Anti-RhoB antibodies: broad spectrum treatment for autoimmune disease
Autoimmune disorders, including rheumatoid arthritis (RA) and lupus, are skyrocketing in incidence in the developed world. Current rheumatoid arthritis 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. There is no cure for lupus, and as in RA, current treatments are not disease-selective.
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 RA, 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. RA and lupus may represent 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 1% of the global population are affected. The global market for RA therapy is expected to increase from US $1.7B in 2017 to US $2.3B 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 5 million people throughout the world have lupus. The global market for lupus treatment, which includes systemic lupus erythematosus and lupus nephritis, is expected to increase from US $1.2B in 2015 to US $3.2B by 2025, according to research and consulting firm GlobalData.
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.
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.
Potential new treatment for autoimmune diseases, including rheumatoid arthritis and lupus.
Stage of development
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.
- RhoB antibodies and uses: U.S. Patent No. 9,879,092 (issued Jan. 30, 2018).
- Additional PCT application filed US, Australia, Canada, Europe, Japan, Korea, Russia.
Seeking licensee for commercialization or collaboration to complete pre-IND development.
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.
Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]
L2C Partners contact: Merle Gilmore, 610.662.0940, [email protected]