Senti Bio为其新的可编程生物学平台和癌症疗法筹集了1.05亿美元

Senti Biosciences是一家使用新的可编程生物学平台开发癌症疗法的公司，该公司表示，该公司已经获得了1.05亿美元的新一轮融资，由生命科学巨头拜耳（Bayer）的风险投资部门牵头。

该公司的技术使​​用新的计算生物技术来制造细胞和基因疗法，从而可以更精确地靶向体内的特定细胞。

Senti Bio的首席执行官Tim Lu将其公司的新技术与基本编程和面向对象编程之间的区别进行了比较。卢说：“您可以创建'if'语句和面向对象的编程，而不必创建只显示'Hello world'的程序。”

通过构建可以靶向多种受体的遗传物质，Senti Bio的疗法可以更精确地识别体内遗传物质并将各种疗法直接传递给病原体。他说：“现在，细胞不再表达单个受体了……现在我们有了两个受体。”

该公司最初将其基因电路技术平台应用于开发疗法，该疗法使用所谓的嵌合抗原受体自然杀伤细胞（CAR-NK）来靶向体内的癌细胞并消除它们。许多现有的细胞和基因疗法都使用嵌合抗原受体T细胞，它们是人体内的白细胞，对免疫应答和破坏人体内的细胞病原体至关重要。

但是，基于T细胞的疗法可能对患者有毒，刺激免疫应答，其危险性几乎与病原体本身一样危险。使用CAR-NK细胞可产生相似的结果，副作用更少。

卢说，这与基因电路无关。 “基因回路使您具有特异性……现在，当您使用CAR-T细胞或CAR-NK细胞时，您会找到一个靶标并希望它不会影响正常细胞。我们可以在细胞的基因回路中建立逻辑，这意味着CAR-NK细胞可以识别两个靶标而不是一个。”

增加靶向性意味着降低健康细胞与体内突变或病原体一起被破坏的风险。

对于Lu和他的联合创始人-麻省理工学院的教授Jim Collins，波士顿大学的教授Wilson Wong和长期的合成生物学运营商Phillip Lee-Senti Bio是该领域数十年研究的结晶。

“在将其与半导体工作初期相提并论的过程中，” Lu说到开发这种基因电路技术的旅程。 “研究实验室正在开发一些零碎的技术，但是要实现您需要的规模，必须在工业级别上做到这一点。”

因此，来自麻省理工学院，波士顿大学和斯坦福大学的许可工作，陆和他的联合创始人着手将这项工作带出实验室，以创立一家公司。

陆说：“公司成立之初就是一袋工具以及如何使用它们的专有技术。”但这不是一个完整开发的平台。

这就是该公司现在所拥有的，借助拜耳Leaps及其其他投资者的新资本，Senti准备开始商业化。

该公司在一份声明中说，首批产品将用于治疗急性髓细胞性白血病，肝细胞癌和其他未公开的实体瘤靶标。

拜耳飞跃的负责人尤尔根·埃克哈特（Juergen Eckhardt）医师表示：“拜耳的使命是在突破性技术上进行投资，这些技术可以改变数百万患者的生活。” “我们相信合成生物学将成为下一代细胞和基因治疗的重要支柱，并且Senti Bio在设计和优化生物回路方面的领导地位正符合我们预防和治疗癌症以及再生失去的组织功能的雄心。”

Lu和他的联合创始人也将他们的工作视为开发针对其他疾病和应用的其他细胞疗法的平台，并打算与其他制药公司合作将这些产品推向市场。

“在过去的两年中，我们的团队设计，构建和测试了数千个复杂的基因电路，以驱动强大的产品线，最初侧重于同种异体CAR-NK细胞疗法，以治疗难以治疗的液体和实体瘤适应症，” Lu在一份声明中说。 “我期待平台和管道的不断进步，包括在2021年开始启用IND的研究。”

新一轮融资使Senti的总融资额增加到了近1.6亿美元，Lu表示，这笔新资金将用于加速生产并加快与其他制药公司的合作。

目前的时间表是在2022年末和2023年初获得新的研究性新药许可，并于2023年开始初步临床试验。

基因电路的开发是一个新的且不断扩展的领域，拥有众多参与者，包括Cell Design Labs，该公司于2017年被吉利德（Gilead）以5.67亿美元的价格收购。其他从事类似疗法的公司包括CRISPR疗法，

Senti Bio raises $105 million for its new programmable biology platform and cancer therapies

Senti Biosciences, a company developing cancer therapies using a new programmable biology platform, said it has raised $105 million in a new round of financing led by the venture arm of life sciences giant Bayer.

The company’s technology uses new computational biological techniques to manufacture cell and gene therapies that can more precisely target specific cells in the body.

Senti Bio’s chief executive, Tim Lu, compares his company’s new tech to the difference between basic programming and object-oriented programming. “Instead of creating a program that just says ‘Hello world’, you can introduce ‘if’ statements and object-oriented programming,” said Lu.

By building genetic material that can target multiple receptors, Senti Bio’s therapies can be more precise in the way they identify genetic material in the body and deliver the kinds of therapies directly to the pathogens. “Instead of the cell expressing a single receptor… now we have two receptors,” he said.

The company is initially applying its gene circuit technology platform to develop therapies that use what are called chimeric antigen receptor natural killer (CAR-NK) cells that can target cancer cells in the body and eliminate them. Many existing cell and gene therapies use chimeric antigen receptor T-cells, which are white blood cells in the body that are critical to immune response and destroy cellular pathogens in the body.

However, T-cell-based therapies can be toxic to patients, stimulating immune responses that can be almost as dangerous as the pathogens themselves. Using CAR-NK cells produces similar results with fewer side effects.

That’s independent of the gene circuit, said Lu. “The gene circuit gets you specificity… Right now when you use a CAR-T cell or a CAR-NK cell… you find a target and hope that it doesn’t affect normal cells. We can build logic in our gene circuits in the cell that means a CAR-NK cell can identify two targets rather than one.”

That increased targeting means lower risks of healthy cells being destroyed alongside mutations or pathogens that are in the body.

For Lu and his co-founders — fellow MIT professor Jim Collins, Boston University  professor Wilson Wong and longtime synthetic biology operator Phillip Lee — Senti Bio is the culmination of decades of work in the field.

“I compare it to the early days of semiconductor work,” Lu said of the journey to develop this gene circuit technology. “There were bits and pieces of technology being developed in research labs, but to realize the scale at which you need, this has to be done at the industrial level.”

So licensing work from MIT, Boston University and Stanford, Lu and his co-founders set out to take this work out of the labs to start a company.

“When the company was started it was a bag of tools and the know-how on how to use them,” Lu said. But it wasn’t a fully developed platform. 

That’s what the company now has and with the new capital from Leaps by Bayer  and its other investors, Senti is ready to start commercializing.

The first products will be therapies for acute myeloid leukemia, hepatocellular carcinoma and other, undisclosed, solid tumor targets, the company said in a statement.

“Leaps by Bayer’s mission is to invest in breakthrough technologies that may transform the lives of millions of patients for the better,” said Juergen Eckhardt, MD, head of Leaps by Bayer. “We believe that synthetic biology will become an important pillar in next-generation cell and gene therapy, and that Senti Bio’s leadership in designing and optimizing biological circuits fits precisely with our ambition to prevent and cure cancer and to regenerate lost tissue function.”

Lu and his co-founders also see their work as a platform for developing other cell therapies for other diseases and applications — and intend to partner with other pharmaceutical companies to bring those products to market.  

“Over the past two years, our team has designed, built and tested thousands of sophisticated gene circuits to drive a robust product pipeline, focused initially on allogeneic CAR-NK cell therapies for difficult-to-treat liquid and solid tumor indications,” Lu said in a statement. “I look forward to continued platform and pipeline advancements, including starting IND-enabling studies in 2021.”

The new financing round brings Senti’s total capital raised to just under $160 million and Lu said the new money will be used to ramp up manufacturing and accelerate its work partnering with other pharmaceutical companies. 

The current time frame is to get its investigational new drug permits filed by late 2022 and early 2023 and have initial clinical trials begun in 2023.

Developing gene circuits is a new and expanding field with a number of players, including Cell Design Labs, which was acquired by Gilead in 2017 for up to $567 million. Other companies working on similar therapies include CRISPR Therapeutics,  Intellius and Editas, Lu said.