Anti-HPV-16 E7/HLA-A*0201 TCR T-cell therapy(Kite Pharma, Inc.)

Fosun Pharma plans to pay $27 million to buy Gilead Sciences' Kite Pharma out of its 50% stake in their Chinese joint venture. Gilead Sciences’ Kite Pharma will sell its stake in China’s Fosun Kite Biotechnology nearly eight years after forming the 50-50 cell-therapy-focused joint venture with Fosun Pharma.Fosun plans to pay $27 million to buy Kite out of its 50% share in Fosun Kite, the Chinese company said in a securities filing (PDF) to the Shanghai Stock Exchange on Sept. 13.The transaction will give Fosun full control in China over Yescarta, the star CD19-directed blood cancer therapy that was the first CAR-T therapy approved in China, plus its sister med Tecartus, which is undergoing bridging studies in the country.Kite’s exit from the Fosun JV comes as CAR-T meds continue to navigate patient access and reimbursement dynamics in China. In 2023, Fosun Kite recorded 242 million Chinese yuan ($34 million) in revenue, according to the filing. Relma-cel, a rival CD19 CAR-T drug, brought in 174 million yuan ($25 million) in sales last year.The list price for Yescarta in China is 1.2 million yuan (about $170,000). Although much cheaper than in the U.S., the cost is still astronomical for most Chinese families; China’s annual per capita disposable income last year was about one-thirtieth of that price. Since its approval in June 2021, Yescarta has treated more than 700 large B-cell lymphoma patients in China, according to Fosun Kite’s Website.CAR-T therapies’ high prices make them unlikely to qualify for national coverage under China's state-run insurance scheme.To help with access, Fosun Kite has over the years explored commercial insurance coverage, including a government-devised supplemental insurance program in Shanghai. Such policies have been able to cover up to 42% of the drug's cost, according to the company.And, in January, Fosun Kite worked with (Chinese) a subsidiary of state-run Sinopharm Group to roll out an outcomes-based payment program, offering half of a patient’s out-of-pocket cost back if Yescarta doesn’t induce a complete response by three months. To form the Chinese JV in early 2017, Fosun offered Kite $40 million in an upfront payment and committed $35 million in milestones for Yescarta’s rights in China, plus committed $20 million in initial funding for the new firm. The JV at the time had the option to license additional Kite candidates, including TCR therapies KITE-439 and KITE-718, both of which have since been discontinued at Kite.Now, Fosun said it will invest an additional $10 million in the cell therapy company.After the separation, Kite still grants Fosun rights to Yescarta and Tecartus in China and will supply the viral vectors used to manufacture the products. Kite will also get tiered royalties ranging from 7% to 13% of the drugs’ sales. For Fosun Kite’s pipeline assets, Kite is entitled to 2% to 4% of sales-based royalties if any ever reach the market. Kite’s decision to back out of the JV also follows a recent trend in which foreign pharmas are increasingly leaving management of their products—mostly established medicines—to local companies. Just last month, UCB said it will divest its mature neurology and allergy business in mainland China to local healthcare asset manager CBC Group and Abu Dhabi-based investment firm Mubadala. Days later, Sinopharm’s blood products subsidiary Beijing Tiantan Biological Products disclosed (PDF) that it’s buying a CSL Behring subsidiary in China for $185 million to obtain several albumin and human globulin products.

里程碑！全球首款TCR-T细胞疗法获批上市。 当地时间2024年8月1日，Adaptimmune宣布旗下TCR-T疗法Afami-cel（商品名：Tecelra）获FDA批准上市，用于晚期滑膜肉瘤的治疗。 图1：Afami-cel获批新闻稿（图片来源：Adaptimmune） Afami-cel上市的里程碑意义，不仅仅象征着全球首款，更意味着全新靶点选择空间的开辟，肿瘤治疗靶点从膜上/胞外转移至胞内。 TCR-T，即engineered T cell receptor-T cell（T细胞受体工程T细胞），与我们熟知的CAR-T基本原理相近。 都是对T细胞进行基因改造，以提高其识别和攻击肿瘤的能力。操作流程也大致相同，都是对患者自身的T细胞，进行体外改造，细胞扩增，再到重回输至患者体内。 因此，两者被统称为“T细胞受体重新定向”技术。 但实际运用中，两者在抗原识别、抗原特异性以及适应症上存在较大差别。TCR-T细胞可识别细胞表面或细胞内的特异性抗原，而CAR-T细胞只能是被细胞表面的特异性抗原。 所以，理论上TCR-T更适合实体瘤治疗。 根据Afami-cel的二期临床SPEARHEAD-1研究显示，中位随访32.6个月时，患者ORR达到了39%，中位缓解持续时间（DOR）为11.6个月。 且Afami-cel治疗2年生存率为70%，患者的mOS约为17个月，远超历史数据对照的不足12个月。 据美国滑膜肉瘤基金会首席执行官Brandi Felser所述，目前滑膜肉瘤患者五年生存率低至36%，对于那些确诊时就是晚期的患者，这一比率仅约为20%。 如今Afami-cel上市，便是对TCR-T实体瘤治疗可及性的验证。 时间拉回至今年1月份，当时Afami-cel的上市申请还未获FDA受理，更未获得优先审评资格。 Adaptimmune的首席执行官Adrian Rawcliffe，就在JPM大会上分享，2026年之前公司将推出两款TCR-T疗法，Afami-cel以及lete-cel（靶向NY-ESO-1），两款合计在美国的峰值销售额为4亿美元。 这样的预计不知是多还是少？ 2022年，全球首款TCR疗法Kimmtrak获批上市，用于治疗葡萄膜黑色素瘤。 该药物是一种TCR-scFv双特异性融合蛋白，其TCR部分经过改造提高了靶向gp100的亲和力，scFv部分靶向CD3募集T细胞。所以，与Afami-cel不同。 值得注意的是，Kimmtrak的定价为40万美元/年，并不便宜，但当年（2022年）的销售额却有1.4亿美元。 相比之下，技术难度更高的Afami-cel定价会更高，加上滑膜肉瘤更为罕见，市场规模也会相应缩小。 目前，全球已有多款TCR疗法进入临床阶段，包括吉利德的KITE-439；Immunocore的IMC-C103C、IMC-I109V；香雪生命科学的TAEST16001等，均已进入临床二期。 药物类型除了TCR-T，还有TCR-T双抗、TCR双特异性蛋白，涉及适应症包括，HPV阳性实体瘤、乙肝、胆管癌等等。 至于国内，进展最快的是香雪生命科学。 2024年7月30日，CDE同意香雪生命科学的TCR-T细胞疗法TAEST16001纳入突破性治疗品种名单。 此外，据不完全统计国内还有来恩生物、百吉生物、星汉德、天科雅、华夏英泰、恒瑞源正、可瑞生物、科士华生物、新景智源等17家药企布局。 小结： Afami-cel的获批，再次拓展了CGT的治疗前景。 在昨晚药时代“大话CGT系列：细胞疗法的新突破，大未来”的直播中，药时代邀请到了邦耀生物的CEO郑彪博士，邦耀生物的联合创始人杜冰教授，瑞顺生物的杨黎明博士，和元生物CEO贾国栋博士以及近岸蛋白创始人朱化星博士。 各位行业专家分别从研发药企，CRO，原料药等多个角度，共同探讨我国CGT药物研发的最新进展。 郑彪博士与杜冰教授，共同分享了其新一代同种异体通用型CAR-T疗法TyU19用于治疗自身免疫疾病的研究成果，这是全球首个在治疗自身免疫疾病中获得积极结果的同种异体通用型CAR-T疗法； 瑞顺生物杨黎明博士阐述了通用型CAR-T在自免疾病领域的机会和挑战，并就现货通用型DNT免疫细胞疗法进行探讨； 贾国栋博士对自体CAR-T成本进行解析，提出了背后的生产成本高、个性化基因检测、周期长、自动化生产不成熟等多项定价因素； 朱化星博士则是从原料药的角度，解析工具对研发的影响，包括减少监管压力，研发过程更安全可控等…… 欢迎各位扫码，观看重播！ 封面图来源：网络 版权声明/免责声明 本文为原创文章。 本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。 文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。 如有任何问题，请与我们联系。 衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn RSV疫苗市场遭重创，GSK “低头” 表态 默沙东股价跌近10%，与医药反腐有关？ 药企并购后，高管获得8055万 “意外之喜 ”！并非个例...... 点击这里，发现价值信息！