RBN-3143 – Reducing Th17 and Th2 signaling to treat multiple inflammatory diseases through PARP14 inhibition
Ribon’s second clinical program is RBN-3143, a first in class orally delivered small molecule inhibitor of the monoPARP PARP14, for the treatment of inflammatory diseases. Selective inhibition of PARP14 leads to a decrease in alarmin cytokines and dampening of the IL-17 and IL-4/13 signaling pathways. We have demonstrated efficacy in multiple preclinical models of inflammatory disease, including atopic dermatitis, scleroderma, ulcerative colitis, and asthma.
RBN-3143 has completed IND enabling studies and is being advanced into clinical studies in 2022.
PARP14 is highly expressed in tissues of inflammatory diseases (and not constitutively in normal tissues), leading to the increase of first order cytokines (alarmins) and second order cytokines (Th2 and Th17 cytokines), and ultimately the increase in tissue eosinophils and neutrophils. Targeted reduction of these inflammatory pathways with RBN-3143 is anticipated to have improved efficacy over current therapies, such as those for asthma that only target single cytokines such as the IL-4, IL-5 and/or IL-13.