THE PROBLEM / UNMET NEED

  The Problem

•Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that damages joints. RA leads to disability and increased mortality.  •RA affects ~1% of the global population. In 2023, there were 4.5 million cases of RA in USA, Japan, and Europe. The USA had 35% of these cases. The number of RA cases is expected to grow to 5.2 million by 2043. •The RA market is expected to reach $21.9 billion by 2033 and $24.8 billion in 2028. 

Unmet need

•~20% of people with RA do not get adequate relief from available medications (https://doi.org/10.1007/s40265-020-01309-9, https://doi.org/10.1093/rheumatology/keae544).

 •~40% of patients fail to respond to first-line treatments (disease-modifying antirheumatic drugs (DMARDs) like methotrexate) and require biologic or targeted synthetic DMARDs.

•The 3 main RA drugs are the TNF-alpha inhibitors, Humira and Enbrel, as well as the JAK inhibitor Rinvoq.

•Non-anti-TNF-alpha therapies are needed, as 30-40% of patients with RA are not responsive to TNF-alpha based therapies (https://doi.org/10.1177/1759720X221114).

•DMARDs have numerous safety issues: Liver toxicity (methotrexate); Increased risk of serious infections (TNF-alpha and JAK inhibitors); Increased risk of major adverse cardiovascular events (JAK inhibitors). (https://doi.org/10.1038/s41584-021-00593-3)  

•Fibroblast-like synoviocytes(FLS) proliferate in the bone joints during the development of rheumatoid arthritis (RA) and subsequently degrade the cartilage.

•Zonula has identified novel, small molecules that prevent FLS proliferation and bone degradation.

•These small molecules inhibit the activity of a new RA target expressed by FLS, called N-cadherin. Zonula intends to develop these small molecules as RA therapeutics.