# Novel small molecule HSP90 inhibitor for the management of atopic dermatitis

> **NIH NIH R43** · REGRANION, LLC · 2020 · $252,131

## Abstract

PROJECT SUMMARY
Atopic dermatitis/AD (or ‘atopic eczema’) is a complex, chronic, inflammatory skin disease that affects upwards
of 35 million Americans. AD is characterized by a disruption of epidermal-barrier function, inflamed dry and thick
skin, severe pruritus and significant impact on patients’ quality of life. Current standard of care involves topical
emollients, avoidance of trigger factors and anti-inflammatory strategies including the use of corticosteroids,
antihistamines, or broad and recently also specific immunommodulators, such as dupilumab.
While broad
immunosuppressive therapies can help partly manage the disease, chronic usage results in undesirable side-
effects and drug tolerance, resulting in lowered patient compliance and inefficacy. Furthermore, dupilumab is
ineffective in a significant portion of patients, suggesting the heterogeneity of AD and need for individualized
treatment based on patient profiling. There is a pressing need for the clinical development of targeted
immunomodulatory therapeutics, without immunosuppressive side effects, designed to take into account patient
profiling and to safely and selectively target pathogenic mediators of AD. HSP90 has been recently classified
as an ‘alarmin’ and has key roles in mediating the interplay between the innate and the adaptive immune system
as well as known roles in the JAK/STAT and MAP kinase pathway and IL-4, IL-13, and IL-17 signaling. These
pathways have key roles in AD-related immune dysregulation. Regranion has recently acquired a potent novel
small molecule HSP90 inhibitor (RGRN-305, previously Debio0932) with a good safety profile and attractive
pharmacological properties that shows alleviation of psoriatic symptoms, reduced epidermal thickness, and
dramatic reduction in levels of TNFα and IL-17, pro-inflammatory cytokines in clinically relevant animal models
of psoriasis. These studies laid the foundation for ongoing clinical evaluation in the treatment of moderate-to-
severe psoriasis (ClinicalTrials.gov Identifier: NCT03675542) and set a precedence for investigation of HSP90
as a therapeutic target in AD. The focus of this proposal is to accomplish key milestones that will transition this
technology for commercialization as a safe and efficacious oral AD therapeutic that targets the upstream
proteomic mediators of the disease. The study aims involve i.) rigorous evaluation of the efficacy and mechanism
of action of oral RGRN-305 in multiple clinically relevant AD models that incorporate a comparative efficacy study
versus corticosteroid treatment, and ii.) characterization of the gene and protein expressions of HSP90 pathway-
related markers in normal, nonlesional and AD lesional human skin samples from moderate-to-severe AD
patients. A role for HSP90 in the pathogenesis and persistence of AD has not been elucidated. Given that the
etiology of AD is multifaceted, characterizing the expression profile of epidermal HSP90 pathway and related
cytokines and chemoki...

## Key facts

- **NIH application ID:** 10016726
- **Project number:** 1R43AR077503-01
- **Recipient organization:** REGRANION, LLC
- **Principal Investigator:** Gautam Sudhir Ghatnekar
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,131
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016726

## Citation

> US National Institutes of Health, RePORTER application 10016726, Novel small molecule HSP90 inhibitor for the management of atopic dermatitis (1R43AR077503-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016726. Licensed CC0.

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