中国的生物技术公司的目标是在乙型肝炎中使用PD-L1抗体

StephenW

Chinese biotechs aim PD-L1 antibody at hepatitis B

Cancer therapies could help boost patient's immune system

Ascletis

Checkpoint inhibitors are already making a big impact in cancer, but two Chinese biotechs want to explore their activity in viral diseases, and specifically hepatitis B.

Suzhou Alphamab is already testing its PD-L1 inhibitor antibody KN035 in a number of clinical trials across tumour types in the US, China and Japan, but has licensed rights for viral diseases to Ascletis in China, potentially opening up a new revenue stream for the drug.

The deal stems from speculation that the immune-boosting activity of checkpoint inhibitors could have a role to play in infectious disease, and particularly chronic, hard-to-treat infections like hepatitis B virus (HBV), HIV and tuberculosis.

Under the terms of the deal, Ascletis has agreed to pay an undisclosed upfront cash fee, plus milestones and royalties on any future sales in return for rights in Greater China, where HBV is a major public health problem. Around a third of all the 350 to 400 million people infected with HBV worldwide are in China, with many unaware they are carrying the virus.

HBV can be treated effectively with antiviral drugs but so far no cure has been developed, meaning that there is always a risk of the infection re-emerging to cause liver disease including cancer later in life.

Professor Guiqiang Wang, an infectious disease specialist at Peking University First Hospital, explains that chronic HBV infection leads to the “exhaustion” of T cells that are trying to fight the infection. “Blocking the PD-1/PD-L1 pathway could be an effective immunotherapy approach to improve specific T cell function and lead to a clinical cure,” he suggests.

For Alphamab, handing over rights to KN035 to Ascletis allows it to maintain its focus on the drug in cancer – where it has reached late-stage development in China – and may also allow it to steal a march on more established PD-1/L1 developers.

Front-runners in the immuno-oncology category such as Bristol-Myers Squibb (BMS) with Opdivo (nivolumab) and Merck & Co/MSD with Keytruda (pembrolizumab) have not started trialling their blockbuster drugs in infectious diseases, according to their latest pipeline updates.

KN035 has one additional advantage over its rivals in that it can be delivered by subcutaneous injection rather than intravenously, which should “increase patient compliance in clinical practice,” according to Prof Wang.

BMS and Merck are both trying to develop subcutaneous formulations of their drugs but at the moment they are available as infusions only.

StephenW

中国的生物技术公司的目标是在乙型肝炎中使用PD-L1抗体

癌症疗法可以帮助提高患者的免疫系统

Ascletis

检查点抑制剂已经对癌症产生了重大影响，但是两家中国生物技术公司希望探索它们在病毒性疾病中的活性，特别是乙型肝炎。

苏州Alphamab已经在美国，中国和日本的多种肿瘤类型的临床试验中测试了其PD-L1抑制剂抗体KN035，但已向中国的Ascletis获得病毒性疾病的许可，可能为其开辟新的收入来源。药物。

该协议源于这样的猜测：检查点抑制剂的免疫增强活性可能在传染病中发挥作用，特别是慢性，难以治疗的感染，如乙型肝炎病毒（HBV），艾滋病毒和结核病。

根据交易条款，Ascletis已同意支付未公开的前期现金费，以及任何未来销售的里程碑和特许权使用费，以换取大中华区的权利，其中HBV是一个主要的公共卫生问题。全世界3.5亿至4亿感染HBV的人中约有三分之一在中国，很多人都不知道他们携带病毒。

HBV可以用抗病毒药物有效治疗，但到目前为止还没有治愈，这意味着感染重新出现的风险总是导致肝病，包括晚年的癌症。

北京大学第一医院传染病专家王桂强教授解释说，慢性HBV感染导致T细胞“疲惫”，试图对抗感染。 “阻断PD-1 / PD-L1途径可能是一种有效的免疫治疗方法，可以改善特异性T细胞功能并导致临床治愈，”他建议道。

对Alphamab而言，将KN035的权利移交给Ascletis使其能够继续关注癌症中的药物 - 它已经在中国达到了后期发展 - 并且还可能让它在更成熟的PD-1 / L1上取得进展开发人员。

免疫肿瘤学领域的领跑者，例如Br​​istol-Myers Squibb（BMS）和Opdivo（nivolumab）以及Merck＆Co / MSD和Keytruda（pembrolizumab）尚未开始在传染病中试用他们的重磅药物，根据他们最新的管道更新。

根据王教授的说法，KN035比其竞争对手有一个额外的优势，它可以通过皮下注射而不是静脉注射来提供，这应该“增加患者在临床实践中的依从性”。

BMS和Merck都在尝试开发他们药物的皮下配方，但目前它们仅作为输注使用。

齐欢畅