Generation Bio, a developer of redosable gene therapies, said today it has closed on a $100 million Series B financing, with proceeds intended to advance its first two treatment candidates through Investigational New Drug (IND)-enabling studies, and develop additional programs targeting genetic diseases of the retina, central nervous system (CNS), and lungs.

Generation Bio’s treatments are based on its proprietary GeneWave™ technology, designed to create a new class of genetic medicines capable of being titrated to effect and redosed for the needs of individual patients as they age, while delivering durable, high levels of gene expression.

The therapies are designed to overcome the immunogenicity associated with viral-vector gene therapies, which has proven enough of a challenge to prevent redosing and thus limit the number of patients that can be treated—paving the way for what the company trumpets as “a new era for gene therapy.”

Safety issues connected with vector dosing have resurfaced in recent weeks, after gene therapy pioneer James M. Wilson, M.D., Ph.D., and colleagues detailed instances of severe, life-threatening toxicity in monkeys and piglets given high doses of gene therapy delivered using an adeno-associated virus serotype 9 (AAV9) vector capable of accessing spinal cord neurons.

Since its founding in 2016, Generation Bio said, it has shown durable, dose-dependent expression and the ability to increase expression in the liver with redosing in vivo through the GeneWave platform.

“This will be a critically important year for us as we develop the GeneWave platform and work toward our first development candidates to address rare diseases of the liver,” Generation Bio president and CEO Geoff McDonough, M.D., said in a statement.

Dr. McDonough previously served as CEO of Swedish Orphan Biovitrum (Sobi), and earlier held positions with Genzyme as president of its Europe-Middle East-Africa (EMEA) region, and as general manager of the company’s lysosomal storage disease franchise.

Focus on Liver, Protein Deficiency

Rare genetic diseases of the liver are one of Generation Bio’s two furthest-along “focus areas” of therapeutic interest: “Several diseases, such as progressive familial intrahepatic cholestasis, phenylketonuria, glycogen storage disease 1a, and ornithine transcarbamylase deficiency, may be addressed,” the company states on its website.

The other focus area is “rare genetic disease with protein deficiency,” a category the company defines to include lysosomal storage diseases and hemophilia. Generation Bio is also looking to develop treatments for three “exploratory” areas: genetic eye diseases, genetic lung diseases, and genetic diseases of the CNS: “We are exploring the delivery of full-length CFTR as a means for addressing cystic fibrosis.”

Generation Bio’s core technology was discovered by the company’s scientific founder and head of discovery, Robert Kotin, Ph.D. Dr. Kotin was a senior investigator at the NIH when he identified a novel modality for nonviral gene transfer, known as closed-ended DNA (ceDNA). Manufactured in a serum-free eukaryotic system without the use of animal-derived products, ceDNA is a eukaryotic DNA capable of translocating from the cytoplasm of the cell to the nucleus without the use of a viral capsid.

Once in the nucleus, according to Generation Bio, ceDNA forms stable, nonintegrating episomes that result in high levels of long-term gene expression. The technology can also accommodate much larger genes and regulatory elements, allowing for a greater number of diseases to be addressed.

GeneWave uses a nanoparticle designed to intravenously deliver ceDNA to the liver, where it may attack diseases of the liver or enable it to express systemic proteins to treat a wide variety of genetic diseases—transforming the liver into a “biofactory,” as the company calls it.

Fidelity Management & Research Company led the financing round, with participation by Invus, Deerfield Management, Casdin Capital, Foresite Capital, and Leerink Partners’ Affiliates.

Headquartered in Cambridge, MA, Generation Bio was launched less than two months ago by Atlas Venture, which founded the company with a $25 million Series A financing.

“Generation Bio is creating a breakthrough category of therapeutics and is positioned to be a leader in the gene therapy field,” added Jason Rhodes, a partner at Atlas Venture and a founder and chairman of Generation Bio’s board.

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