Actelion Pharmaceuticals Ltd.

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。

→ The top leadership at Lexicon Pharmaceuticals is still undergoing a major makeover as president and COO Jeff Wade heads for the exit on Sept. 30 after 25 years with the Texas-based biotech. Wade won’t be around for the outcome of Lexicon’s latest attempt at an FDA nod in type 1 diabetes for sotagliflozin , which has a Dec. 20 decision date. The drug has already been approved for heart failure and is marketed as Inpefa . Lexicon laid off about 75 people in its sales and commercial teams in August “to right-size our promotional efforts around Inpefa for heart failure and reallocate resources to prepare for our potential launch” in type 1 diabetes and chronic kidney disease, CEO Mike Exton said in a statement. Exton succeeded Lonnel Coats as CEO a month earlier. → Sarepta Therapeutics has appointed Genmab chair Deirdre Connelly to the board of directors. Connelly had a 26-year career with Eli Lilly before pivoting to GSK in 2009 as president, North America pharmaceuticals until her retirement in 2015. She’s also a board member at Macy’s and Lincoln Financial Group . Like Janet Woodcock before him, CBER Director Peter Marks helped Sarepta cross the goal line with a label expansion in June for its Duchenne muscular dystrophy treatment Elevidys — overruling his own staff and befuddling experts. → Mitchell Chan has replaced Vit Vasista as CFO of Regenxbio at a time when the company plans to start a pivotal study for its own Duchenne gene therapy. It’s another big change for Regenxbio after Ken Mills became executive chairman and Curran Simpson succeeded Mills as CEO on July 1. Chan spent a year with Catalio Capital Management as operating partner after he was elevated to the CFO post at Viela Bio. Vasista had been finance chief since 2009 and will be an advisor until Jan. 3. → Here’s a look at some CEO news that we covered earlier this week: Former Kite Pharma commercial chief Warner Biddle has succeeded Peter Maag as CEO of Kyverna Therapeutics , which also added ex-Kite CEO Christi Shaw to the board. Shares $KYTX of Kyverna have taken a precipitous fall since its $319 million IPO in February. Ochre Bio co-founder Jack O’Meara is calling it quits after five years as CEO, but he tells Lei Lei Wu that he has an Alzheimer’s startup in the works. In a LinkedIn post announcing his departure, O’Meara also said that former F-star CEO and current Levicept chief Eliot Forster will be interim executive chair. And Shilpa Sambashivan has been promoted to CEO of Nura Bio , which stapled an additional $68 million to its Series A — bringing its total to $141 million. Sambashivan was a project team lead at Amgen before becoming a founding member at Nura Bio. → Matt Kane is taking the top spot at Celyad Oncology , a Belgian biotech that has seen considerable turnover at the top. Celyad co-founder Michel Lussier filled in as interim CEO for a second time after Georges Rawadi ’s sudden exit last December; he also took over when Filippo Petti stepped down in 2022. Kane co-founded Precision BioSciences with Derek Jantz and Jeff Smith , leading the company until he joined epigenome editing startup Tune Therapeutics as CEO in 2021. Kane’s LinkedIn page indicates that he left Tune in April, a year after he hired Jantz as CSO. → Ex- Prometheus Biosciences chief Mark McKenna has found a CFO at his new I&I bet, Mirador Therapeutics . Gregg Gilbert had been a managing director in the healthcare investment banking group for Bank of America Securities since 2021 and worked at Bank of America Merrill Lynch for 15 years. After selling Prometheus and its inflammatory bowel disease drug to Merck for $10.8 billion , McKenna wasted little time getting Mirador off the ground with a $400 million Series A in March, one of the largest private financing rounds of 2024. → GLP-1 competitor Structure Therapeutics has promoted Blai Coll to CMO and welcomed Ashley Hall as chief development officer. Coll, who replaces Mark Boch , had led clinical development for Raymond Stevens ’ crew since May 2022 and was cardiovascular and metabolic platform lead, medical affairs at the end of a six-year stint with Amgen. Hall is an Amgen vet in her own right who held the role of development chief at Reneo Pharmaceuticals . Structure’s stock price soared in June $GPCR when it produced efficacy data with its oral GLP-1 GSBR-1290 that was on par with Eli Lilly’s obesity drug orforglipron . → Novartis and Gilead veteran Matthias Will has succeeded Edgar Braendle as chief development officer at Autolus Therapeutics . Will had led clinical development at CRISPR Therapeutics and CytomX before his most recent gig as CMO of Dren Bio . The FDA is expected to make a decision by Nov. 16 on Autolus’ CD19-directed CAR-T obecabtagene autoleucel , or obe-cel . → According to an SEC filing , Crinetics chief commercial officer Jim Hassard will pack his bags on Oct. 14 in what’s described as a “termination without cause.” The 17-year Amgen vet came to Crinetics from Arrowhead Pharmaceuticals in March 2022. Phase 3 successes with its acromegaly drug paltusotine have propelled Crinetics to an NDA filing “later this year” and “an expected market launch in 2025,” CEO Scott Struthers said in the San Diego biotech’s second-quarter report. CFO Mark Wilson cited personal reasons for his own upcoming departure, which was also included in Crinetics’ Q2 update. → Allosteric drug discovery shop HotSpot Therapeutics has introduced Alison O’Neill as CMO. O’Neill is the former medical chief at Surface Oncology , which was acquired by Coherus BioSciences last year for $65 million. She had a senior leadership role in the global oncology division at Sanofi and was VP of clinical development for Radius Health . → Ex- Icosavax CEO Adam Simpson has landed at Frazier Life Sciences as a venture partner on its company creation team and will work out of Frazier’s office in San Diego. Simpson sold the vaccine developer to AstraZeneca last December, and his previous company — celiac disease specialist PvP Biologics — was purchased by Takeda in 2020. → Ruben Tommasi has been named CSO of Entact Bio , a Watertown, MA-based biotech led by ex- Ribon Therapeutics CEO Victoria Richon that is developing enhancement-targeting chimeric molecules, or ENTACs. Tommasi has also held this role at Dunad Therapeutics and AstraZeneca spinout Entasis Therapeutics . Entact Bio has kept a relatively low profile since its $81 million Series A in 2022, but it did show up in Peer Review this spring when it recruited fellow Entasis vet Michael Gutch as COO. → Third Rock ’s Treg developer Abata Therapeutics has resurfaced in Peer Review for the first time in more than a year, naming Joanne Beck as chief technical officer. The Shire and Celgene alum is the ex-technical chief at Aerium Therapeutics , the Covid biotech led by Rajeev Venkayya that recently shut down because of a surge in new variants. In April 2023, Abata poached Sonoma Biotherapeutics CMO Leonard Dragone for the same role . → Led by ex- Teva R&D chief Michael Hayden , neuro biotech Prilenia has tapped Rob Lauzen as CFO and Jason Marks as chief legal officer. Lauzen was VP, investor relations and head of financial planning & analysis at Dyne Therapeutics , which made a CMO change and lost its COO and CBO earlier this month. Marks just had a short stint with Teva as a senior legal advisor to global transactions and global finance. The Bausch Health alum has also been chief legal and compliance officer at Amarin . → San Francisco eye disease biotech Ray Therapeutics has selected Christopher Whitmore as CFO. Whitmore had held the same position with Immune-Onc Therapeutics since July 2022, and he was VP, finance & administration for Harpoon Therapeutics from 2018-21. Ray Therapeutics, which hauled in a $100 million Series A last year, will test its gene therapy RTx-015 in patients with retinitis pigmentosa. → Tris Pharma has promoted VP of marketing Manesh Naidu to the role of chief commercial officer. Naidu joined the New Jersey-based company in 2023 after a stint as chief marketing officer of Althera Pharmaceutical . Naidu’s résumé also includes stints at McKinsey , Mallinckrodt , Novartis, Pfizer and Bellerophon Therapeutics . In May, Tris snagged the first liquid non-stimulant ADHD drug approval in the US. Onyda XR will be used to treat ADHD in children at least 6 years of age. → Backed by Jeff Bezos , Seattle-based Nautilus Biotechnology has named Kentaro Suzuki as chief marketing officer. Suzuki most recently served as VP and general manager of Agilent Technologies’ mass spectrometry division. Before that, he was with Takeda and Hewlett-Packard . → San Francisco-based 89bio has appointed Teresa Perney as chief regulatory and quality officer. Perney held this title at EQRx after five years with Myovant Sciences as SVP of regulatory and quality. Madrigal Pharmaceuticals finally broke through with an FDA approval for metabolic dysfunction-associated steatohepatitis (also referred to as NASH), and 89bio is enrolling patients for late-stage studies of pegozafermin — one for non-cirrhotic MASH and another for MASH with compensated cirrhosis. “I’m eager to leverage my experience to navigate the regulatory landscape and help bring this innovative therapy to patients worldwide,” Perney said in a statement . → There’s also a new regulatory chief at Disc Medicine : Steve Caffé spent five years with CRISPR Therapeutics as head of regulatory affairs until his departure last December. Earlier, he had numerous stops as a regulatory exec with such companies as Ra Pharmaceuticals , Sucampo Pharmaceuticals , AMAG Pharmaceuticals and MedImmune . Shares of Disc $IRON fell sharply in early April after mixed data with its drug for a rare blood disorder called erythropoietic protoporphyria, but have rebounded since. → Although AI-designed drugs haven’t exactly lived up to the hype, companies like BPGbio are trying to flip the narrative. This week, GSK alum John Beeler has joined the team as SVP of business development. Beeler comes to BPGbio from Bristol Myers Squibb , where he took on the role of business development search & evaluation lead. → Macrocycle startup Circle Pharma has brought in Marie Evangelista as SVP and head of cancer biology, and promoted Constantine Kreatsoulas to SVP and head of discovery technology sciences. Evangelista spent the last two years as VP of oncology at one of the most ambitious AI drug developers , Recursion . The longtime Genentech vet also had a brief tenure with Frontier Medicines as senior director of translation medicine. Kreatsoulas had a nine-year run at GSK and was the pharma giant’s interim head, computational toxicology before coming to Circle in 2021 as head of research and VP, research informatics and computational chemistry. Circle disclosed its $54 million Series D in an SEC filing this summer. → South San Francisco-based Ideaya Biosciences has recruited Douglas Snyder as general counsel. Snyder most recently served as chief legal officer and secretary of GW Pharmaceuticals . Earlier in his career, Snyder was general counsel and secretary at Actelion and Eisai . Back in July, Ideaya inked a $406.5 million deal with Biocytogen . → Deerfield Group has rolled out the welcome mat for two new execs: Guy Varady as EVP, integrated marketing and Bob Josefsberg as EVP, communications. Before this, Varady was SVP, management supervisor for DDB Health and held a number of roles at IPG Health and Omnicom Health Group . Meanwhile, Josefsberg was VP, corporate communications at Karuna Therapeutics and managing director at Chamberlain Healthcare Public Relations . → Tempest Therapeutics , which revealed early PFS and OS data for its liver cancer combo last October, has brought on Sheldon Mullins as VP, regulatory affairs. Mullins joins the team after gigs at Arrowhead Pharmaceuticals and Ardelyx . Earlier in his career, Mullins was with Anacor Pharmaceuticals , Onyx Pharmaceuticals and Genentech. In addition to Mullins’ appointment, Darrin Bomba and Henry Johnson have been promoted to the titles of VP, development operations and VP, CMC & medicinal chemistry, respectively. → Entrada Therapeutics CEO Dipal Doshi has picked up a seat on the board of directors at āshibio , a California biotech that will push its ex-Gilead drug andecaliximab into a Phase 2/3 study for patients with an ultra-rare bone disorder called fibrodysplasia ossificans progressiva (FOP). Āshibio came out of stealth mode this summer with a $40 million raise . → Akari Therapeutics , which is developing PAS-nomacopan for geographic atrophy, has elected former Epizyme CEO Rob Bazemore to the board of directors. Bazemore is also a board member at Ardelyx and Nuvation Bio .

SAN DIEGO and RESEARCH TRIANGLE PARK, N.C., Sept. 09, 2024 (GLOBE NEWSWIRE) -- Creyon Bio, Inc. ("Creyon"), a clinical-stage leader in AI/machine learning-enabled engineering of oligonucleotide-based medicines (OBMs), has appointed two prominent venture capitalists, Serge Messerlian, Operating Partner at DCVC Bio, and Shaquille Vayda, Principal at Lux Capital to serve on its Board of Directors. “We are excited to welcome Serge and Shaq officially to our Board of Directors, and their extensive experience in life sciences and technology aligns with Creyon’s mission to reimagine drug development through AI-enabled engineering of oligonucleotide-based medicines,” said Chris Hart, Ph.D., Co-Founder, Chief Executive Officer, and President of Creyon Bio. “Their insight and strategic guidance has been immensely valuable to date as observers and will be instrumental as Creyon advances best-in-class clinical assets created with its pioneering platform of oligonucleotide-based medicines.” Mr. Messerlian brings extensive leadership experience in the life science industry, across various therapeutic areas including hematology, oncology, immunology, and rare diseases. He is Operating Partner at DCVC Bio and currently serves on the boards of Auron Therapeutics and Plexium. He previously served as CEO of Teon Therapeutics, an immuno-oncology biotech, and President of Janssen Oncology, a Johnson & Johnson company. Mr. Messerlian has also held executive leadership positions at Johnson & Johnson's Actelion, Baxalta, and Baxter International. He holds a B.S. in Physiology & Biotechnology and an M.S. in Molecular Genetics from McGill University, as well as an MBA from the Rotman School of Management at the University of Toronto. “The potential applications of Creyon’s foundational technology are vast,” said Mr. Messerlian. “I look forward to working with the Creyon team as they transform the industry standard paradigm from drug discovery to drug engineering.” Mr. Vayda brings diverse experience spanning technology, aerospace, and life sciences, with a focus on discovery and delivery platforms; molecular, phenotypic and computational tools; synthetic biology; and data infrastructure. He is currently Principal at Lux Capital and serves on the boards of several companies including Anagenex, Atavistik, Enveda Biosciences, Gandeeva Therapeutics, LabGenius, Nomic Bio, and Rivet. Prior to joining Lux Capital, Mr. Vayda worked at Parthenon in San Francisco, where he advised private equity and growth equity firms on enterprise technology and healthcare investments. His experience in the life sciences industry includes a position at Illumina, seeing firsthand the impact DNA sequencing has had on ending human suffering. Mr. Vayda's career also spans the aerospace and defense sector with prior roles at NASA and Northrop Grumman. He holds a B.S. in mechanical engineering from the University of Florida. “Creyon is at the forefront of creating the future of medicine by developing the fundamental building blocks that will revolutionize how oligonucleotides are engineered for both safety and targeted delivery to the right cells and tissues,” said Mr. Vayda. “This aligns well with my passion for investing at the intersection of technology and natural sciences. I look forward to being part of Creyon’s growth journey.” About Creyon Bio, Inc.Creyon Bio is a clinical stage biotechnology company developing best-in-class precision medicines with industry-leading efficiency through molecular engineering of Oligonucleotide-Based Medicines (OBMs). These include antisense oligonucleotides, siRNAs, and aptamers. The company is changing how novel OBMs are created, transforming the process from drug discovery to drug engineering. Creyon has built the first and only platform capable of engineering for safety first, translating new target discoveries to OBMs with optimal pharmacological properties. Coupled with our aptamer-based delivery technologies, Creyon is unlocking the full potential of OBMs for common and rare diseases alike. Our platform has already demonstrated promising results in a n-of-1 clinical trial, rapidly progressing from concept to patient treatment in just 13 months. To learn more, visit creyonbio.com. Media Contact Jon YuCreyonPR@westwicke.com