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Intero Biosystems wants drugmakers to test on mini human intestines, not animals

药物开发长期以来一直依赖动物模型，但物种间的差异意味着在动物身上有效的方法并不总能转化为人类的疗效，且大多数药物在开发过程中仍会失败。总部位于丹佛的初创公司 Intero Biosystems 正在开发人类肠道类器官，这是一种模拟肠道的实验室培养组织，作为在人体测试前研究药物和其他化合物如何影响人体的另一种途径。研究人员和制药公司正越来越多地寻找能更好地反映人类生物学的模型，以补充并减少对动物实验的依赖。

Intero, which spun out of the University of Michigan, says its organoids differ from simpler models that replicate only part of the gut. They contain multiple cell and tissue types found in the human intestine, which the company believes makes them a more human-relevant model for testing drugs and other compounds, co-founder and CTO Madeline Eiken told TechCrunch. “Most drugs fail clinical trials, and I think it’s pretty easy to appreciate that we are neither mice nor flat layers of cells,” Eiken said.

Intero 公司从密歇根大学分拆出来，其联合创始人兼首席技术官 Madeline Eiken 向 TechCrunch 表示，他们的类器官与仅复制部分肠道的简单模型不同。这些类器官包含人类肠道中发现的多种细胞和组织类型，公司认为这使其成为测试药物和其他化合物时更具人类相关性的模型。Eiken 说：“大多数药物在临床试验中失败，我认为很容易理解，我们既不是老鼠，也不是平面的细胞层。”

The startup’s flagship product, GastroScreen, is a human intestinal organoid model that it sells to pharmaceutical, biotech, food, and chemical companies for testing drugs and other compounds. Each organoid is about one millimeter across, and the company ships roughly 100 at a time in a tube, co-founder and CEO Charlie Childs said. Customers can use them as healthy intestinal models or induce disease-like conditions to test how the tissue responds to different compounds. “We’re literally shipping mini living organs in the mail to people,” Childs said.

该初创公司的旗舰产品 GastroScreen 是一种人类肠道类器官模型，出售给制药、生物技术、食品和化学公司，用于测试药物和其他化合物。联合创始人兼首席执行官 Charlie Childs 表示，每个类器官直径约一毫米，公司一次通过试管运输约 100 个。客户可以将它们用作健康的肠道模型，或诱导产生类似疾病的状况，以测试组织对不同化合物的反应。Childs 说：“我们实际上是通过邮件向人们运送微型活体器官。”

Beyond the organoids themselves, Intero sells the supplies needed to grow and work with them, such as the nutrient mixes that feed the cells and the chemicals used in experiments. It also runs studies for customers, including designing custom experiments, performing lab tests, and delivering the resulting data. Much of this work focuses on drug safety and disease research. For example, a customer can expose the organoids to a drug candidate to see whether it could harm the gut, or use organoids modeling a gut condition to see how the tissue responds to a compound.

除了类器官本身，Intero 还销售培养和处理它们所需的用品，例如喂养细胞的营养混合物和实验中使用的化学品。它还为客户开展研究，包括设计定制实验、进行实验室测试并提供所得数据。这些工作大部分集中在药物安全和疾病研究上。例如，客户可以让类器官接触候选药物以观察其是否会损害肠道，或者使用模拟肠道疾病的类器官来观察组织对化合物的反应。

Founded in 2024, the startup now has seven employees and just under 10 customers after raising a $2.3 million pre-seed round last year. It generated more than $400,000 in revenue from the fourth quarter of last year through the third quarter of this year, the CEO noted. Regulatory changes have also helped drive interest in alternatives to animal testing. In April of last year, the U.S. Food and Drug Administration (FDA) laid out plans to reduce its reliance on animal testing in drug development, promoting alternatives including organoids, organs-on-chips (small devices that mimic organ functions) and AI-based computational models as potential alternatives.

这家初创公司成立于 2024 年，在去年筹集了 230 万美元的种子轮前融资后，目前拥有 7 名员工和近 10 家客户。首席执行官指出，从去年第四季度到今年第三季度，公司创造了超过 40 万美元的收入。监管政策的变化也推动了人们对动物实验替代方案的兴趣。去年 4 月，美国食品药品监督管理局 (FDA) 制定了减少药物开发中对动物实验依赖的计划，推广包括类器官、器官芯片（模拟器官功能的小型设备）和基于人工智能的计算模型作为潜在替代方案。

In March of this year, the FDA issued draft guidance outlining how drug developers should validate new approach methodologies, or NAMs, a term of non-animal testing methods, when using them to support regulatory submissions. The guidance provides a framework for validation but doesn’t endorse any specific method. Whether a NAM can support a submission depends on factors including the method, how it is used, and the data provided. Changes in U.S. law that allow drug developers to use non-animal testing methods in some cases have made pharmaceutical companies more willing to explore technologies such as organoids, Eiken told TechCrunch. Companies once hesitant about the technology are now looking to bring organoids in-house, she added.

今年 3 月，FDA 发布了指导草案，概述了药物开发人员在利用新方法（NAMs，即非动物测试方法的统称）支持监管申报时应如何进行验证。该指南提供了验证框架，但并未认可任何特定方法。一种 NAM 是否能支持申报取决于包括方法、使用方式和所提供数据在内的多种因素。Eiken 向 TechCrunch 表示，美国法律的变更允许药物开发人员在某些情况下使用非动物测试方法，这使得制药公司更愿意探索类器官等技术。她补充说，曾经对该技术持观望态度的公司现在正寻求将类器官技术引入内部。

Intero isn’t alone in trying to build more human-relevant models of the gut. Altis Biosystems develops stem cell-derived intestinal models, while InSphero offers patient-derived intestinal organoids for gastrointestinal toxicity testing. Other peers like MIMETAS take a different approach with organ-on-chip technology, using microfluidic systems to recreate aspects of the environment inside human tissues. Intero says it sets itself apart from competitors in the complexity and scalability of its model. Unlike intestinal models grown from tissue collected through procedures such as colonoscopies, GastroScreen is derived from induced pluripotent stem cells, which are adult cells reprogrammed to become almost any cell type and can be generated from a blood sample, Eiken explained. That approach gives the startup the potential to personalize its models to different patients and scale production more easily, she added.

Intero 并非唯一一家试图构建更具人类相关性肠道模型的公司。Altis Biosystems 开发干细胞衍生的肠道模型，而 InSphero 提供用于胃肠道毒性测试的患者来源肠道类器官。其他同行如 MIMETAS 则采用不同的器官芯片技术，利用微流控系统重现人体组织内部环境的各个方面。Intero 表示，其模型在复杂性和可扩展性方面与竞争对手不同。Eiken 解释说，与通过结肠镜检查等程序收集组织培养的肠道模型不同，GastroScreen 源自诱导多能干细胞，这是一种被重编程为几乎任何细胞类型的成体细胞，可以从血液样本中生成。她补充说，这种方法使该初创公司有潜力针对不同患者个性化其模型，并更容易地扩大生产规模。

When asked what evidence shows GastroScreen can predict human drug responses more accurately than existing animal or cell-based models, Childs said the company is still building that evidence and is now in the second stage of a three-stage validation process. Having first shown that GastroScreen contains the key tissues of the human gut, Intero is now testing well-known drugs with documented effects in humans. GastroScreen has shown expected responses to drugs that reduce intestinal inflammation and to compounds known to damage the gut, Childs told TechCrunch. In the final stage, the company will compare GastroScreen’s results directly with pharmaceutical companies’ existing animal and clinical data. Those studies are underway with several pharmaceutical companies, using both existing compounds and new drug candidates, Childs said.

当被问及有什么证据表明 GastroScreen 比现有的动物或基于细胞的模型能更准确地预测人类药物反应时，Childs 表示公司仍在积累这些证据，目前正处于三阶段验证过程的第二阶段。在证明了 GastroScreen 包含人类肠道的关键组织后，Intero 目前正在测试在人类身上有记录效果的知名药物。Childs 向 TechCrunch 表示，GastroScreen 对减少肠道炎症的药物和已知会损害肠道的化合物表现出了预期的反应。在最后阶段，公司将把 GastroScreen 的结果直接与制药公司现有的动物和临床数据进行比较。Childs 说，这些研究正在与几家制药公司合作进行，同时使用了现有化合物和新的候选药物。

Intero doesn’t use AI to build its organoids. Instead, Childs sees an opportunity to use the organoids to generate the biological data AI models need, and the company plans to license such datasets to pharmaceutical and AI companies. In the near term, Intero is focused on scaling production. It can currently make a few thousand organoids at a time and is working to automate manufacturing, with the goal of producing hundreds of thousands per batch, Childs said. Longer term, it wants to move into personalized medicine, using a patient’s cells to create organoids that could te

Intero 并不使用人工智能来构建其类器官。相反，Childs 认为有机会利用这些类器官来生成人工智能模型所需的生物数据，公司计划将此类数据集授权给制药和人工智能公司。短期内，Intero 专注于扩大生产规模。Childs 表示，目前一次可以制造几千个类器官，并正在努力实现制造自动化，目标是每批生产数十万个。从长远来看，它希望进入个性化医疗领域，利用患者的细胞来创建类器官，从而进行测试。