EpiVax funded to advance research using Tregitopes on a new, improved version of the hemophiliac drug FVIII
July 10, 2012 (Providence, RI)— EpiVax, Inc, a leader in genome-derived vaccines, announced today that it has received a grant to reengineer factor eight (FVIII), the primary therapeutic used to control bleeding and foster wound healing in hemophiliacs.
This project is funded by a Small Business Innovation Reward (SBIR) by the National Heart Lung and Blood Institute (NHLBI), a division of the National Institutes of Health (NIH). The grant will provide $381,361 to fund the production of a combined clotting Factor VIII replacement and immunomodulatory therapy that will provide FVIII-specific tolerance induction at therapeutic doses for Hemophilia A patients.
“Our unique approach to developing safe and effective protein therapeutics by modifying T cell epitopes is at the core of this research effort,” said Anne De Groot, M.D., President and CEO of EpiVax. “This funding results from our demonstrated ability to use our immunoinformatics tools to screen and reengineer protein therapeutics. Using the same approach, we anticipate that we’ll be able to create a whole range of effective and “second generation” biologics such as toxins and monoclonal antibodies at a highly accelerated pace”.
In hemophiliacs, the FVIII protein is missing or non-functional and thus their blood does not clot properly. The FVIII protein can be produced in the laboratory and administered as therapy. Hemophiliacs with <1% functional FVIII are classified as severe and must receive regular doses of replacement factor. A major issue with successful FVIII replacement therapy is overcoming the neutralizing antibody response which delays or inhibits clotting by interfering with FVIII binding to its ligands. There is an urgent need for a safe, biologically rational and cost effective approach to induce long-term immune tolerance to FVIII.
“Tregitopes” are immunoglobulin-derived natural regulatory T-cell (nTreg) epitopes that expand a subset of circulating nTregs, leading to suppression of inflammation and, when administered with a target antigen, adaptive tolerance. As a natural immune system ‘off switch,’ Tregitopes have great potential as therapeutics to induce immunological tolerance to co-administered proteins. EpiVax plans to couple Tregitopes with FVIII to produce a novel combined replacement and tolerance induction therapy.
The EpiVax research program will be carried out in collaboration with the University of Maryland (Dr. David Scott). For more information on hemophilia and FVIII, please visit the National Hemophilia Foundation at http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=0&contentid=1.
According to the Centers for Disease Control and Prevention (CDC), hemophilia is an inherited bleeding disorder that affects 18,000 persons (primarily males) in the United States. The disorder results from deficiencies in blood clotting factors and can lead to spontaneous internal bleeding and bleeding following injuries or surgery. These bleeding episodes can cause severe joint damage, neurological damage, damage to other organ systems involved in the hemorrhage, and, in rare cases, death. Treating the bleeding episodes involves the prompt and proper use of clotting factor concentrates.
Tregitopes are a set of peptides that specifically activate CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). Tregitopes are promiscuous MHC Class II T cell epitopes located in the Fc and framework regions of Fab from IgG. In vitro, co-incubation of antigens with Tregitopes in vitro leads to a suppression of effector cytokine and chemokine secretion, reduced proliferation of effector T cells, and expansion of antigen-specific adaptive Tregs (aTregs). In vivo, co-administration of Tregitopes with a wide range of proteins (such as FVIII, thyroid stimulating hormone receptor, ovalbumin, and autoantigens) leads to suppression of T cell and antibody responses to test antigens.
EpiVax, Inc. is dedicated to merging in vitro immunology research with bioinformatics to generate new therapeutics for cancer and autoimmune diseases as well as new vaccines for infectious diseases such as HIV, TB, and hepatitis. T cell epitope mapping, the selection of target peptides from any protein sequence, is a powerful resource for the development of novel protein therapeutics. EpiVax research shows that peptides chosen by EpiMatrix™ software are highly likely to provoke an immune response when presented to T cells. EpiVax tools can also accurately deimmunize proteins. For more information about EpiVax, please visit www.epivax.com.