BEN-2293 – a topical best-in-class PanTrk inhibitor in development to relieve inflammation and rapidly resolve itch in patients with atopic dermatitis (AD): Phase IIa top-line data expected in Q1 2023
Unmet need for an effective and safe topical therapy
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, characterised by intensely itchy, red and swollen skin.1
There is an unmet need for treatments that address itch and inflammation in mild to moderate patients, with fewer side effects than steroid creams and various inhibitor treatments that are currently the dominant forms of treatment.
of children affected2
of all cases are mild to moderate3
of adults affected2
Phase Ib/IIa clinical trial results and status
BEN-2293, a selective inhibitor of the three tropomyosin-related kinase (Trk) receptors (TrkA, TrkB and TrkC) formulated to be administered topically, is being evaluated in adults with mild to moderate AD in a Phase Ib/IIa double-blind, placebo-controlled, first-in-patient, two-part clinical study. The Phase Ib safety and tolerability portion of the study in 32 patients was successfully completed in December 2021. Although the Phase Ib part of the study was not powered to assess efficacy, there was a trend towards a clinically meaningful effect in skin treated with BEN-2293 (reduction from baseline in the percentage of body surface area affected). Data from the Phase IIa portion in 90 patients is expected early in 2023.
TARGET MECHANISM AND VALIDATION
Trk receptor biology and BEN-2293 expected mechanism of action
We identified the role of the Trk receptors as mediators of both itch and inflammation in AD. Inhibition of TrkA is expected to suppress the itch reflex, while inhibition of TrkB and TrkC should reduce inflammation. Thus we expect BEN-2293 to both provide symptomatic relief and reverse disease progression.
Preclinical validation of pan-Trk inhibition in AD
BEN-2293 dose-dependently inhibited the release of pro-inflammatory cytokines, such as TNF and IL-4, from activated human primary mononuclear cells. Topical application of a pan-Trk inhibitor from the BEN-2293 series significantly reduced ear inflammation in a mouse model of chemically induced skin inflammation, performing comparably well to a topical steroid ointment.
This is an exciting time for BenevolentAI, and as we evaluate the efficacy of this drug, we are hoping to see results that could significantly improve the quality of life for children and adults suffering from this disease.
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- Weidinger et al. Nat Rev Dis Primers 4, 1 (2018).
- GlobalData Report 2018: Atopic Dermatitis: Global Drug Forecast and Market Analysis to 2027.
- GlobalData Report 2018: Atopic Dermatitis: Epidemiology Forecast to 2027.