Letetresgene autoleucel

Tecelra will continue to be available to patients without interruption US WorldMeds plans to bring lete-cel to market and will continue development of uza-cel in collaboration with Galapagos Purchase price is $55m in cash to be paid upon consummation of the sale with up to $30m in potential future payments upon achievement of certain milestones Adaptimmune will retain rights to its preclinical assets including PRAME, CD70, and its allogeneic program Adaptimmune will restructure to support the transition of these therapies to US WorldMeds and to maximize value from its remaining assets Adaptimmune's Board of Directors determined this transaction is in the best interest of all stakeholders following a comprehensive review of all strategic alternatives Philadelphia, Pennsylvania and Oxford, United Kingdom--(Newsfile Corp. - July 28, 2025) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, today announced its entry into a definitive agreement for the sale of TECELRA, lete-cel, afami-cel, and uza-cel cell therapies to US WorldMeds. Consummation of the sale is expected to occur before the end of the week. Adrian Rawcliffe, Adaptimmune's Chief Executive Officer: "Adaptimmune has been at the forefront of solid tumor cell therapy and delivering groundbreaking treatments to patients for more than a decade. We were the first company to obtain a marketing authorization for an engineered TCR T-cell therapy, TECELRA, and we have a second cell therapy, lete-cel, with approval anticipated in 2026. However, given the financial situation of the Company, it is clear that securing the right strategic option was critical to maximize value for all of our stakeholders and importantly ensure our patients continue to receive TECELRA. After an extensive review of all strategic alternatives available to Adaptimmune we are convinced that this transaction represents the best path forward for Adaptimmune, our patients and stakeholders." Breck Jones, US WorldMeds Chief Executive Officer: "Anchored by a first-in-class commercial therapy and a promising pipeline, this acquisition is a meaningful step forward in our mission to bring hope and innovation to patients who need it most. US WorldMeds deeply respects the strong foundation Adaptimmune has built in the cell therapy space and is committed to carrying that work forward - advancing and delivering these important therapies to the people and families who are counting on them." Under the terms of the asset purchase agreement, US WorldMeds will purchase the TECELRA, uza-cel, afami-cel and lete-cel cell therapy assets of Adaptimmune (the "Assigned Assets") and all intellectual property rights exclusively relating to such Assigned Assets. In return, Adaptimmune will receive $55 million in cash upon consummation of the sale. In addition, US WorldMeds has agreed to make future payments of up to $30 million to Adaptimmune upon the achievement of certain milestones. Adaptimmune and US WorldMeds will also enter into a license agreement pursuant to which, among other things, US WorldMeds will be exclusively licensed residual intellectual property rights necessary for the manufacture and commercialization of the Assigned Assets and non-exclusively licensed intellectual property rights in Adaptimmune's vector manufacturing process. Adaptimmune will also provide certain transition services to US WorldMeds pursuant to a transition services agreement on terms specified therein. US employees involved in the development and commercialization of the Assigned Assets will be offered employment with US WorldMeds to ensure the ongoing success and ability to supply those Assigned Assets. Following the transaction Adaptimmune intends to restructure to support the continued development by US WorldMeds of lete-cel, TECELRA and uza-cel and to maximise value from its remaining assets including its PRAME and CD70 directed T-cell therapies. TD Cowen acted as financial advisor, and Ropes & Gray LLP provided legal counsel, to Adaptimmune. Gibson, Dunn & Crutcher LLP provided legal counsel to US WorldMeds. The transaction will be financed by debt financing led by funds managed by Oaktree Capital Management, L.P. (“Oaktree”), with participation from funds managed by Athyrium Capital Management, LP (“Athyrium”). Forward-Looking Statements This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Actual events or results may differ materially from these forward-looking statements. Words such as "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "future," "opportunity" "will likely result," "target," variations of such words, and similar expressions or negatives of these words are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of such forward-looking statements include, but are not limited to, express or implied statements regarding: the proposed transaction and related matters; the impact of the proposed transaction on Adaptimmune's share price; the anticipated benefits of the proposed transaction for Adaptimmune's financial results and business performance; Adaptimmune's targets, plans, objectives or goals for future operations, including those related to Adaptimmune's products or product candidates, research and development, product candidate introductions and product candidate approvals as well as cooperation in relation thereto; projections of or targets for revenues, costs, income (or loss), earnings per share, capital expenditures, dividends, capital structure, net financials and other financial measures; future economic performance, future actions and outcome of contingencies such as legal proceedings; the assumptions underlying or relating to such statements; and other risks and uncertainties contained in Adaptimmune's filings with the U.S. Securities and Exchange Commission (the "SEC"), including Adaptimmune's most recently filed Annual Report on Form 10-K and 10-Q. These forward-looking statements speak only as of the date of this release, and Adaptimmune undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by applicable laws. About Oaktree Oaktree is a leader among global investment managers specializing in alternative investments, with $203 billion in assets under management as of March 31, 2025. The firm emphasizes an opportunistic, value-oriented, and risk-controlled approach to investments in credit, equity, and real estate. The firm has more than 1,200 employees and offices in 25 cities worldwide. For additional information, please visit Oaktree’s website at http://www.oaktreecapital.com/. About Athyrium Athyrium is a specialized asset management company formed in 2008 to focus on investment opportunities in the global healthcare sector. Athyrium advises funds with over $4.6 billion in committed capital. The Athyrium team has substantial investment experience across a wide range of asset classes including public equity, private equity, fixed income, royalties, and other structured securities. Athyrium invests across all healthcare verticals including biopharma, medical devices and products, healthcare focused services, and healthcare information technology. For more information, please visit www.athyrium.com. Investor Relations and Media Relations Adrian Rawcliffe - Chief Executive Officer Adrian.Rawcliffe@adaptimmune.com Patient Advocacy and Medical Affairs Laura Gunn - Vice President, Global Medical Affairs Laura.Gunn@adaptimmune.com To view the source version of this press release, please visit https://www.newsfilecorp.com/release/260248 SOURCE Adaptimmune Therapeutics PLC Released July 28, 2025

近期，全球权威医学期刊《Nature Medicine》报道的一项研究在抗癌领域引发轰动：一位67岁的腹膜间皮瘤（MPM）患者在尝试所有常规治疗方案无效后，接受了新型TCR-T疗法仅25天，其体内肿瘤便显著缩小，随后几乎完全消退，实现了临床意义上的“重获新生”。 值得关注的是，这类带来突破的TCR-T免疫疗法中，一款名为“Afami-cel”的产品已于2024年8月在美国获批上市，用于治疗成年患者的不可切除或转移性滑膜肉瘤。更令人振奋的是，这款备受国际关注的疗法目前已在我国针对多种癌种启动多项临床研究，有望为全球患者带来新的治疗希望！ ▲截图源自“Nature medicine” gavo-cel TCR-T精准锁杀间皮瘤、卵巢癌、胆管癌等，77%疾病受控，一例治疗25天全身多处肿瘤消退 间皮素是一种细胞表面糖蛋白，正常情况下仅在胸膜、腹膜和心包的间皮细胞中表达；但在约30%的人类癌症中存在过表达，这使其成为靶向治疗（包括T细胞疗法）中极具吸引力的肿瘤抗原。gavocabtagene autoleucel（gavo-cel）正是由单结构域抗间皮素抗体组成的一种新型疗法，该抗体可整合到内源性T细胞受体（TCR）中，在与间皮素结合后能启动TCR的完整信号传导，从而精准靶向癌细胞。 全球权威期刊《Nature Medicine》报道了gavo-cel治疗难治性间皮素表达实体瘤的1/2期试验（NCT03907852）第1阶段数据，结果令人振奋。该研究共入组32例中位年龄为63岁（范围：28-84岁）的患者，包括23例间皮瘤、8例卵巢癌、1例胆管癌患者；其中3例接受gavo-cel单药治疗，29例在淋巴细胞清除（LD）后接受治疗gavo-cel治疗。 结果显示：在30例可评估患者中， 总缓解率（ORR）为20% （其中确诊部分缓解率13%）， 疾病控制率（DCR）达77%，6个月总生存率为70% 。除2例外，其余患者的靶病灶直径总和均缩小， 减小幅度4%-80% （详见下图）；尤其值得注意的是，淋巴细胞清除（LD）后接受治疗的患者肿瘤消退更显著， 8例（5例间皮瘤、2例卵巢癌、1例胆管癌）缩小超过30% ，且消退程度与输注前肿瘤负荷无关。另有 1例间皮瘤患者（患者3）出现逐渐缓解 ，虽3个月时靶病灶消退不足30%，但 6个月时消退超30% 。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 此外，所有患者的的 中位无进展生存期（PFS）为5.6个月 （95％CI，3.1–5.8，详见下图a）， 中位总生存期（OS）为10.6个月 （95％CI，6.6–15.6，详见下图b）。 6个月OS为70.2％ 。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 值得一提的是，有三例患者的治疗过程，直观展现了gavo-cel的疗效。 其中一位67岁女性转移性上皮样间皮瘤患者（患者15），在4种前期治疗失败后，入组接受淋巴细胞清除（LD）+gavo-cel治疗。 结果显示：治疗第5天，血清乳酸脱氢酶（LDH）升高（提示肿瘤细胞被杀伤），第9天达峰后逐渐下降。 第25天的CT扫描显示肿瘤显著缩小（大部分已变为液体） ， ¹⁸F-氟脱氧葡萄糖（FDG）摄取大幅降低，随后几乎完全消退 。 这种缓解状态持续了12个月 （详见下图a、b）。治疗第64天的胸壁肿块活检显示： 肿瘤完全坏死，且无任何间皮素表达。 ▼该患者输注gavo-cel前、输注后约1个月、输注后8个月获得的18F-FDGPET最大强度投影正面图 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 另一例36岁上皮样恶性腹膜间皮瘤男性（患者4），在检查点抑制剂治疗失败后接受了gavo-cel治疗， 肿瘤明显消退 ：基线MRI与治疗后6个月的CT扫描对比显示 ，毗邻左肾的病变（病变1）已完全消退，直肠腹膜反射处的病变（病变2）也显著缩小 （详见下图）。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 还有一例70岁铂类难治性高级别浆液性卵巢癌女性（患者5），接受gavo-cel治疗后同样 出现肿瘤消退 ：代表性CT扫描显示，治疗后1个月和3个月时， 纵隔淋巴结（病灶1）与腹部腔静脉后淋巴结（病灶2）的靶病灶均持续缩小，且这一效果维持至治疗后6个月 （详见下图）。 ▲图源“Nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 Lete-cel疗法精准锁定NY-ESO-1靶点，让2类难治肉瘤迎转机，总缓解率达40% Lete-cel是一种自体工程化T细胞受体疗法，其靶点为NY-ESO-1睾丸癌抗原——该抗原在滑膜肉瘤（SyS）和粘液样/圆细胞脂肪肉瘤（MRCLS）中高表达。初步研究已显示，在NY-ESO-1阳性的SyS或MRCLS患者中，Lete-cel展现出良好疗效。 2024年美国临床肿瘤学会（ASCO）大会上，Lete-cel的2期临床试验（NCT03967223）公布了惊艳数据。该研究共纳入73例转移性或不可切除的滑膜肉瘤（SyS）或粘液样/圆细胞脂肪肉瘤（MRCLS）患者，中位年龄为46.0岁（范围：18-68岁），均接受Lete-cel治疗。 结果显示：在45例可评估疗效的患者中， 总缓解率（ORR）达40% （18/45，20.3%-62.3%），其中 包括2例完全缓解（CR）、16例部分缓解（PR）。中位缓解持续时间为10.6个月 （95%CI：3.3-未达到）。 ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 细分癌种来看， 滑膜肉瘤（SyS）患者缓解率为39% （9例）， 粘液样/圆细胞脂肪肉瘤（MRCLS）患者为41% （9例）。 ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 综上，Lete-cel在IGNYTE-ESOSS2研究的初始分析达到主要终点，为作为晚期或转移性SyS、MRCLS患者的新型疗法奠定了坚实基础，凸显出广阔应用潜力。 ADP-A2M10 TCR-T疗法精准攻坚非小细胞肺癌：71.4%患者病情受控，中位生存期达132天 《免疫肿瘤学杂志》报道了一项关于ADP-A2M10细胞治疗非小细胞肺癌的I期临床研究（ADP-0022-003，NCT02592577），为非小细胞肺癌患者带来了新的曙光！ 该研究共纳入11例HLA-A*02阳性的晚期（IIIB或IV期）非小细胞肺癌患者，包括8例腺癌、3例鳞状细胞癌。入组后，所有患者均接受淋巴细胞清除术联合ADP-A2M10治疗——这种经基因改造的自体T细胞可表达MAGE-A10特异性T细胞受体（TCR）。 结果显示：在7例可评估疗效的患者中，71.4%（5例）达到病情稳定（SD），中位无进展生存期（PFS）为58天，中位总生存期（OS）更是长达132天。 尤为值得关注的是其中1例患者（患者9）：首次TCR-T细胞回输后， 肿瘤显著缩小25% （详见下图）；在第2次输注8周后， 进一步达到部分缓解 （PR）。 ▼患者9在治疗前、治疗第12周、治疗结束时的CT图像对比 ▲图源“BMJ”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 注： ①红色箭头：代表右下叶（RLL）肺肿块； ②蓝色箭头：代表左上叶（LUL）肺肿块。 小编寄语 TCR-T疗法创新性地开创了“抗癌+抗病毒”双效合一的治疗范式。近年来，科研团队正加速探索其在病毒相关性实体瘤领域的应用，尤其是乙肝病毒引发的肝细胞癌，以及人乳头瘤病毒（HPV）相关的宫颈癌等重点癌种。值得振奋的是，随着2024年首款TCR-T细胞治疗产品成功获批上市，标志着这一前沿技术正式迈入临床应用阶段！我们期待未来有更多突破性抗癌疗法获批，助力实体瘤患者实现长期带瘤生存的希望。 参考资料 [1]Hassan R,et al.Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results[J]. Nature medicine, 2023, 29(8): 2099-2109. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41591-023-02452-y [2]D'Angelo S P,et al.Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial[J]. 2024. https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.16_suppl.2500 [3]Blumenschein GR,et al.Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. J Immunother Cancer. 2022 Jan;10(1):e003581. https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC8796260/ 本文为全球肿瘤医生网原创，未经授权严禁转载