AUTO-3

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）。因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。 关键词：ALL；Tecartus；新疗法 10月1日，吉利德旗下的凯特制药宣布FDA批准其Tecartus（brexucabtagene autoleucel）用于治疗成人复发或难治性B细胞前体急性淋巴细胞白血病（ALL）患者。 Tecartus是一种自体抗CD19 CAR-T细胞疗法，2020年7月被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）的复发或难治性套细胞淋巴瘤（R/R MCL）成人患者。 此次Tecartus获批治疗ALL是基于1/2期研究ZUMA-3的数据。该研究是一项国际多中心、单臂、开放标签注册研究，在接受标准系统疗法或造血干细胞移植后难治或复发的成人ALL患者中展开，主要终点为由独立审查委员会评估的完全缓解（CR）或血液学不完全恢复的完全缓解。 结果显示：中位随访时间12.3个月，在疗效可评估患者中 65%患者达到CR或血液学恢复不完全的 CR，超50%患者的CR持续时间超过12个月，中位缓解持续时间 (DOR) 为 13.6 个月。安全性方面，在接受目标剂量治疗的患者中，3级以上细胞因子释放综合征和神经毒性事件发生率分别为26%和35%，通常可控。   急性淋巴细胞白血病（ALL）是一种常见的恶性血液病，以骨髓和淋巴组织中不成熟淋巴细胞的异常增殖和聚集为特点，可累及淋巴结、脾脏、肝脏、中枢神经系统和其他器官。ALL主要分为T细胞ALL、前体B细胞ALL和成熟B细胞白血病三类，其中前体B细胞ALL是ALL的最常见形式，约占75%。 目前，ALL治疗除传统的化疗和造血干细胞移植，全球已经批准了多款新疗法，其中Gleevec/Glivec、Sprycel和Iclusig均属于酪氨酸激酶抑制剂 (TKI)，Blincyto是全球获批的首个CD19-CD3双特异性T细胞衔接（BiTE）免疫疗法，Besponsa是一款CD22靶向抗体药物偶联物（ADC），而Kymriah是一种CD19靶向的基因修饰自体T细胞免疫细胞疗法（CAR-T疗法）。 而且，近年来FDA还批准另外两款新的ALL药物，即施维雅的Asparlas（calaspargase pegol-mknl，Cal-PEG）和Jazz制药的Rylaze。其中Asparlas是一种长效天冬酰胺特异性酶，2018年12月被FDA批准作为多药化疗方案的一个组成部分，用于1个月至21岁的儿童和青少年ALL患者的治疗。Rylaze 是一种生物制剂重组的菊欧文氏菌天冬酰胺酶，以特殊荧光菌的技术平台研发而来，2021年7月被FDA批准作为化疗方案的一部分，治疗对常见化疗方案中大肠杆菌源性天冬酰胺酶制品过敏的ALL和淋巴母细胞淋巴瘤（LBL）的1个月龄以上的儿童和成人患者。 此外，目前还有其他几款药物被开发用于治疗ALL，如亘喜生物的GC027、Autolus Therapeutics的AUTO3。其中GC027利用亘喜生物独有的TruUCAR专利技术以及无需进行HLA匹配的健康供者T细胞开发的一款即用型CAR-T细胞疗法，通过靶向CD7抗原表达的肿瘤细胞治疗T细胞恶性肿瘤。目前，该药治疗R/R急性T淋巴细胞白血病(T-ALL)的一项I期临床试验取得积极结果。AUTO3是一种自体富集T细胞，经单个逆转录病毒载体修饰表达2个独立的嵌合抗原受体（CAR），分别靶向B淋巴细胞抗原CD19和CD22，并且每个CAR都针对单个靶点活性进行了独立优化。通过同时针对2种B细胞抗原，AUTO3旨在减少B细胞恶性肿瘤患者因单一抗原丢失导致的复发。2019年4月，该药被FDA授予治疗ALL的孤儿药资格（ODD）。 药事纵横投稿须知：稿费已上调，欢迎投稿 各位朋友好，觉得本文对您有帮助，请随手点一下下方的在看，以便让你的朋友也能看到哦。

LONDON, May 06, 2021 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announced its operational and financial results for the quarter ended March 31, 2021. “We have had a productive first quarter and are on track for multiple clinical read outs during the remainder of this year and into 2022,” said Dr. Christian Itin, chief executive officer of Autolus. “We are excited by the unique characteristics of AUTO1 and encouraged by what we believe is the significant clinical benefit AUTO1 can offer for patients with relapsed/refractory (r/r) Acute Lymphoblastic Leukemia (ALL). AUTO1 is being evaluated in the P1b/2 FELIX study in adult ALL patients with data expected in 2022. In addition, AUTO1 is being explored in patients with B-NHL and in primary CNS lymphoma, and we are also evaluating AUTO1/22 in pediatric ALL patients. Finally, several programs are expected to enter the clinic in 2021, including our next generation program AUTO6NG in Neuroblastoma, setting up clinical news flow for 2022 and beyond.” Key Pipeline Updates: Operational Highlights: Key Upcoming Clinical Milestones: Financial Results for the Quarter Ended March 31, 2021 Cash at March 31, 2021 totaled $239.0 million, as compared to $153.3 million at December 31, 2020. In January 2021, the company sold 1.7 million ADSs under its Open Market Sales AgreementSM with Jefferies LLC as sales agent, resulting in net proceeds of $15.3 million and in February 2021, the company sold 16.4 million ADSs representing 16.4 million ordinary shares in a follow-on, public offering, including the exercise in full by the underwriters of their option to purchase an additional 2.1 million ADSs, at a public offering price of $7.00 per ADS, yielding net proceeds of $106.9 million. Net total operating expenses for the three months ended March 31, 2021 were $39.9 million, net of grant income of $0.3 million, as compared to net operating expenses of $38.6 million, net of grant income of $0.3 million, for the same period in 2020. Research and development expenses decreased to $30.7 million for the three months ended March 31, 2021 from $31.3 million for the three months ended March 31, 2020. Cash costs, which exclude depreciation and amortization as well as share-based compensation, increased to $30.7 million from $25.6 million. The increase in research and development cash costs of $5.1 million consisted primarily of (i) an increase in compensation and employment related costs, net of lower travel costs (as a result of restricted travel due to the ongoing COVID-19 pandemic), of $3.5 million due to a combination of an increase in employee headcount to support the advancement of our product candidates in clinical development and severance payments related to the reduction in workforce that began to take place during the quarter, (ii) an increase of $2.2 million in facilities costs related to the continued scaling of manufacturing operations, and (iii)  an increase of $0.4 million related to cell logistics, which is offset by decreases in purchased materials in the amount of $0.6 million and project expenses of $0.4 million. Non-cash R&D costs decreased to $36,000 for the three months ended March 31, 2021 from $5.7 million for the three months ended March 31, 2020. The decrease is primarily related to share-based compensation expense included in research and development expenses, which decreased by $6.2 million as a result of forfeitures of incentive share options related to employees affected by the reduction in workforce. This was offset by an increase in depreciation of $0.5 million. General and administrative expenses increased to $8.7 million for the three months ended March 31, 2021 from $7.6 million for the three months ended March 31, 2020. Cash costs, which exclude depreciation expense as well as share-based expense compensation increased to $7.6 million from $5.9 million. The increase in general and administrative cash costs of $1.7 million related to an increase of (i) $0.4 million in facilities cost, (ii) an increase of $0.6 million in legal fees and audit fees, (iii) an increase of $0.3 million of expenses related to preparations for becoming a commercial stage company, and (iv) an increase of  $0.4 million in compensation and employment related costs due to an increase in headcount, and severance payments related to the reduction in workforce that began to take place during the quarter. Non-cash general and administrative costs decreased to $1.1 million for the three months ended March 31, 2021 from $1.7 million for the three months ended March 31, 2020. The decrease is attributed to share-based compensation expense as a result of the lower fair value of stock options recognized during the period. Loss on disposal of leasehold improvements of $0.7 million related to the leasehold improvements no longer being utilized in the facility in White City, London. Interest income decreased by $0.5 million for three months ended March 31, 2021 due to lower interest rates for cash held on deposit. Other income decreased by $3.7 million for the three months ended March 31, 2021 from other income of $4.5 million for the three months ended March 31, 2020 to $0.8 million. There was a decrease of $5.6 million primarily due to the weakening of the U.S. dollar exchange rate relative to the pound sterling during the three months ended March 31, 2021 as compared to the three months ended March 31, 2020, offset by gains on lease terminations of $2.0 million, net of the related expenses. Income tax benefit increased to $5.7 million for the three months ended March 31, 2021 from $3.7 million for the three months ended March 31, 2020 due to increased research and development credits. As research and development credits grew at a faster rate than our net loss before income tax, this led to a higher effective tax rate. Research and development credits are obtained at a maximum rate of 33.35% of our qualifying research and development expenses, and the increase in the net credit was primarily attributable to an increase in our eligible research and development expenses. Net loss attributable to ordinary shareholders was $33.3 million for the three months ended March 31, 2021, compared to $29.9 million for the same period in 2020. The basic and diluted net loss per ordinary share for the three months ended March 31, 2021 totaled $(0.53) compared to a basic and diluted net loss per ordinary share of $(0.60) for the three months ended March 31, 2020. Autolus estimates that its current cash on hand will provide the Company with a cash runway into the first half of 2023. Conference Call Management will host a conference call and webcast today at 8:30 am ET/1:30 pm BST to discuss the company’s financial results and provide a general business update. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website. The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 7756178. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 7756178. About Autolus Therapeutics plcAutolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit . About AUTO1 AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with our academic partner, UCL, AUTO1 is currently being evaluated in a Phase 1 clinical trial in adult ALL and B-NHL. The company has also progressed AUTO1 to the FELIX study, a potential pivotal study. About AUTO1 FELIX study The FELIX Phase 1b/2 clinical trial is enrolling adult patients with relapsed / refractory ALL. The trial has a short Phase 1b component prior to proceeding to a single arm Phase 2 clinical trial. The primary endpoint is overall response rate, and the key secondary endpoints include duration of response, MRD negative CR rate and safety. The trial will enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the United States, United Kingdom and Europe. About AUTO3AUTO3 is a programmed T cell investigational therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. AUTO3 is designed to combine a favorable safety profile with a reduced risk of relapse due to single antigen loss. AUTO3 is has been tested in diffuse large B cell lymphoma in the ALEXANDER clinical trial demonstrating a high level of clinical activity with a favorable safety profile. The ALEXANDER study included a 20-patient out-patient cohort and demonstrated feasibility of AUTO3 delivery in an outpatient setting. About AUTO4AUTO4 is a programmed T cell product candidate in clinical development for T cell lymphoma, a setting where there are currently no approved programmed T cell therapies. AUTO4 is specifically designed to target TRBC1 derived cancers, which account for approximately 40% of T cell lymphomas, and is a complement to the AUTO5 T cell product candidate, which is in pre-clinical development. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus’ realigned business strategy, including specifically on the development of the AUTO1 program; the future clinical development, efficacy, safety and therapeutic potential of its product candidates, including progress, expectations as to the reporting of data, conduct and timing and potential future clinical activity and milestones; expectations regarding the initiation, design and reporting of data from clinical trials; the efficacy, safety and therapeutic potential of AUTO3 and ability for Autolus to obtain a partner for next stages of clinical development; Autolus’ needs for additional funding and ability to raise additional capital; Autolus’ ability to attract and retain qualified employees and key personnel; the restructuring program and Autolus’ expected cash savings as a result of the restructuring program and operational changes; and Autolus’ expected cash runway. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus’ preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; possible safety and efficacy concerns; and the impact of the ongoing COVID-19 pandemic on Autolus’ business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus’ actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 4, 2021, as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law. Contact: Julia Wilson+44 (0) 7818 430877 j.wilson@autolus.com Susan A. NoonanS.A. Noonan Communications+1-212-966-3650susan@sanoonan.com Financial Results for the three months ended March 31, 2021 Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited)(In thousands, except share and per share amounts) Condensed Consolidated Balance Sheets (Unaudited)(In thousands, except share and per share amounts)