Forge Biologics has something rare for most early-stage biotech startups: revenue from customers. Now it has $40 million to expand its model, which places contract manufacturing alongside the development of its own gene therapies, the most advanced of which is being readied for tests in humans.
From operations in Columbus, OH, Forge makes gene therapies for other companies. The company was initially conceived solely as a contract manufacturer, CEO Tim Miller (pictured above) told Xconomy. The explosion of gene therapy research is leading to growing demand for manufacturing capabilities—much more than the industry is forecast to supply in coming years. Miller says Forge will do its part to help address those needs.
But Forge’s founders realized that the company could funnel the manufacturing revenue into the development of its own gene therapies. This model reduces the financial burden on the company and by providing it with cash to pay for R&D.
“It didn’t start that way, but we grew into it, and that’s the model that’s resonated with investors and key members that wanted to sign on,” Miller says.
The most advanced Forge program is a gene therapy for Krabbe disease, an inherited neurological disorder caused by a loss of myelin, a protective covering of the nerve cells. Krabbe disease is caused by mutations in a gene called GALC, which provides the instructions for making a key protein needed to break down fats called galactolipids. The enzyme deficiency causes lipids to build up to toxic levels in myelin, eventually leading to the death of these cells.
The most common form of Krabbe affects infants and leads to problems such as muscle weakness, difficulty eating, and delayed physical and mental development. Most babies diagnosed with Krabbe die before reaching age 2.
Forge’s Krabbe gene therapy candidate, FBX-101, uses an engineered adeno-associated virus (AAV) to ferry its genetic payload into cells. Other gene therapies also use these viruses, but they have been linked to dangerous side effects, including death, says Miller, who was previously the president and CEO of New York-based cell and gene therapy developer Abeona Therapeutics (NASDAQ: [[ticker:ABEO]]).
Such side effects are an immune response to AAV, and they can be a challenge at higher doses, Miller says. Forge aims to overcome these problems by combining its Krabbe gene therapy with an umbilical cord transplant. The transplant of cord blood, which is rich in stem cells, is currently the standard of care for Krabbe patients. While the treatment has been shown to improve the symptoms of the disease and correct the enzyme deficiency in the brain, Forge says these transplants don’t fix the deficiency in the peripheral nervous system.
The company hopes that combining a cord blood transplant with the gene therapy will overcome that shortcoming. Miller adds that the cord blood effectively replaces the infant’s immune system with one that does not react adversely to the gene therapy. This combination approach was pioneered by Maria Escolar, a pediatrician and Krabbe disease expert at the University of Pittsburgh. She has joined Forge as its chief medical officer.
According to preclinical research published in 2011 in The Journal of Neuroscience, the combination of a bone marrow transplant and gene therapy helped on several measures, including
