Building on long-standing studies of the disease-promoting small GTPase RhoB, including in selectively driving production of autoantibodies, LIMR scientists have developed a cell-permeable anti-RhoB antibody that exhibits therapeutic efficacy in preclinical models of rheumatoid arthritis, lupus and diabetes. In principle, this invention affords a general strategy for treating autoimmune disorders driven by autoantibody production as a single class by administering a single biologic agent directed against a nodal signal transduction modifier. LIMR’s innovative approach incorporates the leading edge in targeting intracellular antigens generally considered inaccessible to antibody-based therapies.
LIMR’s technology that is focused on RhoB offers a disease-specific approach to the treatment of autoimmune disease that is currently lacking in the field, where management is based on a general ablation of inflammatory signals or the immune system as a whole. Preclinical research highlights a unique feature of RhoB targeting, which specifically ablates the production of pathogenic autoantibodies, without affecting the production of non-pathogenic antibodies. Thus, the cell-permeable antibody developed at LIMR acts in a highly selective way to blunt what may be a fundamental pathogenic process in autoimmune disease. Preclinical genetic and therapeutic proof of concept in mice for this novel mechanism of action has been published. A chimeric humanized antibody (‘rhoboximab’) has been generated, and current work aims at pre-IND development of fully humanized RhoB-binding antibodies for clinical testing.
Autoimmune disorders are skyrocketing in incidence in the developed world, perhaps explained by the widely cited hygiene hypothesis. LIMR technology affords a unique opportunity to attack autoimmune disease as a class, by targeting a signaling molecule that selectively modifies a pathogenic process. This is a novel, exciting opportunity offering broad market access. Rheumatoid arthritis (RA) and lupus represent perhaps the largest markets for new treatments for autoimmune diseases known to be driven by production of pathogenic autoimmune antibodies.
RA is a chronic autoimmune disease caused by an aberrant immune attack on joints, but in advanced cases, elements of the cardiovascular and respiratory systems are also affected. Over 1.5 million Americans and about one percent of the global population are affected. Current treatments only ease symptoms or slow disease course. They do not target the disease itself but simply ablate the immune system generally, elevating risks of infection and other immune-based diseases such as cancer.
The global market for RA therapy is expected to increase from US $1.7 billion in 2017 to US $2.3 billion in 2022, according to the market information resource BCC Research.
Lupus is an autoimmune disorder associated with chronic inflammation that can damage any part of the body. An estimated 1.5 million Americans have lupus, with an additional 16,000 new cases reported each year, according to the Lupus Foundation of America. It is believed that about five million people throughout the world have lupus. There is no cure for lupus, and as in RA, current treatments are not disease-selective.
The global market for lupus treatment, which includes systemic lupus erythematosus and lupus nephritis, is expected to increase from US $1.2 billion in 2015 to US $3.2 billion by 2025, according to research and consulting firm GlobalData.
Intellectual property position
- RhoB antibodies and uses: U.S. Patent No. 9,879,092 (issued 30 Jan 2018).
Mandik-Nayak L, DuHadaway JB, Mulgrew J, Pigott E, Manley K, Sedano S, Prendergast GC and Laury-Kleintop LD (2017). RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus. Dis Model Mech 10: 1313-22.