Omalizumab

- Clinically meaningful and statistically significant improvements across multiple angioedema measurements and barzolvolimab dose groups -- Sustained activity with rapid onset within 2 weeks -- Data further support barzolvolimab clinical benefit to patients with CSU - HAMPTON, N.J., June 02, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced data demonstrating that barzolvolimab profoundly improves angioedema at 12 weeks in the Company’s Phase 2 clinical trial in chronic spontaneous urticaria (CSU). Angioedema, characterized by swelling of the deeper dermal layers of the skin and mucous membranes, is a painful, debilitating symptom of CSU that has significant impact on quality of life. It commonly affects the face (lips and eyelids), hands, feet, and genitalia but can also involve the tongue, uvula, soft palate, and pharynx1. The data were presented today by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin, in an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024. Celldex previously announced that the Phase 2 study in CSU met its primary and secondary endpoints at 12 weeks with clinically meaningful and statistically significant decreases in UAS7 (weekly urticaria activity score) compared to placebo across multiple dose groups and demonstrated a favorable safety profile. The data presented today further support these results by demonstrating improvements in AAS7 (weekly angioedema activity score) and additional measures of angioedema control. “The majority of patients with severe CSU suffer with angioedema, which is often extremely painful and causes disfigurement, dramatically impacting quality of life,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "Consistent with previously reported clinical outcomes, we observed rapid, durable and significant angioedema relief, including in omalizumab refractory disease. These data continue to support barzolvolimab’s potential to become a transformative treatment option for CSU and we look forward to moving closer to this goal with the initiation of our Phase 3 studies this summer.” Phase 2 Barzolvolimab Study in CSU (n=208)Summary of Angioedema Clinical Activity Assessments at Week 12 300 mg Q8W(n=51)150 mg Q4W(n=52)75 mg Q4W(n=53)Placebo(n=51)Angioedema at baseline, n (%)42 (82%)35 (67%)40 (75%)32 (63%)AAS7 ChangesBaseline AAS7 (mean)53.1554.6054.0556.30LS Mean difference from placebo (Confidence Interval, p value)-25.32 (CI:-36.32, -14.32)p<0.0001-23.56(CI:-35.08, -12.04)p<0.0001-17.52(CI:-29.35, -5.69)p=0.0039 >8 point improvement in AAS7 (%)85.0P<0.0587.1P<0.0582.9P<0.0557.1Angioedema Free Days (mean)65.1P<0.0554.5P<0.0543.336.2AAS7 data were analyzed using ANCOVA model and multiple imputation. Data are presented for patients with angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at Week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks).Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p<0.05).Barzolvolimab increased angioedema free days compared to placebo through 12 weeks. Patients in the 300 mg cohort were angioedema free 77% of the time over the 12 week period. Phase 2 Study Design The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to Week 12 in UAS7 (weekly activity score). Secondary endpoints include other assessments of safety and clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hives severity score) and AAS7 (weekly angioedema activity score). For additional information on this trial (NCT05368285), please visit www.clinicaltrials.gov 1DermNet. About Chronic Spontaneous Urticaria (CSU)CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling and inflammation of the skin that can go on for years or even decades. Current therapies provide symptomatic relief only in some patients. About BarzolvolimabBarzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN) and eosinophilic esophagitis (EOE) with additional indications planned for the future, including atopic dermatitis (AD). About Celldex Therapeutics, Inc.Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com. Forward Looking Statement This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully complete research and further development and commercialization of Company drug candidates, including barzolvolimab (also referred to as CDX-0159), in current or future indications; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; our ability to continue to obtain capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise. Company ContactSarah CavanaughSenior Vice President, Corporate Affairs & Administration(508) 864-8337scavanaugh@celldex.com Patrick TillMeru Advisors(484) 788-8560ptill@meruadvisors.com

这是一个关于企业商业化视野的命题：视野局限在产品的投入-产出比，市场潜力就会局限在一个产品；当放大到产品背后的疾病领域，市场潜力就扩大一层；放大到疾病背后的专科发展，市场还会再扩大；当视野触及最根本的患者需求，市场潜力才能得到充分释放。田瑀说，承诺中华，患者为先，诺华免疫始终坚定践行的“以患者为中心"的承诺从来不是纸上谈兵，而是全情的投入和不懈的努力。诺华对于中国自免疾病市场的初心与韧性就在于此。跨国药企为何总能扮演市场生态构建者的角色？诺华免疫在可善挺（司库奇尤单抗注射液）登陆中国市场五年的时间，谱写了一份跨国药企打开市场、助力生态建设，并成为引领者的模范案例。五年前，可善挺作为首个白介素治疗产品上市并于第二年进入国家医保目录，点燃中国市场自免领域的“燎原之火”；五年来，诺华免疫以学术引领市场，促进规范化诊疗，助力学科发展和专科人才培养。可善挺的商业化进程不仅是将创新产品引入市场，中国的自免疾病市场也在此过程中完成了向生物制剂治疗时代的蝶变。诺华中国副总裁、免疫治疗领域负责人 田瑀就像取名的寓意“承诺中华”，诺华中国副总裁、免疫治疗领域负责人田瑀认为，比起单一产品的商业化，诺华免疫始终以推进规范化诊疗为理念，秉持决心与韧性，赋能整个疾病领域的发展，让广大中国患者获益。01立足创新产品，引领生态建设通常意义上，以一款核心产品打开市场是制药企业的惯常“打法”，但诺华免疫的与众不同之处在于，以可善挺为前锋，重新构建了中国银屑病领域的生态。2024年5月标志着可善挺在中国市场上市的第五年。五年来，中国的银屑病市场不仅开启了白介素治疗时代，中国银屑病诊疗水平也正在持续升级中。可善挺不仅是目前中国唯一获批成人银屑病、儿童银屑病、强直性脊柱炎和银屑病关节炎适应症的IL-17A抑制剂，也是中国唯一获批三种规格（300mg、150mg、75mg）的全人源IL-17A抑制剂。在可及性方面，可善挺率先在2020年，也就是其登陆中国市场的第二年，响应国家政策号召 ，以超过60%的降幅顺利进入国家医保目录，彼时欧美市场价格高达数千美元一支，两相对比，足以体现诺华实实在在惠及更多患者的赤诚决心。田瑀告诉E药经理人，可善挺在中国上市至今累计已经让超过50万患者获益，作为国内市场第一个面向银屑病患者的白介素产品，可善挺的上市带动了整个疾病领域的发展。除此之外，2022年，诺华的另一款重磅自免产品茁乐（奥马珠单抗注射液）还获批了第二个适应症，用于治疗成人和青少年慢性自发性荨麻疹，成为我国唯一批准用于该疾病的生物制剂。同样也是响应国家政策号召，在获批当年，茁乐的这一适应症就成功进入国家医保目录，至今累计已有近20万患者获益。创新产品力与迅速的医保准入是诺华打出组合优势的第一个层级——以学术引领市场。在田瑀看来，要实现产品最大化惠及患者，制药企业还要深入助力疾病背后的学科发展，助力实现规范化诊疗。这也是诺华能够将优势从创新产品辐射到整个银屑病生态，并成为引领者的关键一步。02助力规范诊疗，实现多方共赢从产品优势做到市场引领者，田瑀认为诺华下好了四步“先手棋”——“极速可及、全面覆盖、助力学科、守护患者”。2018年8月，国家药监局药品审评中心首次发布《关于征求境外已上市临床急需新药名单意见的通知》，可善挺赫然在列。鼓励创新的政策红利叠加产品力，可善挺从诺华申请提交到获批，仅历时6个多月；从获批上市到医院落地可及，仅用时50天；上市第二年即快速进入医保，这些都展示了诺华的“极速可及”。诺华的“全面覆盖”则在于日拱一卒，从市场教育到患者教育，秉持“承诺中华”的初心与韧性，投入广、程度深，聚焦中国市场。在田瑀看来，进行规范化诊疗，首先需要明确诊疗标准，其次是要进行专病门诊建设以及专科医师的培养，最后是推进患者长期管理，如此才能保证诊疗质量。因此，诺华自2020年起，就公益支持国家皮肤与免疫疾病临床医学研究中心发起“银屑病规范化诊疗中心“建设项目，旨在推动各地银屑病诊疗水平均质化发展。截至目前，该项目医院覆盖全国31个省级行政区，共纳入494家诊疗中心和908家专病医联体。通过该项目，实现医院、科室银屑病专病门诊建设最深入渗透。规范化诊疗的要素不仅有科室，也要有人才。人才是学科建设的基础，也是基层诊疗能力提升最直接的体现。为助力培养专科人才，诺华与国家卫生健康委人才交流服务中心、中国医学装备协会于2023年进博会共同签署中国卫生高质量发展战略合作谅解备忘录，并启动“百城千县，万人赋能”项目。合作内容涵盖三四线地市和基层县医院管理能力建设培训项目、皮肤科及风湿科诊疗能力提升、基层心血管慢病管理培训和基层护理能力提升培训等多个项目。本次签约是贯彻落实《公立医院高质量发展促进行动（2021-2025年）》《“千县工程”县医院综合能力提升工作方案（2021-2025年）》等文件精神，助力中国卫生健康高质量发展行动的一次有益尝试，将对促进优质医疗资源扩容下沉和区域均衡布局、加快实现卫生健康事业高质量发展，发挥积极作用。中国卫生高质量发展战略合作谅解备忘录签约现场在采访过程中，田瑀着重提及了“百城千县，万人赋能”项目能够持续扩大规模，涵盖100多个地市和900多个县，覆盖万名基层医生，并取得学协会以及基层医疗系统的大力支持和认可，离不开对于学科人才发展的关注。该项目不仅培养了专科医生，还帮助医院建立起银屑病和荨麻疹的专病门诊；同时，项目契合自免疾病需要长期护理的需求，提升了医院护理水平；此外，该项目还搭建了高质量的交流与培训平台，助力专科发展与学科建设。在此过程中，诺华免疫的人才发展战略与基层诊疗能力提升始终相辅相成。在诺华内部打造了超过2000人的一线团队，实现从一线城市到基层市场的全覆盖。03聚焦患者获益，惠及广大患者不过，患者获益始终是出发的原点以及上下求索的核心。随着医学的进步，多数疾病在21世纪已经进入了生物制剂治疗时代，自免疾病也是如此。集合12万患者真实患者数据编撰而成的《中国银屑病诊疗现状蓝皮书2023》在今年4月底发布。其中显示，在2020-2023年间，接受局部治疗和系统治疗(非生物制剂)的患者比例逐年下降，而接受生物制剂治疗的患者比例呈现逐年上升趋势，越来越多的患者获益于创新生物制剂。规范化诊疗是推动银屑病领域诊疗水平提升的一面，另一面是患者认知的普及。通常意义上，银屑病呈现出遍布全身的皮损，并且具有病程慢性、容易复发、终身伴随的特征。因此，银屑病常常被误解具有传染性，患者也往往容易在心理上伴随“病耻感”，甚至因为既往治疗无效而放弃治疗。这也对药企的患者教育提出了更高要求——如何让已经对治愈失去信心的患者重燃治疗的意愿？如何共情患者身、心痛点以及诊疗难点，提供全病程关爱、正确的科普支持从而全方位提升生活质量？田瑀将这一工作称为“患者全面关爱支持”，“诺华在规范化诊疗的推进过程中，还会进行疾病公益科普，消除银屑病传染性误解的同时，也鼓励患者积极进行科学规范化治疗。”这一切不只是口头的承诺，而是通过长久以来切实的行动在体现。今年2月，由诺华公益支持的国内首部银屑病主题公益大电影《你好，我的银色恋人》上映。截至目前，全网播放量已超800万，B站评分9.8分，话题讨论量超1500万。田瑀说，“电影的高热度是源于对银屑病患者的共情。这部电影不仅是对疾病的关注，更是对患者真实生活的关注。电影中所传达的积极阳光的精神，对梦想和爱情勇敢追求的精神。不仅激励了患者群体，也同样激励了我们每一个普通人。”诺华公益支持的电影自今年2月陆续上线B站、芒果TV以及央视频APP等平台，引发无数人共情(图片由被访者提供)同时，诺华还通过与基金会合作，连续三年开展“至净新生”患者关爱公益行活动，赋予医生科普、医患交流、患者互动分享平台，让医生更懂患者、患者更懂规范诊疗知识。目前已在全国举办30多场线下活动，惠及超2000位患者。公益电影、医患互动等科普行动只是诺华疾病教育工程的一角。自2022年起，诺华便与世界领先的美妆巨头欧莱雅集团携手进行行业首创的“药、妆“跨界合作，通过充分发挥双方在免疫治疗及科学护肤领域的深厚专长，为银屑病患者打造“治护一体”的全方位解决方案，从而全面提升患者的生活质量，助力他们重拾健康与自信。此外，在今年下半年，由诺华支持编写的患者科普书籍《银屑病365问》将会出版面世，通过全国范围内征集银屑病患者、患者家属及医护人员最关心的问题，邀请全国超百位皮肤科专家共同撰稿，兼具便携与实用，将成为银屑病患者必备的百科全书。04秉持初心韧性，践行承诺中华即使在跨国药企中，如同诺华免疫一般，由制药企业支持某一疾病领域从0到1发展起来的庞大工程也不多见。田瑀认为，商业化前景与其视野直接相关：视野局限在产品的投入-产出比，市场潜力就会局限在一个产品；当放大到产品背后的疾病领域，市场潜力就扩大一层；放大到疾病背后的专科发展，市场还会再扩大；当视野触及最根本的患者需求，市场潜力才能得到充分释放。她说：“站在高处，就要拿出高处的实力与担当。”回溯诺华在中国自免疾病市场一路的开疆拓土：从创新产品引入，到自免疾病的规范化诊疗；从商业化人才团队组建到助力地市级、县域医院专科医生培养、专病门诊打造；从开展患者疾病教育到促进基层医疗资源均质化发展……田瑀告诉E药经理人，诺华免疫对中国市场的聚焦与投入，直接践行了“承诺中华”的寓意，象征着对中国患者的承诺和决心。凡是过往，皆为序章。田瑀表示，未来，诺华免疫将依托现有优势，以现有产品的契合度为基础，从庞大未被满足临床需求出发，拓展更广泛适应症，引进更多自免领域创新产品。短期内，已经有三项上市计划的蓝图在田瑀的脑海中绘成：第一，可善挺治疗化脓性汗腺炎（HS）适应症在美国FDA及欧盟均已获批，可善挺也有望成为中国唯一获批HS的生物制剂，为诺华免疫的产品组合，保持“快”的优势基础上，再添新动力。第二，在推动慢性自发性荨麻疹规范化诊疗的同时，诺华还将在2025年引入一款口服BTK抑制剂Remibrutinib，该产品有望成为十年来全球及中国首个治疗慢性自发性荨麻疹的口服靶向药物。该产品与茁乐的组合还将助力诺华进一步推动疾病领域的发展，或将再复制可善挺在银屑病领域的领导者地位。第三，诺华免疫还将视野放到了干燥综合征领域，抗B细胞活化因子受体（BAFF-R）全人源单克隆抗体Ianalumab（VAY736）被寄予厚望。该产品也是目前全球进展最快，且唯一进入临床III期的靶向BAFF-R抑制剂。长期而言，诺华免疫行稳致远的蓝图刚刚绘下一角。追风赶月莫停留，平芜尽处是春山。可善挺登陆中国五周年，也是下一个五年的新起点，在田瑀的设想中，诺华免疫的治疗领域要做的事情还有很多，争取免疫新产品未来能同步甚至更早一步在中国首发，更重要的是推进整个自免疾病规范化诊疗，实现基层优质医疗资源均质化。承诺中华，患者为先。诺华免疫始终坚定践行的“以患者为中心”从来不是纸上谈兵的空话，而是夜以继日、前赴后继的不懈努力以及全情投入。我们有理由相信，在这样的初心与韧劲之下，“让每一位患者都能及时得到规范化诊疗，共享健康美好的生活”的星辰大海终将抵达。诺华免疫，一路同行，未来可期。