Kythera Biopharmaceuticals LLC

SOUTH SAN FRANCISCO, Calif., July 16, 2024 (GLOBE NEWSWIRE) -- Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, today announced changes to its leadership team. Nadir Mahmood, Ph.D., will join Nkarta as President this month, sharing executive leadership responsibilities with Paul J. Hastings, who continues in his role as Chief Executive Officer. Additionally, Nkarta has broadened the role of David R. Shook, M.D., to Chief Medical Officer, Head of Research & Development. Drs. Mahmood and Shook will both report to Mr. Hastings. "This new leadership structure enables Nkarta to meet this transformative moment for cell therapy as we embark on groundbreaking clinical trials and expand our footprint in multiple autoimmune disease settings. These executive changes are expected to significantly enhance our ability to accelerate the development and ultimate commercialization of pioneering NK cell therapies for patients that need them," said Paul J. Hastings, CEO of Nkarta. "I am thrilled to have Nadir, a trusted thought partner of many years, join Nkarta. His expertise will be invaluable as we continue to drive innovation and growth." Nadir Mahmood, Ph.D., was previously the Chief Executive Officer of Rezo Therapeutics, a private-stage drug-discovery company. Prior to joining Rezo, he served as Chief Financial and Business Officer at Nkarta, where he played a direct role in corporate strategy, including the company’s private and public financings as well as the formation of its in-house manufacturing capabilities. In this newly created role of President, Dr. Mahmood will be responsible for driving the strategic focus, operational excellence and overall business and technical success at Nkarta. He will lead cross-functional activities to guide company-wide strategic alignment and value creation across pipeline programs, technical and business operations and lifecycle planning. "We’re at the starting point of a potentially disruptive opportunity for CAR NK cell therapy in autoimmune disease,” said Dr. Mahmood, incoming President of Nkarta. “With Nkarta’s differentiated technology, pioneering clinical programs and strong balance sheet, I believe the company is well positioned for success in this emerging therapeutic area. I’m incredibly excited to work with the exceptional team at Nkarta and help advance innovative and accessible therapies that can make a meaningful impact on the lives of patients.” Earlier in his career, Dr. Mahmood led corporate development at Second Genome, where he was responsible for establishing the company’s strategy and partnerships. Previously, he was a staff scientist at Kythera Biopharmaceuticals, where he oversaw preclinical research for the company’s lead molecule, Kybella®. Dr. Mahmood has also worked in equity research at Goldman Sachs and consulted for early-stage companies in the life sciences and clean energy sectors. He earned a B.S. in biochemistry from the University of Texas at Austin and a Ph.D. in cell regulation from the University of Texas Southwestern Medical Center, and completed postdoctoral research at the Scripps Research Institute in La Jolla, CA. In addition to Dr. Mahmood’s appointment, David R. Shook, M.D., has been promoted to Chief Medical Officer, Head of Research and Development to reflect his newly-designated oversight of the R&D organization – in addition to his prior responsibilities leading the clinical development, regulatory and translational science functions. James Trager, Ph.D., Nkarta’s former Chief Scientific Officer, recently transitioned to a special advisory role for the company due to personal family and health reasons. “James’ work has greatly contributed to the advancement of our science and mission. We are extremely grateful for his many contributions during his tenure, and we are fortunate to have the opportunity to continue to call him an advisor and friend," said Mr. Hastings. “David, an experienced physician-scientist in the field of cell therapy, has contributed significant expertise and leadership in the field of NK cell biology, and with James’ transition, we will look to him to advance Nkarta’s innovative research while continuing to drive our overall development initiatives.” Nkarta recently initiated Ntrust-1, a multi-center clinical trial of NKX019 in lupus nephritis. Additionally, the company recently announced the U.S. Food and Drug Administration (FDA) has cleared Nkarta's second Investigational New Drug (IND) application for NKX019 in autoimmune disease, paving the way for Ntrust-2, a multi-center clinical trial evaluating NKX019 for the treatment of systemic sclerosis (SSc, scleroderma), idiopathic inflammatory myopathy (IIM, myositis) and ANCA-associated vasculitis (AAV). The company expects to announce preliminary data from the Ntrust-1 and Ntrust-2 clinical trials data in 2025. About NKX019NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed chimeric antigen receptor (CAR) for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies. About NkartaNkarta is a clinical-stage biotechnology company advancing the development of allogeneic, off-the-shelf, on-demand natural killer (NK) cell therapies. By combining its cell expansion and cryopreservation platform with proprietary cell engineering technologies and CRISPR-based genome engineering capabilities, Nkarta is building a pipeline of future cell therapies engineered for deep therapeutic activity and intended for broad access in the outpatient treatment setting. For more information, please visit the company’s website at www.nkartatx.com. Cautionary Note on Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “potential,” "projects,” “would” and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include, but are not limited to, statements concerning Nkarta’s expectations regarding any or all of the following: Nkarta’s plans, strategies and timelines (including initiation of further clinical trials) for the continued and future clinical development and commercial potential of NKX019 for the treatment of autoimmune disease, including lupus, systemic sclerosis, myositis and vasculitis; the therapeutic potential, accessibility, tolerability, advantages, and safety profile of NK cell therapies, including NKX019, for the treatment of autoimmune disease, including lupus, systemic sclerosis, myositis and vasculitis; the potential impact of Nkarta’s new executive appointments and leadership structure; Nkarta’s ability to advance and accelerate the development and future commercialization of NKX019 as a treatment for autoimmune disease; and Nkarta’s plans and timelines for the future availability and disclosure of clinical data from Ntrust-1 and Ntrust-2 or other updates regarding the clinical trials. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Nkarta’s limited operating history and historical losses; Nkarta’s lack of any products approved for sale and its ability to achieve profitability; the risk that the results of preclinical studies and early-stage clinical trials may not be predictive of future results; Nkarta’s ability to raise additional funding to complete the development and any commercialization of its product candidates; Nkarta’s dependence on the clinical success of NKX019; that Nkarta may be delayed in initiating, enrolling or completing its clinical trials; competition from third parties that are developing products for similar uses; Nkarta’s ability to obtain, maintain and protect its intellectual property; Nkarta’s dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; and the complexity of the manufacturing process for CAR NK cell therapies. These and other risks and uncertainties are described more fully in Nkarta’s filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of Nkarta’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, filed with the SEC on May 9, 2024, and Nkarta’s other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Nkarta undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Nkarta Media/Investor Contact:Greg MannNkarta, Inc.gmann@nkartatx.com

衰老，是人类不可避免的过程。随着时间的推移，人们的实际年龄逐渐增长，形态也随之发生变化——头发变白、皱纹出现、牙齿松动脱落……伴随着这一变化的，还有生理功能和主要感官功能的减弱衰退，导致患上癌症、心脑血管、代谢等多种疾病的易感性增加，最终趋向死亡。“生老病死、万物皆有终结”是一条已被无数生物学家和科学家证明且无法避免的铁律。尽管如此，如何延缓衰老仍然是人们探讨的一个永恒话题。随着人类寿命延长和人口老龄化现象加剧，抗衰老已然成为产业和资本关注的一个重点领域。此前，已有众多科研、产业界的精英人士深入探索“长生不老”的秘密，他们发现，虽然衰老不可避免，但它却是一个可延缓的过程。随着研究的深入，目前研究人员总结出衰老的12大特征，包括细胞衰老、端粒损耗、干细胞耗竭等1，这也成为人们探索衰老过程、研发抗衰老疗法的切入点。而已有越来越多的研究显示，清除体内衰老细胞可减缓衰老对机体的影响并延长健康寿命2。根据这一理论，科学家们开发出了Senolytic疗法，即通过摧毁衰老细胞（Senescent cells），有可能实现改善健康状况、延长健康寿命的目的。Senolytic疗法自提出时就一直吸引着众多专注于衰老的初创公司，Unity Biotechnology（以下简称“Unity”）便是其中一员。Unity是一家专注于开发senolytic疗法的抗衰老明星企业。自2009年成立以来，它便致力于开发出可选择性消除或调节衰老细胞的药物，从而预防和治疗与衰老相关的疾病，以实现延长健康寿命的目标。截至目前，Unity在临床上布局了多条在研管线，适应症包括糖尿病性黄斑水肿（DME）、认知障碍等与年龄相关的眼科和神经系统疾病。其中，公司针对DME的主要在研药物UBX1325进展最快，目前正处于2b期临床研究阶段。    4位医学专家联合创立，获26家投资机构支持自2009年成立发展至今，Unity一路走来备受关注。公司曾在9年时间里完成了6轮融资并于2018年成功IPO，目前共筹集了2.949亿美元资金。在一众投资者中，世界前首富、亚马逊创始人杰夫·贝佐斯（Jeff Bezos）俨然在列，与此同时，药明康德、梅奥诊所风险投资、通和毓承等共26家知名投资机构和企业也重金支持Unity发展Senolytic疗法。Unity融资过程  数据来源：公开信息整理，动脉网制图除此之外，在2016年，Unity与亚盛医药（6855.HK）达成战略授权许可合作。根据协议条款，亚盛医药授权Unity在年龄相关疾病领域开发UBX1325的权益，并且拥有该化合物的大中华地区权益，未来计划和Unity成立合资公司，共同在中国市场开发及商业化该化合物。在明星资本和知名公司的支持下，Unity发展一路高光，其市值曾一度达到9.72亿美元。其背后，是4位具备多年经验和专业知识的创始人引领公司前进。而明星团队的组建离不开Unity的联合创始人Nathaniel David博士。Nathaniel David是一位具有多年行业经验的科学家兼企业家，进入生物医疗领域创业前，他曾获得哈佛大学生物学学士学位和加州大学伯克利分校分子与细胞生物学博士学位。在攻读博士学位的最后一年，Nathaniel David与他人创立了自己的第一家生物制药公司Syrrx。2005年，Syrrx被武田以2.7亿美元收购。值得注意的是，2013年FDA批准的一款糖尿病药物Nesina正是在Syrrx的研发下诞生。在Syrrx工作期间，Nathaniel David也被《麻省理工学院技术评论》评为全球35岁以下最佳创新者之一。在此之后，Nathaniel David先后创立了Achaogen（NASDAQ：AKAO）、Kythera Biopharmaceuticals（被Allergan以21亿美元收购）、Sapphire Energy三家生物制药公司。这几家公司不仅给Nathaniel David带来了丰富的行业经验，也将多位合作伙伴带到他的身边，其中就包括曾先后担任Kythera和Unity首席执行官一职的Keith Leonard。在此之前，Keith Leonard在安进工作了13年，曾担任安进欧洲公司的高级副总裁兼总经理，负责28个国家和地区的商业运营工作。而Nathaniel David创立一家公司研发专有Senolytic疗法的想法来源于Jan van Deursen博士的实验室研究。Jan van Deursen是一名分子生物学家，他曾是梅奥诊所（Mayo Clinic）衰老学教授，在小鼠转基因和基因敲除方面拥有20年研究经验。2011年，Jan van Deursen在Nature发表的一篇论文表明，人们可以简单地去除衰老细胞，在论文中介绍了一种转基因策略，即通过靶向衰老特征的蛋白质，选择性清除小鼠中稳定复制停滞的细胞：肿瘤抑制因子p16lnk4a，可改善其健康状况33。在论文发表几周后，Nathaniel David找到了Jan van Deursen并与他达成合作，以研发用于清除人类衰老细胞的药物化合物。而Jan van Deursen也于2014年正式成为Unity的科学联合创始人。除此之外，Nathaniel David还吸引了两位衰老、癌症研究领域的专家进入到公司创始人团队，分别是巴克衰老研究所教授Judith Campisi博士、梅斯癌症中心药物开发副主任Daohong Zhou博士。自此，Unity的核心团队基本组建完成，并于2016年走出隐匿模式。Unity走进大众视野后，又陆续发表了多篇研究论文以证明清除衰老细胞可改善健康状况甚至延缓寿命。其研究吸引了更多行业专家的加入，其中包括Biogen前高级副总裁兼研发主管、哈佛医学院博士后Anirvan Ghosh，曾在辉瑞和ISTA公司担任过临床开发和运营等职务的Sharon Klier博士以及加拿大视网膜细胞生物学研究主席Mike (Przemyslaw) Sapieha博士等，他们的加入为Unity的senolytic疗法提供了更多研发动力。53%的受试者48周内无需额外给药，Unity核心管线临床效果显著依托研发团队优势，Unity在眼科和神经病学领域布局了4条在研管线，以开发针对衰老相关疾病的Senolytic疗法。 Unity的在研管线 图源：Unity官网其中，UBX1325是Unity目前重点推进的核心在研产品。UBX1325是一款BCL-xL小分子抑制剂，被开发用于治疗与年龄相关的眼部疾病，包括DME和湿性老年性黄斑变性（AMD）等。其中，Bcl-xL是Bcl-2细胞凋亡调节蛋白家族的成员，其在视网膜病理血管中高表达。DME是糖尿病在眼部的主要并发症，也是成人糖尿病患者失明的主要原因。Unity研究团队发现，视网膜中衰老细胞的不断增加和堆积是引发DME的主要原因。其研究结果显示，持续的高血糖会引起血管内皮细胞亚群的细胞衰老，进而使血－视网膜屏障功能丧失以及微炎症，最终导致毛细血管渗漏，从而引发DME。因此，研究人员认为，通过去除血管中的衰老细胞可以改善DME患者视觉功能，并且可能帮助眼睛愈合。在此基础上，Unity推出了UBX1325，旨在抑制衰老细胞赖以生存的蛋白质的功能，选择性消除患者血管中积累的衰老细胞，同时使功能性、健康的血管重组再生，重建眼睛的屏障功能，最终达到治疗目的。UBX1325的2期BEHOLD研究结果显示，65名DME患者在单次10微克UBX1325注射后48周后，其最佳矫正视力（BCVA）较基线增加了+6.2 ETDRS字母，表现出统计学上显著且具有临床意义的改善。此外，53%的受试者在48周内无需其他任何抗血管内皮细胞生长因子（vascular endothelial growth factor，VEGF）药物辅助治疗。在整个研究期间，UBX1325治疗患者的视网膜结构均保持稳定，并且无眼内炎症、视网膜动脉阻塞、眼内炎或血管炎病例，UBX1325显示出良好的安全性和耐受性。基于此次研究的积极数据，Unity目前正在一项2b期临床试验（ASPIRE）中进一步测试UBX1325。ASPIRE是一项多中心、随机、双盲、主动对照研究，旨在评估UBX1325与再生元的抗VEGF药物Eylea（阿柏西普）在既往接受过治疗的DME患者中的安全性和有效性，研究结果将于2024年第四季度公布。遭遇两次临床试验失败后，持续探索全新senolytic疗法Unity的发展并非一路坦途，其中也曾遭遇波折。在Unity成立之初，Jan van Deursen和Nathaniel David共同在巴克衰老研究所的Campisi实验室找到了一个有望清除衰老细胞的潜在化合物nutlin-3a，并根据该化合物开发出了一款MDM2（小鼠双微体2）小分子抑制剂UBX0101，旨在治疗膝骨关节炎。Unity宣布推出UBX0101后，其身价也曾一度因UBX0101上涨。但UBX0101也是一把“双刃剑”。2020年8月17日，Unity宣布，UBX0101在一项183名中度至重度疼痛性膝关节骨关节炎患者参与的2期临床中未能击败安慰剂组。消息一出，Unity股价应声暴跌48%，截至2022年5月公司的市值缩水为5858万美元。除此之外，UBX1325的一项2期ENVISION研究也曾失败。2023年3月27日，Unity公布了该研究的A部分结果。数据显示，对照组患者每8周接受一次阿柏西普治疗，患者在第2周意外地增加了3.5个ETDRS字母，并在研究期间基本保持不变。对照组的强劲效果使得该研究在24周内未达到非劣效性阈值。受这一消息影响，Unity当日股价大跌46.25%。但是，这两次临床试验失败并未阻挡Unity继续探索senolytic疗法的步伐。Unity仍在坚持研发senolytic疗法，持续推进其在研管线UBX1325的研究。除此之外，公司还在同步推进研发一款用于消除中枢神经系统中的衰老细胞的senolytic药物UBX2089。目前，研究人员正在临床前动物模型中探索UBX2089的治疗活性，不日或将推进临床研究阶段。而如今，在众多如Unity一样的企业以及研究人员的努力探索下，目前已有达沙替尼和槲皮素、非瑟酮（漆黄素）等Senolytics疗法药物被证明可以有效减少衰老细胞的数量并改善衰老指标。不过，正当众多企业和科学家迫切想要研发出一款Senolytics药物时，部分科学家却对senolytics疗法的安全性表示存疑。如何确保Senolytics仅杀死有害的衰老细胞而又不伤害其他健康细胞，以及确认最佳安全剂量成为当下亟须解决的问题。梅奥医学中心的James L. Kirkland教授也在论文中表明，尽管Senolytics在临床前模型中显示有益的结果，有望延缓多重病症并增加健康期，此外随机对照试验也将确定Senolytics策略的安全性和潜在效益，但如果Senolytics要用于临床，则须解决科学和监管方面的挑战4。尽管如此，仍有众多企业入局这一领域以期研发新款senolytics药物，例如Oisin Biotechnologies、Decidious Therapeutics以及StarkAge Therapeutics等，他们正在开展的相关细胞衰老研究，正在加深人们对senolytics的理解。未来，在科研界和产业界的人员推进下，Senolytics疗法或将迎来更好的发展。* 参考资料：1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. PMID: 36599349.2. Gasek, N.S., Kuchel, G.A., Kirkland, J.L. et al. Strategies for targeting senescent cells in human disease. Nat Aging 1, 870–879 (2021).3. Baker, D., Wijshake, T., Tchkonia, T. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).4. Chaib, S., Tchkonia, T. & Kirkland, J.L. Cellular senescence and senolytics: the path to the clinic. Nat Med 28, 1556–1568 (2022).动脉网第八届未来医疗100强大会现已升级为，将于2024年5月7日-10日在北京·北人亦创国际会展中心盛大举行。本届展会为15000+人次、10000平规模，围绕新产品、新技术、新服务、新生态、新合作构建体系，为医疗健康产业的创新力展示搭建最佳舞台。这里是，公认的医疗产业创新洞察的生成地，年度趋势分享与学习交流的口碑盛会；优秀的医疗创新企业和创新产品都在这，是企业展示创新和面谈合作的最佳场景；这里有，最具前瞻力的思享盛会：500+大咖嘉宾莅临分享，3天主论坛、40余场主题论坛，只做干货议题！最具创新力的生态链接：5大展区，200+首发首创新品、3000+企业、500+投资团，全球买手云集！最具影响力的榜单发布：上市公司创新力榜+未来医疗100强榜+创新力产品榜，700+上榜企业现场交流！目前已有超过600家企业和产品确认参加展会，展览面积预订超过70%，全球买手团已合作了印度尼西亚、新加坡、比利时、爱尔兰、西班牙、德国、澳大利亚、英国、加拿大等国家。余下的合作席位已不多，欢迎企业、品牌方、买手团或相关组织洽谈参会。在这个充满不确定性的时代，寻求高价值资源和高效率链接，将是您的首选。即刻报名，限时福利！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

SAN FRANCISCO--(BUSINESS WIRE)-- Rezo Therapeutics, a biotechnology company pioneering the integrated mapping of disease networks for precision therapeutics, today announced the appointment of Nadir Mahmood, Ph.D., as chief executive officer and board member. Dr. Mahmood previously served as chief financial and business officer of Nkarta and brings significant leadership experience in corporate development, research and finance in the biopharmaceutical industry. Dr. Mahmood succeeds Rezo co-founder Nevan Krogan, Ph.D., who has served as interim chief executive officer and president since the company’s formation and will continue in the role of president. “Nadir is a seasoned biotech leader and we are thrilled to welcome him to lead Rezo as our chief executive officer,” said Dr. Krogan. “This appointment underscores the strong progress we have made at Rezo in advancing our leading protein-protein interaction platform to create comprehensive, unprecedented maps of molecular disease networks to inform the development of a new wave of precision therapeutics.” “Rezo’s platform integrates cutting-edge approaches in proteomics, genetics, structural biology, chemistry and machine learning to enable advanced insights into disease biology and how to modulate it for therapeutic discovery,” said Dr. Mahmood. “This is an incredible opportunity to lead a company that has the potential to fundamentally shift the way we understand disease biology by unlocking the universe of protein-protein interactions. This will allow us to approach drug discovery in a completely new way to develop new precision therapeutics for patients.” Prior to Nkarta, Dr. Mahmood led corporate development at Second Genome, where he was responsible for establishing strategy and partnerships across the company’s portfolio of programs. Earlier in his career, he was a staff scientist at Kythera Biopharmaceuticals (acquired by Allergan), where he oversaw preclinical research for the company’s lead molecule, Kybella®. Dr. Mahmood has also worked in equity research at Goldman Sachs and consulted for early-stage companies in the life sciences and clean energy sectors. He earned a B.S. in biochemistry from the University of Texas at Austin and a Ph.D. in cell regulation from the University of Texas Southwestern Medical Center, and completed postdoctoral research at the Scripps Research Institute in La Jolla, CA. About Rezo Therapeutics Rezo is pursuing an integrated approach to drug discovery that leverages the multiple technologies and tools needed to bring disease networks into focus, pinpointing novel targets and therapies with more clarity. Rezo’s Sequence to Systems to Drugs platform integrates proteomics, genetics, structural biology, chemistry, artificial intelligence and machine learning to create maps of molecular disease networks. Based on the work of the founding team at the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), the company’s mission is to break the mold in traditional drug development, which is slow and often siloed. The company’s initial focus is in oncology, with plans to explore additional therapeutic areas through collaborations and partnerships. To learn more, visit the company’s website at or its LinkedIn.