Los Angeles

洛杉矶

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Artificial intelligence (AI)-based drug discovery continues to tout accelerated timelines and novel and effective treatments, yet today’s clinical success rates remain at a low 10%.

基于人工智能（AI）的药物发现不断宣称可缩短时间并提供新颖有效的治疗方法，但目前的临床成功率仍然低至10%。

On Wednesday, Recursion announced favorable efficacy data in the Phase II trial for REC-994, the company’s lead AI-derived candidate to treat the potentially fatal brain disease, cerebral cavernous malformation (CCM), in a late-breaking presentation at the International Stroke Conference (ISC) held in Los Angeles.

周三，Recursion公司在洛杉矶举行的国际卒中大会（ISC）上，通过一项晚期突破性报告宣布了其主导的AI衍生候选药物REC-994在治疗潜在致命性脑疾病——脑海绵状血管畸形（CCM）的II期试验中取得的积极疗效数据。

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CCM is characterized by collections of small blood vessels in the brain that become enlarged and irregular in shape. These vessels can alter blood flow and place patients at risk for seizures, headaches, progressive neurological deficits, and potentially fatal hemorrhagic stroke. Currently, CCM treatment is limited to non-pharmacological options, such as surgery and radiation therapy..

CCM的特征是大脑中聚集的小血管变得扩张且形状不规则。这些血管会改变血流，使患者面临癫痫、头痛、进行性神经功能缺损以及可能致命的出血性中风的风险。目前，CCM的治疗仅限于非药物选择，如手术和放射治疗。

According to the results of the 62-person Phase II study, 50% of patients with cerebral lesions on the highest dose of REC-994 (400 mg) showed reduction in total lesion volume compared to 28% of patients on the placebo after 12 months of treatment. Patients on the lower dose of REC-994 (200 mg) had similar changes in lesion volume compared to placebo.

根据62人参与的第二阶段研究结果，在最高剂量REC-994（400毫克）治疗12个月后，50%的脑部病变患者的总病变体积有所减少，而安慰剂组仅为28%。低剂量REC-994（200毫克）组患者的病变体积变化与安慰剂组相似。

Similar trends were seen in patients with brainstem lesions, a population with high unmet need as cavernomas located in the brainstem are not amenable to surgical intervention. .

在脑干病变患者中也观察到了类似的趋势，这是一个需求高度未满足的群体，因为位于脑干的海绵状血管瘤不适合进行手术干预。

Additionally, the modified Rankin Scale, which is widely recognized and approved by the U.S. Food and Drug Administration (FDA) to assess functional outcomes in acute stroke trials, indicated positive trends in patients on the 400 mg arm.

此外，改良Rankin量表（广泛认可并经美国食品药品监督管理局（FDA）批准用于评估急性卒中试验中的功能结局）显示，400 mg剂量组的患者呈积极趋势。

“My co-investigators and I are encouraged by these initial findings and we look forward to continued work with Recursion on the REC-994 program,” said Jan-Karl Burkhardt, MD, division head, cerebrovascular surgery at University of Pennsylvania and principal investigator of the study.

“我和我的共同研究者对这些初步发现感到鼓舞，我们期待与Recursion在REC-994项目上继续合作，”宾夕法尼亚大学脑血管外科主任、该研究的主要研究者Jan-Karl Burkhardt医学博士说道。

CCM is caused by gene mutations that impact redox homeostasis. Specifically, loss-of-function mutations activate pathways associated with downstream elevation in reactive oxygen species (ROS).

CCM是由影响氧化还原稳态的基因突变引起的。具体来说，功能丧失性突变会激活与下游活性氧（ROS）升高相关的通路。

REC-994 is a redox-cycling nitroxide compound

REC-994是一种氧化还原循环的氮氧自由基化合物

and free-radical scavenger that is hypothesized to treat CCMs through a reduction in ROS.

一种自由基清除剂，假设通过减少活性氧（ROS）来治疗CCMs。

Najat Khan, PhD, chief R&D officer and chief commercial officer at Recursion, emphasized that these data are particularly relevant as CCM lesion volume and CCM brainstem are among the top predictors of re-hemorrhage risk.

Najat Khan博士，Recursion公司的研发主管兼首席商务官强调，这些数据尤为重要，因为CCM病变体积和CCM脑干是再出血风险的最主要预测因素之一。

“These preliminary results show promising MRI-based and functional outcome signals, and we look forward to continued discussions with the FDA, and the CCM scientific and patient communities on next steps,” Khan told

“这些初步结果显示出了基于核磁共振成像和功能结果的积极信号，我们期待继续与FDA、CCM科学界及患者群体就下一步行动进行讨论，”Khan表示。

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Najat Khan, PhD, chief R&D officer and chief commercial officer at Recursion

Najat Khan博士，Recursion公司研发负责人兼首席商务官。

CCM impacts approximately 360,000 symptomatic individuals in the U.S. and EU.

CCM在美国和欧盟影响了大约36万有症状的个体。

Connie Lee, PsyD, CEO of the patient advocacy group, the Alliance to Cure Cavernous Malformation, and Amy Akers, PhD, the organization’s CSO, concurred that Recursion’s phase II data show “tremendous progress in the research space and provide hope for our community.”

患者倡导组织“治愈海绵状血管瘤联盟”的首席执行官Connie Lee（心理学博士）和首席科学官Amy Akers（博士）一致认为，Recursion的二期数据显示了“研究领域的巨大进展，并为我们的社区带来了希望”。

“With no approved therapy and brain surgery as an option for only a subset of the population, CCM patients frequently face stepwise decline from the oozing and growth of cavernous malformation lesions. We look forward to working with Recursion and regulatory agencies to continue this momentum on our path to better treatments,” Lee told .

“由于没有获批的疗法，且脑部手术仅适用于部分患者，CCM患者常常面临海绵状血管瘤病变渗漏和生长导致的逐步衰退。我们期待与Recursion及监管机构合作，继续保持这一势头，朝着更好的治疗方法迈进，”Lee说道。

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Lagging indicator of modern AI

现代人工智能的滞后指标

Last September, Recursion announced that REC-994 had met its primary endpoint of safety and tolerability, a readout that failed to impress investors. With REC-994’s encouraging efficacy data in hand, experts are mulling over the new data as they reflect on whether drug discovery’s new AI paradigm is starting to fulfill its promise..

去年九月，Recursion宣布REC-994达到了其主要的安全性和耐受性终点，但这一结果未能打动投资者。如今，随着REC-994令人鼓舞的有效性数据出炉，专家们正在仔细评估这些新数据，思考药物研发中的人工智能新范式是否开始兑现其承诺。

Krish Ramadurai, PhD, partner at AIX Ventures, focuses on the intersection of healthcare, life sciences, and AI. He states that the first wave of AI-driven drug candidates has fueled both optimism and skepticism, given past “breakthroughs” that failed to solve drug development’s translatability crisis.

克里希·拉马杜莱（Krish Ramadurai）博士是AIX Ventures的合伙人，专注于医疗保健、生命科学和人工智能的交叉领域。他表示，鉴于过去一些“突破性”成果未能解决药物开发的可转化性危机，第一波由人工智能驱动的候选药物既激发了乐观情绪，也引发了质疑。

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“Positive efficacy data for REC-994 would illustrate that AI-generated hypotheses can yield real patient benefits—evidence that could accelerate investment in AI-driven platforms, as oftentimes, many platform technologies have failed to develop a pipeline of clinically relevant therapies with accelerated asset development timelines,” Ramadurai told .

“REC-994的积极疗效数据将表明，人工智能生成的假设能够为患者带来实际益处——这一证据可能会加速对人工智能驱动平台的投资，因为很多时候，许多平台技术未能开发出具有加速资产开发时间表的临床相关疗法管线，”Ramadurai说道。

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While promising efficacy data provides positive proof points for AI pipelines, today’s clinical readouts are lagging indicators of the technology.

尽管有前景的疗效数据为人工智能管道提供了积极的证据点，但目前的临床结果仍然是该技术的滞后指标。

Dylan Reid leads life science investments as managing director at Zetta Venture Partners, an early-stage venture firm focused on AI native startups. Reid said the field of machine learning has come a long way since REC-994 was discovered.

迪伦·里德（Dylan Reid）在Zetta Venture Partners担任董事总经理，负责生命科学领域的投资。Zetta Venture Partners是一家专注于人工智能原生初创企业的早期风险投资公司。里德表示，自REC-994被发现以来，机器学习领域已经取得了长足的进步。

“We take the pace of AI innovation for granted in most domains, but the feedback loops are long when it comes to drug development. The early signals look strong, but it will be a couple of years before we see the impact of modern AI in the clinic,” Reid told

“我们在大多数领域对人工智能创新的速度习以为常，但在药物研发方面，反馈周期很长。早期的信号看起来很强劲，但要看到现代人工智能在临床中的影响，还需要几年的时间，”里德说道。

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At Recursion, modern AI continues to play out through new drug candidates and platform expansion.

在Recursion，现代人工智能通过新药候选物和平台扩展不断发挥作用。

Last October, REC-1245,

去年十月，REC-1245，

Recursion’s first program to emerge from its end-to-end AI pipeline

Recursion从其端到端AI流程中推出的首个项目

, received IND approval to tackle biomarker-enriched solid tumors and lymphoma. The first patient was dosed in a Phase I/II trial during the fourth quarter of 2024. The trial is active and enrolling at five U.S. sites, with data set to be read out in the first quarter of 2026.

获得了IND批准，用于治疗富含生物标志物的实体瘤和淋巴瘤。首例患者在2024年第四季度接受了I/II期试验的给药。该试验在美国五个地点正在进行并招募患者，数据预计在2026年第一季度公布。

Additionally in November,

此外，在十一月，

Recursion completed its combination with U.K.-based Exscientia

递归完成了与英国Exscientia的合并

in one of the largest M&A events in the AI drug discovery field. According to Recursion, the agreement combined Recursion’s scaled biology exploration for target identification with Exscientia’s precision chemistry for lead optimization for a complementary pipeline.

在人工智能药物发现领域最大的并购事件之一中。据Recursion公司称，该协议将Recursion在靶点识别方面的规模化生物学探索与Exscientia在优化先导化合物方面的精准化学相结合，形成了互补的研发管线。

Recursion’s on-premise supercomputer, Biohive2. [Recursion Pharmaceuticals]

Recursion的本地超级计算机Biohive2。[Recursion制药公司]

First-in-disease challenge

首次疾病挑战

Recursion CEO Chris Gibson, PhD, said REC-994 originated from his

Recursion首席执行官Chris Gibson博士表示，REC-994源自他的

graduate school work

研究生院工作

at the University of Utah in the lab of Dean Li, MD, PhD. (Li is now executive vice president and president, Merck Research Labs.) Leveraging open-source software developed by Anne Carpenter, PhD, who is now senior director of the Imaging Platform at the Broad Institute, Gibson used AI-based imaging screens of healthy and diseased cells to identify REC-994..

在犹他大学Dean Li医学博士、哲学博士的实验室中（李现任默克研究实验室执行副总裁兼总裁），Gibson利用Anne Carpenter博士开发的开源软件（Carpenter现任布罗德研究所成像平台高级总监），通过基于人工智能的健康与病变细胞成像筛选，识别出了REC-994。

Chris Gibson, PhD, CEO and Co-founder of Recursion

克里斯·吉布森博士，Recursion首席执行官兼联合创始人

“After that work, I said, ‘Well, let’s go start a company and try and do this for many other diseases.’ And after a couple of years of building the platform, we went back to the university and licensed the know-how around REC-994 as one of our first candidates,” Gibson told

“在那项工作之后，我说，‘好吧，让我们去成立一家公司，尝试为许多其他疾病做这件事。’在搭建平台几年后，我们回到大学，将REC-994的相关技术许可作为我们的首批候选之一，”吉布森说道。

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last September.

去年九月。

In contrast to other CCM drug candidates, such as Neurelis’ NRL-1049 and Ovid and Graviton’s OV-888/

与其他CCM候选药物（如Neurelis的NRL-1049以及Ovid和Graviton的OV-888/）相比，

GV101

``` GV101 ```

, Gibson said Recursion is the first company to do an institutionally backed clinical trial in CCM and claims his company is “several years ahead of any other kind of commercial opportunity.”

吉布森表示，Recursion是首家在CCM领域进行机构支持的临床试验的公司，并声称他的公司“比其他任何类型的商业机会领先几年”。

“The challenge of being first in disease is, it’s an exciting opportunity to make an impact for patients. It also means that there’s an increased burden to not only prove out the molecule, but the path itself towards the treatment,” Gibson continued.

“在疾病领域成为第一的挑战在于，这是一个为患者带来影响的激动人心的机会。这也意味着不仅需要证明分子的有效性，还需要证明治疗路径本身的负担增加了，”吉布森继续说道。

At the core of Recursion’s AI-based discovery pipeline today is the Recursion Operating System (OS), a platform powered by the company’s proprietary phenomic datasets, spanning transcriptomics, proteomics, metabolomics, and more. The platform leverages Maps of Biology, which create millions of biological relationships by perturbing human cell lines to instill a disease state and testing compounds to reverse the cells to healthy function. .

如今，Recursion基于人工智能的发现流程的核心是Recursion操作系统（OS），这是一个由公司专有的表型数据集驱动的平台，涵盖转录组学、蛋白质组学、代谢组学等多个领域。该平台利用生物学图谱，通过对人类细胞系进行扰动以诱导疾病状态，并测试化合物以将细胞恢复至健康功能，从而创建了数百万种生物关系。

As Recursion

作为递归

continues to expand its clinical pipeline

继续扩大其临床管线

, so has its focus on AI-based clinical development.

，因此其关注点也放在了基于人工智能的临床开发上。

“[Clinical trials are] not only the most expensive and time-consuming part of drug discovery and development (~70% of the total cost to bring a drug to market) but also where 90% of drugs in development fail, with later-stage clinical trials having the highest failure rates,” Khan told

“[临床试验是]药物发现和开发中最昂贵、最耗时的部分（约占药物上市总成本的70%），同时也是90%在研药物失败的地方，后期临床试验的失败率最高，”汗说道。

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“Just as we are leveraging fit-for-purpose data, AI, and machine learning to drive unbiased, data-driven discovery into novel targets and for first-in-class and best-in-class new molecules, we’re using AI to design and simulate better clinical trial programs, accelerate enrollment, and strengthen evidence generation,” Khan continued..

“正如我们正在利用适合用途的数据、人工智能和机器学习来推动无偏见、数据驱动的新靶点发现，以及开发首创和最佳的新型分子一样，我们也在使用人工智能来设计和模拟更好的临床试验项目，加速患者招募，并加强证据生成，”Khan继续说道。

To support this goal, Recursion has established data partnerships with Tempus and Helix, which gives the company access to hundreds of thousands of insights drawn from patient records, including whole exome and whole genome sequencing. Recursion has also partnered with Faro Health to leverage their software to better automate and optimize the protocol design of clinical trials..

为实现这一目标，Recursion与Tempus和Helix建立了数据合作伙伴关系，使公司能够从患者记录中获得数十万条洞察，包括全外显子组和全基因组测序数据。此外，Recursion还与Faro Health合作，利用其软件更好地自动化和优化临床试验的方案设计。

Recursion’s clinical portfolio now includes 10 clinical and preclinical and 10 advanced discovery pipeline programs. Khan says the company is doubling down primarily in oncology and rare diseases. Additionally, Recursion has 10 active-partnered programs with top pharma companies including Roche, Bayer, Merck KGaA, and Sanofi across immunology, oncology, and neuroscience..

Recursion的临床产品组合目前包括10个临床和临床前项目以及10个先进发现管线项目。Khan表示，公司正主要在肿瘤学和罕见疾病领域加大投入。此外，Recursion还与罗氏、拜耳、默克集团和赛诺菲等顶级制药公司在免疫学、肿瘤学和神经科学领域展开了10个活跃的合作伙伴项目。

As AI-based drug discovery continues to accelerate, REC-994 is but one thread in a growing tapestry. As Ramadurai says: “The industry will need multiple consistent successes across therapeutic indications and clinical phases to establish AI-based pipelines as the new paradigm in biotech.”

随着基于人工智能的药物研发持续加速，REC-994只是日益壮大的画卷中的一条线索。正如拉马杜莱所言：“行业需要在多种治疗领域和临床阶段取得一系列持续成功，才能确立基于人工智能的研发管道作为生物科技领域的新范式。”

Fay Lin, PhD, is senior editor for

``` 林菲博士，资深编辑 ```

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