Engineered viruses are a mainstay in genetic medicine due to their ability to ferry genetic cargo into cells. But limitations of this approach have sparked research into methods that don’t rely on such viruses. Eli Lilly is adding one of them to its toolbox by acquiring Engage Bio, a preclinical startup with proprietary non-viral DNA delivery technology.
Financial details are scant for the deal announced Wednesday. The companies said Lilly will pay up to $202 million, which includes an unspecified upfront payment and subsequent milestone payments.
One key limitation of viral-based delivery is that viruses are at odds with the immune system. Even if a virus is engineered so it doesn’t replicate and cause infection, the body still sees it as foreign and produces antibodies against it. Consequently, a viral-based therapy is a one-time treatment because another dose would be rendered ineffective by those antibodies. Like many biotech startups pursuing non-viral approaches, the therapies of San Carlos, California-based Engage use lipid nanoparticles (LNPs). The body doesn’t see lipids as foreign, so an LNP-delivered therapy can be redosed. But Engage goes further.
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Engage aims to make therapies that are more potent for greater efficacy, but at the same time are less toxic to improve on safety. The startup says its technology, called Tethosome, localizes DNA to the nucleus of a cell, increasing its expression there. Also, the immune system does not view therapies from this technology as foreign so it does not mount an immune reaction. The company adds that its DNA payloads are engineered to improve tolerability while retaining durability and programmability.
In a LinkedIn post, Engage CEO Will Olsen wrote that his team was able to build a platform “that achieves non-viral DNA delivery with meaningful improvements in tolerability, expression, and redosing.”
“In Lilly, we found a partner that is willing to take early and decisive bets on potentially transformative technologies,” Olsen said. “We believe the combination of Engage’s platform with Lilly’s vast capabilities holds the potential to rapidly advance the development of innovative DNA medicines.”
Engage is still preclinical and has not disclosed specific disease targets. It was founded in 2021 and graduated from startup accelerator Y Combinator in 2022. The company said its seed financing came from SciFounders, Pioneer Fund, Cal Innovation Fund, Y Combinator, and the Cystic Fibrosis Foundation. Engage also received non-dilutive funding from the Gates Foundation and the National Center for Advancing Translational Sciences, part of the National Institutes of Health. No financial details for the funding was disclosed.
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The Engage acquisition is the latest deal in a growing list of Lilly business development moves in genetic medicines. Last summer, Lilly paid $1 billion to buy Verve Therapeutics, developer of in vivo gene-editing medicines for cardiovascular diseases. In February, Lilly acquired Orna Therapeutics, a clinical-stage startup that employs LNPs to deliver circular RNA that enable in vivo production of cell therapies for autoimmune disorders. The Orna deal could reach up to $2.4 billion. Last month, Lilly agreed to pay $3.25 billion up front for Kelonia Therapeutics, a startup with a platform technology for engineering lentiviruses to enable the body to produce vivo cell therapies.
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