Immunocore肝病学领域发表临床前数据，显示ImmTAV®双特异

StephenW

Immunocore announces publication of preclinical data in Hepatology showing the potential of ImmTAV® bispecific molecules for functional cure of chronic hepatitis B
Email Print Friendly Share
August 27, 2020 02:00 ET | Source: Immunocore Limited

PRESS RELEASE

Immunocore announces publication of preclinical data in Hepatology showing the potential of ImmTAV® bispecific molecules for functional cure of chronic hepatitis B

New preclinical data show potential of ImmTAV platform to facilitate specific and rapid elimination of Hepatitis B‐infected cells with the goal of achieving functional cure

Lead bispecific candidate, IMC-I109V, to progress into first‐in‐human clinical trials for the treatment of chronic Hepatitis B

(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 27 August 2020) Immunocore (or the “Company”), a pioneering, clinical‐stage T cell receptor biotechnology company working to develop and commercialise a new generation of transformative medicines to address unmet needs in cancer, infection and autoimmune disease, today announces publication of a novel therapeutic approach with the potential to provide a functional cure for chronic hepatitis B, in leading peer reviewed journal Hepatology.

Achieving functional cure, a sustained loss of circulating HBsAg and HBV DNA, is a challenge for the field due to the persistence of cells capable of producing HBsAg and which act as a reservoir for virus production. These cells can contain integrated HBV-DNA or long-lived covalently closed circular DNA (cccDNA), both of which are difficult for direct-acting anti-viral therapies to permanently eradicate. Additionally, HBV-specific immune responses in people living with Hepatitis B are often exhausted, making it difficult for them to eliminate the infected cells.

With this in mind, the team at Immunocore is utilising its immune‐mobilising monoclonal T cell receptors against virus (ImmTAV®) platform to address these challenges. These bi-specific molecules consist of a targeting arm which tightly binds viral protein fragments on the surface of infected hepatocytes, and an immune‐activating arm to redirect non-exhausted T cells to eliminate infected hepatocytes, bypassing exhausted HBV‐specific T cells. The team were able to generate multiple ImmTAV molecules to specifically recognise fragments of 3 different viral proteins and achieve potent T cell redirection in vitro.

To achieve a functional cure, sources of HBsAg (Env) must be eliminated. Therefore, ImmTAV-Env molecules were further characterised and shown to redirect a broad range of T cells subsets towards HBsAg positive cells, with T cell responses observed from both healthy and HBV‐infected donors. Crucially, the redirection of T cells by ImmTAV‐Env resulted in elimination of cells representative of both major sources of HBsAg, hepatocellular carcinoma (HCC) cells containing integrated HBV-DNA, and cells infected with HBV in vitro, causing a substantial reduction of HBeAg and specific elimination of up to 97% of cells expressing viral RNA.

Importantly, activated T cells did not attack healthy, un-infected human hepatocytes and furthermore, could be switched off by the addition of a corticosteroid. This demonstrates the feasibility of controlling the activity of the ImmTAV-Env molecule in order to safeguard against excessive cytokine release.

Collectively, these data support on-target efficacy of the lead HBV ImmTAV against HBV-infected hepatocytes. Following completion of preclinical development earlier this year, Immunocore has been granted regulatory approval to move forward with a first-in-human trial of IMC-I109V (#ACTRN12620000403932p).

“Hundreds of millions of people are chronically infected with HBV worldwide and current treatment options require lifelong adherence to be effective. There is an urgent need for new therapies to provide a functional cure, defined as absence of detectable HBV or viral proteins in the bloodstream after standard of care drugs are withdrawn,” said David Berman, Head of Research and Development at Immunocore. “These highly encouraging preclinical data demonstrate the ability of our novel ImmTAV‐Env molecule to redirect T cells to target and kill cells infected with HBV, representing a potential therapeutic option for patients with chronic Hepatitis B. We look forward to progressing IMC-I109V into first‐in‐human clinical trials.”

- Ends -

About ImmTAV molecules and infectious diseases
Chronic viral infections such as Hepatitis B occur when the virus succeeds in hiding from the immune system or drives the immune system to exhaustion. Immunocore's bi‐specific T cell receptor (TCR) technology platform is being investigated to offer a new approach for the treatment of chronic infections by redirecting non‐exhausted immune cells to attack infected cells, even if those cells present levels of target that are too low for the natural immune system to see.

ImmTAV (Immune mobilising mTCR Against Virus) molecules are novel small protein bispecific molecules that, like ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules, enable the immune system to recognize and kill diseased cells, in this case, virally infected cells. ImmTAV and ImmTAC molecules resemble each other in appearance and function, although ImmTAV molecules are designed to specifically recognise and kill virally infected cells.

Immunocore aims to achieve sustained loss of circulating viral antigens and markers of viral replication for people living with chronic hepatitis B, after stopping medication. This is known as “functional cure”

About Immunocore
Immunocore is a pioneering, clinical‐stage T cell receptor biotechnology company working to develop and commercialise a new generation of transformative medicines to address unmet needs in cancer, infection and autoimmune disease. The Company’s most advanced programmes are in oncology and it has a rich pipeline of programmes in infectious and autoimmune diseases. Immunocore’s lead programme, tebentafusp (IMCgp100), has entered pivotal clinical studies as a treatment for patients with metastatic uveal melanoma. Collaboration partners include Genentech, GlaxoSmithKline, AstraZeneca, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Immunocore is headquartered at Milton Park, Oxfordshire, UK, with offices in Conshohocken, Pennsylvania and Rockville, Maryland in the US. For more information, please visit www.immunocore.com.

For more information, please contact:

Immunocore
Debra Nielsen, Head of Communications
T:  +1 (610) 368-8602
E: [email protected]
Follow on Twitter: @Immunocore

Consilium Strategic Communications (corporate and financial)
Mary-Jane Elliott/ Chris Welsh/ Sukaina Virji
T: +44 (0)203 709 5700
E: [email protected]

StephenW

Immunocore宣布在肝病学领域发表临床前数据，显示ImmTAV®双特异性分子在慢性乙型肝炎的功能治疗中的潜力
电子邮件打印友好分享
东部时间2020年8月27日02:00 |资料来源：Immunocore Limited

新闻稿

Immunocore宣布在肝病学领域发表临床前数据，显示ImmTAV®双特异性分子在慢性乙型肝炎的功能治疗中的潜力

新的临床前数据表明，ImmTAV平台具有促进特异性和快速消除感染乙肝的细胞的潜力，以实现功能性治愈

领先的双特异性候选药物IMC-I109V，将进入用于治疗慢性乙型肝炎的首次人类临床试验

（英格兰OXFORDSHIRE和宾夕法尼亚州CONSHOHOCKEN，美国马里兰州罗克维尔，2020年8月27日）Immunocore（或“公司”），一家致力于临床阶段T细胞受体生物技术的开拓性公司，致力于开发和商业化新一代的解决癌症，感染和自身免疫疾病未满足需求的转化药物，今天在领先的同行评审期刊《肝病学》（Hepatology）上宣布发布一种新颖的治疗方法，有望为慢性乙型肝炎提供功能性治疗。

由于能够产生HBsAg的细胞的持久性并充当病毒生产的储存库，因此实现功能性治疗，循环HBsAg和HBV DNA的持续损失是该领域面临的挑战。这些细胞可以包含整合的HBV-DNA或长寿命的共价闭合的环状DNA（cccDNA），这两种化合物都难以直接作用的抗病毒疗法永久根除。此外，乙型肝炎患者的HBV特异性免疫反应常常很累，使他们难以清除感染的细胞。

考虑到这一点，Immunocore的团队正在利用其针对病毒的免疫活动性单克隆T细胞受体（ImmTAV®）平台来应对这些挑战。这些双特异性分子包括与感染的肝细胞表面上的病毒蛋白片段紧密结合的靶向臂和免疫激活臂，用于使未用尽的T细胞重新定向以消除感染的肝细胞，从而绕过疲惫的HBV特异性T细胞。该团队能够产生多个ImmTAV分子，以特异性识别3种不同病毒蛋白的片段，并在体外实现有效的T细胞重定向。

为了实现功能性治愈，必须消除HBsAg（Env）的来源。因此，对ImmTAV-Env分子进行了进一步表征，结果表明它可以将多种T细胞亚群重定向至HBsAg阳性细胞，同时从健康和HBV感染的供体中均观察到T细胞反应。至关重要的是，通过ImmTAV-Env重定向T细胞导致消除了代表HBsAg主要来源的细胞，含有整合的HBV-DNA的肝细胞癌（HCC）细胞以及体外感染HBV的细胞，从而导致HBeAg大量减少并特异性消除多达97％的表达病毒RNA的细胞。

重要的是，活化的T细胞不会攻击健康的，未感染的人类肝细胞，而且可以通过添加皮质类固醇来关闭。这证明了控制ImmTAV-Env分子的活性以防止过度的细胞因子释放的可行性。

总体而言，这些数据支持铅HBV ImmTAV对HBV感染的肝细胞的靶向作用。在今年早些时候完成临床前开发后，Immunocore已获得监管部门的批准，可以进行IMC-I109V（＃ACTRN12620000403932p）的首次人体试验。

“全世界有数以亿计的人长期感染HBV，目前的治疗选择要求终身坚持才能有效。迫切需要提供功能性治疗的新疗法，这被定义为撤消标准护理药物后血液中没有可检测到的HBV或病毒蛋白。” Immunocore研究和开发负责人David Berman说。 “这些令人鼓舞的临床前数据表明，我们新颖的ImmTAV-Env分子能够将T细胞重定向到靶向并杀死感染HBV的细胞，这代表了慢性乙型肝炎患者的潜在治疗选择。我们期待着将IMC-I109V逐步发展为首次人类临床试验。”

-完-

关于ImmTAV分子和传染病
当病毒成功躲避免疫系统或驱使免疫系统衰竭时，就会发生慢性病毒感染，例如乙型肝炎。正在研究Immunocore的双特异性T细胞受体（TCR）技术平台，以提供一种新的方法来治疗慢性感染，方法是将未用尽的免疫细胞重定向到攻击受感染的细胞，即使这些细胞的靶标水平太低为自然免疫系统所见

ImmTAV（针对病毒的免疫动员mTCR）分子是新颖的小蛋白双特异性分子，与ImmTAC（针对癌症的免疫动员单克隆TCR）分子一样，能够使免疫系统识别并杀死患病的细胞，在这种情况下为病毒感染的细胞。 ImmTAV和ImmTAC分子在外观和功能上相似，尽管ImmTAV分子被设计用来特异性识别和杀死病毒感染的细胞。

Immunocore的目标是在停止药物治疗后，使慢性乙型肝炎患者的循环病毒抗原和病毒复制标记持续丢失。这就是所谓的“功能性治疗”

关于Immunocore
Immunocore是一家具有开拓性的临床T细胞受体生物技术公司，致力于开发和商业化新一代转化药物，以满足癌症，感染和自身免疫性疾病的未满足需求。该公司最先进的计划是肿瘤学，并且拥有丰富的传染病和自身免疫性疾病计划。 Immunocore的主要计划tebentafusp（IMCgp100）已进入关键的临床研究，作为转移性葡萄膜黑色素瘤患者的治疗方法。合作伙伴包括Genentech，葛兰素史克，阿斯利康，礼来公司以及比尔和梅琳达·盖茨基金会。 Immunocore的总部位于英国牛津郡的弥尔顿公园，在宾夕法尼亚州的康斯霍肯和美国马里兰州的罗克维尔设有办事处。有关更多信息，请访问www.immunocore.com。

获取更多资讯，请联系：

免疫核心
传讯主管Debra Nielsen
电话：+1（610）368-8602
电子邮件：[email protected]
在Twitter上关注：@Immunocore

Consilium战略传播（企业和财务）
玛丽·简·埃利奥特/克里斯·威尔士/苏卡娜·维吉
电话：+44（0）203709 5700
电子信箱：[email protected]