CRISPR Therapeutics
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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.
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Mammoth Biosciences aims to be Illumina for the gene editing generation
In 1998, the startup company Illumina launched a revolution in the life sciences industry by developing technology to slash the costs of identifying and mapping genetic material.
Now, a little over 20 years later, Mammoth Biosciences is hoping to do the same thing for gene editing tools.
The company, co-founded by Jennifer Doudna, who did some of the pioneering work to discover the gene editing enzyme known as CRISPR, has just raised $45 million as it looks to bring to market products that can be used not only for disease detection, but are more precise editing tools for genetic material.
Rather than get bogged down in the patent dispute that raged over the provenance and ownership of applications for the original CRISPR enzyme — the Cas9 discovered by Doudna and developed for clinical applications at the Broad Institute — Mammoth has joined a number of startups in identifying new enzymes with a broader array of properties.
“From the very beginning of the company we’ve only worked with novel new enzymes to create these diagnostic products and the new novel diagnostic and editing,” says Trevor Martin, Mammoth Biosciences co-founder and chief executive.
Chiefly, the company is touting its Cas14 enzyme, which the company says opens up new possibilities for programmable biology thanks to its small size, diverse targeting ability and high fidelity — meaning that there are no unforeseen side effects to edits made using the enzyme (something that has arisen with Cas9 applications).
“There’s not one protein that’s going to be the best at everything,” says Martin. “For any particular product that you’re building, at Mammoth, we have the broadest toolbox.”
The Cas14 enzyme can be used to make gene edits in-vivo, meaning in live organisms, instead of ex-vivo, or outside of an organism. The in-vivo use-case could accelerate the time it takes to conduct experiments or develop treatments.
“Twenty years from now, when the umpteenth drug gets approved using Crispr and some nuclease named Cas132013, people are going to look back on this patent battle and think, ‘what a godawful waste of money,’ ” Jacob Sherkow a patent law scholar at New York Law School told Wired back in 2018.
Already, Horizon Discovery, a Cambridge, U.K.-based gene editing technology developer, is using the new tools developed by Mammoth Bioscience to create new CRISPR tools for Chinese Hamster Ovary cell line editing.
That partnership is an example of how Mammoth is thinking about the commercialization of the new Cas14 enzyme line and its role in biological engineering.
“You will need a full toolbox of CRISPR proteins,” says Martin. “That will allow you to interact with biology in the same way that we interact with software and computers. “From first principles, companies will programmatically modify biology to cure a disease or decrease risk for a disease. That’s going to be really kind of a turning point.”
To achieve its vision, Mammoth has managed to nab top talent from the life sciences industry, including Peter Nell, a co-founder of Casebia (a joint venture between Bayer and CRISPR Therapeutics), who came on board as chief business officer, and Ted Tisch, a former executive at Synthego and Bio-Rad, who joined the company as chief operating officer.
The company also nabbed $45 million of funding, including investment firms Mayfield, NFX, Verily (the Alphabet subsidiary) and Brook Byers, which was led by Decheng Capital — bringing the company to more than $70 million in funding.
“There are a dozen or so products that are in clinical development with CRISPR,” says Ursheet Parikh, a partner with Mayfield. “Maybe that number would go up by five or 10 without Mammoth, but it will go up by one or two orders of magnitude with Mammoth.”
To Parikh, Mammoth is the best positioned of the CRISPR development tools, because the company is building a whole platform that customers can license and use to develop products using gene editing.
The thinking, according to Parikh, is as follows, “if this technology can power lots of applications, let’s basically ensure that lots of these applications can come to market and as that happens I get my app store cut.”
“It’s an Illumina-like business,” Parikh says. “Just as anybody who is innovating with genomics needs an Illumina sequencer because they want to be able to do the sequencing… if someone wants to do editing… This gives them the access to do the right sequencing.”
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