Therapeutic Focus

Multiple Sclerosis

We have created AZ01 which is a PEGylated interferon beta for the treatment of multiple sclerosis, a chronic disease characterized by demyelination of nerve fibers, which leads to severe nerve damage. MS symptoms include fatigue as well as cognitive and visual impairment. There is no cure for MS which affects approximately 400,000 people in the US and 2.5 million people worldwide. There are seven drugs currently marketed as disease-modifying treatments for RRMS, including three interferon beta therapies, which represented approximately two thirds of worldwide MS drug sales in 2009. Currently marketed interferon betas are administered between every other day and once weekly and are often associated with flu-like symptoms and injection site reactions following each administration. These side effects, in addition to a frequent dosing regimen, can lead to reduced patient compliance. Copaxone® is not an interferon beta, and patients taking Copaxone® tend to experience milder flu-like symptoms than with the interferon class of drugs. Copaxone® is, however, injected more frequently than the interferon betas and is associated with injection site reactions. Tysabri® and Gilenya®, both immunosuppressive drugs, have recently entered the market. These drugs have not replaced interferon betas as the standard of care, given their significant adverse side effects, including opportunistic infections. In addition, fatalities have been associated with the ongoing administration of Tysabri® and Gilenya®. Accordingly, these drugs are typically reserved for patients who manifest more aggressive forms of the disease.

Leading MS clinicians believe there is significant need for new therapies that can offer improved efficacy and side effect profiles. In addition, there is a clear unmet medical need for more convenient dosing regimens and improved tolerability of these agents.

We believe that AZ01 has several competitive advantages, including:

• Improved pharmacokinetic, safety and tolerability profile compared with currently available interferon β products approved for treatment of MS
• Significant dosing convenience through a potential monthly dosing regimen
• Efficient manufacturing process enabling high yields and competitive cost of goods at commercial scale

Crohn’s Disease

We have created AZ17, which is a bispecific molecule for the treatment of autoimmune and inflammatory diseases such as Crohn’s disease. Crohn’s is a chronic inflammatory disease caused by an autoimmune attack mounted against tissues of the gastrointestinal tract. The disease typically progresses to chronic inflammation leading to fever, diarrhea, abdominal pain and permanent tissue damage. There is currently no cure for Crohn’s with a prevalence of over 400,000 in North America. The current standard of care for treatment of moderate to severe cases is an antibody based therapy known as a tumor necrosis factor (TNF) inhibitor. TNF inhibitors, such as Humira™, Remicade™ and Cimzia™, represented $8.6 billion or 63% of the 2006 autoimmune disease market and are expected maintain their pole position through 2016. Although TNF inhibitors hold a dominant market position, they are limited in their ability to treat inflammatory and autoimmune diseases by targeting this downstream inflammatory molecule.

AZ17 is composed of two scFvs linked together using our CAESAR platform and targets two upstream cytokines involved in the TH17 pathway. TH17 cells have been strongly associated with the development of inflammation and autoimmunity. These cells have a unique differentiation pathway, which provides specific points of intervention where their development and activation may be blocked.

We believe that AZ17’s novel mode of action will allow it to compete for this market space by offering the following competitive advantages:

• The independent inhibition of targeted cytokines is proven and safe
• Targeting multiple cytokines of the same pathway inherently increases responding patient population
• Low cost of goods due to expression in E. coli
• The nature of the linker affords customization of in vivo half-life to indication