Generation Bio has received $110 million in funding to advance its non-viral gene therapy lead programs — designed to treat phenylketonuria (PKU) and hemophilia A — toward investigational new drug-enabling clinical trials.
With the closing of a Series C financing, the company will use its new proceeds to further its two lead liver-targeted programs.
PKU is caused by mutations in the PAH gene, which carries the instructions for producing an enzyme called phenylalanine hydroxylase (PAH). PAH is responsible for the conversion of phenylalanine — an amino acid obtained through the diet — into another amino acid, tyrosine. Amino acids are the building blocks of proteins.
PAH mutations lower the levels of PAH activity, leading to the toxic buildup of phenylalanine in the blood and organs. This causes organ damage, particularly in the brain.
Gene therapy has the potential to target PKU’s underlying cause by delivering a functional copy of the PAH gene to patients. This would promote a sustained production of PAH and prevent further damage.
To deliver the functional gene into cells, current gene therapies rely on modified and harmless versions of an adeno-associated virus (AAV) to serve as the “vehicle.” Liver cells are a frequent target, as the liver plays a central role in metabolism and in the production of blood proteins.
Despite increasing promising data on the use of viral-based gene therapy for the treatment of genetic diseases, this strategy is associated with some safety issues, including immune responses. It also does not allow re-dosing, and requires complex, expensive, time-consuming manufacturing processes.
Generation Bio’s new non-viral gene therapy platform overcomes some of these limitations. The platform is based on the company’s proprietary GeneWave technology, designed to develop re-dosable, long-lasting, scalable gene therapies for severe diseases.
Instead of viruses, the Generation Bio gene therapy uses a new gene delivery system based on liver-targeting fat nanoparticles, which deliver the gene through a new DNA construct known as closed-ended DNA.
These fat nanoparticles bind to the membrane of liver cells and deliver the selected gene in a close-ended DNA construct that leads to high and sustained production of the gene-resulting protein.
This new DNA construct also allows the delivery of much larger genes, which expands the spectrum of diseases that could benefit from gene therapy.
Since Generation Bio’s gene therapy does not involve the use of viruses, it can be used to treat patients who have pre-existing immune responses to AAV or who have already received a virus-based gene therapy, working as re-dosing.
Re-dosing allows not only the optimization of the therapy’s dose based on patients’ responses, but also the repeated administration of the therapy according to the individual’s needs.
Moreover, the high-capacity manufacturing process behind both technologies — the fat-based gene delivery system and the closed-ended DNA construct — allows their large-scale production and the treatment of diseases affecting large, global patient populations.
“Our vision is to develop re-dosable, long-lasting gene therapies manufactured at a scale that leaves no patient or family behind,” Geoff McDonough, MD, president and CEO of Generation Bio, said in a press release.
In addition to its lead liver-targeted programs in PKU and hemophilia A — a genetic bleeding disorder caused by a deficiency in a specific clotting protein — the company is developing programs for people with genetic diseases affecting the eye, the skeletal muscle, and the brain.
“Since our founding, we have had the support of high-quality investors who share our excitement about our potential to lead a new generation of gene therapy as we advance our lead programs toward the clinic,” McDonough said.
The funding, led by T. Rowe Price, included Farallon, Wellington Management Company, the investors Atlas Venture (Generation Bio’s founder), Fidelity, Invus, Casdin, Deerfield, Foresite Capital, and a partner of SVB Leerink.
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