Roche is betting more on artificial intelligence, unveiling Monday a collaboration that leans on a startup’s technology to find new ways to transport medicines into the brain.

罗氏公司正在加大对人工智能的投入，周一宣布了一项合作，依靠一家初创公司的技术来寻找将药物输送到大脑的新方法。

For $55 million, Roche has gained access to the drug discovery tools at Manifold Bio, a Boston-based company using AI to identify biological pathways that can direct therapies to specific tissues. Manifold says its platform can measure thousands upon thousands of “shuttles” that may be able to cross the blood-brain barrier — a casing that shields the organ from not only harmful substances, but also beneficial therapies..

罗氏公司以5500万美元获得了位于波士顿的Manifold Bio公司的药物发现工具使用权，该公司利用人工智能来识别能够引导治疗到特定组织的生物通路。Manifold表示，其平台可以测量成千上万种可能能够穿越血脑屏障的“载体”——这一屏障不仅屏蔽了有害物质，还屏蔽了有益的疗法。

This barrier, known as the “BBB” for short, has thwarted so many attempts at treating neurological diseases that a new class of companies has emerged with technologies designed specifically to overcome it. Just last month, Dublin-based Aerska, which is hoping to get RNA-interfering drugs into the brain, .

这个屏障简称“BBB”，它阻碍了众多治疗神经系统疾病的尝试，以至于出现了一批专门利用技术来克服这一障碍的新型公司。就在上个月，总部位于都柏林的Aerska公司希望能够将RNA干扰药物送入大脑。

launched with $21 million

以2100万美元启动

supplied by more than half a dozen investment firms.

由半打以上的投资公司提供。

“It's always felt like going into clinical trials with your hands tied behind your back, because you never could really engineer a molecule that could successfully, fully get into the brain,” Gleb Kuznetsov, Manifold’s CEO and co-founder, said in an interview. “That's why there's been such a strong push into these brain-shuttling technologies.”.

“这一直感觉像是双手被绑在背后进入临床试验，因为你永远无法真正设计出一个能够成功、完全进入大脑的分子，”Manifold的首席执行官兼联合创始人格莱布·库兹涅佐夫在一次采访中说道。“这就是为什么这些大脑运输技术受到如此强烈的推动。”

Manifold touts how its approach, unlike older ones, evaluates shuttles in a living organism, or “in vivo,” rather than in a petri dish or test tube. This, the company argues, should significantly speed up the process of translating basic research into actual drugs.

曼尼福尔德公司吹捧其方法与旧方法不同，它是在活生物体或“体内”评估穿梭蛋白，而不是在培养皿或试管中进行。该公司认为，这将大大加快将基础研究转化为实际药物的过程。

In explaining his company’s aim, Kuznetsov finds it helpful to picture an autobody shop.

在解释公司的目标时，库兹涅佐夫发现把公司想象成一个汽车车身修理厂很有帮助。

“If we could just take diseased cells out of a human body — like we could take engine out of car — repair them and put them back in, we will have cured many diseases. Of course, it is very hard to do that,” Kuznetsov said.

“如果我们可以像从汽车里取出发动机一样，将病变的细胞从人体中取出，修复它们后再放回去，那么我们就能治愈很多疾病。当然，这很难做到，”库兹涅佐夫说道。

“And so a big part of drug design and drug engineering is effectively bringing the mechanic to the broken cells in the body,” he added. Getting potential medicines to the right tissues, and understanding how they’ll interact with the body, “that is why in vivo measurement is very, very important.”

“因此，药物设计和药物工程的一个重要部分实际上就是将‘修理工’带到身体内受损的细胞处，”他补充道。让潜在的药物到达正确的组织，并了解它们如何与身体相互作用，“这就是为什么体内测量非常、非常重要。”

The shuttles Manifold ultimately finds the most suitable are then fused to engineered antibodies or genetic medicines: the types of therapies the BBB is particularly adept at keeping out.

最终，曼尼福德发现最合适的穿梭分子与工程化抗体或基因药物融合：这些疗法正是血脑屏障特别擅长阻挡的类型。

Steve Holtzman, Manifold’s executive chairman, believes the company’s work will lead to medicines that can be effective at lower, safer doses and given in more convenient, comfortable ways.

史蒂夫·霍尔茨曼，Manifold的执行主席，认为公司的工作将带来更有效、更安全的药物，并且能够以更低的剂量和更方便、舒适的方式给药。

Roche and Manifold aren’t yet revealing exactly what diseases they’re targeting, but, according to Kuznetsov, some are “massive” in scope and “in many ways, diseases of aging.”

罗氏和Manifold尚未透露他们具体针对哪些疾病，但据库兹涅佐夫称，其中一些疾病“规模巨大”，而且“在许多方面，是与衰老相关的疾病”。

In addition to the upfront payment, Manifold could take home north of $2 billion more if it hits certain research, development and sales milestones. The company will lead activities related to discovering and advancing novel shuttles that are tailored to Roche-selected therapeutic payloads. Roche will then take the reins for preclinical and human testing, along with commercialization..

除了首付款之外，如果 Manifold 达到特定的研究、开发和销售里程碑，还可能额外获得超过 20 亿美元的收入。该公司将主导与发现和推进针对罗氏选定治疗载荷量身定制的新型穿梭载体相关的活动。随后，罗氏将接手进行临床前和人体试验，以及商业化工作。

Per deal terms, Manifold may receive tiered royalties on resulting products. It also maintains the right to opt-in and co-fund development of one product candidate.

根据协议条款，Manifold 可能会获得分级版税收益。它还保留选择参与并共同资助一个候选产品开发的权利。

For Roche, technologies like Manifold’s could be especially valuable, given the Swiss pharmaceutical giant stands as one of the more prolific brain drug researchers. It currently lists 21 neuroscience programs in human trials, including more than a dozen for not-yet-approved drugs. The programs mostly target rare illnesses, multiple sclerosis, and neurodegenerative diseases like Alzheimer’s, Parkinson’s and Huntington’s..

对于罗氏而言，像Manifold这样的技术可能尤其有价值，因为这家瑞士制药巨头是最多产的脑部药物研究者之一。目前，该公司正在进行21个神经科学项目的人体试验，其中包括十多个尚未获批的药物。这些项目主要针对罕见病、多发性硬化症以及阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病。

Last year, sales from Roche’s neuroscience products increased 13% — to 9.3 billion Swiss francs, or roughly $10.6 billion — and accounted for 20% of overall pharmaceutical sales.

去年，罗氏神经科学产品的销售额增长了 13%——达到 93 亿瑞士法郎，约合 106 亿美元——占制药总销售额的 20%。

In neuroscience, which investors often describe as a high-risk, high-reward area, Roche has veered toward collaborations and licensing agreements rather than all-out acquisitions. In 2023, it paid Ionis Pharmaceuticals $60 million for

在神经科学领域，投资者常将其描述为高风险、高回报的领域，罗氏倾向于合作和许可协议，而非全面收购。2023年，罗氏向Ionis Pharmaceuticals支付了6000万美元。

rights to two RNA medicines

两种RNA药物的权利

meant to combat Alzheimer’s and Huntington’s. The following year, it

旨在对抗阿尔茨海默病和亨廷顿病。第二年，它

licensed some technology

授权了一些技术

from Sangamo Therapeutics for another shot at an Alzheimer’s treatment, and

来自Sangamo Therapeutics的另一款阿尔茨海默病治疗药物，

partnered with an RNA editing specialist

与RNA编辑专家合作

in a deal structured similarly to the Manifold pact.

在这项与Manifold协议结构相似的交易中。

Roche became a leader in the field of BBB shuttles over the past 15 years, and so is well-versed in the persistent obstacles. One of the company’s most closely watched candidates, the

罗氏在过去15年中成为了BBB穿梭领域里的佼佼者，因此非常熟悉持续存在的障碍。该公司最受关注的候选药物之一，

Alzheimer’s drug trontinemab

阿尔茨海默病药物曲坦尼单抗

, was built using shuttle technology.

，是使用航天飞机技术建造的。

The Manifold deal is therefore exciting, Boris Zaïtra, Roche’s head of corporate business development, said in a statement, as it holds the potential to “tackle some of the most important neurological and neurodegenerative diseases.”

因此，罗氏公司企业业务发展主管鲍里斯·扎伊特拉在一份声明中表示，Manifold 交易令人兴奋，因为它有潜力“解决一些最重要的神经和神经退行性疾病。”

Yet, it also carries risk. While AI promises to drastically speed up the discovery and development of new drugs, its impact on the sector so far has been modest. Some of the premier companies built around AI drug discovery, among them Recursion Pharmaceuticals, have struggled to prove themselves.

然而，它也带来了风险。尽管人工智能有望极大地加速新药的发现和开发，但迄今为止其对这一领域的影响甚微。一些围绕人工智能药物发现建立的顶级公司，例如Recursion Pharmaceuticals，也难以证明自身的价值。

Roche may understand these risks better than its peers, having inked several AI-focused deals over the past several years. It’s been working with

罗氏可能比其同行更了解这些风险，因为它在过去几年中签署了多项专注于人工智能的交易。它一直在与

Dyno Therapeutics

动力治疗公司

to craft gene therapies for neurological diseases, as well as the world’s most valuable company,

为神经系统疾病设计基因疗法，以及成为世界上最有价值的公司，

chipmaker Nvidia

芯片制造商英伟达

. Roche’s Genentech division also agreed in late 2021 to partner with Recursion to speed up the process of identifying new targets for cancer or nervous system medicines.

罗氏的基因泰克部门还在2021年底同意与Recursion合作，以加快确定癌症或神经系统药物新靶点的过程。

As for Manifold, executives claim the new alliance provides not only validation that the company has a valuable technology, but also a “foundational partnership” that allows it to keep growing independently. Holtzman noted how terms of the deal give Roche rights to specific product candidates, but Manifold retains ownership of the shuttles and can use them create other drugs for the same or different diseases..

至于Manifold，公司高管表示，这项新的合作不仅验证了公司拥有有价值的技术，还提供了一个“基础性合作伙伴关系”，使其能够保持独立发展。霍尔茨曼指出，该协议的条款赋予罗氏特定候选产品的权利，但Manifold仍保留对“穿梭”技术的所有权，并可将其用于开发针对相同或不同疾病的其他药物。

“AI, in and of itself, is really no longer an edge,” said Pierce Ogden, the company’s chief technology officer and fellow co-founder. “It has to be paired with quality and relevant data. And that's really what makes Manifold unique.”

“人工智能本身已经不再是一个优势了，”该公司首席技术官兼联合创始人皮尔斯·奥格登表示。“它必须与高质量和相关数据相结合。而这正是让Manifold与众不同的地方。”