Facing down Factor VIII intolerance

“The potential therapeutic impact of this product could be an important step in the fight to help hemophilia A patients who cannot benefit fully from Factor VIII replacement therapy. We are pleased that this is the product to make the next step into development,” Dr. Keith Martin, Apitope’s CEO, commented in a statement.

Hemophilia A is the most common form of hemophilia and is characterized by a deficiency in clotting Factor VIII, one of the proteins that aids in the clotting of blood when a person is wounded. Currently, there are approximately 12,000 patients with hemophilia A in the United States, and roughly the same number in Europe, according to Apitope. The common treatment for this condition is to administer Factor VIII, but since hemophilia A patients have little or no exposure to natural Factor VIII, their immune systems are not fully tolerant to the treatments, and according to Apitope, some 20 percent to 30 percent of patients develop inhibitor antibodies to Factor VIII. This not only severely limits the efficacy of such treatments, but it can also lead to joint damage, brain damage and even death. As Apitope notes on its website, “There are currently no treatments available to prevent or treat the development of neutralizing antibodies.”

Apitope’s work with ATX-F8-117 has confirmed that the two peptides in the therapy have the potential to treat and prevent inactivating alloantibody development in hemophilia patients receiving Factor VIII treatment.

“Bringing the next product through into preclinical development is a milestone event for Apitope,” Prof. David Wraith, chief scientific officer and founder of Apitope, said in a press release. “This further demonstrates that Apitope’s discovery platform can generate new potentially life-changing therapies for development and validates the scientific basis of our approach.”

Before one of the company’s Apitopes—Antigen Processing Independent epiTOPES—is moved into preclinical development, it is characterized in both in-vitro and in-vivo assays. Apitope’s in-vitro screening method can identify peptides that “do not require processing by antigen-presenting cells but are capable of binding to MHC II molecules on the surface of these cells and thereby activating regulatory T cells,” as noted on its website. Apitope begins by using human MHC class II receptors to generate specific T cell reagents, which are then used to identify T cell epitopes. The company’s proprietary process enables the selection of Apitopes, and an in-vivo model assesses each Apitope’s ability to “induce tolerance to the auto-antigen from which they were developed.”

“At Apitope, our focus is on the discovery and development of life-changing peptide therapies for autoimmune and allergic conditions that treat the underlying cause of disease by restoring the immunological balance. We are building a strong portfolio of development candidates as well as expanding our discovery capabilities to fully exploit the scientific expertise now established at Apitope. We expect 2014 to be an important year for us with respect to our lead programs moving through development,” according to Martin.

Apitope currently has six other programs in its pipeline aimed at addressing a number of conditions. ATX-UV1 and ATX-UV2, which are both indicated for the treatment of uveitis (swelling and irritation of the uvea, the middle layer of the eye), are approaching preclinical development, as are ATX-MS2 and ATX-MS3, which are partnered with Merck Serono and under development for multiple sclerosis. ATX-GD-459, indicated for the treatment of Graves’ disease, is also in preclinical development. Apitope’s most advanced candidate, ATX-MS-1467, is in Phase 2 development against multiple sclerosis and is being developed in partnership with Merck Serono.