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腹黑王爷的绝色弃妃-带你进入前所未有的购物盛宴
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腹黑王爷的绝色弃妃-带你进入前所未有的购物盛宴

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出品|妙投APP

作者|张贝贝

头图|AI生图

4月11日消息,FDA官网更新政策,逐步取消单克隆抗体疗法等药物研发中对动物实验的强制性要求,引发了业内的较大关注,以动物实验为主且有美国业务的昭衍新药或将率先受到冲击。

实际上,2022年FDA就通过了《FDA现代化法案2.0》,提倡寻找动物实验的替代方案,但最新政策更加具体,指明了智能计算模型、类器官与器官芯片、跨物种数据整合的三大替代方向。这是该消息一经发布,市场关注度较高的重要原因。

受此消息影响,昭衍新药资本市场当天直接跌停。

不过市场对此争议较大,有人认为,“不用动物直接在人身上做试验,这不是开玩笑吗?”,也有人认为,这是猴子我国多,特意出政策限制的;但也有人认为,或许不是空穴来风,真有可能实现,因为给了更具体的替代思路。如若真是这样,昭衍新药的猴子或许就白囤了。

接下来从动物实验替代方案的可行性以及结合昭衍新药的中美业务占比等角度,关于该政策对昭衍新药的业务短中长期影响进行分析。

动物实验并未被取缔,但未来可能会减少

其实有关取消动物实验的话题,这两年一直在业界讨论。

数十年来,动物一直是新药研究的关键。因为许多动物在生物学上与人类足够相似,而且会患上与人类相同的疾病,所以动物试验能较大程度规避在人身上可能出现的危险。

然而,反对者认为动物试验太过残忍,每年有那么多动物死去,太不人道,而且动物试验并不能完全可靠地预测人体试验结果,毕竟有许多药物在动物身上一试挺好,但到人身上就不行。如结合2008-2013年期间,新药临床试验1期、2期、3期以及新药注册成功率分别为4%、12%、40%和57%,可以看到在动物上安全有效的药物,仅有不到1%的药物成功获批。

再加上,动物实验花费高,实验周期长、动物实验室的管理和运营也相当繁琐。如开发一款单抗一般需要使用144只非人灵长类动物,每只成本高达5万美元(FDA发布的路线图),成本高昂。

从此意义上说,FDA推动器官芯片、AI等逐步取代实验动物,若能成功,将是医药行业新药研发的里程碑事件。从这个维度看,FDA的动物试验替代政策对全球新药研发都有影响,或不仅是打击国内CXO企业而推行。

那么,替代方案可行性究竟如何?

先来看近几年爆火的AI技术,FDA鼓励开发者利用计算机建模和人工智能来预测药物的行为。如,软件模型可以模拟单抗在人体内的分布情况,并根据这种分布以及药物的分子组成可靠地预测副作用。该技术需要试验验证。

而相比AI,器官芯片技术并非全新的名词和技术,它们已经存在十几年了。其中,器官芯片以类器官(通过自组装手段,模拟人体组织和器官功能)为基础,可以通过工程化手段调控器官的生理剪切力等微环境,进一步提升模型的仿真度,并在芯片上构建三维的人体器官生理微系统。

且器官芯片技术在药物研发上是有实质进展的。

据公开资料,2022年8月,FDA批准赛诺菲的新药进入临床试验,就是基于器官芯片研究获得的临床前数据,这也是FDA首次批准完全依赖非动物实验数据的新药进入临床试验。

这意味着,FDA此次并非是“拍脑门”推出的政策,或许有一定的依据。

但要注意的是,器官芯片成功应用于临床试验申请有一个重要前提,就是NCT04658472此前已被FDA批准用于其他适应症,已有动物试验安全性数据作为支撑,而器官芯片只是提供了新适应症的临床前疗效数据,并非完全取代动物实验。(该项临床实验是治疗两种罕见的自身免疫性脱鞘神经疾病,之前缺乏理想的动物模型,无法针对这些疾病开展研究)

则器官芯片数据虽然在新药研发领域有进展,但只是在曾经做过动物试验的基础上,对于新适应证提供了临床前疗效数据,并非完全取代动物实验。从此维度看,短期内动物试验难被完全取缔,但可能会减少,如新适应症开发上,用非动物试验替代。

何况,基于FDA路线图的减少动物试验测试规划,可看到未来3年内,将以单克隆抗体(mAb)药物为试点产品,减少灵长类动物长期毒性试验从常规6个月,缩短至3个月;同时建立国际药物毒性数据库,利用现有临床数据替代部分动物实验。未来3-5年,致力于使动物试验成为临床前安全测试的“例外”,而非“常规”。

由上也可知,最起码未来3-5年内,动物试验不会完全被取消,只是使用减少。

关键是,此情形下,昭衍新药会受到怎样的影响?

谋求其他“出路”,迫在眉睫?

昭衍新药是国内以非临床研究业务为主的CRO企业,2024年收入贡献高达95%。其中,动物试验占到70%左右,这部分是在未来会受到上述FDA政策直接冲击的业务。

且要注意的是,虽然昭衍新药有78%的业务来自于国内市场,仅有22%左右来自于国外(主要是美国)。但参考国内首家从事“类器官+AI“赋能创新药研发的公司希格生科创始人兼CEO张海生博士所说,目前,希格生科与北大、清华、大连化物所等高校科研机构,以及中检院和药监部门正在积极推进类器官技术的行业标准的沟通制定,以期推进类器官和器官芯片技术的进展(来源于同写意《FDA终结百年动物实验史》)。

可看到,中国的药监机构也在积极推进类器官等技术的推进。

则,2025年因为FDA政策刚落地推进,或对公司业务经营影响不大。但未来几年内,昭衍新药的动物试验业务或将处于“达摩克利斯之剑”在头顶悬着的境遇中。

若再结合财报,公司2019-2024年,共新增生物药约1758个、化学药约1276个、中药50余个的非临床研究项目看,公司非临床业务中有一半可能是生物药。再结合近几年国内药企在单抗药物领域的扎堆布局,昭衍新药的动物试验中或有较大比例的单抗药物订单。若占到一半比例,则单抗药物订单在公司整体业绩的比重或能达到:70%*50%*50%=17.5%。

除此之外,若未来动物试验减少,则猴价可能会下滑,从当下的一只10万元继续降价至疫情前的几千块并不是没有可能。此情况下,昭衍新药自建猴场囤的“猴子”,也会面临损失。当然,实验模型销售也会承压。

届时,公司的业绩增长或将主要压在临床业务上了。

但要注意的是,昭衍新药的临床业务主要在早期临床阶段,且国内CRO几乎都在往临床业务拓展,竞争激烈。这也是2024年昭衍新药临床业务虽然在加大拓展下收入有增长,但市场竞争下,该业务毛利率却下滑,显然难以扛起“赚钱的大旗”。

由上可看到,昭衍新药即使在短期受到的扰动不大,毕竟未来1-3年是单抗产品作为试点的测试期,但长远来看,若未来动物试验“变成例外而非常规”情况下,昭衍新药若没有其他新业务贡献更多业绩增量,业绩增长承压或较大。从此维度看,昭衍新药未来能否谋求到新的“出路”,或变得尤为关键。

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