News Article

Adding genetic circuits to make cell and gene therapies safer and better
Date: Oct 02, 2018
Author: Nick Paul Taylor
Source: Fierce Biotech ( click here to go to the source)

Featured firm in this article: Senti Biosciences Inc of South San Francisco, CA

CEO: Tim Lu
Based: South San Francisco, California
Founded: 2016
Clinical focus: Cancer and autoimmune diseases

The scoop: Cell and gene therapies have started to come of age over the past year, but the pioneering first-generation products on the market have major limitations. Notably, the therapies can trigger events that are hard to predict and control. One patient may suffer cytokine release syndrome, threatening their safety. The tumor of another patient may undergo antigen escape, rendering it invisible to the immune system tasked with its destruction.

For Senti Bio, the answers to these problems lie in synthetic biology. By adding genetic circuits to cell and gene therapies, Senti is designing treatments that sense and adapt to their environment, enabling them to avoid the safety and efficacy pitfalls that blight their cruder predecessors.

What makes Senti fierce: The biotech world is well stocked with startups focused on making CAR-Ts and other advanced therapies safer and more broadly efficacious, but few of these companies can match Senti's credentials. Senti's co-founders and collaborators have spent the past 15 years defining and advancing the field of synthetic biology.

Now, the Senti scientists think the field is mature enough to rewrite what cell and gene therapies can do. The idea is underpinned by synthetic gene circuits. Senti is putting these genetically engineered elements into cells to enable the resulting therapies to sense and adapt to their environment, or be otherwise controlled.

"In our solid tumor program, we're working with cell therapies that we can engineer to be localized to the tumor microenvironment instead of freely circulating throughout the entire body," Tim Lu, M.D., Ph.D., co-founder and CEO of Senti, said.

These therapies sense chemokines and other signals that characterize the tumor microenvironment. By identifying these signals, Senti's cell therapies can zero in on the tumor, resulting in a strong, local immune response and minimal effect on healthy tissue.

Senti is also exploring the use of synthetic circuits to create CAR-T cells that feature two-component receptor systems rather than the single, fixed CAR typically found on such therapies. This format opens up new therapeutic opportunities. Senti could configure the system so adaptor molecules regulate the efficacy of the cells or shut them down completely. Alternatively, Senti could design the cells to only activate in the presence of two different antigens, thereby increasing their specificity.

Lu thinks the nature of many cancers means that a belt-and-braces approach to targeting will be vital to success in certain indications.

"Oftentimes, it's going to require more than a single antigen to get enough specificity so you don't go after the normal tissues," he said.

Senti spent its first two years establishing a cell engineering platform capable of quickly designing, building and testing gene circuits at scale. The effort gave Senti an in-house vivarium and experts in computational design and synthetic biology capable of designing circuits, testing them in vivo and using the results to inform the next design.

With that foundation in place, Senti raised a $53 million series A round earlier this year to support its push toward the clinic. Senti has since grown its head count to 35 and hired experts in ovarian cancer and disease to support the progress of its most advanced programs. Lu expects to nominate the first development candidates early next year.

In parallel, Senti is lining up partnerships. Lu is open to partnering in cancer if the right deal comes along, but the main goal of the business development strategy is to expand use of the platform into new therapeutic areas. Senti sees opportunities to use its gene circuits to improve fields including regenerative medicine.

Investors: New Enterprise Associates, 8VC, Amgen Ventures, Pear Ventures, Lux Capital, Menlo Ventures, Allen & Company, Nest.Bio, Omega Funds, Goodman Capital and LifeForce Capital