Indero have successfully completed a study introducing a novel, gene-expression–based approach for rapidly evaluating topical new chemical entities in early-phase clinical research. This shows that meaningful efficacy signals can be detected within just 24–72 hours using microdosing, offering a faster, smarter and more cost-effective path for topical drug development.
Early proof-of-concept studies for topical dermatology therapies have traditionally relied on clinical endpoints assessed over extended treatment periods.
Typical phase 1 or exploratory studies enrol 30 to 50 patients and run for eight to 12 weeks, creating significant time and cost burdens before any insights into pharmacodynamic activity can be gained. This model can delay decision making and slow the progression of promising compounds into later-phase development.
To address these limitations, a recent clinical study examined molecular changes in the skin to identify early indicators of treatment success.1 This collaborative study between Indero and researchers at the Icahn School of Medicine at Mount Sinai explored whether short-duration microdosing combined with quantitative gene expression analysis could detect meaningful biological responses within days rather than weeks.
Using molecular signals to accelerate insights
The study focused on patients with atopic dermatitis (AD), a condition with well-characterised inflammatory pathways that responds well to topical treatments. Rather than relying on visible clinical effects, treatment efficacy was evaluated using molecular signals, including shifts in epidermal gene expression.
The aim was to determine if this approach could reveal pharmacodynamic activity within the first few days of treatment. Participants received a microdose of a mid-potency corticosteroid applied to small, defined areas of affected skin.
Skin samples were collected using minimally invasive tape-strip sampling and analysed using RNA sequencing to assess transcriptomic changes shortly after treatment initiation.
Dr. Robert Bissonnette, Executive Chairman and Founder of Indero, explained: “Our goal was to rethink how to study topical drugs in early phase studies. The results of this research demonstrate that microdosing for only three days can provide meaningful efficacy signals.
Within just 24 hours, we observed alterations in gene expression after applying a microdose of mid-potency corticosteroid on the patients’ skin. Within 72 hours, Th2-, Th22- and Th17-specific biomarkers were significantly reduced. This outcome is exactly what we hoped for and opens the door to faster, smarter drug development strategies, demonstrating the potential for this method to be used effectively in early phase 1 studies.”
Supporting early-phase evaluation
Although the study was conducted in AD, the underlying approach is not disease-specific, as many other dermatological conditions are commonly treated with topical drugs. The findings suggest that combining microdosing with sensitive molecular assays could provide a broadly applicable framework for early-phase evaluation of topical therapies.
One notable advantage of this model is the ability to perform controlled, within-patient comparisons, minimising variability between individuals and improving the interpretability of pharmacodynamic data.
Different concentrations, formulations or vehicles can be applied to separate skin sites on the same participant, with each site independently sampled and analysed. Because treatment is localised and short in duration, the approach can also lower participant numbers, total drug exposure and overall study complexity in the earliest stages of development.
“This strategy represents a paradigm shift in topical drug development. It allows physicians and researchers to accelerate innovation while minimizing patient exposure and resource use. The implications for both the industry and patients are tremendous,” said Emma Guttman-Yassky, MD, PhD, Waldman Professor of Dermatology and Immunology and Health System Chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai.
Implications for early clinical development
The results of this exploratory study highlight several potential benefits for early-phase topical drug development. Early molecular readouts provide rapid confirmation of biological engagement, allowing development teams to identify promising candidates sooner.
Compounds that fail to demonstrate expected pathway modulation can therefore be deprioritised early, avoiding prolonged investment in lengthy exploratory trials. The microdosing approach also offers reduced preclinical toxicology requirements compared with conventional phase 1 designs, supporting earlier transition into human studies. Importantly, molecular endpoints do not replace clinical outcomes but complement them.
Transcriptomic data can provide early evidence of biological activity that precedes visible clinical improvement, offering a valuable decision-making tool during the most uncertain stages of development.
Reference
Bissonnette, R. et al. (2025). Improvement of skin transcriptome and pruritus within 24 hours with topical triamcinolone in atopic dermatitis: A randomized, vehicle-controlled study [Conference poster]. International Society for Dermatology Symposium (ISDS) 2025.
