Anti-IDO2 antibodies: new treatment for rheumatoid arthritis and lupus

Lead investigators: Laura-Mandik-Nayak, PhD, Lisa Laury-Kleintop, PhD and George C. Prendergast, PhD

Unmet need

Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs when the body’s immune system attacks joints, creating debilitating inflammation and pain. Left unchecked, it can permanently damage joints and possibly parts of the cardiovascular and respiratory system.

Current treatments ease symptoms or slow disease course, but they do not target the disease itself. Instead, they simply ablate the immune system generally, elevating risks of infection and other immune-based diseases such as cancer.

The market for RA treatment 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 (SLE) is a systemic 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. 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 $1.2B in 2015 to US $3.2B by 2025, according to research and consulting firm GlobalData.

Opportunity

LIMR’s technology, focused on IDO2, offers a disease-specific approach to the treatment of autoimmune disease that currently is lacking in the field. Unlike current treatments, which generally blunt inflammatory signals or block the immune system as a whole, the IDO2-targeting antibody developed at LIMR acts selectively within B cells to attenuate pathogenic autoantibody production without ablating normal immune function.

Unique attributes

The immunomodulatory enzyme IDO2, discovered by LIMR scientists, has been identified as an essential mediator of autoimmune disease. In preclinical models of RA, systemic administration with a cell-permeable monoclonal antibody developed at LIMR specifically binds IDO2 in pathogenic B cells where it is activated, reduces autoreactive T and B cells, and alleviate pathogenic symptoms. LIMR’s innovative approach incorporates a leading edge in targeting intracellular antigens generally considered inaccessible to antibody-based therapies.

Clinical applications

Anti-IDO2 antibody exhibits therapeutic efficacy in RA and lupus models. In principle, this invention affords a general strategy to treat autoimmune disorders driven by autoantibody production as a single class by administering a biologic agent directed against a nodal modifier of pathogenic signal transduction in B immune cells. Accordingly, clinical development against a variety of orphan autoimmune diseases, e.g., myasthenia gravis, can be conceived as a rapid pathway to proof of concept, in addition to established pathways in RA and lupus where non-selective antibody drugs have been developed previously.

Stage of development

Preclinical genetic and therapeutic proof of concept in mice has been published for this novel mechanism of action.

The current stage of work is humanization of IDO2-binding antibodies with suitable properties for clinical translation.

Intellectual property

  1. IDO2 nucleic acid sequences: U.S. Patent No. 8,058,416 (issued Nov 15, 2011)
  2. IDO2 antibodies: U.S. Patent No. 8,436,151 (issued May 7, 2013).
  3. IDO2 antibody uses: U.S. Patent Application No. 15/742972 (also pending in Canada, Australia, Europe, Japan), filed Jan 9, 2018.

Collaboration opportunity

LIMR seeks partners to humanize new IDO2 monoclonal antibodies for therapeutic testing.

Relevant publications

Contacts

Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, prendergast@limr.org

L2C Partners contact: Merle Gilmore, 610.662.0940, gilmore@l2cpartners.com