Selexipag

1 整体表现 JNJ连续两个季度医药部分收入站上$14.5b，市值也略有回升、但依然回不到$400b大关，与GLP-1双雄LLY和NOVO的距离仍然很大。 三季度扣除新冠影响的收入增长为6.3%，扣除并购影响下全年EPS指引调增到9.2%，在MNC里面应该属于中规中矩的表现。 2 已上市产品 自免板块正在非常微妙的转折点：Ustekinumab在高位维持，LTM累计已达到$11b，不过随着生物类似药马上进入欧洲、明年进入美国，必然到来的巨大专利悬崖让全公司时刻处在达摩克利斯之剑下；而公司力推的Guselkumab也不负厚望在奋力填补Ustekinumab身后的空档，LTM累计$3.6b；Infliximab和Golimumab两个则确实彻底失去增长动力了。 肿瘤板块仍然在高歌猛进：Daratumumab上市已近十年，甚至还能维持着二阶导增速，LTM累计已达到$11.1b；Apalutamide也仍在持续爬坡中，LTM累计也达到$2.9b；Cilta-cel的产能瓶颈看起来已经基本缓解、公司明确批准Ghent工厂已经投产，单季度一跃而升至$286m，环比增长都超过50%，与Daratumumab青老配合几乎在多发性骨髓瘤领域可预期着一手遮天的局面（说老实话不太理解传奇当天大跌10%是啥情况）；Teclistamab双抗的爬坡也并不理想，连续几个环比处于停滞；Ibrutinib则持续被AZ和百济侵蚀。 心血管板块里，Rivaroxaban在达峰后的衰退通道中略有反弹，但Macitentan和Selexipag两个PAH产品爬坡势头略有迟缓，单季度总算堪堪突破了$1b大关，似乎想要配得上当初$30b收购Actelion的价格仍有很大距离。 传染病板块就实在没什么看头了。 精神板块虽然Paliperidone早已失去增长，但Esketamine爬坡还是相当有盼头、不声不响LTM累计已接近$1b。 3 在研管线 近期最靓的仔毋庸置疑是EGFR/cMET双抗Amivantamab，这个季度连续收获了两个新的批准，分别是针对EGFRm NSCLC的联用Lazertinib一线方案和联用SOC化疗二线方案，背后则MARIPOSA和MARIPOSA2两个注册临床中显著的PFS获益；值得一提的是，正是Ami的异军突起，成了康方AK112冲击EGFRm setting半路杀出的程咬金（参见【药海听涛】不及的到底是什么“预期”：康方AK-112与其他药物临床数据对比）。 JNJ在肿瘤板块寄予厚望的另一组待放之花则是膀胱灌注的Taris系列，近期则是喜忧参半：在针对BCG无响应的高风险NMIBC的二期临床SunRISe-1试验中，TAR-200单药的CR高达84%、甚至高于联用PD-1；在针对铂类不耐受的MIBC新辅助治疗的二期临床SunRISe-4试验中，TAR-200联用PD-1的ORR高达60%、CR高达42%；而在治疗MIBC的三期临床SunRISe-2试验中，TAR-200与放化疗标准治疗方案相比未能显示出优效，因而试验被终止。 多发性骨髓瘤是JNJ绝对的基本盘（参见【药海听涛】强生的“遮断式”布局：BCMA×CD3双抗治疗多发性骨髓瘤获批），这个适应症的耕耘依然持续不断：围绕CD38单抗Daratumumab皮下制剂的四联方案（D-VRd）获批治疗适合移植的新发MM，治疗不适合移植的新发MM的三期临床CEPHEUS试验公布积极结果、并提交了上市申请，现在能理解Dara上市十多年来为什么销售额持续在爬坡了；此外，Carvykti也公布了治疗2L MM的三期临床CARTITUDE-4研究数据更新，在三年随访时间内对比标准PVd/DPd方案能带来45%的OS获益。 自免板块最重磅的进展当属FcRn单抗Nipocalimab终于递交了BLA，终于向argenx的领先地位发起挑战，能不能值回$6.5b的票价也到了见真章的时候。 诚然Ustekinumab作为自免大哥和公司台柱，专利悬崖的压力无可回避且迫在眉睫，公司颇为兴奋的点了几个填坑选手的名：IL23p19单抗Guselkumab在IBD的巨大优势，有可能带来比Ustekinumab更大的体量，虽然目前也就只到后者的40%；口服IL23R多肽药物JNJ-2113，在银屑病的一系列三期临床（包括与TYK2抑制剂头对头）和IBD的二期临床，都非常值得期待；此外还有Guselkumab和Golimumab的复方JNJ-4804，也在同时攻略IBD，似将在这一广阔适应症上形成类似MM领域的遮断之势。 除此以外，值得关注的进展还包括：FGFR抑制剂Erdafitinib获得欧盟批准，PAH药物Macitentan的幼儿适应症获得欧盟批准、并向FDA递交上市申请，NMDAR拮抗剂Esketamine递交难治性抑郁症的上市申请。 JNJ凭借肿瘤和自免两大板块多年来的强势表现，不仅一直是MNC中业绩成长较为稳定的一家，而且那种对重要疾病领域“遮断式”的深耕制霸方式尤为值得学习，前有MM、后可能有IBD，外加异军突起的Ami和Taris系列，都将是支撑未来多年公司价值的基石。

Two-thirds of patients saw a sustained reduction in their pulmonary arterial pressure. Cereno Scientific’s hypertension drug was shown to improve the risk score of 43% of patients in a phase 2 study.Of the 21 participants with pulmonary arterial hypertension (PAH), nine demonstrated an improved risk score—a measurement of the risk of death from the condition—after 12 weeks of treatment with Cereno’s histone deacetylase (HDAC) inhibitor, dubbed CS1.A further six patients reported a stable risk score, meaning 71% of patients saw their score either improve or hold steady, the Swedish biotech noted in a post-market release Friday.Two-thirds of patients saw a sustained reduction in their pulmonary arterial pressure, while a third reported an improved functional class, a term for symptoms and physical capacity.Cereno’s shares were trading up 25% on the Stockholm stock exchange at 8.72 Swedish krona on Monday afternoon local time compared to a Friday closing price of 7 krona.The trial was also a success on its primary endpoint of proving the safety and tolerability of CS1, with no treatment-related serious adverse events. No changes in liver lab values or clinically significant drug-related bleedings or decreases in platelet counts were recorded, Cereno said. The company is now looking at moving CS1 into a pivotal trial and said it will use Friday’s “encouraging results” as the basis for opening talks with regulators.“We are excited to take the next steps in our journey to make a meaningful impact for patients with PAH,” Cereno’s Head of R&D Rahul Agrawal said in the release.“The CS1-003 trial demonstrated compelling signs of clinical efficacy already over a 12-week treatment period and we expect to see additional positive impact of CS1 with longer use of our drug in patients with PAH,” Agrawal added.HDACs help regulate gene expression. The FDA has already improved four HDAC inhibitors to treat blood cancers, including Merck & Co.’s Zolinza. Cereno is hoping CS1 will have success against PAH by “targeting the root cause of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries.”PAH is a rare, rapidly progressing disease in which the blood vessels narrow in the lungs, increasing blood pressure and leading to heart failure. Johnson & Johnson dominates the PAH market with its prostacyclin receptor agonist Uptravi and the endothelin receptor agonist Opsumit.In March, Merck & Co. muscled in on the action with the approval of the activin signaling inhibitor Winrevair, which the pharma has touted as acting directly on the underlying problem that causes the disease.Despite the increasingly crowded space, Cereno claimed in its release that “existing treatment alternatives are insufficient and do not address the root cause of the disease.”