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.

Source: TechCrunch

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