The last year has been a busy one for Bedford, Mass.-based Homology Medicines. Albert Seymour, Homology’s chief science officer, took time out to talk to BioSpace about the company and where it’s headed.
The last year has been a busy one for Bedford, Mass.-based Homology Medicines. In late March 2018, the company launched its initial public offering (IPO), raising an initial $144 million. It has since then built a manufacturing facility for its gene therapy products, and on April 4, 2019, received the go-ahead from the U.S. Food and Drug Administration (FDA) to begin its Phase I/II pheNIX clinical trial for HMI-102 for phenylketonuria (PKU).
Homology was one of BioSpace’s NextGen “Class of 2017” Life Science Startups to Watch.
Albert Seymour, Homology’s chief science officer, took time out to talk to BioSpace about the company and where it’s headed.
Seymour indicates that the company was formed in early 2016, built around the discovery of 15 new adeno-associated viruses (AAVs) by Saswati Chatterjee, a member of the Beckman Research Institute at the City of Hope in California. Because they were discovered in human hematopoietic stem cells, they have been dubbed AAVHSCs (adeno-associated virus human stem cells). Seymour says, “We can use them to treat genetic diseases, which is why we describe ourselves as a genetic medicines company. We think of the AAVHSCs as delivering genetic medicines. It’s more like a gene transfer.”
He also points out that another component of their tech platform allows them to direct the gene therapy “inside the genome in a very specific spot. We can use that platform and develop it and the gene transfer part, for cells that don’t divide very rapidly or not at all, such as to the liver or central nervous system. For the editing side, we really try to tackle diseases that divide very rapidly.”
Essentially, the company has two main approaches. One is gene editing, using the naturally occurring process of homologous recombination. The AAVHSCs do not require a nuclease for gene cutting, allowing to focus on a method of gene editing called gene correction.
The other is a gene therapy approach, which also uses AAVHSCs as vectors to deliver a functional gene to a cell. This is where the PKU therapy falls.
The company’s lead program is HMI-102, a one-time gene therapy for PKU, a rare genetic disease caused by a mutation in the PAH gene. The current standard of care is a highly restrictive diet, but it’s not always effective. If untreated, it can result in progressive and severe neurological impairment. About 15,000 people in the U.S. have been diagnosed with the disease, with about 300 newborns newly diagnosed each year.
The FDA recently approved the company’s Investigational New Drug (IND) application for HMI-102. The IND package included data showing that administration of the gene therapy restored the phenylalanine metabolic pathway, which normalized blood phenylalanine levels and increased neurotransmitter production in a PKU animal model.
HMI-102 uses AAVHSCs to deliver a functional copy of the PAH gene to the liver.
Seymour says, “We’re very excited. It’s a program we developed at Homology from scratch. We took one of our 15 AAVHSCs, which we selected because it has high tropism for the liver, higher than the others, and engineered the inside construct so we can deliver the normal or functional form, of PHA.”
Early successes in gene therapy have been in eye diseases, primarily Spark Therapeutics’ Luxturna (voretigene neparvovec) for a rare, genetic form of blindness. One reason gene therapies have started in optical diseases is because of the relative ease of delivering a gene directly into the eye. Delivering gene therapies systemically, typically through an infusion, have a disadvantage in that they spread throughout the entire body.
All of Homology’s AAVHSCs have an affinity for liver cells, which is one reason the company chose to initially focus on PKU. Seymour told BioSpace, “The main organ involved, the main cell you need for PKU activity, is in the hepatocytes in the liver. So we tried to limit that by using a liver-specific promoter to get the enzyme expressed in the right cell types.”
He went on to say, “Strategically, when we set up the company, we had these novel AAVs, which we knew would go to the liver. But in order to get some validation on the platform, we selected a liver indication that had significant unmet medical need. We felt as we moved forward, we could generate safety data around that particular aspect and bring a treatment for the disease.”
As mentioned earlier, part of the funds raised in the IPO in 2018 was used to build the company’s GMC manufacturing plant in Bedford, Mass. It recently opened and is 25,000 square feet. Seymour says, “Our lead program is around manufacturing. As a company, we made a concerted effort very early on to invest in that, not just from a development point of view, but now that we have it, we’re a fully integrated pharmaceutical company. It’s under our guidance, under our prioritization. We made sure we owned, if you will, everything from idea and discovery, through entering the clinic, and it all involves manufacturing our clinical supply. That was something we felt very passionate about—making sure we had it under our control.”
Meanwhile, the company’s pace is continuing. They are in the process of selecting sites for the PKU clinical trial and getting them up and running. Seymour says, “We’re well on track to report out clinical data on the first few patients by the end of this year.”
The company also has programs for metachromatic leukodystrophy (MLD) and pediatric PKU, which he says they expect to discuss with the FDA this year as well. Other programs in preclinical stages are in hemoglobinopathy, such as sickle cell disease, and eye diseases.
