New subsidiary, new AAV gene therapies

The most immediately promising of the therapies is Tamid-001, which targets the ocular manifestations of mucopolysaccharidosis type I (MPS I), a rare and progressively debilitating disorder caused by mutations in the IDUA gene. Preclinical testing suggests that Tamid-001 may provide a single-intervention treatment of the disease while preventing further damage.

Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunction of lysosomal enzymes that the body needs to break down glycosaminoglycans (GAGs), which then accumulate in multiple organs. In MPS I, otherwise known as hereditary ocular disease, these GAGs build up in the eye, which causes corneal clouding and can eventually lead to blindness. Tamid has successfully established proof of principle in canines, with Tamid-001 effectively clearing existing GAGs from the eye and seeming to block the accumulation of more.

Existing treatments for MPS I are traditional enzyme replacement therapies (ERTs), which require ongoing treatment because their large molecular size does not allow them to cross the ocular membrane. These ERTs may stem the disease, but the disease often continues to progress and can lead to blindness. Tamid-001 is a new AAV gene therapy which is administered through a single, continuously expressing intra-ocular injection.

“Tamid-001 proves a significant improvement as a single lasting injection directly to each eye which clears existing GAGs and prevents the buildup of new ones in the future,” says A.J. Ross, the vice president of business development at Fortress who oversees Tamid.

Tamid-001 works by delivering the missing enzyme, alpha-L-iduronidase, directly to the eye. Preclinical development of Tamid-001 has involved canine testing, where equivalent enzyme malfunctions are naturally occurring. In repeated tests, GAGs were cleared out within 10 days of the injection and did not recur.

The development and testing of Tamid-001 in dogs has shown consistent, well-tolerated results, with no safety concerns emerging and no toxicology issues. Tamid anticipates initial pre-Investigational New Drug meetings with the FDA this year, and expects a relatively straightforward path to commence clinical trials in humans. Tamid-001 can offer researchers a better understanding of what causes the disease, and may lead to preventing onset in the first place.

In addition to Tamid-001, they are also working with Hirsch and UNC on two other early-stage AAV assets, one which will target dysferlinopathies (causing muscular degenerative diseases) and one aimed at preventing corneal transplant rejection. The corneal asset uses HLA-G, which is shown to play a role in immune tolerance in pregnancy and helps to prevent fetal rejection.

Dr. Lindsay A. Rosenwald, Fortress Biotech’s chairman, president and CEO, said, “We are thrilled to be working with Dr. Hirsch to develop novel gene therapies in areas of unmet medical need. Early preclinical data have demonstrated the potential of his AAV technologies to significantly improve treatment options for patients. Fortress looks forward to collaborating with Tamid and Dr. Hirsch to rapidly advance these therapies toward clinical trials.”

Fortress Biotech is a biopharmaceutical company dedicated to acquiring, developing and commercializing novel pharmaceutical and biotechnology products. Fortress develops and commercializes products both within Fortress and through certain subsidiary companies, also known as Fortress Companies.

According to Ross, “Fortress serves as a parent company for a number of subsidiaries—remaining agnostic on the technology. We work with researchers to identify assets in different stages of development and serve as a backbone to bring them to market. We support early-phase work for researchers, then map the pathway to bring the product to clinical testing.”