Welichem Biotech, Inc.

在此前买入拜耳弃子后，“变废为宝”的二手商Roivant又有了新动作，不过，这次并非是买入而是售出。出售的是Roivant旗下的另一个“Vant”，Dermavant。收购方Organon将以预付款1.75亿美元，含里程碑付款的总额12亿美元收购Dermavant。Organon将支付未来的特权使用费给Dermavant的股东。 虽然价格和此前卖给罗氏71亿美元相比要低得多，还是有条件的里程碑付款，但是此举却被认为是卖出了“烫手山芋”。 Dermavant的困境 Dermavant本身是专注于皮肤病的分公司，管线同样来自于收购其他公司不要的管线。目前已上市核心管线是Tapinarof。 Tapinarof是一种“first-in-class”的芳香烃受体调节剂。上世纪90年代末，在加拿大读博的陈庚辉博士团队从土壤线虫的共生细菌代谢产物中分离出来一种小分子化合物，这就是后来的Tapinarof（中文名：本维莫德）。该小分子分子量仅有254 Da，且具备良好的皮肤渗透性，考虑到这款产品具有非激素类小分子药物的特性，陈庚辉博士等人据此在加拿大成立了公司Welichem Biotech公司开发这类小分子化合物。 在研发过程中，它展现了治疗皮肤病的潜力，特别是针对银屑病等炎症性和自身免疫性疾病。后来陈庚辉博士回国发展事业，创立了北京文丰天济医药科技有限公司（后成为冠昊生物子公司），在国内成功商业化Tapinarof，2019年上市，中文名本维莫德乳膏产品（商品名：欣比克）。如今这位科学家依旧在研发一线，创立了泽德曼医药，开发下一代芳香烃受体 改良调节剂。 而Tapinarof在大中华区外的权益就几经转手，最后在2018年由GSK卖给了Roivant。 后续在2022年在美国以成人轻度、中重度斑块状银屑病适应症获批，虽然在美国市场成功上市，投资者对于Tapinarof的态度可以说是有些冷淡。 这款产品销售额只有千万美元的量级，但支出却不少。去年一年2亿美元的运营费用足够让Roivant承担不菲的运营压力，虽然说产品近期增长确实有起色，但只是几百万美元的增长并不能弥补运营费用上的压力，今年运营费用的压力也不小，相当烧钱，将产品卖出反而是最合理的举措。 而与之相比，中国市场的运营成本显然没有2亿美元这么夸张，以2024年年中报为例，营业收入约2400万元，而营业成本只有约384万元，毛利率可观。 当然，Roivant毕竟主业是二手商，买入卖出才是常态，运营费用花费巨大，现在卖出去就不用担心这一问题了，即便有充裕的现金，仍然要考虑到如何最大化股东利益。 总结 卖出Dermavant后，Roivant的现金仍旧很充裕，有分析师认为，这笔费用可能会被纳入另外一家子公司Immunovant的R&D，该公司预计将在未来几年启动几项关键的III期研究。Immunovant正在开发自身免疫性疾病疗法，包括用于重症肌无力和甲状腺眼病的batoclimab。 这一预测不无道理，根据Roivant财报，Immunovant将迎来数个重点里程碑。这恐怕才是Roivant的攻坚战。 参考来源： http://www.guanhaobio.com/uploads/file/20240828160817d4.pdf https://investor.roivant.com/news-releases/news-release-details/roivant-reports-financial-results-first-quarter-ended-june-30-0

The Roivant Sciences strategy of finding shelved drug candidates and castoff research from big pharmaceutical companies has paid off. A compound that Roivant acquired from GlaxoSmithKline now has FDA approval for treating the inflammatory skin condition plaque psoriasis, giving the company its first product that it will commercialize on its own. The drug, tapinarof, was developed by Roivant subsidiary Dermavant Sciences. That company will market the topical cream under the name “Vtama.” While other topical products are available for treating plaque psoriasis, many of them first reached the market for other indications. Dermavant says its product is the first novel topical drug approved for plaque psoriasis in 25 years. In a prepared statement, Mark Lebwohl of the Icahn School of Medicine at Mount Sinai and lead author of the Phase 3 research that was published in The New England Journal of Medicine, said the Dermavant drug has the potential to become the preferred topical treatment for plaque psoriasis patients. “Following 20-plus years of minimal innovation in the topical psoriasis treatment space, I believe the approval of Vtama cream is an important step in establishing a new treatment option for adults with mild, moderate and severe plaque psoriasis,” Lebwohl said. Psoriasis is a chronic condition in which the body’s immune system attacks its own cells. The results of this attack appear prominently on the skin as red and dry patches. The condition affects an estimated 8 million people in the U.S. and up to 125 million people worldwide, according to Dermavant. Plaque psoriasis is the most common form of psoriasis, leading to darker and thicker raised patches on the skin that may be itchy and painful. Treatments for plaque psoriasis include drugs that work by tamping down the immune system. Topical steroids are widely prescribed for the condition, but long-term use can lead to thinner skin and these drugs lose their efficacy over time. These drugs can also cause problems if used on sensitive areas, such as the face and genitals. Several biologic drugs have approvals in psoriasis, including products from Amgen, AbbVie, Johnson & Johnson, Eli Lilly, and Sanofi. But these injectable medicines circulate systemically, which means that side effects can happen throughout the body. These blockbuster drugs are also very expensive. For both reasons, physicians typically start patients on topical products first and try biologicals only if the disease does not respond. Vtama is a steroid-free cream developed for once-daily application to the skin, including sensitive areas. The drug, a small molecule, is designed to block inflammatory proteins called cytokines. It’s also intended to promote the return of normal skin appearance as well as reduce the oxidative stress that contributes to inflammatory skin conditions. Dermavant said in an investor presentation that its drug could supplant steroids as the standard of care for plaque psoriasis. The FDA based its approval of the Dermavant drug on the results of two pivotal studies enrolling more than 1,000 total patients. In both studies, the drug met the main goal of showing a statistically significant improvement in skin appearance after 12 weeks of treatment compared against a cream that contained no active ingredient. Adverse events reported in the study were mild to moderate and included inflammation of hair follicles, inflammation in the nose and throat, and contact dermatitis, which is red and itchy skin that appears due to an allergic reaction. Furthermore, the drug has a long-lasting effect once treatment stops with skin clearance continuing for a median of four months. Dermavant set a $1,325 wholesale price for a tube of Vtama, which is more expensive than some topical plaque psoriasis products currently available, but less than the $1,950 wholesale price of Incyte’s Opzelura, according to the investor presentation. The Incyte product’s approval last September covers atopic dermatitis, a different autoimmune skin condition. Physicians are free to prescribe atopic dermatitis products for treating plaque psoriasis, and they often do. Dermavant said in the presentation that Vtama’s price reflects its differentiated profile and a drug label reflecting the strongest skin clearance effect for a topical plaque psoriasis product. Though Roivant has diversified its approach to drug development, its initial business model involved scouting for drug assets that were overlooked or stalled at big pharma companies and acquiring their rights. Around each compound, the company sets up subsidiaries around each compound, dubbed “Vants,” each of those units sharing in resources of the parent. Dermavant is one of 14 Vant companies. In 2018, Dermavant paid GSK £150 million (about $191 million) for global rights to tapinarof, excluding China. With the drug’s U.S. approval, Dermavant is on the hook to pay GSK £100 million (about $133 million). According to the purchase agreement, that payment must happen within 70 days of the approval decision. No further payments, royalties or otherwise, are owed to GSK. However, Dermavant assumed GSK’s obligations to British Columbia-based Welichem Biotech, from which the British pharma giant acquired tapinarof. Under the agreement, Dermavant is responsible for up to 80 million Canadian dollars (about $61 million) in development milestone payments and up to CA$100 million (about $76 million) more tied to commercialization milestones. Though Vtama marks Roivant’s first drug approval, it is not the first drug from a Vant company to pass regulatory muster. In 2019, Sumitomo Dainippon Pharma of Japan paid $3 billion to acquire five Vants. Those companies have gone on to win FDA approvals in overactive bladder, advanced prostate cancer, uterine fibroid bleeding, and pediatric congenital athymia. Dermavant has plans for its lead asset that go beyond plaque psoriasis. Last September, the company began a Phase 3 study testing the drug in atopic dermatitis. The program will enroll up to 800 participants, both adults and children with moderate-to-severe disease. Preliminary data from both studies are expected in the first half of next year. Dermavant Chief Medical Officer Philip Brown said that the company is also exploring other potential uses for the drug in dermatology and other immunology indications.

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）。 1Tapinarof (DMVT-505) 2020年8月26日，Dermavant Sciences宣布，该公司在研进度最快的产品Tapinarof (DMVT-505)（1%乳膏剂型），两项多中心、随机双盲，空白基质对照的名为PSOARING 1和PSOARING 2的针对成人斑块状银屑病（plaque psoriasis）适应症的3期临床达到主要终点。 Tapinarof是一种在研治疗性芳烃受体调节剂（TAMA），可用于治疗银屑病和特应性皮炎（AD）。Tapinarof可调节淋巴细胞酪氨酸激酶和芳香烃受体活性，抑制银屑病中的炎症性细胞因子产生、炎症细胞的浸润、角质形成细胞的异常角色化增生和血管形成与增生等病理变化。 具体而言，在名为PSOARING 1（N=510）和PSOARING 2（N=515）的3期临床试验中，与空白基质对照组相比，接受Tapinarof (DMVT-505)（1%乳膏剂型）（每天使用一次）治疗的患者在接受治疗12周后，达到医生整体评估（PGA，Physician Global Assessment）评分为0（皮肤症状完全清除），或1（皮肤症状几乎完全清除）且评分与基线相比至少提高两级的患者比例显著高于对照组，达到试验的主要终点（P<0.0001)）。关键的次要临床终点PASI75（Psoriasis Area and Severity  Index）(银屑病面积严重性指数 (PASI) 评分取得75%改善)也达到预期（P<0.0001）。 2021年4月23日 ， Dermavant公布Tapinarof (DMVT-505)（1%乳膏剂型）在银屑病患者的PSOARING 1和PSOARING 2临床试验的最新数据分析。试验结果显示，大约五分之一的患者在接受Tapinarof (DMVT-505)（1%乳膏剂型）治疗12周之后达到银屑病面积严重性指数 (PASI) 评分取得90%改善（PASI 90）的标准。此外患者的瘙痒程度和生活质量也得到改善。 Dermavant预计将在 今年年中向美国FDA递交本品新药上市申请(NDA)。 Dermavant产品线，Tapinarof (DMVT-505)等 2新药的来源及历程 Tapinarof (DMVT-505)（中文名：本维莫德）最早由加拿大Welichem Biotech发明。该公司核心创始人：陈庚辉、John M. Webster、李健雄。 据陈博士介绍，上世纪90年代初，他在加拿大攻读博士期间，与导师John M. Webster、博士后李健雄通过共生微生物线虫和细菌，发现新的广谱杀菌剂和其它生物活性物质。本维莫德的研发始于1999年，是从一种土壤线虫的共生细菌代谢产物中分离出来小分子化合物。“在一般皮肤上，分子量超过500Da的分子穿过角质层吸收就受影响，本维莫德分子量仅为254Da，因此针对皮肤局部作用起效，不存在治疗相关的系统性不良反应，药物安全性非常理想，而且具有作用持久，起效快，停药后复发率低、缓解期长等显著优势。     2012年5月，GSK（葛兰素史克）旗下公司Stiefel花费可能高达2.3亿美元里程碑付款购（首付款为3500万加元）得本维莫德（当时代号WBI-1001）除中国大陆、台湾、香港和澳门市场以外的独家开发以及市场权益。 2018年7月 ，GSK宣布Roivant Sciences子公司Dermavant Sciences购买在研银屑病和特应性皮炎新药Tapinarof除中国区以外的市场所有权，合作总额可达2.5亿英镑。起始合作付款高达1.5亿英镑。 Tapinarof /Benvitimod（中文名：本维莫德，曾用名:苯烯莫德）中国权益在冠昊生物及北京文丰天济医药手中。2019年5月，本维莫德乳膏通过中国国家药品监督管理局（NMPA）优先审批程序批准上市。目前在国内获批的适应症为用于治疗轻至中度稳定性寻常型银屑病。 我国银屑病患者已超过650万，且多为轻、中度患者，寻常型银屑病占比超过9成。银屑病患者长期饱受瘙痒、脱屑等症状困扰，承受着经济、心理等多方面的疾病负担。国内学者研究显示，57%的银屑病患者心情压抑、抑郁，产生自卑感。且银屑病由于其无法根本治愈，因此反复发作长期困扰着患者，延长治疗的缓解期也是皮肤科医生治疗银屑病的首要治疗目标之一。目前外用药治疗适用于绝大多数银屑病患者，且为首选治疗方法，在银屑病治疗中处于基础地位。但是，目前外用治疗仍然不能满足临床需求，如治疗满意度不高、反复发作等问题。企业方表示，本维莫德作为首个外用靶向免疫调节剂——芳香烃受体（AhR）调节剂，有着优于金标准的确切疗效，治疗后可长期缓解症状，在三期临床研究中中位缓解期长达9个月。2020年底，本品进入国家医保目录。本维莫德医保谈判后降幅达到72%，现价138元/支。 在2019年冠昊生物年报显示报告期内实现新药本维莫德产品收入 1386 万元。2020年上半年药融云数据（www.pharnexcloud.com）显示，新药本维莫德实现销售收入2699万元；2020年全年约4000万元人民币。 更多信息，请扫免费注册的药融云数据或网站www.pharnexcloud.com 参考： NMPA/CDE； 药融云数据  www.pharnexcloud.com； FDA/EMA/PMDA； 相关公司公开披露； Dermavant to Showcase PASI90, Itch and Quality of Life Data from Phase 3 Pivotal Trials for Tapinarof at AAD VMX 2021.  https://www.dermavant.com/dermavant-to-showcase-pasi90-itch-and-quality-of-life-data-from-phase-3-pivotal-trials-for-tapinarof-at-aad-vmx-2021/； Dermavant Reports Positive Phase 3 Results for Tapinarof Cream in Adult Patients with Plaque Psoriasis，https://www.dermavant.com/dermavant-reports-positive-phase-3-results-for-tapinarof-cream-in-adult-patients-with-plaque-psoriasis/； https://adisinsight.springer.com/search； Dermavant Bags GSK Phase III-Ready Psoriasis Treatment in $330 Million Deal； http://www.stiefel.com/； 葛蘭素史克旗下公司 Stiefel 與 Welichem Biotech, Inc. 達成協議，收購治療牛皮癬和過敏性皮炎的新型局部藥劑，https://hk.prnasia.com/story/62513-2.shtml； http://www.welichem.com/； http://www.welichem.com/static/wbi_5111.html； http://www.most.gov.cn/gnwkjdt/201907/t20190712_147685.htm； 冠昊生物2020年报，https://pdf.dfcfw.com/pdf/H2_AN202103081469763650_1.pdf?1615237212000.pdf； www.guanhaobio.com； https://www.dermavant.com/2018/07/； https://www.dermavant.com/roivant-subsidiary-dermavant-sciences-signs-agreement-with-gsk-to-purchase-rights-to-tapinarof/；等等。 药事纵横投稿须知：稿费已上调，欢迎投稿各位朋友好，觉得本文对您有帮助，请随手点一下下方的在看，以便让你的朋友也能看到哦。