Sebaceous hyperplasia

心房颤动（房颤）是最常见的持续性心律失常，严重时会导致血栓栓塞、脑卒中、心力衰竭等并发症，发生率通常随着年龄增长成倍增加。现阶段临床上房颤治疗的主流方式是导管消融，包括射频消融、冷冻消融和脉冲电场消融（PFA）。从临床治疗效果和实践操作来看，传统的射频消融和冷冻消融都存在一定不足，两者都存在温度依赖性。剂量过大时容易产生肺静脉狭窄、心房食管瘘、膈神经损伤等并发症；剂量过小时，会导致消融不彻底，容易复发。近年来兴起的PFA技术主要是通过破坏细胞膜，进而破坏细胞内环境稳态，最终导致细胞凋亡。通过PFA可以损伤肺静脉的前庭心房肌，使肺静脉中的电位无法传出，最终达到治疗房颤的目的。相比之下，PFA主要具有两个优势，一是具有组织选择性，不损伤周围血管、神经和食管，且采用非热能消融方式，减少高温或冷冻带来的其他组织损伤；二是放电时间短，可以大大提高手术的安全性，缩短手术时间。Pulse Biosciences（以下简称Pulse）是一家新型生物电医药公司。其唯一的商业产品是CellFX系统，该系统应用了公司专有的纳秒脉冲场消融(nsPFA)技术。动脉网获悉，2023年5月1日，Pulse（纳斯达克股票代码：PLSE）与该公司的执行主席Robert Duggan签署协议。根据协议，Duggan将以每股6.51美元的价格购买1002.2937万股普通股，该协议获得资金偿还了公司2022年9月向Duggan贷款的6500万美元。信息一经公布，公司股价呈上升趋势，最高于5月4日上涨到9.36美元。股票走势图 图源：Pulse官网基于纳秒级脉冲技术，从皮肤科转向心血管目前的大多数PFA系统都还处于微秒级，在使用过程中会刺激骨骼肌，引起患者疼痛和痉挛，需要进行全麻。而纳秒级PFA（nsPFA）作为新一代PFA技术，脉冲持续时间更短，很好地解决了现有PFA技术麻醉要求高、患者疼痛等问题。Pulse的专有技术是纳米脉冲刺激（NPS），可以向非热能透明细胞提供纳秒级电能脉冲，同时保护邻近的非细胞组织，脉冲持续时间从十亿分之一秒到百万分之一秒不等。NPS技术用于消融细胞组织时被称为纳秒脉冲场消融（nsPFA）技术。当作用于靶组织时，nsPFA能量脉冲进入细胞，改变线粒体和内质网等内部细胞器的功能，随后细胞内的级联破坏导致调节性细胞死亡（RCD），从而去除病变细胞组织。RCD是细胞维持组织形态和功能必不可少的稳态机制。基于nsPFA，公司推出了首款商业化产品CellFX系统。CellFX由控制台、手柄和尖端组成，重点关注皮肤病领域，如皮脂腺增生、脂溢性角化病、皮肤非生殖器疣、痤疮等。使用基于nsPFA的CellFX系统进行治疗，可以在治疗过程中保留皮肤的胶原蛋白，降低疤痕产生的风险并避免对治疗组织的创伤，这也是nsPFA相较于一般的PFA的优势。CellFX系统 图源：Pulse官网2021年，CellFX获得美国FDA许可，可用于需要消融和重塑皮肤的皮肤科手术。同年，该系统获得了欧洲、加拿大和澳大利亚的监管批准，顺利在皮肤科商业化，用于治疗良性皮肤病变。2022年，获得美国FDA批准扩大治疗头的能量设置范围，以便用于更广泛的病变组织治疗。目前，CellFX系统已安全有效地治疗6000多名心脏病学之外的患者。然而，2022年9月，Pulse宣布停止CellFX系统在皮肤科的所有商业销售和营销业务，将治疗重点从皮肤科转移到心血管领域，扩大其在心脏病学、肿瘤学、胃肠病学、妇科和其他领域的应用开发。贷款6500万美元支持战略重组，已拥有130多项专利Pulse总部位于美国加利福尼亚州海沃德市，于2014年成立，2016年上市，代表着欧道明大学和南加州大学研究人员对NPS的突破性研究成果。2021年，Pulse入选世界百强医疗科技企业。迄今为止，Pulse在全球拥有130多项专利。由于运营费用过于高昂，在治疗重点转移的同时，Pulse也对公司结构进行调整和重组。一是对领导层进行调整，二是对销售部门进行裁员，以专注提高商业诊所的利用率，并降低对系统销售的重视程度。公司与Duggan签订协议偿还的6500万美元贷款，就是用于支持这一战略的进行。前首席商务官Kevin Danahy将接替Darrin Uecker担任首席执行官。Kevin于2022年2月加入Pulse。此前，Kevin曾任职捷迈邦美（Zimmer Biomet）、美敦力（Medtronic）、强生（Johnson & Johnson）、直觉外科公司（Intuitive Surgical），积累了骨科器械研发、手术机器人研发、慢性病治疗等多领域的从业经验。Darrin Uecker转而担任公司的首席技术官，专注技术研发和产品开发。他在医疗器械领域拥有超25年的经验，拥有70多项美国专利。加入公司前，Uecker曾担任数字医疗公司Progyny的总裁兼首席运营官，该公司开发了Eeva，这是第一个由FDA批准的胚胎生存力测试系统。Uecker还曾担任女性医疗保健公司Gynesonics的研发部副总裁，领导开发了世界上第一个集成射频消融的子宫内超声系统，用于子宫肌瘤的无切口治疗。另外，担任北美销售副总裁的Joe Talarico将成为业务发展副总裁。董事会主席Robert Duggan将担任公司新设立的执行主席。2015年以来，Duggan一直担任风险投资和公共股权投资公司Duggan Investments的首席执行官。目前，Duggan是Pulse的最大的股东，拥有约69%的股份。从左往右：Kevin Danahy、Darrin Uecker、Robert Duggan从70万美元年收入到0营收，5400万美元还能撑多久？到目前为止，Pulse的收入和盈利能力完全取决于CellFX系统和纳米脉冲刺激专利技术。2021年，CellFX系统打开了皮肤科市场从而开始创收，但收入也并不可观，全年仅141.8万美元。2022年战略方向的改变更是对公司的财务表现产生了较大的影响。根据Pulse的财报显示，2023年第一季度未实现营收，2022年总收入为70万美元，同比2021年下降了50.63%，主要归结于皮肤科市场扩张的停止。从运营费用来看，研发费用比2021年减少780.1万美元，主要是公司高层管理人员变动，导致股票薪酬和员工工资减少。收入成本增加了近1000万，原因是为推进皮肤科以外领域治疗的研究，注销了850万美元的过量和过时库存。2021年-2023Q1 Pulse的财务表现数据来源：Pulse财报自成立以来，公司每年都会出现经营亏损，仅2021和2022两年净亏损就超过1.2亿美元。在接下来的几年里，由于战略方向的改变，公司会持续产生亏损。从现金储备来看，截至2023年3月31日，公司拥有5410万美元，比上一季度末减少704万美元。根据公司目前的运营状态，这一金额基本满足接下来三个季度的预计运营需求。但由于公司目前一直处于净亏损状态，且正在探索新的治疗领域，若要满足未来更多的增长需求，公司仍需通过公共或私人股本发行、债务融资、潜在的新合作来获得源源不断的资金支持。美敦力、强生纷纷押注，脉冲电场消融将迎来百亿市场房颤消融手术市场中以射频消融为主，冷冻消融为辅。相比之下，尚处于起步阶段的脉冲电场消融（PFA）优势明显，是电生理领域看好的下一代房颤消融技术，拥有极大的市场前景。国内外不少企业已经在此赛道上布局。2021年，波士顿科学的FARAPULSE系统先后获得了FDA突破性医疗器械认定和欧盟CE认证，成为全球首个获批上市的PFA产品。随后美敦力、强生的PFA产品进入中国国家药监局（NMPA）绿色通道。除此之外，加拿大Kardium、美国Galvanize Therapeutics、美国Galaxy Medical等企业也在此领域进行了积极探索。在中国，房颤患者人数已高达2000万。且随着老龄化社会的加速到来，未来房颤患者人数将进一步增加。患者基数逐步扩大，市场需求不断释放，电生理市场规模也在稳步增长。根据弗若斯特沙利文数据显示，中国心脏电生理器械2020年市场规模达51.5亿元，并预计2024年将达到211.1亿元。但国内的电生理手术渗透率仍低于1%，国产品牌市占率不足10%，有极大的国产替代空间。不少国内企业悄然发力，纷纷布局PFA赛道发展国产产品。如德诺电生理、玄宇医疗、锦江电子、洲瓴医疗、睿笛生物等。目前国内还没有PFA产品获批，国内企业若要实现弯道超车，改变电生理进口垄断的格局，还需要在核心技术层面继续努力。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

Zenas BioPharma is preparing to take its lead drug candidate into a global Phase 3 test and it now has $118 million to finance the clinical research. The Zenas drug, obexelimab, is being developed as a treatment for IgG4-RD, a chronic inflammatory disease that affects multiple organs. First-line treatment includes steroids, but these drugs can have toxic effects and relapse is common. Obexelimab is intended to tamp down the activity of B cells, a type of immune cell. The drug is a bispecific antibody. One part of the drug binds to CD19, a protein on the surface of B cells. The other part of obexelimab binds to another immune cell target called FcYRIIB. According to the company, binding to both targets simultaneously mimics a natural antigen-antibody complex that down regulates B cell activity. This approach has potential applications in many autoimmune disorders. Zenas acquired global rights to obexelimab from Xencor last year, issuing equity to that company as an upfront payment. According to the deal terms, Xencor could receive up to $480 million in milestone payments depending on Zenas’s progress with the drug. In addition to supporting obexelimab, Zenas said the new capital, a Series B financing, will also go toward advancing other programs into clinical development in 2023. Enavate Sciences led the latest investment in Waltham, Massachusetts-based Zenas. Other new investors in the company include Longitude Capital, Vivo Capital, Rock Springs Capital, Perceptive Advisors, Agent Capital, Pivotal bioVenture Partners and Superstring Capital. Earlier investors Fairmount, Wellington Management, Tellus BioVentures, Quan Venture Fund, and Xencor also participated in the financing Zenas’s $118 million financing was the biggest biotech financing of this week. Here’s a look at other companies that raised money: —Bringing computational techniques to the study of secreted proteins, Juvena Therapeutics is developing new drugs for chronic disorders and diseases of aging. Juvena’s lead program is in preclinical development for the muscle disorder myotonic dystrophy type 1 and the Redwood City, California-based startup has raised $41 million to support that drug and others in the pipeline. Mubadala Capital and Horizons Ventures led Juvena’s Series A financing. —Sensorium Therapeutics emerged with $30 million in funding to develop psychoactive molecules to address mental health disorders. Founded by scientists from Massachusetts General Hospital and Harvard Medical School, Sensorium’s research has produced a lead program, SENS-01, for anxiety and depression. The Boston-based biotech said it expects to begin preclinical research that could support an investigational new drug application in 2023, laying the groundwork to reach clinical testing by early 2024. Santé Ventures led Sensorium’s Series A financing. —New investors pumped money into Lipidio Pharmaceuticals, extending the biotech’s Series A round of financing to more than $20 million. San Diego-based Lipidio is developing drugs for metabolic and skin disorders. Lead drug candidate GDD3898 is in development for treating acne, sebaceous hyperplasia, obesity, and Prader-Willi syndrome. The company said it expects to complete three early-stage studies of the drug by the end of this year, laying the groundwork for data analysis and a Series B financing planned for the first quarter of 2023. —Blood transfusion technology company Hemanext raised $18 million. The Lexington, Massachusetts-based company has CE mark certification in Europe for a red blood cell processing and storage system and is working to expand its presence into additional European markets in 2023. Hemanext described the latest financing as the first close of its Series B round. The company says it has raised about $130 million total to date. —Neuroscience company NRG Therapeutics closed £16 million in financing to continue development of small molecule drugs that penetrate the brain to potentially slow or halt neurodegeneration. The drugs of the Stevenage, England-based company target mitochondria, the powerhouses of cells. The Series A round of financing was led by Omega Funds. NRG plans to use the capital to advance its molecules through the preclinical research needed to support an investigational new drug application. Picture: Feodora Chiosea, Getty Images

SAN DIEGO, Nov. 10, 2022 /PRNewswire/ -- Lipidio Pharmaceuticals Inc. (Lipidio), a biopharmaceutical company developing novel therapeutics for dermatological and metabolic diseases, announced today the close of an extension to its Series A financing, bringing the total amount raised to over $20M. In addition to current Series A investors, this extension was led with participation of several new investors, including Nancy Chang (former Founder and CEO of Tanox), John Maraganore (former Founding CEO of Alnylam) and Brent Saunders (former Chairman & CEO of Allergan), along with a selected group of world-renowned dermatologists. Previous investors in the Series A include other successful, serial entrepreneur biopharma executives, as well as two Institutional Investor firms, Alethea Capital and 3E Bioventures. "We are thrilled to raise this extension from several of the most accomplished and well-known executives in our industry. I want to sincerely thank Brent, John and Nancy, along with all our investors for their support, as we continue to advance GDD3898 in the clinic," said J. Gordon Foulkes, Ph.D., CEO of Lipidio. "Our investors are highly encouraged by our recent clinical data and new insights into the multiple mechanisms induced by GDD3898 in the skin, which provide a strong rationale for expansion of our current indications. The Series A extension funds will provide ample runway to analyze data from the three clinical trials anticipated to complete before the end of this year, and to support the launch of our Series B financing in the first quarter of 2023." John Maraganore, Ph.D., added, "I am excited about the innovative and differentiated approach that Lipidio is taking to tackle serious dermatological conditions. Gordon and his team have discovered a novel mechanism of action for GDD3898, and they are pursuing indications for which there are no approved therapies and no competing drugs in development. I believe GDD3898 holds tremendous potential as a novel topical product that could change the treatment paradigm for dermatologic and potentially other diseases." "I am proud to participate in this financing with such a stellar group of biopharma leaders," commented Brent Saunders. "GDD3898 has the potential to emerge as a first-in-class product for acne and sebaceous hyperplasia, filling a major gap in treatment and disrupting the market. I'm excited to work with the world-class team at Lipidio to bring this exciting product to patients." About the Series A Extension Syndicate Nancy Chang, Ph.D., is Chairperson of Ansun Biopharma, a company focused on the development of unique host-directed anti-viral therapies for respiratory viruses including Parainfluenza virus (PIV) and Influenza virus (Flu). She also serves as CEO and President of Apex Enterprises, Inc., an investment management company focused on investments in healthcare, education, and socially responsible ventures. From 2007 to 2012, she was Chairperson and Senior Managing Director of Orbimed Asia LLC. Prior to OrbiMed, Nancy was the Co-Founder, Chairperson and CEO of Tanox (1986-2006). In 2000, Tanox went public on NASDAQ, raising $250M and making it the second-largest Biotech IPO ever done at that time. Tanox research led to the FDA approval of Xolair and its acquisition by Genentech for over $900M in 2007. John Maraganore, Ph.D., was the founding CEO and a Director of Alnylam from 2002 to 2021, where he built and led the company from an early research platform forming over 20 major pharmaceutical alliances through to the global approval and commercialization of the first four RNAi therapeutic medicines. John created one of our Industry's most successful companies, with a current market capitalization of approximately $25B. He is also a member of the Board of Directors of the Biotechnology Innovation Organization (BIO) and served as the Chair of BIO from 2017-2019. John is currently a Venture Partner at ARCH Venture Partners and Atlas Ventures, an Executive Partner at RTW Investments, a Senior Advisor at Blackstone Life Sciences, and serves on the Board of the Termeer Foundation. Brent L. Saunders is Executive Chairman of the Beauty Health Company (Nasdaq: SKIN) and Chairman, Co-Founder and CEO of Vesper Health. Mr. Saunders served as Chairman and CEO of Allergan until May 2020, when the company was acquired by AbbVie Inc. in a transaction valued at approximately $63B. Brent's first role as a senior executive in the healthcare sector began in 2003 at Schering-Plough as President of their Global Consumer Health Care Division. While at Schering-Plough, Brent led the integration of the company's $14B acquisition of Organon Biosciences, as well as the merger between Schering-Plough and Merck & Co., Inc. in 2009. Brent also served as CEO of Bausch + Lomb Inc., until its acquisition by Valeant Pharmaceuticals, Inc. for approximately $9B. He then became the CEO of Forest Laboratories Inc., leading the company's merger with Actavis in 2014, and in 2015, Actavis' acquisition of Allergan, renaming the combined company Allergan PLC. About Lipidio Pharmaceuticals Lipidio Pharmaceuticals is a biopharmaceutical company focused on transforming molecules into the right medicines for dermatological and metabolic diseases. Lipidio's lead program, GDD3898, is in clinical development for the treatment of multiple conditions with unmet medical needs including dermatological conditions such as moderate to severe acne and sebaceous hyperplasia, nonalcoholic steatohepatitis (NASH), and obesity. Lipidio is headquartered in San Diego, CA. To learn more, please visit https://lipidiopharma.com/.