脓肿和炎性结节减少至少75%）的主要终点。受此消息影响，Acelyrin当日股价盘后暴跌62%。Izokibep为一种小分子量的IL-17A抑制剂（分子量仅为传统单抗的十分之一），其可以通过皮下注射，达到传统单抗静脉给药的吸收水平。这项随机双盲、安慰剂对照、多中心试验旨在175例中重度HS患者中评估Izokibep（160mg/QW和160mg/Q2W）相较于安慰剂的疗效与安全性。该试验采用非应答者归因（NRI）分析方法评估各种疗效终点，包括治疗16周时的主要终点HiSCR75。研究结果显示，Izokibep 160mg/QW治疗组中，39%的患者在第16周达到HiSCR75；Izokibep 160mg/Q2W治疗组中这一比例为34%，而安慰剂组为29%，没有实现统计学意义上的改善。尽管如此，Acelyrin还是认为Izokibep显示出了早期的HiSCR100应答，药代动力学暴露和HiSCR应答都支持明确的剂量效应，即每周用药160mg，没有证据表明安全性或耐受性受到限制。Acelyrin还在探索Izokibep治疗银屑病关节炎等适应症，预计2024年一季度获得银屑病关节炎IIb/III期研究的顶线数据。Izokibep由Affibody研发。2021年11月，Acelyrin引进该产品的部分权益，支付2500万美元预付款以及3亿美元里程碑金额。创响生物于2020年5月引进了Izokibep在大中华区、韩国的独家开发和商业化权利，以及日本外亚太地区的临床开发权利。7. NASH新药IIb期SYMMETRY研究10月10日，Akero Therapeutics公布了efruxifermin（EFX）治疗代偿性肝硬化（F4）非酒精性脂肪性肝炎（NASH）患者的IIb期SYMMETRY研究中期分析结果。EFX通过模仿天然FGF21的生物活性谱设计而成，通过融合Fc延长半衰期，同时替换了FGF21序列中的某些氨基酸。其半衰期达到3-4天，可以实现每周1次或每2周1次皮下注射给药。SYMMETRY研究是一项随机双盲、安慰剂对照的多中心IIb期临床，旨在评估EFX在肝硬化NASH患者中的有效性和安全性，为期96周。试验中182例受试者被随机分组，接受28mgEFX、50mgEFX和安慰剂治疗。主要终点是第36周时肝纤维化改善≥1级且NASH没有恶化的受试者比例。结果显示，第36周时，试验观察到了肝纤维化改善的主要终点趋势，但不具有统计学意义。28mg和50mgEFX治疗组分别有22%和24%的患者实现了至少一个阶段的肝纤维化改善且没有NASH恶化，而安慰剂组为14%。每个EFX治疗组中，有4%的患者实现了2或3级的肝纤维化改善且没有NASH恶化，即从F4到F1（无间隔纤维化）或F2（轻度间隔纤维化），而安慰剂组为0%。此外，第36周时，28mg和50mg EFX治疗组获得NASH缓解的患者分别有63%和60%，而安慰剂组为26%，具有统计学意义，这是迄今为止该患者群体中获得NASH缓解最高的患者比例。安全性方面，总体耐受性良好，仅安慰剂组有一例患者死亡。研究中共报告了21例严重不良事件，各剂量组之间基本平衡；共有12名患者因研究者确定为药物相关的不良事件而停药，安慰剂组1名，28mgEFX组3名，50mgEFX组8名，多为1-2级腹泻。此消息一出，Akero公司股价当天大跌62%。此后，股价不断小幅下跌。截至本月底，Akero公司总市值为6.33亿美元。8. DMD基因疗法III期确证性研究10月30日，罗氏宣布Elevidys（delandistrogene moxeparvovec）治疗4-7岁杜氏肌营养不良症（DMD）非卧床患者的III期确证性EMBARK研究未达到主要终点。Elevidys是一款基于腺相关病毒（AAV）载体的基因疗法，通过基因工程办法将编码微抗肌萎缩蛋白的靶基因递送到骨骼和心肌肌肉组织，以弥补抗肌萎缩蛋白缺失。2019年12月，罗氏与Sarepta达成协议，以可能高达28.5亿美元（11.5亿首付款+17亿里程碑付款）的总交易额获得Elevidys在美国以外地区的商业化权利，并分摊Elevidys的全球临床开发成本。Elevidys则负责SRP-9001的临床开发和生产。今年6月，Elevidys基于I期和II期研究数据获FDA加速批准上市，适用于4-5岁携带抗肌萎缩蛋白基因突变的非卧床DMD患者在EMBARK研究中，Elevidys组患者的NSAA评分（一项衡量运动功能的指标）在治疗52周后提高了2.6分，而安慰剂组提高了1.9分（0.65；n=125；P=0.24），未达到主要终点。但是，所有预先指定的定时功能性关键次要终点，即起立时间和10米步行测试，均实现了临床意义和统计学意义的改善。这两个终点都是疾病进展和丧失行走能力的预后因素。罗氏表示，目前正在对所有数据进行进一步分析，并将与监管部门进行讨论，以确定今后的发展方向。“DMD患者的需求仍未得到满足，我们对创新基因疗法Elevidys在所有关键次要功能终点上取得的一致且有意义的结果感到鼓舞。”罗氏首席医学官兼全球产品开发主管、医学博士Levi Garraway表示：“我们将努力进一步分析EMBARK的结果，并尽快与监管部门协商。”9. 凝血因子XIa抑制剂预防卒中III期研究11月19日，拜耳宣布将提前终止asundexian用于预防有卒中风险的房颤患者发生卒中或体循环栓塞的III期OCEANIC-AF研究，原因为独立数据监测委员会（IDMC）在分析数据时发现asundexian的疗效不如对照组（阿哌沙班）。Asundexian是拜耳开发的一种新型口服的凝血因子XIa抑制剂，可作用于参与凝血过程的凝血因子XIa（FXIa），从而预防病理性血栓形成。但asundexian不会对正常生理性止血过程产生不利影响，因而不会相应增加与当前护理标准（SoC）相关的出血风险。针对asundexian，拜耳共开展了两项III期研究，另一项为OCEANIC-STROKE。OCEANIC-STROKE研究旨在评估asundexian用于预防急性非心源性栓塞型缺血性脑卒中或高风险短暂性脑缺血发作患者发生缺血性脑卒中的有效性和安全性。此外，拜耳曾在本月初宣布将启动asundexian的第3项III期研究（OCEANIC-AFINA），以评估该药物用于不适合接受口服抗凝剂治疗的房颤患者预防卒中的有效性和安全性。该研究为OCEANIC-AF研究的补充。在本次分析中，IDMC仅建议终止OCEANIC-AF研究，并建议按计划继续开展 OCEANIC-STROKE研究。而对于OCEANIC-AFINA研究，拜耳表示将重新评估其试验设计的合理性。此外，Asundexian在OCEANIC-AF研究中的安全性与此前无异。拜耳也表示，将进一步分析OCEANIC-AF研究现有数据以了解具体情况，分析结果后续也会公之于众。10. evobrutinib治疗多发性硬化症两项III期研究12月6日，默克公布了evobrutinib治疗复发性多发性硬化症的两项III期EVOLUTION研究（evolutionRMS 1和evolutionRMS 2）最新结果：与特立氟胺相比，evobrutinib未达到降低年化复发率（ARR）的主要终点。Evobrutinib是一种口服、高度选择性的共价布鲁顿酪氨酸激酶（BTK）抑制剂，具有中枢神经系统渗透性，有望能突破血脑屏障进而遏制阴燃病灶以控制RMS的疾病进展。2022年10月，默克曾宣布evobrutinib在一项II期研究中取得积极结果，在接受该药物治疗的3年半期间，RMS患者ARR低且扩展残疾状态量表（EDSS）评分稳定。今年4月，由于III期研究中有2例患者因药物出现肝损伤，FDA对evobrutinib新招募患者和给药不足70天的患者实施部分临床暂停。不过，默克指出，患者并未出现相关症状，也不需要任何医疗干预或住院治疗，且肝酶指标在停用研究药物后恢复正常。对于本次III期研究，默克表示，在全面评估研究数据后，再公布具体结果。BTK抑制剂已在自免领域鏖战数场。今年11月，罗氏的非共价BTK抑制剂fenebrutinib用于多发性硬化症（MS）的临床开发项目被FDA部分暂停，因为最近在针对复发性多发性硬化症的III期FENhance研究中有两例肝转氨酶（肝酶）升高并伴有胆红素升高的病例，提示肝损伤风险。无独有偶。因肝损伤风险，赛诺菲的tolebrutinib针对MS和重症肌无力（MG）的III期研究也于2022年被FDA部分暂停。之后，赛诺菲在2022年全年财报中也宣布了终止tolebrutinib用于MG的III期研究。赛诺菲的另一款BTK抑制剂rilzabrutinib在治疗天疱疮的III期研究以未达主要和关键次要终点收场。2022年12月，诺诚健华的奥布替尼也因在治疗MS的II期临床中观察到肝损伤病例而被FDA部分暂停，此后渤健与其解除了关于奥布替尼的合作协议。不过值得关注的是，诺华的BTK抑制剂remibrutinib治疗慢性自发性荨麻疹（CSU）的III期REMIX-1和REMIX-2两项研究均取得积极结果，达到所有主要终点和次要终点，这是BTK抑制剂首次在血液肿瘤之外的适应症取得III期研究成功。而这一消息对于将BTK抑制剂开发用于自免疾病的其他企业来说也释放了一个积极信号。Copyright © 2024 PHARMCUBE. 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Former and First Arcutis CFO, John Smither, Appointed InterimWESTLAKE VILLAGE, Calif., Aug. 18, 2023 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), an early commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced that John W. Smither, who served as Arcutis’ first Chief Financial Officer (CFO) from 2019 to 2021, has been appointed interim CFO effective August 31. He is replacing Scott Burrows, who is leaving the Company as of such date to pursue an external opportunity. “We are delighted that John has agreed to step in as interim CFO. He brings an incredible depth and breadth of both financial acumen and dermatology experience from his 25+-year career in the pharmaceutical industry, culminating in five successive CFO roles including his previous stint at Arcutis,” said Frank Watanabe, President and Chief Executive Officer of Arcutis. “On behalf of our Board and team, I would like to thank Scott for his tremendous contributions to Arcutis. We are grateful for his leadership, which was critical to the evolution of our financial organization in order to support the establishment and growth of our commercial operations in the United States and Canada, and we wish him success in his future endeavors.” “I am excited to rejoin the Arcutis team as interim CFO and continue the Company’s success delivering new innovations for serious skin diseases,” added John Smither. “With the first topical phosphodiesterase-4 inhibitor approved for plaque psoriasis and the potential approval of roflumilast foam for seborrheic dermatitis anticipated later this year, the Company is well positioned to further its leadership in medical dermatology.” “It’s been a privilege to be a part of Arcutis’ growth over the last four years,” said Scott Burrows. “The Company has made great progress with the launch of ZORYVE® (roflumilast) cream 0.3% in plaque psoriasis and has the potential of multiple subsequent approvals and launches in the next 18 months. I wish the entire team great success in the future.” As Arcutis’ first CFO, John led the successful IPO in 2020, and built the finance function from the ground up. Prior to Arcutis, Mr. Smither served as CFO for Sienna Biopharmaceuticals from January 2016 to March 2017 and again from March 2018 to April 2019. From October 2017 to April 2018, he was interim CFO for Kite Pharma during its integration with Gilead, and prior to that, was CFO at Unity Biotechnology from January 2016 to 2017. Earlier, he served as CFO of Kythera Biopharmaceuticals, Inc. from November 2007 until it was acquired by Allergan in October 2015 for $2.1 billion. In his various CFO positions, Mr. Smither oversaw multiple private and public financing rounds, including Kythera’s initial public offering, and initial IPO preparations at Unity and Sienna. He also serves on the Board of Directors of eFFECTOR Therapeutics, Applied Molecular Transport Inc. and NewAmsterdam Pharma Company N.V. About ZORYVE®ZORYVE (roflumilast) cream 0.3% is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 12 years of age and older. IMPORTANT SAFETY INFORMATION The use of ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). The most common adverse reactions (≥1%) include diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application site pain (1%), upper respiratory tract infection (1%), and urinary tract infection (1%). Please see full Prescribing Information. About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is an early commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio that harnesses our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis’ dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, atopic dermatitis, seborrheic dermatitis, and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, and Twitter. Forward-Looking StatementsArcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the potential for ZORYVE to simplify disease management for care of plaque psoriasis; the potential of real-world use results of roflumilast cream, as well as the commercial launch of ZORYVE in plaque psoriasis, and the timing of regulatory filings and potential approvals for a number of dermatology indications for roflumilast in the United States and Canada. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, the impact of competition and other important factors discussed in the "Risk Factors" section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 28, 2023, as well as any subsequent filings with the SEC. You should not place undue reliance on any forward-looking statements in this press release. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts:MediaAmanda Sheldon, Head of Corporate Communicationsasheldon@arcutis.com InvestorsEric McIntyre, Head of Investor Relationsemcintyre@arcutis.com

WESTLAKE VILLAGE, Calif., Aug. 18, 2023 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), an early commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced that John W. Smither, who served as Arcutis’ first Chief Financial Officer (CFO) from 2019 to 2021, has been appointed interim CFO effective August 31. He is replacing Scott Burrows, who is leaving the Company as of such date to pursue an external opportunity. “We are delighted that John has agreed to step in as interim CFO. He brings an incredible depth and breadth of both financial acumen and dermatology experience from his 25+-year career in the pharmaceutical industry, culminating in five successive CFO roles including his previous stint at Arcutis,” said Frank Watanabe, President and Chief Executive Officer of Arcutis. “On behalf of our Board and team, I would like to thank Scott for his tremendous contributions to Arcutis. We are grateful for his leadership, which was critical to the evolution of our financial organization in order to support the establishment and growth of our commercial operations in the United States and Canada, and we wish him success in his future endeavors.” “I am excited to rejoin the Arcutis team as interim CFO and continue the Company’s success delivering new innovations for serious skin diseases,” added John Smither. “With the first topical phosphodiesterase-4 inhibitor approved for plaque psoriasis and the potential approval of roflumilast foam for seborrheic dermatitis anticipated later this year, the Company is well positioned to further its leadership in medical dermatology.” “It’s been a privilege to be a part of Arcutis’ growth over the last four years,” said Scott Burrows. “The Company has made great progress with the launch of ZORYVE® (roflumilast) cream 0.3% in plaque psoriasis and has the potential of multiple subsequent approvals and launches in the next 18 months. I wish the entire team great success in the future.” As Arcutis’ first CFO, John led the successful IPO in 2020, and built the finance function from the ground up. Prior to Arcutis, Mr. Smither served as CFO for Sienna Biopharmaceuticals from January 2016 to March 2017 and again from March 2018 to April 2019. From October 2017 to April 2018, he was interim CFO for Kite Pharma during its integration with Gilead, and prior to that, was CFO at Unity Biotechnology from January 2016 to 2017. Earlier, he served as CFO of Kythera Biopharmaceuticals, Inc. from November 2007 until it was acquired by Allergan in October 2015 for $2.1 billion. In his various CFO positions, Mr. Smither oversaw multiple private and public financing rounds, including Kythera’s initial public offering, and initial IPO preparations at Unity and Sienna. He also serves on the Board of Directors of eFFECTOR Therapeutics, Applied Molecular Transport Inc. and NewAmsterdam Pharma Company N.V. About ZORYVE® ZORYVE (roflumilast) cream 0.3% is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 12 years of age and older. IMPORTANT SAFETY INFORMATION The use of ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). The most common adverse reactions (≥1%) include diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application site pain (1%), upper respiratory tract infection (1%), and urinary tract infection (1%). Please see full Prescribing Information. About Arcutis Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is an early commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio that harnesses our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis’ dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, atopic dermatitis, seborrheic dermatitis, and alopecia areata. For more information, visit or follow Arcutis on LinkedIn, Facebook, and Twitter. Forward-Looking Statements Arcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the potential for ZORYVE to simplify disease management for care of plaque psoriasis; the potential of real-world use results of roflumilast cream, as well as the commercial launch of ZORYVE in plaque psoriasis, and the timing of regulatory filings and potential approvals for a number of dermatology indications for roflumilast in the United States and Canada. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, the impact of competition and other important factors discussed in the "Risk Factors" section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 28, 2023, as well as any subsequent filings with the SEC. You should not place undue reliance on any forward-looking statements in this press release. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts: Media Amanda Sheldon, Head of Corporate Communications asheldon@arcutis.com Investors Eric McIntyre, Head of Investor Relations emcintyre@arcutis.com