RPT193: CCR4 Antagonist for Allergic Inflammatory Disease
RPT193 is a small molecule CCR4 antagonist that blocks the recruitment of inflammatory immune cells, known as Th2 cells, which are clinically implicated in allergic inflammatory disorders. We are developing RPT193 for the treatment of a broad range of allergic inflammatory diseases, the first of which is atopic dermatitis (AD), a chronic inflammatory skin disease characterized by skin barrier disruption and immune dysregulation.
We intend to initiate a seamless first in human trial in 2019 starting with Phase 1a single and multiple dose escalation cohorts in healthy volunteers followed by placebo-controlled Phase 1b testing in patients with moderate to severe atopic dermatitis. We anticipate proof of concept clinical results from this study by mid-2020.
While there are marketed injectable products for the treatment of atopic dermatitis, as well as oral and injectable drug candidates in development, we believe there is an unmet need for a safe, oral treatment with comparable efficacy. Our preclinical pharmacology and toxicology results for RPT193 suggest (i) efficacy similar to that of drugs targeting clinically validated pathways in allergic inflammatory disease models (ii) once daily oral dosing and (iii) a safety profile which supports chronic dosing in humans. We believe this profile is competitive to standard of care, including steroids and dupilumab, as well as to clinical drug candidates, such as the JAK inhibitors, currently in late-stage clinical development.
CCR4 is highly expressed on Th2 cells. In allergic inflammatory diseases, including AD, chemokines recruit Th2 cells via CCR4 in to inflamed tissues. Once Th2 cells enter tissues such as the skin or the airways in the lung, they secrete proteins known to drive the inflammatory response. The role of Th2 cells has been clinically validated by, among others, dupilumab, an injectable biologic targeting this pathway. Further evidence of CCR4’s role in AD includes the observation of higher levels of CCR4 ligands (CCL17 and CCL22) in AD patients compared with healthy humans; these ligands also correlate with the severity of disease. We believe that by inhibiting CCR4, RPT193 has the potential to bring therapeutic benefit to patients across a broad spectrum of additional allergic inflammatory diseases, including asthma, chronic urticaria, chronic rhinosinusitis, allergic conjunctivitis and eosinophilic esophagitis.
We are developing RPT193 initially in AD because there is:
- an unmet need for a safe and effective oral treatment;
- a potential efficient path to proof of concept, due to high prevalence of disease and short time to clinically relevant endpoints;
- a well defined set of clinical endpoints that have historically been accepted for regulatory approval, which are usable for proof of concept as well as for subsequent pivotal studies;
- easy access to patient samples, such as skin biopsies, to interrogate mechanisms of action and clinical biomarkers of efficacy; and
- a precedent that proof of concept in AD historically has translated into Th2 driven allergic inflammatory diseases.