T cell replacement therapy (Kiadis Pharma)

近日，赛诺菲关闭其收购的NK细胞疗法公司Kiadis，收购而来的唯一一款临床管线SAR445419如今已经被终止开发。放弃Ⅲ期临床管线Kiadis成立于1997年，2015年在欧交所上市。Kiadis最初致力于T细胞疗法的开发，在2019年4月收购CytoSen Therapeutics公司后才转向了NK细胞疗法领域。在此之前，ATIR101是Kiadis主要的候选管线，已经推进到了临床III期阶段，公司曾计划寻求在欧洲的上市批准。ATIR101是一种HSCT的辅助疗法，从患者家属身上获取成熟的免疫细胞，从中去除可能攻击患者的淋巴细胞。这些细胞被注射到患者体内后，可以帮助患者抵抗感染和消灭残余肿瘤细胞，帮助患者度过HSCT之后的危险期。然而ATIR101在III期临床中表现不佳，未能显示出比标准护理（环磷酰胺-PTCy）方案）的优越性。2019年10月，Kiadis向投资人发出警告表示，EMA有极大可能拒绝批准ATIR101，一个月后，Kiadis正式宣布放弃对ATIR101的开发。而从CytoSen收购而来的NK细胞疗法管线则成为公司推进的核心候选人。转向NK细胞疗法CytoSe公司建立了两大NK技术平台，PM21（纳米颗粒技术）和FC21（细胞饲养技术）。PM21能够将刺激NK细胞增殖和激活的配体附着在纳米颗粒上，刺激NK细胞迅速扩增，产生大量高活性以及具有细胞毒性的NK细胞。FC21生产的K-NK细胞，和PM21技术生产的K-NK细胞之间具有相似性。2020年7月，赛诺菲以1750万欧元+8.75亿欧元里程碑付款，外加特许权使用费从Kiadis引进一个临床前的NK细胞疗法K-NK004，并在2020年11月，以每股5.45欧元、总价3.08亿欧元现金收购了该公司，受此影响，Kiadis股价大涨超249%。彼时被收购的Kiadis共有5款在研管线，其中K-NK002进展最快，已进入II期临床阶段，作为HSCT的辅助免疫疗法。然而，在赛诺菲于2023年2月3号公布的产品线中，处于临床阶段的细胞疗法只有SAR445419。如今这款唯一的在研管线被放弃开发，这意味Kiadis的旅程也彻底走到尽头。参考出处https://endpts.com/exclusive-sanofi-to-close-dutch-nk-cell-therapy-biotech-acquired-in-2020/http://www.pmlive.com/pharma_news/sanofi_set_to_acquire_kiadis_for_308m_1355944

Amsterdam, The Netherlands, April 17, 2019 - Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company, today announced that it has entered a definitive agreement to acquire US-based CytoSen Therapeutics, Inc. (“CytoSen”), subject to Kiadis’ shareholder approval and customary closing conditions. Privately held CytoSen has developed a proprietary natural killer (NK)-cell platform to enable NK-cell therapy with broad anti-cancer potential. It was founded on technology exclusively licensed from the University of Central Florida (UCF) and further developed at Nationwide Children’s Hospital (NCH). The company’s founders, including Dean Lee, Stefan Ciurea and Robert Igarashi, are leading physicians and scientists at NCH, MDACC and UCF, respectively. Following the transaction, Dr. Carl June, a pioneer in the development of CAR T-cell therapy and current scientific advisor to CytoSen, will join Kiadis’ Scientific Advisory Board. The transaction creates a leader in cell-based cancer immunotherapy. The combined company has a complementary development pipeline focused on improving outcomes for patients undergoing hematopoietic stem cell transplants (HSCT). Kiadis’ lead T-cell product ATIR101 is in EU registration and a global Phase 3 clinical trial; CytoSen’s lead NK-cell product candidate, CSDT002-NK, building on promising clinical proof-of-concept studies in 25 patients carried out at MD Anderson Cancer Center, is expected to enter the clinic in the US in 2020. The unique combination of proprietary and synergistic NK-cell and T-cell therapy platforms has the potential to revolutionize HSCT and enables Kiadis to create a pipeline with novel cancer treatments. Arthur Lahr, CEO of Kiadis commented: “Our vision is to leverage the strengths of the human immune system to help patients with life-threatening diseases. With the addition of CytoSen, we can create cell therapy treatments that combine the innate and adaptive arms of the immune system. The ATIR T-cell and CSDT002-NK-cell programs each have the potential to make transplants safer and more effective. In combination, they have the potential to revolutionize HSCT, making it suitable for an even wider group of patients. This transaction will transform Kiadis into a unique company with two synergistic proprietary cell-based immunotherapy platforms and the opportunity to create a pipeline of innovative treatments for cancer patients.” Carl H. June, MD, Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania, commented: “NK-cell therapy could significantly advance the field of immuno-oncology. Also, I believe the fields of NK-cells and T-cells are enormously synergistic and the combination could potentially help patients with devastating diseases. I am pleased to be joining the Scientific Advisory Board of Kiadis.” Dean A. Lee, MD, PhD, co-founder of CytoSen and director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s Hospital (NCH), commented: “CytoSen has the most advanced NK-cell technology to enable NK-cell therapy with broad anti-cancer potential. The strong experience, infrastructure, and competencies of Kiadis in cell therapy will accelerate our delivery of NK-cells to patients, and the new opportunities for exploring NK-cell and T-cell synergies will enable disruptive innovation in the cell therapy space. I am excited to collaborate with Kiadis to bring this innovation to patients.” NK-cells are one of the body’s first lines of immunological defense with an innate ability to rapidly and selectively destroy abnormal cells, such as cancer or virally-infected cells. Advancing research into the biology of NK-cells, as well as emerging early-stage clinical evidence, has increasingly shown that NK-cell immunotherapy has the potential to be at the forefront of cancer immunotherapy. CytoSen’s patented nanoparticle processing technology enables improved ex vivo expansion and activation of NK-cells supporting multiple high dose infusions with potent anti-cancer cytotoxicity. CytoSen’s lead program, CSTD002-NK in HSCT, is built on proof-of-concept studies in 25 patients carried out at MDACC. First results of these studies demonstrated a relapse rate of 8% and progression-free survival (PFS) of 66% (published in Blood, with follow up data presented at the American Society of Hematology (ASH) annual meeting in 2018). The upcoming clinical study with CSDT002-NK, expected to start in 2020, has been designed with and will be supported by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The study will enroll high-risk acute myeloid leukemia (AML) patients undergoing a haploidentical HSCT at a consortium of leading US transplant centers in the BMT CTN network. Additionally, CytoSen’s NK-cell therapy will be investigated for other cancer treatments based on an 8-patient proof-of-concept study conducted at MDACC in refractory AML. Transaction Details: At closing, CytoSen shareholders will receive upfront consideration of 1.94 million shares of Kiadis stock. The upfront consideration constitutes approximately 7.4% of Kiadis’ shares outstanding after the transaction. In addition, CytoSen shareholders are eligible to receive potential future consideration of up to 5.82 million additional shares of Kiadis stock upon the achievement of six clinical development and regulatory milestones, with the final milestone being first FDA approval of an NK-cell product based on CytoSen’s technology. The majority of the Kiadis shares issued to the CytoSen shareholders, including to its Executive Chairman and founders, will be subject to a lock-up for a period of two years from closing. At signing, CytoSen held approximately USD 6 million in net cash, which will remain in the combined company. Saola Healthcare Partners acted as financial advisor to Kiadis in the transaction. Shareholder Approval: The transaction is subject to the approval of Kiadis’ shareholders. The Company has called an extraordinary meeting of shareholders (EGM) to be held on Wednesday, May 29, 2019, at which the proposal supporting the transaction will be voted upon. Kiadis’ two largest shareholders (funds represented by and/or affiliated with Life Sciences Partners and Draper Esprit), together representing 31.5% of Kiadis stock, have executed voting agreements in favor of the transaction. In the event that the transaction does not complete because the General Meeting withholds its approval, CytoSen is entitled to a USD 1 million break fee to be paid in cash or Kiadis shares. Kiadis Business Update: Conference Call / Webcast Information: Kiadis’ management will host a webcast / conference call for analysts and investors today, April 17, 2019 at 3:00pm CEST / 2:00pm BST / 9:00am EDT. To participate in the conference call, please call one of the following numbers ten minutes prior to commencement of the call: Confirmation Code: 5737097 Participant dial-ins: Belgium: +32 (0)2 400 6926, Norway: +47 2350 0296, Finland: +358 (0)9 7479 0404, Sweden: +46 (0)8 5065 3942, France: +33 (0)1 76 77 22 57, Switzerland: +41 (0)22 567 5750, Germany: +49 (0)69 2222 2018, United Kingdom: +44 (0)330 336 9411, Netherlands: +31 (0)20 703 8261, United States: +1 323-794-2093. Webcast: https://webcasts.eqs.com/osc20190417 A question and answer session will follow the presentation. The presentation may be accessed by visiting http://www.kiadis.com/financial-news. About CytoSen Therapeutics, Inc.: CytoSen is a private biopharmaceutical company on the front line of advancing development of next generation NK-cells with the first scalable, therapeutic platform for high dose, cancer-killing NK-cells calibrated to each cancer target while reinforcing immune defenses. Born from the intersection of cellular immunotherapy and nanotechnology, CytoSen’s NK-cell therapy harnesses the power of the immune system to treat cancer. About the BMT CTN: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducts multi-institutional clinical trials of high scientific merit, focused on improving survival for patients undergoing hematopoietic cell transplantation (HCT) and/or receiving cellular therapies. The BMT CTN is funded by the National Heart, Lung, and Blood Institute and National Cancer Institute at the National Institutes of Health (NIH) and is a collaborative effort of 20 Core Transplant Centers/Consortia, The Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Donor Program (NMDP)/Be The Match and Emmes, a clinical research organization. CIBMTR is a research collaboration between the NMDP/Be The Match and the Medical College of Wisconsin. More information about the BMT CTN can be found at www.bmtctn.net. About Kiadis Pharma: Kiadis is developing its lead product candidate, ATIR101, for use in conjunction with haploidentical HSCT for adult blood cancers to address key limitations of haploidentical HSCT, without prophylactic immunosuppression and its associated morbidity and mortality. Based on the positive results from the single dose Phase II CR-AIR-007 study, the Company submitted a marketing authorization application to the European Medicines Agency in April 2017 for approval of ATIR101 as an adjunctive treatment in haploidentical HSCT for high risk adult hematological malignancies. If the product is conditionally approved, Kiadis intends to launch ATIR101 in Europe through its own commercial organization by year end 2019. In December 2017, Kiadis commenced an international, multicenter, randomized and controlled Phase III clinical trial of ATIR101 against the Post-Transplant Cyclophosphamide, or PTCy protocol, the main protocol used to perform a haploidentical HSCT. The trial will be performed in 250 patients with acute leukemia and myelodysplastic syndrome at approximately 50 sites in the United States, Canada, Europe and certain additional countries. ATIR101 received regenerative medicine advanced therapy designation from the FDA in September 2017, which provides benefits that are materially equivalent to a breakthrough designation from the FDA. In addition, ATIR101 has been granted multiple orphan Drug designations both in the European Union and the United States. The Company’s shares are listed on Euronext Amsterdam and Brussels under the ticker KDS.