17 March 2023 - - US-based clinical-stage biotechnology company Ribon Therapeutics has dosed the first patient in the open-label cohort of patients with moderate-to-severe atopic dermatitis to measure the pharmacodynamic activity of RBN-3143 and evaluate the safety and preliminary efficacy of 28 days of administration of RBN-3143 in this target population, the company said.

PARP14 is a NAD+-utilizing monoART (mono-ADP-ribosyltransferase) controlling cell signaling and regulating protein function.

PARP14 expression is elevated in tissues of various inflammatory diseases, but it is not highly expressed in normal tissues.

Elevated PARP14 expression leads to higher levels of first order cytokines, specifically alarmins, and second order cytokines, Th2 and Th17 cytokines, in the inflammatory lesion, and ultimately the increase in disease tissue eosinophils and neutrophils which drive pathology.

RBN-3143, a first-in-class, oral small molecule inhibitor of PARP14, has the potential to be a differentiated therapy for the treatment of numerous inflammatory diseases.

This is the second program emerging from the BEACON+ platform to enter clinical development.

Selective inhibition of PARP14 leads to a decrease in alarmins and dampening of the IL-17 and IL-4/13 signaling pathways.

Ribon has demonstrated efficacy in multiple preclinical models of inflammatory disease. RBN-3143 is currently being evaluated in a Phase 1 clinical study in healthy volunteers and atopic dermatitis patients.

Ribon Therapeutics is a clinical-stage biotechnology company developing therapeutics targeting novel enzyme families activated under cellular stress conditions that contribute to disease.

Ribon's portfolio includes two oral, first-in-class clinical programs, RBN-2397 (a PARP7 inhibitor) and RBN-3143 (a PARP14 inhibitor), targeting broad indications in oncology and inflammatory diseases, respectively.

The company explores novel areas of biology with the goal of developing effective treatments for patients with limited therapeutic options.

Leveraging its proprietary BEACON+ (Blocking the Enzyme Activity Component of NAD+) platform, Ribon is building a pipeline of selective, small molecule inhibitors to numerous NAD+-utilizing enzymes, beginning with monoARTs (mono-ADP-ribosyltransferase), which have applications across multiple therapeutic areas. Ribon is located in Cambridge, Massachusetts.