Recurrent B Acute Lymphoblastic Leukemia

– Relapse-free/progression-free survival for NKTR-255 plus CD19-22 CAR-T cell therapy at 12 months was double that of historical controls (67% vs 38%) – – Eight of nine patients achieved complete remission, all without detectable MRD – SAN FRANCISCO, Oct. 17, 2024 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the publication of the first clinical data from a Phase 1 study evaluating NKTR-255 in combination with an autologous bispecific chimeric antigen receptor (CAR)-T cell therapy targeting CD19 and CD22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, the peer-reviewed medical journal of the American Society of Hematology. NKTR-255 is a novel IL-15 receptor agonist currently being studied in clinical trials in combination with cellular therapies and immune checkpoint inhibitors. NKTR-255 has shown in previous clinical studies that it can proliferate a range of immune cells and augment lymphocyte trafficking.1,2 The data published in Blood showed favorable efficacy with eight out of nine patients (89%) whom successfully received CAR19-22 followed by NKTR-255 achieving measurable residual disease (MRD) negative remission. The study further demonstrated that, at 12 months, relapse-free/progression-free survival for NKTR-255 in combination with the CD19-22 CAR-T cell therapy was double that of historical controls (67% vs 38%). "We are encouraged by these first clinical data that clearly demonstrate the ability of NKTR-255 to potentiate CAR-T cell therapy," said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar. "Data showed NKTR-255 in combination with CD19-22 CAR-T cell therapy resulted in a 67% 12-month relapse-free survival rate in relapsed or refractory B-ALL and investigators observed significant increases in proinflammatory cytokines and chemokines which suggest lymphocyte trafficking to tissues." The Phase 1 single-center, single-arm dose-escalation study was conducted by Stanford Medicine and evaluated NKTR-255 in combination with CD19-22 CAR-T cell therapy in patients with relapsed or refractory B-ALL (NCT03233854). "While CAR-T cell therapies have transformed the treatment landscape for B-cell malignancies, there remains a significant unmet need to drive durable treatment outcomes as relapse occurs in the majority of patients," said David Miklos, MD, Chief of BMT and Cell Therapy Program at Stanford Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy. The primary outcomes of this study were feasibility and safety. Secondary endpoints were assessed for patients who received NKTR-255 (n=9) and included pharmacokinetics of NKTR-255 as measured by IL-15 levels in blood and efficacy as measured by remission free survival (RFS). Exploratory endpoints included cytokine profiling, CAR19-22 expansion in blood, bone marrow, and cerebrospinal fluid (CSF), and long-term CAR-T persistence. Key findings are summarized below: No dose-limiting toxicities related to NKTR-255 were observed. The most common adverse events in patients receiving NKTR-255 in combination with the CD19-22 CAR-T cell therapy were fevers, chills, and myelosuppression, which were either self-limiting or manageable with supportive care. The toxicities observed with the combination treatment were similar to those seen after CD19-22 CAR-T cell therapy alone. Cytokine and chemokine profiling showed significant increases in IL-15 levels. Increase in CXCL9 and CXCL10 were associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood, and ten-fold increases CAR-T cells in CSF, suggesting lymphocyte trafficking to tissue. Favorable efficacy was observed in patients with relapsed or refractory B-ALL treated with NKTR-255 in combination with CD19-22 CAR-T. Eight out of nine patients achieved complete remission with or without hematologic recovery, all without detectable MRD. Compared to Stanford's control group previously treated with the CD19-22 CAR-T cell therapy, NKTR-255 when added to the cell therapy increased the 12-month relapse free survival from 38% to 67%. The median RFS for the CAR T cell only cohort was 3.9 months. For the cohort treated with NKTR-255 and the CD 19-22 CAR-T cell therapy, the median RFS has not been reached with over 14 months of follow up. Only three patients who received combination therapy (33%) relapsed, suggesting administration of NKTR-255 to the CD19-22 CAR-T cell therapy helps prevent early disease recurrence. The full citation of this article can be accessed here (Volume 144, Issue 16, Pages 1649-1753). About NKTR-255 NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response. In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta Pharma, Inc., which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma.(NCT05327530) About Nektar Therapeutics Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Our pipeline also includes a preclinical candidate NKTR-0165, which is a bivalent tumor necrosis factor receptor type II agonist antibody. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco, California. For further information, visit and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "expect," "develop," "potential," "advance," "anticipate," "can," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, NKTR-255. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-255 is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) NKTR-255 is in clinical development, and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2024. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Contact: For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: David Rosen of Argot Partners (212) 600-1902 [email protected] Hirayama A. et al. Pharmacodynamic Analysis of CAR-T Cell Persistence in Patients with Hematologic Malignancies Treated with NKTR-255, an IL-15 Receptor Agonist That Enhances CD8 + T-Cells: Preliminary Results from a Phase 1 Study. Poster presented at: 63rd ASH Annual Meeting; Dec 11-13, 2021; Atlanta, GA Altan M. et al. NKTR-255+cetuximab in patients with solid tumors: interim safety and efficacy results from the phase 1b dose-escalation study. Poster presented at: SITC 2021; Nov 10-14, 2021; Washington, D.C. SOURCE Nektar Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

1981年，英国剑桥大学科学家Martin Evans和同事们成功从小鼠胚胎中分离出胚胎干细胞，奠定了细胞与基因治疗的基础。此后，细胞与基因治疗（CGT）技术迅速发展。 2017年，诺华Kymriah登陆美国，成为FDA批准的第一个CAR-T细胞疗法；同年，FDA批准全球首款基因治疗产品Luxturna；2023年，基于CRISPR/Cas9基因编辑疗法Casgevy的获批，开启了基因编辑的新时代。 CGT的技术迭代和在临床上取得的成功，将越来越多的产品推向市场。IQVIA报告显示，截至2023年底，总计76款细胞和基因疗法获得全球监管机构的批准上市，与2013年的总数相比翻了一倍多。 尤其在中国，CGT已成为生物制药的一块创新热土，并催生了许多现象级产品。这一定程度刺激资本市场的活跃：截至今年上半年，国内超过40家CGT公司披露新一轮融资。 1 “全球首款”上市疗法 1 CAR-T疗法 • 首款治疗ALL和MCL的CAR-T疗法——吉利德 2020年7月，吉利德靶向CD19的自体CAR-T疗法Tecartus获FDA加速批准，用于治疗先前接受过2种或多种系统疗法（包括一种BTK抑制剂）的R/R MCL成人患者。 Tecartus是继诺华Kymriah和Kite的Yescarta之后第三个获得FDA批准的CAR-T疗法（后两者均于2017年获得批准），是第一个被批准用于治疗成人复发/难治性B细胞前体ALL患者的CAR-T细胞疗法，同时也是全球首个MCL CAR-T疗法。 财报显示，2024上半年，Tecartus营收2.07亿美元，同比增长17%。 • 首款BCMA CAR-T疗法——BMS&2seventy bio 2021年3月，全球首个BCMA CAR-T疗法Abecma获得FDA批准，用于治疗既往至少接受过4种癌症治疗无效或复发的多发性骨髓瘤患者。该产品由BMS和2seventy bio联合开发。 BCMA是一种几乎普遍在多发性骨髓瘤癌细胞上表达的蛋白质。作为一种抗BCMA CAR-T细胞疗法，Abecma识别并结合BCMA，导致表达BCMA的细胞死亡。 Abecma是获批治疗复发性/难治性多发性骨髓瘤的三种CAR-T疗法之一，也是FDA批准的第五款CAR-T疗法。2024上半年，Abecama营收1.77亿美元，同比下降37%。 • 首款获得FDA批准的CGT“国货”——传奇生物&强生 2022年2月，由强生和传奇生物共同开发的CAR-T疗法西达基奥仑赛（商品名Carvykti），获得FDA批准上市，用于治疗复发/难治性多发性骨髓瘤成人患者。这是首款由中国技术转移获得FDA批准的细胞治疗产品。 2024年4月，FDA扩大了Carvykti适应症批准范围，令其成为首个且唯一获批用于多发性骨髓瘤患者二线治疗的BCMA靶向疗法。 根据金斯瑞发布的公告，Carvykti在2024年第二季度销售达到1.86亿美元，相比第一季度1.56亿美元增长了3000万美元，半年销售额达到3.42亿美元。 2 TIL疗法 • 全球首款TIL疗法——Iovance Biotherapeutics 2024年2月，FDA加速批准Iovance Biotherapeutics开发的Amtagvi上市，用于治疗晚期黑色素瘤。Amtagvi成为全球首款获批上市的TIL细胞疗法。 与CAR-T类似，TIL细胞疗法属于过继性免疫治疗的一种。TIL疗法从肿瘤中分离浸润的淋巴细胞，体外扩增后回输给患者，由于存在大量患者抗原特异性的TIL细胞，可以特异性识别患者的癌细胞进行杀伤。 Amtagvi定价51.5万美元，2024年第二季度产品总收入为1280万美元，是Amtagvi在美国销售的第一季度。 3 TCR-T疗法 • 全球首款TCR-T细胞疗法——Adaptimmune Therapeutic 2024年8月，Adaptimmune Therapeutics宣布，FDA加速批准其TCR-T治疗产品Tecelra用于治疗无法切除或转移性滑膜肉瘤的成年患者，这些患者既往接受过化疗，HLA-A*02:01、-A*02:02、-A*02:03 或 -A*02:06 呈阳性，且肿瘤表达 MAGE-A4 抗原。 Tecelra是一种针对黑色素瘤相关抗原A4（MAGE-A4）的工程化TCR-T疗法。Tecelra使用每个患者自身的免疫细胞在一次性输注治疗中识别和攻击癌细胞，这与目前晚期滑膜肉瘤的治疗标准有显著不同。 值得一提的是，Tecelra不仅是全球首个获批上市的实体瘤癌症T细胞疗法，也是全球首款获批上市的TCR-T疗法。Adaptimmune计划今年至少开设6到10个授权治疗中心，并在头两年内开设大约30个治疗中心。 4 胰岛细胞疗法 • 首款同种异体胰岛细胞疗法——CellTrans 2024年6月，FDA批准CellTrans开发的同种异体胰岛细胞疗法Lantidra上市，用于治疗1型糖尿病。 Lantidra是FDA批准的首款从逝去供体获得的胰腺细胞生成的同种异体胰岛细胞疗法，用于治疗即使接受强力糖尿病治疗和教育，仍然由于严重低血糖的反复发作，无法达到目标糖化血红蛋白水平的1型糖尿病成人患者。 Lantidra利用死亡捐献者的正常胰岛细胞，通过导管注入到患者的肝门静脉中，从而补充患者体内缺乏的胰岛素和其他激素，增强血糖控制和减少低血糖发作。 5 基因疗法 • 首个获批用于治疗早期CALD的一次性基因疗法——Bluebird 2022年9月，Bluebird宣布，FDA已加速批准Skysona用于减缓患有早期活动性脑肾上腺脑白质营养不良（CALD）的4-17岁男孩神经功能障碍的进展。 Skysona是首个获批用于治疗早期CALD的一次性基因疗法，旨在将ABCD1 cDNA的功能性拷贝添加到患者自身的造血干细胞中，从而产生功能性肾上腺脑白质营养不良蛋白。 财报显示，2023年，Skysona销售额为1240万美元。 • 全球首款可重复给药的基因疗法——Krystal Biotech 2023年5月，FDA批准Krystal Biotech开发的外用凝胶药物Vyjuvek上市，用于治疗6个月或以上的营养不良性大疱性表皮松解症（DEB）患者。 Vyjuvek是首款可重复给药的基因疗法，每周一次局部应用于伤口，也是FDA批准的首个且唯一一个用于治疗隐性和显性DEB的药物。DEB属于罕见的遗传性皮肤病，主要表现为皮肤或黏膜脆性增加，即受到轻微外伤或摩擦后出现破损、水疱或大疱改变。 Vyjuvek的定价约为2.4万美元/瓶，平均每位患者每年使用26瓶。这意味着每位患者每年的费用约为63万美元，经过政府强制折扣后为48.5万美元。2024上半年，Vyjuvek营收1.156亿美元。 • 全球首款DMD基因疗法——Sarepta Therapeutics 2023年6月，Sarepta Therapeutics开发的Elevidys作为全球首款DMD一次性基因疗法获得FDA批准上市，用于治疗4-5岁可独立行走的DMD儿童。 今年6月，FDA批准Elevidy扩展适应症，允许用于治疗4岁及以上必须携带确认的DMD基因突变的DMD患者。其中，对所有4岁及以上确诊DMD基因突变的患者，FDA给予传统批准；对无法行走的患者，给予加速批准。Elevidys禁用于DMD基因第8和/或第9外显子有缺失的患者。 随着辉瑞的同类产品PF-06939926临床开发失败，目前还未有具有潜在竞争力的候选产品。财报显示，Elevidys在2023年销售额超2亿美元，远超预期。2024上半年，Elevidys销售额为2.56亿美元。 • 全球首款血友病A基因疗法——BioMarin Pharmaceutical 2023年6月，FDA批准BioMarin Pharmaceutical开发的Roctavian用于治疗严重A型血友病成人患者。具体适应症为：无因子VIII抑制剂史且未检测到AAV5抗体的重度A型血友病成人患者。 由此，Roctavian成为A型血友病领域的首款基因疗法。Roctavian使用AAV5病毒载体递送表达凝血因子VIII的转基因。它的优势在于，患者可能只需要接受一次治疗，肝细胞就可以持续表达凝血因子VIII，从而不再需要长期接受预防性凝血因子注射。 2024上半年，Roctavian营收0.083亿美元。 • 全球首款CRISPR基因疗法——Vertex&CRISPR Therapeutics 2023年11月，Casgevy获MHRA有条件上市许可，用于治疗12岁及以上镰状细胞病（SCD）与输血依赖性β地中海贫血（TDT）患者，成为全世界首款获批上市的CRISPR基因编辑疗法。 次月，FDA也批准Casgevy用于治疗SCD，定价220万美元。今年1月，该疗法再获FDA批准用于治疗12岁及以上TDT患者。 Casgevy利用CRISPR/Cas9基因编辑系统，在体外对来自患者的造血干细胞进行编辑，使血红细胞生产高水平的胎儿血红蛋白。2015年，Vertex和CRISPR Therapeutics达成战略研究合作，最终推出Casgevy。 • 全球首款MLD基因疗法——Orchard Therapeutics 2024年3月，FDA批准由Orchard Therapeutics开发的Lenmeldy，用于治疗满足特定条件的异染性脑白质营养不良（MLD）儿童患者。此次获批，标志着Lenmeldy成为首个针对MLD的基因疗法。 Lenmeldy旨在通过将一个或多个功能性人类ARSA基因的副本在体外插入患者自身造血干细胞的基因组中，使用慢病毒载体来纠正MLD的潜在遗传原因。修复的基因细胞被输回患者体内，一旦植入，它们会分化成多种细胞类型，其中一些会越过血脑屏障进入中枢神经系统并表达功能性酶。这种方法有望通过一次治疗恢复酶功能以停止或减缓疾病进展。 Lenmeldy在美国的定价为425万美元，刷新“天价药”记录。Lenmeldy上市前，协和麒麟已完成对Orchard的收购。 6 小核酸 • 治疗遗传性ALS的首款疗法——Ionis Pharmaceuticals 2023年4月，FDA加速批准Qalsody（tofersen）用于治疗具有SOD1突变的ALS成人患者，这一适应症是根据Qalsody治疗的患者血浆神经丝轻链的减少而加速批准的。 Qalsody是一种ASO药物，它可以与编码SOD1的mRNA结合，造成其被核糖核酸酶RNase-H降解，进而减少突变的SOD1蛋白生成。这是FDA批准治疗遗传性ALS的首款疗法，也是首款基于生物标志物加速批准的ALS疗法。 2024上半年，Qalsody全球销售额为0.1亿美元。 • 全球首款可通过自动注射器自行给药用于治疗ATTRv-PN的药物——阿斯利康&Ionis Pharmaceuticals 2023年12月，阿斯利康和Ionis联合研发的Wainua（eplontersen）获FDA的批准，用于治疗成人遗传性转甲状腺素蛋白介导的淀粉样变性的多发性神经病。Wainua是首个可通过自动注射器自行给药用于治疗ATTRv-PN的获批药物。 作为一种ASO-GalNAc缀合物，Wainua通过与TTR mRNA结合引起突变型和野生型TTR mRNA降解，从而减少血清TTR蛋白和组织中TTR蛋白沉积。其旨在通过抑制错误折叠突变TTR蛋白的产生来减缓疾病的进展并改善患者的生活质量。患者可自己皮下注射，每月使用一次。 2024上半年，Wainua销售额为0.21亿美元。 2 率先取得监管里程碑的本土创新 已上市产品 • 中国首个获批的CAR-T疗法——复星凯特 2021年6月，复星凯特阿基仑赛注射液已正式获得NMPA批准，这意味着中国迎来首款获批上市的CAR-T疗法。 阿基仑赛注射液是复星凯特从吉利德子公司Kite制药引进的靶向CD19自体CAR-T细胞治疗产品Yescarta，拥有其在中国包括香港、澳门的商业化权利，并于中国境内（不包括港澳台）进行本地化生产。 在完成治疗成人复发难治性大B细胞淋巴瘤的中国境内桥接临床试验后，2020年2月复星凯特在国内提交阿基仑赛注射液上市申请，用于治疗成人复发难治性大B细胞淋巴瘤，包括DLBCL非特指型、原发性纵隔B细胞淋巴瘤（PMBCL）、高级别B细胞淋巴瘤和滤泡淋巴瘤转化的DLBCL，并于3月13日被CDE纳入优先审评。 • 全球首款全人源BCMA CAR-T——驯鹿生物 2023年6月，驯鹿生物申报伊基奥仑赛注射液（商品名：福可苏）获得NMPA批准上市，用于治疗既往经过至少3线治疗后进展（至少使用过一种蛋白酶体抑制剂及免疫调节剂）的复发或难治性多发性骨髓瘤成人患者。 该产品是全球首个获批的全人源BCMA CAR-T细胞治疗产品。 近日，驯鹿生物宣布，伊基奥仑赛注射液用于治疗非肾脏SLE、SLE性肾炎的IND申请已获得FDA的默示许可，这是该产品在自身免疫性疾病领域于中美两国获得的第五个临床批件。 • 中国首款治疗白血病的CAR-T——合源生物 2023年11月，NMPA通过优先审评审批程序附条件批准合源生物的纳基奥仑赛注射液（商品名：源瑞达）上市，用于治疗成人复发或难治性B细胞急性淋巴细胞白血病。这是中国首款白血病治疗领域CAR-T产品，打破白血病30年治疗困境。 申报上市 • 我国首款申报上市的干细胞新药——铂生卓越生物 2024年6月，铂生卓越生物“艾米迈托赛注射液”NDA正式获NMPA受理并被纳入优先审评品种。据悉，这是我国首款申报上市的干细胞新药，其申请的临床适应症为激素失败的急性移植物抗宿主病（aGVHD）。 aGVHD是一种罕见的危及生命的疾病，发生在同种异体造血干细胞移植（HSCT）后，由于供体的免疫细胞攻击宿主的健康细胞导致。该病通常影响皮肤、胃肠道和肝脏。胃肠道急性移植物抗宿主病是HSCT后发生死亡的主要原因。 值得一提的是，在2004年，赵春华教授所在的协和基础所注册申报的中国也是全球第一个干细胞新药正式获准进入临床试验。2006年，其团队研发的第二个干细胞新药“间充质干细胞心梗注射液”也获得了临床批件。两个新药临床批件适应症涵盖了以移植物抗宿主病（GVHD）和心脑血管疾病为代表的难治性疾病。“骨髓原始间充质干细胞”于2006年4月获得II期临床批件，在2020年获批进入III期临床，是国内第一个研发进展进入III期阶段的干细胞药物。 • 国内首个递交NDA的AAV基因治疗药物——信念医药 2024年7月，信念医药宣布，NMPA已正式受理BBM-H901注射液用于治疗血友病B成年患者的新药上市申请。 BBM-H901注射液以静脉给药的方式将人凝血因子IX基因导入血友病B患者体内持续表达，提高并长期维持患者的凝血因子水平，用于预防血友病B成年患者出血。 2022年，BBM-H901注射液被CDE纳入“突破性治疗品种”名单。2024年，该款产品成为国内首个递交新药上市申请的AAV基因治疗药物。 获批IND 1 TIL疗法 • 国内首个进入临床的TIL疗法——沙砾生物 2023年4月，由沙砾生物开发的TIL疗法GT101注射液正式获得NMPA的临床试验默示许可，成为国内目前第一个也是唯一一个进入关键临床阶段的TIL产品。 GT101注射液通过从患者体内获取肿瘤组织并提取TIL，再经过沙砾生物StemTexp®生产平台扩增至10亿量级后输注回患者体内以对抗肿瘤。 • 全球首个采用无需清淋级预处理、无需IL-2注射的TIL疗法——君赛生物 砂砾生物之后，君赛生物的GC101 TIL疗法仅隔2天获得IND批准，全球首个采用无需清淋级预处理、无需IL-2注射临床方案，在多种类型实体瘤的I期临床试验中展现良好疗效。据悉，GC101 TIL疗法首个优选适应症即将进入关键II期临床。 • 全球首款进入临床的肝癌TIL产品——百吉生物 BST02是百吉生物全球首款针对肝癌的TIL产品，自2024年1月同时获得中美临床批件，7月完成中美双报双批临床I期首例受试者入组。 作为基于患者自身肿瘤浸润淋巴细胞扩增的T细胞治疗产品，BST02属于过继性免疫细胞治疗技术，具有治疗所有类型肝癌的潜力。与传统的TIL药物相比，BST02具有可冻存、突破距离限制、无需高剂量白介素-2辅助用药等优势。 • 全球首款非病毒载体基因修饰TIL疗法获批IND——君赛生物 GC203是君赛生物自主研发的全球首款非病毒载体基因修饰TIL疗法，是天然TIL细胞的“加强版”，使TIL细胞稳定产生可自聚集的膜结合细胞因子IL-7，其临床试验已于2024年4月获国家药监局批准。 GC203以天然TIL细胞为基础，通过非病毒载体介导的基因工程技术，使TIL细胞稳定表达膜结合型、可自发聚集的细胞因子。生产过程无需滋养细胞，工艺更简便；基因修饰过程，采用非病毒载体，成本更低，安全性更高，修饰效率与病毒载体相当（平均45%）。 2 CAR-T疗法 • 全球首款利用基因沉默技术而降低CRS和ICANS的CAR-T进入临床——优卡迪生物 U01（CD9-CART-shRNA-IL6）是全球唯一通过小干扰RNA基因沉默技术而降低CRS和ICANS的新一代CAR-T产品，已于2020年获得CDE批准进入临床。 U01除能治疗除难治复发B-ALL外，还可以被批准容许治疗“脑白”患者，目前正处于临床Ⅱ期。据悉，这是国际上首款打破“脑白”这一禁忌症的CAR-T疗法，对白血病中枢浸润的治疗具有重要意义。 • 全球首个获批进入临床的T细胞系恶性肿瘤自体CD7-CAR-T疗法——博生吉医药 2021年8月，由博生吉医药自主研发的自体CD7-CAR-T产品（PA3-17注射液）获CDE的IND批准，用于治疗难治/复发T淋巴母细胞白血病/淋巴瘤。这是全球首个以T细胞系肿瘤为适应症被批准进入临床的自体CD7-CAR-T产品，2021年11月和2022年12月分别被FDA和欧盟委员会（EC）授予了孤儿药资格认定。 PA3-17注射液是一款基于CD7纳米抗体开发的自体CAR-T产品，采用非基因编辑策略攻克了诸多CMC挑战，并开发成功了高度优化的全自动制备工艺。目前注册临床一期剂量爬坡试验已完成。 • 首款非病毒快速制备的CAR-T疗法获批IND——星尘生物 2023年10月，星尘生物宣布其非病毒快速制备的FIT-CD19 CAR-T免疫疗法治疗非霍奇金淋巴瘤已获FDA对IND申请的批准。 这一创新性疗法的独到之处在于采用非病毒制备技术，将制备时间缩短至仅需两天，而成本仅为目前上市产品的几分之一。这一突破性技术的成功应用，不仅提高生产效率，降低治疗成本，也为更广泛的患者提供一种更为便利、经济的治疗选择。 • 首个中美双报获批IND靶向EpCAM的CAR-T产品——易慕峰 2024年2月，易慕峰自体CAR-T细胞注射液产品（IMC001）IND申请临床试验申请在中国CDE批准之后，又获得了美国FDA的临床研究许可，用于治疗上皮细胞黏附分子（EpCAM）表达阳性的晚期消化系统肿瘤，包括但不限于晚期胃癌（GC）/食管胃结合部腺癌（GEJ）。EpCAM CAR-T可以同时靶向原发灶、CTC、转移灶。 IMC001成为全球首个中美双报获批IND的靶向EpCAM的CAR-T产品，已在IIT研究中展示出良好的安全性和有效性。 • 全球首创中美双报双批靶向EB病毒抗原CAR-T——百吉生物 2024年8月，百吉生物自主研发的BRG01注射液（EBV特异性CAR-T）获得FDA批准其开展关键性II期临床试验。 数据显示，BRG01展现出了卓越的安全性和初步有效性：75%高剂量患者肿瘤病灶缩小且代谢活性降低。部分患者甚至实现了肿瘤病灶的100%完全缓解。此外，BRG01还表现出卓越的抗EB病毒效力，患者回输后外周血中的EB病毒载量显著降低至正常水平。 • 全球同类首创CLDN18.2 CAR-T完成II期入组——科济药业 2024年8月，科济药业宣布，全球同类首创、靶向CLDN18.2自体CAR-T细胞候选产品舒瑞基奥仑赛注射液，在中国进行的针对晚期胃癌/食管胃结合部腺癌的确证性II期临床试验，已按照临床方案完成全部受试者的入组和随机。 2022年3月，CT041于北京大学肿瘤医院完成了中国确证性Ⅱ期临床试验的首例患者入组，主要治疗既往接受过至少二线治疗失败的CLDN18.2表达阳性的晚期胃癌/食管胃结合部腺癌。 CT041成为全球首个进入到确证性Ⅱ期临床试验的用于治疗实体瘤的CAR-T细胞候选产品；也是全球首个已获得FDA和CDE以及加拿大卫生部的IND/CTA批准、并正在进行临床试验研究的靶向CLDN18.2的CAR-T细胞候选产品。 3 CAR-NK疗法 • 国内首个获FDA IND批准的非基因修饰异体外周血NK疗法——恩凯赛药 2024年1月，由恩凯赛药开发的NK010获得FDA I期临床试验许可，首选卵巢癌适应症进行探索。该产品为国内首个获得FDA临床批准的非基因修饰异体外周血NK细胞药物。 NK010具有受体谱最优化、靶点多样化、高纯度、普适性等高抗癌优势，使其具有治疗多类型肿瘤的潜力。NK010也存在扩展至非肿瘤疾病治疗的潜在空间，还是后续一系列合成NK细胞药物的最佳底盘细胞。 • 国内首个通用型CAR-NK治疗SLE获批IND——先博生物 2024年2月，先博生物自主研发的靶向CD19的嵌合抗原受体基因修饰的NK细胞注射液正式获得CDE的临床默示许可，适应症为中重度难治性系统性红斑狼疮（SLE）。这是SLE适应症在国内首个通用型NK产品获批IND。 通用型CAR-NK疗法，与其它创新细胞治疗产品相比显著降低患者的经济负担并且即时可用。叠加NK细胞突出的安全性优势，让NK疗法有望在不断发展的自身免疫性疾病领域脱颖而出。 • 国内首个获批临床的通用型实体瘤细胞疗法——羿尊生物 2024年7月，由羿尊生物自主开发的CNK-UT002细胞注射液的IND成功获得CDE默示许可，适应症为晚期实体瘤 （包括但不限于肝癌和黑色素瘤），这是国内首个获批临床的通用型实体瘤细胞疗法 CNK-UT002细胞注射液采用的是一种集成了CNK-T和U-T两大平台技术的通用型细胞技术，采集健康供者的T细胞经基因编辑改造后，赋予NK细胞识别功能并具有T细胞的激活打击能力，能特异性地识别和治疗各种实体和血液肿瘤，同一款CNK-UT细胞药物可实现对肝癌、黑色素瘤、结直肠癌、肾癌、T细胞白血病等多种实体肿瘤和白血病细胞的杀伤。 • 国内首款获批IND的非基因修饰同种异体NK疗法——希灵生物 2024年7月，希灵生物的“CEL001注射液”获得临床试验默示许可，适应症为晚期实体肿瘤。这是国内首款批准IND的非基因修饰同种异体NK细胞候选产品。 CEL001注射液来源于健康人外周血，是基于体外培养技术，经过分离、活化、增殖等步骤，获得的一类具有高表达激活性受体、高水平表达颗粒酶、穿孔素、兼具细胞因子分泌功能和细胞杀伤作用的通用现货型NK细胞候选产品。 • 3款首创同源异体现货通用型非病毒载体非基因编辑的抗体NK偶联药物进入临床——英百瑞 1. IBR854是全球首款进入注册临床阶段靶向5T4治疗实体瘤的抗体偶联NK细胞产品（2023年1月获得CDE临床默示许可）。 2. IBR733是全球首款双靶向CD33/CLL1治疗AML进入注册临床阶段的抗体偶联NK细胞产品（2023年12月获得CDE临床默示许可）。 3. IBR822是全球首款进入注册临床阶段靶向Trop2治疗实体瘤的抗体偶联NK细胞产品（2024年4月获得CDE临床默示许可）。 4 iPS疗法 • 全球首款进入注册临床的iPSC衍生通用型帕金森细胞治疗产品——睿健医药 2023年8月，由睿健医药通用型细胞治疗产品NouvNeu001（人源多巴胺能前体细胞注射液）获得NMPA批准进入I/II期联合临床，用于治疗中晚期帕金森病。这是全球首款进入注册临床的iPSC衍生通用型帕金森细胞治疗产品，也是全球首个进入临床阶段的基于化学诱导的通用型细胞治疗产品。 2024年1月，NouvNeu001在北京医院完成了注册临床阶段首例患者给药。目前已经进入剂量拓展阶段。2024年6月，NouvNeu001获得FDA批准进入海外临床I期。同时，睿健开创性产品被FDA授予特别豁免权，也是全球唯一获得FDA“特殊豁免”的通用型细胞治疗产品。 • 中国首例临床级iPS衍生细胞移植治疗帕金森病给药——士泽生物 2024年1月，士泽生物临床级自体iPSC衍生多巴胺能神经前体细胞注射液经颅内立体定位注射微创手术方式移植治疗帕金森病，在上海市东方医院（同济大学附属东方医院）成功完成。据悉，这是中国首例临床级iPS衍生细胞移植治疗帕金森病，也是中国首例、世界第二例自体iPS衍生细胞替代性移植治疗帕金森病。 该项目是我国首个正式获批的iPS衍生细胞治疗神经系统疾病的国家级干细胞备案临床研究项目。手术在两小时以内完成：首例受试者接受临床级iPS衍生细胞移植后，无手术及围术期的并发症或其他不良安全事件，各项检测指标正常且已顺利出院，平稳度过观察期并进入正式随访期。 • 全球首个ipsc衍生前脑神经前体注射液获中美IND批准——霍德生物 2024年3月，霍德生物开发的iPSC衍生异体通用型前脑神经前体细胞注射液hNPC01，在30天默许期内提前收到FDA通知可以开展针对缺血性脑卒中偏瘫后遗症的I/IIa注册临床试验，无附加条件。 hNPC01已知是目前全球首个进入注册临床的多能干细胞（包括iPSC及胚胎干细胞ESC）衍生的前脑神经前体细胞产品，同时也是中国首个原研并成功获得美国IND批准的多能干细胞衍生产品（包含衍生间充质样、神经、心肌、免疫细胞、胰岛细胞等所有品类）。 5 TCR-T疗法 • 国内首个获批IND的TCR-T疗法——香雪制药 2024年7月，CDE同意香雪制药的TAEST16001注射液纳入突破性治疗品种名单，标志着该产品作为中国第一个IND获批开展临床试验的TCR-T细胞治疗新药取得重大突破。 TAEST16001注射液是香雪制药的一款靶向NY-ESO-1的亲和力增强的TCR-T细胞免疫治疗产品，其首个临床研究适应症是HLA-A*02:01阳性且表达NY-ESO-1抗原的晚期软组织肉瘤患者。该产品是中国首个获得IND批件的TCR-T产品，也是中国唯一进入II期临床的TCR-T产品。 • 全球首款实体瘤的TCR-T产品——百吉生物 BRL03是百吉生物自主研发的全球首款针对肺癌和胃癌等多种实体肿瘤的TCR-T产品，I期临床试验也在今年6月完成首例受试者入组，并计划在今年年底完成所有I期受试者入组。 BRL03是第四代TCR-T细胞疗法，是基于其自主创新技术平台IDENTIFIER®开发的,能够针对多种实体瘤。而另一个自主研发的平台MSE-T使得BRL03具有额外的功能模块组件，减少细胞耗竭以提升抗肿瘤的持久性。 6 基因疗法 • 首个戈谢病AAV基因疗法获批IND——凌意生物 2024年1月，凌意生物旗下LY-M001注射液的IND申请获得NMPA的默示许可。这是中国首个自主研发，针对I型或III型戈谢病的AAV基因治疗药物。该产品使用重组腺相关病毒rAAV为载体，通过单次静脉输注给药后即可表达患者所需的葡萄糖脑苷脂酶。去年10月，该产品获得美国FDA孤儿药资格认定，用于治疗戈谢病。 • 首个采用“两质粒包装系统”的AAV基因疗法获批IND——金唯科生物 2024年2月，金唯科生物研发的针对新生血管性年龄相关性黄斑变性（nAMD）基因治疗产品“JWK001注射液”的IND申请获得NMPA批准。 J这是首个采用“两质粒包装系统”的AAV基因疗法，通过视网膜下给药将承载着全新自主设计的抗VEGF蛋白表达框的AAV递送至眼部细胞中，可持续高效表达抗VEGF蛋白。JWK001注射液设计多靶点基因表达框，增加覆盖单一靶点不敏感患者，提升药物疗效。 • 国内首个LNP-mRNA体内基因编辑药物获批临床——尧唐生物 2024年3月，尧唐生物宣布，CDE批准了YOLT-201的临床试验申请，这也是国内首个采用脂质纳米颗粒（LNP）介导的体内基因编辑药物获得临床试验批准。 YOLT-201通过LNP以mRNA形式递送CRISPR-Cas9基因编辑系统，在人肝脏中实现高效特异的转甲状腺素蛋白（TTR）靶基因编辑，以永久性降低血液中的TTR蛋白水平，有望实现转甲状腺素蛋白淀粉样变（ATTR）的终身治疗，包括转甲状腺素蛋白淀粉样变性多发性神经病（ATTR-PN）和转甲状腺素蛋白心脏淀粉样变（ATTR-CM）。 • 国内首个获批临床的碱基编辑疗法——正序生物 2024年4月，正序生物CS-101注射液获得NMPA的IND批准，正式启动了临床I期试验，成为国内首个获批临床的碱基编辑疗法。同月，正序生物入组了首位临床试验患者。 CS-101的原理是通过采集患者自体造血干细胞，利用高精准变形式碱基编辑器tBE（transformer Base Editor），对患者自体造血干细胞中的HBG1/2启动子区域进行精准碱基编辑，模拟健康人群中天然存在的有益碱基突变，重新激活γ-珠蛋白的表达，重建血红蛋白的携氧功能。 7 溶瘤病毒 • 国内自研首个获批临床的溶瘤痘苗病毒产品——华药康明 2022年9月，华药康明的溶瘤痘苗病毒产品KM1的IND申请获得NMPA批准。2022年12月，KM1的IND申请获得FDA批准。 这是国内自研首个获得临床批件的溶瘤痘苗病毒产品。该产品携带免疫调节基因IL-21和4-1BBL，旨在更好地激活抗肿瘤的免疫反应。目前KM1在中国开展I期临床试验中。 • 全球首款静脉疱疹溶瘤产品完成美国临床I期——亦诺微医药 2023年11月，亦诺微医药宣布，全球首款处于临床阶段的静脉疱疹溶瘤病毒产品MVR-T3011 IV，已在美国成功完成针对多个晚期大瘤种适应症进行的临床I期试验。 MVR-T3011是亦诺微医药拥有自主知识产权的三合一疱疹溶瘤病毒创新产品，其基于对野生HSV-I型疱疹病毒骨架的全新设计，确保病毒在肿瘤细胞内拥有强劲的复制能力的同时，在正常细胞内复制能力得到抑制，实现最优减毒效果。此外，MVR-T3011携带了两个最新且被充分验证过的外源性免疫调节基因——PD-1抗体和IL-12，以促进肿瘤微环境的免疫反应。 IND获受理 1 基因疗法 • 全球首个用于GA-I的基因治疗产品IND获受理——天泽云泰 2023年4月，据CDE官网公示，天泽云泰的基因治疗产品“VGM-R02b”新药临床试验申请获得受理。 据悉，VGM-R02b是一款用于治疗戊二酸血症I型（GA-I）的基因治疗产品，属于儿童专用创新药。2022年5月，该产品已被FDA授予用于治疗GA-I的罕见儿科疾病认定（RPDD）资格。同时，VGM-R02b也是全球首个用于GA-I的基因治疗产品，将有机会以罕见儿科疾病产品申请美国儿科孤儿药优先审评券（PRV）。 2 CAR-T疗法 • 全球首个针对CLDN18.2表达阳性的晚期实体瘤恶性腹腔积液治疗的细胞药物产品IND获受理——华道生物 2024年8月，华道生物生产的HD004CAR-T细胞于获CDE正式受理。 HD004CART是全球首个针对CLDN18.2表达阳性的晚期实体瘤恶性腹腔积液治疗的首个细胞药物产品。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

SAN FRANCISCO, Aug. 8, 2024 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today reported financial results for the second quarter ended June 30, 2024. Cash and investments in marketable securities at June 30, 2024 were $290.6 million as compared to $329.4 million at December 31, 2023. Nektar's cash and marketable securities are expected to support strategic development activities and operations into the third quarter of 2026. "We continue to make excellent progress advancing rezpegaldesleukin in Phase 2 studies in patients with atopic dermatitis and alopecia areata," said Howard W. Robin, President and CEO of Nektar. "We are particularly pleased that enrollment is on track for topline data in the first half of 2025 for atopic dermatitis and topline data in mid-2025 for alopecia areata. For our TNFR2 agonist antibody, NKTR-0165, we are conducting IND-enabling studies with the goal of preparing for an IND submission in the middle of 2025. Recent data at the 2024 EULAR Congress highlighted the potential of this unique AI-generated antibody in inflammatory disorders. Finally, we remain in a strong financial position with a cash runway extending into the third quarter of 2026." Summary of Financial Results Revenue in the second quarter of 2024 was $23.5 million as compared to $20.5 million in the second quarter of 2023. Revenue for the first half of 2024 was $45.1 million as compared to $42.1 million in the first half of 2023. Total operating costs and expenses in the second quarter of 2024 were $73.3 million as compared to $71.1 million in the second quarter of 2023. Total operating costs and expenses in the first half of 2024 were $130.3 million as compared to $227.4 million in the first half of 2023. Operating costs and expenses for the first half of 2024 decreased due to a decrease in restructuring, impairment and costs of terminated program and a one-time $76.5 million non-cash goodwill impairment recognized in the first quarter of 2023. R&D expense was $29.7 million in the second quarter of both 2024 and 2023. R&D expense in the first half of 2024 was $57.1 million as compared to $60.2 million for the first half of 2023. R&D expense decreased for the first half of 2024 primarily due to decreases in employee costs and related facilities costs as well as development expense for NKTR-255 offset by increases in development expenses for rezpegaldesleukin and NKTR-0165. G&A expense was $20.5 million in the second quarter of 2024 as compared to $17.9 million in the second quarter of 2023. G&A expense was $40.7 million in the first half of 2024 as compared to $39.0 million in the first half of 2023. G&A expense increased for both the second quarter and first half of 2024 primarily due to a reduction of facilities costs allocated to research and development expenses partially offset by a decrease in employee costs. Non-cash restructuring and impairment charges in the second quarter of 2024 were $13.3 million and $14.3 million in the first half of 2024. These non-cash charges are related to the declining San Francisco commercial real estate market and real estate lease obligations held by Nektar. Net loss for the second quarter of 2024 was $52.4 million or $0.25 basic and diluted loss per share as compared to a net loss of $51.1 million or $0.27 basic and diluted loss per share in the second quarter of 2023. Net loss in the first half of 2024 was $89.2 million or $0.44 basic and diluted loss per share as compared to a net loss of $188.1 million or $0.99 basic and diluted loss per share in the first half of 2023. Excluding the $13.3 million and $14.3 million in non-cash restructuring and real estate impairment charges, net loss, on a non-GAAP basis, for the second quarter and first half of 2024 were $39.1 million and $74.9 million, respectively, or $0.19 and $0.37 basic and diluted loss per share, respectively. Second Quarter 2024 and Recent Business Highlights In July 2024, our collaborators at Stanford published data from a Phase 1 trial evaluating NKTR-255 in combination with CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, an open-access journal of the American Society of Hematology. These data showed that, at 12 months, remission-free survival for NKTR-255 was double that of historical controls (67% vs 38%). The data also showed that eight out of nine patients (89%) achieved complete remission with or without hematologic recovery, all without detectable measurable residual disease (MRD). In June 2024, Nektar presented the first preclinical data on NKTR-0165 at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress. The data presented show that NKTR-0165 is a unique antibody that selectively binds to TNFR2 on Tregs to enhance its immunosuppressive activities, and could potentially become a first-in-class treatment for various autoimmune diseases, including ulcerative colitis and vitiligo. Nektar plans to initiate first-in-human studies in the first half of 2025. Enrollment remains on track for the two Phase 2b studies of rezpegaldesleukin, one in patients with moderate-to-severe atopic dermatitis and one in patients with severe to very severe alopecia areata. Nektar expects topline data from these studies, respectively, in the first half and in the middle of 2025. Nektar also announced upcoming presentations at the following scientific congress: 2024 European Academy of Dermatology and Venereology (EADV) Congress ePoster P0662: "Serum proteomic biomarker analysis of the interleukin-2 receptor pathway agonist rezpegaldesleukin in patients with atopic dermatitis", Yu, D. ePoster P0600 (Trial in Progress): "A Phase 2b, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled, International, Multicenter, Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in Adults with Moderate-to-Severe Atopic Dermatitis", Gkalpakiotis, S. ePoster P2080 (Trial in Progress): "A Phase 2b Study Evaluating the Efficacy and Safety of Single Agent Rezpegaldesleukin, an Interleukin-2 Receptor (IL-2R) Pathway Agonist, in the Treatment of Severe to Very Severe Alopecia Areata", Reich, A. Conference Call to Discuss Second Quarter 2024 Financial Results Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time, August 8, 2024. This press release and live audio-only webcast of the conference call can be accessed through a link that is posted on the Home Page and Investors section of the Nektar website: . The web broadcast of the conference call will be available for replay through September 8, 2024. To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call. About Nektar Therapeutics Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Our pipeline also includes a preclinical candidate NKTR-0165, which is a bivalent tumor necrosis factor receptor type II agonist antibody. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco, California. For further information, visit and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "expect," "develop," "potential," "advance," "anticipate," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, rezpegaldesleukin, NKTR-0165, and NKTR-255. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of rezpegaldesleukin, NKTR-0165, and NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin, NKTR-0165, and NKTR-255 are investigational agents and continued research and development for these drug candidates is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin and NKTR-255 are in clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by health epidemics, including the COVID-19 pandemic, regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) we may not achieve the expected cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (vi) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vii) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2024. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Contact: For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: David Rosen of Argot Partners (212) 600-1902 [email protected] SOURCE Nektar Therapeutics