Letetresgene autoleucel

▎药明康德内容团队报道2024年美国临床肿瘤学会（ASCO）年会已于今日（当地时间5月31日）在美国芝加哥正式开幕。根据ASCO官网摘要信息，今年共有5800+项研究入选本届大会，其中有426项研究入选了“口头报告环节（Oral Abstract Session）”和“快速口头报告（Rapid Oral Abstract Session）环节”。梳理这些口头报告研究，我们发现有近20项细胞疗法相关研究入选，包括了CAR-T细胞疗法、TCR-T细胞疗法、TIL疗法、基于细胞的现货型免疫疗法等等。在这其中，多家中国公司的细胞疗法也入选了ASCO大会口头报告，如科济药业Claudin18.2靶向CAR-T、艺妙神州靶向GUCY2C的CAR-T、博生吉CD7靶向CAR-T产品等。我们注意到，入选本次ASCO大会口头报告的细胞疗法中，有至少6项研究针对的适应症为实体瘤，涵盖胃肠道肿瘤、滑膜肉瘤、肝癌、乳腺癌、黑色素瘤等。在细胞治疗领域，实体瘤曾经是一座难以逾越的高峰，而近年来越来越多的新疗法、新技术正在解决这一挑战，并取得临床突破。本文中我们将一起看看针对实体瘤适应症的细胞疗法，看看它们的临床表现如何？注：本表由《医药观澜》根据ASCO官网摘要整理，如有遗漏，欢迎补充。西比曼生物/阿斯利康：C-CAR031作用机制：自体抗GPC3 CAR-T疗法适应症：肝细胞癌C-CAR031是一种针对肝细胞癌的自体抗GPC3的CAR-T疗法。本次入选口头报告的是该产品治疗晚期肝细胞癌（HCC）患者的1期研究结果。GPC3是HCC中过表达的表面抗原，在健康组织中几乎不存在。截至2024年1月5日，共有24例患者接受了4个剂量水平（DLs）的C-CAR031输注。所有患者均可进行安全性评估。未观察到剂量限制性毒性和免疫效应细胞相关神经毒性综合征（ICANS）。22个患者可评估疗效。90.9%的患者肿瘤缩小，肝内病变和肝外病变患者的中位肿瘤缩小率为44.0%（范围为3.4%~94.4%）。所有患者疾病控制率（DCR）为90.9%，客观缓解率（ORR）为50.0%，DL4的ORR为57.1%。该研究显示C-CAR031在接受过重度治疗的晚期HCC患者中具有可控的安全性和增强的抗肿瘤活性。艺妙神州：IM96作用机制：靶向GUCY2C的CAR-T疗法适应症：结直肠癌IM96是一款靶向鸟苷酸环化酶2C（GUCY2C）的CAR-T疗法，本次入选口头报告的是该产品治疗转移性结直肠癌患者的1期研究结果。GUCY2C在结直肠癌的所有阶段均异位表达。截至2023年12月，20名患者入组并注射了IM96，所有患者随访时间为7~19个月。安全性数据显示，只有5%的患者表现出神经毒性和3级细胞因子释放综合征（CRS），研究没有达到剂量限制毒性和最大耐受剂量。19例可评估患者中，DCR为73.7%，ORR为26.3%。DL3组（12×108）患者的ORR为40.0%，与肝转移与否无关。DL3组中位无进展生存期为7个月，中位缓解持续时间为10个月。在所有患者中，肿瘤应答与癌胚抗原水平的显著降低相关。本研究表明，IM96在错配修复完整（pMMR）mCRC患者中具有持久的疗效和可接受的安全性，特别是在肝转移患者中显示出较高的治疗潜力。科济药业：CT041作用机制：靶向Claudin18.2自体CAR-T细胞候选产品适应症：胃肠道肿瘤CT041是一种靶向Claudin18.2蛋白的自体CAR-T细胞候选产品，正在针对晚期胃癌/食管胃结合部腺癌的确证性2期临床试验。本次入选口头报告的是一项治疗胃肠道肿瘤患者的1期临床研究数据。疗效数据显示，所有患者的ORR和DCR分别达到37.8%和75.5%。所有患者的中位无进展生存期（PFS）和中位总生存期（OS）分别为4.4个月和8.4个月。在接受CT041单药治疗的可评估疗效的胃癌患者中，有可测量疾病（n=47）的ORR和DCR分别达到57.4%和83.0%，所有可评估疗效的胃癌患者（n=55）的中位PFS和中位OS分别为5.8个月和9.7个月。研究人员认为，CT041在大量预处理的Claudin18.2阳性晚期GI癌症患者中显示出有希望的安全性和高度令人鼓舞的疗效。Adaptimmune：letetresgene autoleucel（lete-cel）作用机制：靶向NY-ESO-1抗原的TCR-T疗法适应症：滑膜肉瘤或粘液样/圆形细胞脂肪肉瘤Lete-cel为一种靶向NY-ESO-1实体瘤抗原的工程化T细胞受体（TCR）-T细胞疗法。NY-ESO-1通过在HLA-A*02于滑膜肉瘤和黏液样/圆细胞脂肪肉瘤（MRCLS）中高度表达。本次入选口头报告的是一项2期临床研究结果。研究纳入98名滑膜肉瘤和MRCLS患者，45名患者可评估疗效。结果显示，总体ORR为40%（包括2例CR，16例PR），其中滑膜肉瘤和MRCLS患者的ORR分别为39%和41%。中位反应持续时间为10.6个月。在该研究中，不良事件与先前观察到的一致。研究人员认为，该研究进一步支持了Lete-cel作为晚期滑膜肉瘤和MRCLS疗法的潜力。Obsidian Therapeutics：OBX-115作用机制：靶向IL-15的TIL疗法适应症：黑色素瘤OBX-115是一款保留白细胞介素2（IL2）的工程化肿瘤浸润淋巴细胞（TIL）疗法，该产品使用经FDA批准的小分子药物乙酰唑胺（ACZ）调节膜结合IL15的表达，为TIL的扩增和存续提供细胞因子支持，因此患者在接受该疗法治疗时不需要同时接受高剂量IL2。该产品目前正处于1/2期多中心研究阶段。入选口头报告的是一项1期研究结果，评估了OBX-115方案在ICI耐药、不可切除/转移性黑色素瘤患者中的疗效和安全性。截至2024年1月2日，9名黑色素瘤患者接受了OBX-115输注，他们既往治疗的中位线为3。在至少12周随访的患者中（n=6），按RECIST v1.1计算的ORR为50%（2例CR，1例PR，3例SD）；所有反应都发生在第6~18周之间，最长反应持续时间>12个月。研究人员认为，OBX-115治疗耐受性良好，产生持续加深和持久的反应，表明其可能介导无大剂量IL2的ICI耐药转移性黑色素瘤的完全缓解和持久的临床益处。BriaCell公司：Bria-IMT（SV-BR-1-GM）作用机制：基于细胞的靶向免疫疗法适应症：乳腺癌Bria-IMT方案是一种基于异体全细胞免疫疗法，可刺激患者的免疫系统诱导靶向杀死癌细胞。根据ASCO官网介绍，经皮内照射Bria-IMT的乳腺癌细胞会分泌GM-CSF，并在HLA-I和II分子上呈递肿瘤相关抗原（TAAs），直接刺激抗肿瘤免疫。PD-1免疫检查点抑制剂（CPI）进一步刺激T细胞并与SV-BR-1-GM协同作用。入选口头报告的是评估该产品结合CPI，治疗既往经过多次治疗（包括ADC和CPI治疗失败）的晚期/转移性乳腺癌的疗效和安全性。共有54例患者接受治疗，结果显示Bria-IMT方案耐受性良好，仅9%因AE退出。在接受SV-BR-1-GM III期制剂治疗的患者中（n=23，结果可评估），ORR为13%，DCR为61%，中位PFS和OS分别为4.1个月和13.3个月。研究结果显示，BRIA-IMT已显示出良好的安全性，同时为重度治疗的晚期/转移性乳腺癌患者提供益处。这项2期研究也为正在进行的3期临床研究提供了依据。值得一提的是，今年1月，BriaCell公司宣布Bria-IMT在伴有中枢神经系统（CNS）转移的晚期乳腺癌患者中达成71%的颅内客观缓解率（iORR）。目前该疗法的的关键3期试验正在进行中。除了上述产品，还有一些其它的细胞疗法入选了本届ASCO大会口头报告，用于治疗不同类型的血液肿瘤（见下表），限于篇幅，此处不再一一介绍。如欲获取本届ASCO大会口头报告的细胞疗法管线和临床试验数据，请扫描下方二维码下载表格查看。相关阅读：2024年ASCO口头报告ADC研发管线一览参考资料：[1]ASCO大会官网. From https://conferences.asco.org/am/abstracts[2]各公司公开资料及官方新闻稿本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Afami-cel commercial and regulatory update presented at Company's Investor Day (replay HERE); FDA review and inspections progressing with PDUFA date of August 4th, 2024 Commercial and manufacturing infrastructure in place to support afami-cel commercial launch upon approval Data from SPEARHEAD-1 pivotal trial with afami-cel published in The Lancet; data from a planned interim analysis of pivotal lete-cel IGNYTE-ESO trial to be presented at ASCO Cash runway into late 2025 Conference call today at 8 a.m. EDT webcast link HERE Philadelphia, Pennsylvania and Oxford, United Kindgom--(News - May 15, 2024) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, today reports financial results and business updates for the first quarter ended March 31, 2024. The Company will host a live webcast at 8:00 a.m. EDT (1:00 p.m. BST) today. Adrian Rawcliffe, Adaptimmune's Chief Executive Officer: "Support from the sarcoma community continues to highlight the high unmet medical need for new therapies for synovial sarcoma and we are making great progress preparing for the commercial launch of afami-cel on approval. Behind afami-cel, we plan to launch lete-cel for synovial sarcoma and MRCLS in 2026 with projected peak US sales of $400 million for our sarcoma franchise." Sarcoma Franchise with afami-cel and lete-cel U.S. FDA accepted the BLA for afami-cel for the treatment of advanced synovial sarcoma with priority review and a PDUFA date of August 4th, 2024 The BLA mid-cycle review meeting was held with FDA in April FDA GCP Bioresearch Monitoring Program (BIMO) inspections have been conducted at Adaptimmune and at selected clinical sites that participated in the pivotal SPEARHEAD-1 trial FDA GMP Pre-license inspections (PLI) have taken place at the Company's Navy Yard facility and at the lentiviral vector contract manufacturer's facility Preliminary plans for confirmatory evidence for afami-cel's full approval were previously agreed with FDA, including Cohort 2 Adaptimmune expects to discuss post-marketing requirements and commitments at the late-cycle meeting which is scheduled for the second half of May To date, the FDA has not requested an Advisory Committee meeting or a REMS program The marketing application for the companion diagnostic for MAGE-A4 is currently under FDA review and is expected to be approved contemporaneously with the BLA Adaptimmune is preparing to launch afami-cel on approval in the U.S. Initially, launch will be focused on 6-10 selected treatment centers ("Authorized Treatment Centers" or "ATCs") and will expand to up to ~30 ATCs. 100% of the customer facing commercial and medical affairs teams is now in place Company launched : an unbranded website aimed at educating healthcare providers about TCR T-cell therapy in solid tumors, including synovial sarcoma, and the role of biomarkers and testing to determine future treatments The second product in Adaptimmune's sarcoma franchise, lete-cel, is being investigated in the pivotal IGNYTE-ESO trial (NCT03967223), which at a planned interim analysis exhibited response in 18/45 of patients (ORR 40%). The primary efficacy endpoint requires 16/60 patients have responses, so this trial has met its primary endpoint for efficacy. The full pivotal analyses are anticipated in late 2024. Lete-cel will enable Adaptimmune to expand its addressable synovial sarcoma patient population by targeting the NY-ESO cancer antigen, in addition to MAGE-A4 targeted by afami-cel, as well as treating Myxoid Round Cell Liposarcoma (MRCLS) patients. Sarcoma franchise of afami-cel and lete-cel leverages same development and commercial footprint with US peak year sales projected to be up to $400 million Data presentations Data from pivotal SPEARHEAD-1 trial with afami-cel published in The Lancet: article entitled "Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial" Data from the planned interim analysis of the pivotal IGNYTE-ESO trial with lete-cel to be presented by Dr. Sandra P. D'Angelo, M.D., Sarcoma Medical Oncology, Memorial Sloan Kettering Cancer Center, in an oral presentation at ASCO entitled "Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial" during the Developmental Therapeutics-Immunotherapy session in Hall D2 on June 3, 2024 at 11:30 a.m. CDT Clinical pipeline Uzatresgene autoleucel ("uza-cel", formerly ADP-A2M4CD8) is being investigated in the SURPASS-3 Phase 2 clinical trial (NCT05601752) for the treatment of platinum-resistant ovarian cancer. Uza-cel received FDA RMAT designation in 2022 for the treatment of patients with platinum resistant ovarian cancer. The SURPASS-3 trial is currently enrolling patients. Cohorts in the Phase 1 SURPASS trial are ongoing for people with head & neck and urothelial (bladder) cancers with uza-cel in combination with standard of care checkpoint inhibitor therapy. Preclinical pipeline IND-enabling studies are underway for ADP-600 (PRAME) and ADP-520 (CD70) programs. Wholly owned allogeneic pipeline advancing; process development in progress at Adaptimmune's allogeneic manufacturing facility in Milton Park, UK. Data presentation Poster presented by George Pope, Ph.D., Associate Director Preclinical Safety at Adaptimmune, entitled "Development and Preclinical Characterization of an Engineered T-Cell Therapy Targeting PRAME-Expressing Solid Tumors" at the American Society of Gene & Cell Therapy (ASGCT) Annual meeting Corporate news As announced earlier today, Adaptimmune has secured up to $125 million in debt financing with Hercules Capital with the first tranche of $25 million available upon closing; and an additional $25 million available upon afami-cel approval Cash runway into late 2025 which includes current cash on hand, anticipated revenues from the launch of afami-cel, expected future income from partners and other non-dilutive capital sources including the Company's new debt facility with Hercules Capital Company announced that its strategic collaboration with Genentech was terminated Financial Results for the three months ended March 31, 2024 Cash / liquidity position: As of March 31, 2024, Adaptimmune had cash and cash equivalents of $140.7 million and Total Liquidity[1] of $143.7 million, compared to $144.0 million and $146.9 million respectively, as of December 31, 2023. Revenue: Revenue for the three months ended March 31, 2024, was $5.7 million compared to $47.6 million for the same period in 2023. Revenue has decreased in 2024, compared to the same period in 2023 primarily due to the termination of the Astellas collaboration in the first quarter of 2023, resulting in the remaining deferred income for the collaboration being recognized as revenue in March 2023. Research and development (R&D) expenses: R&D expenses for the three months ended March 31, 2024, were $35.2 million compared to $25.5 million for the same period in 2023. R&D expenses in the three months ended March 31, 2024 increased in employee-related costs and additional costs associated with lease properties following the acquisition of TCR2 in June 2023 and a decrease in offsetting reimbursements receivable for research and development tax and expenditure credits. General and administrative (G&A) expenses: G&A expenses for the three months ended March 31, 2024, were $19.7 million compared to $20.4 million for the same period in 2023. G&A expenses in the three months ended March 31, 2024 decreased due to restructuring and charges recognised in the first quarter of 2023 and a decrease in other corporate costs due to an increase in accounting, legal and professional fees incurred in relation to the TCR2 Therapeutics, Inc merger agreement that were not repeated in 2024, offset by an increase in depreciation due to leasehold improvements capitalised in 2023. Net loss/profit: Net loss attributable to holders of the Company's ordinary shares for the three months March 31, 2024, was $48.5 million ($(0.03) per ordinary share), compared to a profit of $1.0 million ($0.00 per ordinary share), for the same periods in 2023. Financial Guidance The Company believes that its existing cash, cash equivalents and marketable securities, together with anticipated revenues from the launch of afami-cel, expected future income from partners and other non-dilutive capital sources including the Company's new debt facility with Hercules Capital announced earlier today, will fund the Company's current operations into late 2025, as further detailed in the Company's Quarterly Report on Form 10-Q for the three months ended March 31, 2024, to be filed with the Securities and Exchange Commission following this earnings release. Today's Webcast Details A live webcast and replay can be accessed at . Call in information is as follows: 1-800-806-5484 (US or Canada) or +416-340-2217 (International and additional options available HERE) and the passcode is 3025919#. Callers should dial in 5-10 minutes prior to the scheduled start time and simply ask to join the Adaptimmune call. About Adaptimmune Adaptimmune is a clinical-stage biopharmaceutical company focused on designing, developing, and delivering cell therapies to transform the lives of people with cancer. The Company's unique engineered T-cell receptor (TCR) platform enables the engineering of T-cells to target and destroy cancers across multiple solid tumor types. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Annual Report on Form 10-K filed with the Securities and Exchange Commission for the year ended 31 December, 2023, our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and other filings with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. Total Liquidity (a non-GAAP financial measure) Total Liquidity (a non-GAAP financial measure) is the total of cash and cash equivalents and marketable securities (available-for-sale debt securities). Each of these components appears separately in the condensed consolidated balance sheet. The U.S. GAAP financial measure most directly comparable to Total Liquidity is cash and cash equivalents as reported in the condensed consolidated financial statements, which reconciles to Total Liquidity as follows (in thousands): March 31, December 31, 2024 2023 Cash and cash equivalents $ 140,670 $ 143,991 Marketable securities - available-for-sale debt securities 2,982 2,947 Total Liquidity $ 143,652 $ 146,938 The Company believes that the presentation of Total Liquidity provides useful information to investors because management reviews Total Liquidity as part of its assessment of overall solvency and liquidity, financial flexibility, capital position and leverage. Condensed Consolidated Statement of Operations (unaudited, in thousands, except per share data) Three months ended March 31, 2024 2023 Revenue $ 5,678 $ 47,601 Operating expenses Research and development (35,207) (25,548) General and administrative (19,732) (20,397) Total operating expenses (54,939) (45,945) Operating (loss)/profit (49,261) 1,656 Interest income 1,345 676 Other income (expense), net (61) (671) (Loss)/profit before income tax expense (47,977) 1,661 Income tax expense (526) (625) Net (loss)/profit attributable to ordinary shareholders $ (48,503) $ 1,036 Net (loss)/profit per ordinary share Basic $ (0.03) $ 0.00 Diluted $ (0.03) $ 0.00 Weighted average shares outstanding: Basic 1,451,241,661 991,330,402 Diluted 1,451,241,661 1,000,276,615 Condensed Consolidated Balance Sheets (unaudited, in thousands, except share data) March 31, December 31, 2024 2023 Assets Current assets Cash and cash equivalents $ 140,670 $ 143,991 Marketable securities - available-for-sale debt securities (amortized cost of $2,981 and $2,940) net of allowance for expected credit losses of $0 and $0 2,982 2,947 Accounts receivable, net of allowance for expected credit losses of $0 and $0 8,404 821 Other current assets and prepaid expenses 34,847 59,793 Total current assets 186,903 207,552 Restricted cash 2,858 3,026 Operating lease right-of-use assets, net of accumulated amortization of $14,381 and $13,220 19,434 20,762 Property, plant and equipment, net of accumulated depreciation of $48,445 and $46,020 48,291 50,946 Intangible assets, net of accumulated amortization of $5,198 and $5,155 524 330 Total assets $ 258,010 $ 282,616 Liabilities and stockholders' equity Current liabilities Accounts payable $ 6,587 $ 8,128 Operating lease liabilities, current 5,250 5,384 Accrued expenses and other current liabilities 23,050 30,303 Deferred revenue, current 31,524 28,973 Total current liabilities 66,411 72,788 Operating lease liabilities, non-current 18,442 19,851 Deferred revenue, non-current 147,365 149,060 Other liabilities, non-current 1,417 1,404 Total liabilities 233,635 243,103 Stockholders' equity Common stock - Ordinary shares par value £0.001, 1,702,760,280 authorized and 1,532,974,878 issued and outstanding (2023: 1,702,760,280 authorized and 1,363,008,102 issued and outstanding) 2,081 1,865 Additional paid in capital 1,096,690 1,064,569 Accumulated other comprehensive loss (2,720) (3,748) Accumulated deficit (1,071,676) (1,023,173) Total stockholders' equity 24,375 39,513 Total liabilities and stockholders' equity $ 258,010 $ 282,616 Condensed Consolidated Cash Flow Statement (unaudited, in thousands) Three months ended March 31, 2024 2023 Cash flows from operating activities Net (loss)/profit $ (48,503) $ 1,036 Adjustments to reconcile net loss to net cash used in operating activities: Depreciation 2,771 1,659 Amortization 59 186 Share-based compensation expense 3,102 1,676 Unrealized foreign exchange losses 305 563 (Accretion)/amortization on available-for-sale debt securities (23) 112 Other (19) 134 Changes in operating assets and liabilities: Increase in receivables and other operating assets 15,620 3,683 (Decrease)/increase in payables and other current liabilities (7,650) 21 Decrease/(increase) in deferred revenue 2,388 (46,353) Net cash used in operating activities (31,950) (37,283) Cash flows from investing activities Acquisition of property, plant and equipment (102) (2,349) Acquisition of intangible assets (256) (173) Maturity or redemption of marketable securities — 50,863 Net cash (used in)/provided by investing activities (358) 48,341 Cash flows from financing activities Proceeds from issuance of common stock from offerings, net of commissions and issuance costs 29,161 188 Proceeds from exercise of stock options 74 8 Net cash provided by financing activities 29,235 196 Effect of currency exchange rate changes on cash, cash equivalents and restricted cash (416) 588 Net (decrease)/increase in cash, cash equivalents and restricted cash (3,489) 11,842 Cash, cash equivalents and restricted cash at start of period 147,017 109,602 Cash, cash equivalents and restricted cash at end of period $ 143,528 $ 121,444 Adaptimmune Contact Investor Relations Juli P. Miller, Ph.D. - VP, Corporate Affairs and Investor Relations T : +1 215 825 9310 M : +1 215 460 8920 Juli.Miller@adaptimmune.com Media Relations Dana Lynch, Senior Director of Corporate Communications M: +1 267 990 1217 Dana.Lynch@adaptimmune.com [1] Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below To view the source version of this press release, please visit