SM-020 is a selective and potent AKT inhibitor applied by patients at home to their seborrheic keratoses lesions.

More than 80% of seborrheic keratosis (SK) lesions treated for 14 to 28 days with DermBiont’s SM-020 gel 1.0% had at least a one-point improvement in Physician’s lesion assessment (PLA) score at last visit, according to Phase 2 trial data presented at the 2023 American Academy of Dermatology Annual Meeting in New Orleans.

SM-020 is a selective and potent AKT inhibitor applied by patients at home to their SK lesions. DermBiont expects to file its Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in Q2 2023, and subsequently initiate a Phase 2b trial in 2023.

The gel met its primary endpoint of a one point improvement in PLA score at last visit and safety via local tolerability, as well as key multiple secondary endpoints including complete clearance of treated lesions. 

Prior to the Phase 2 trial of SM-020, the topical therapy was demonstrated to induce apoptosis of SK cells in vitro in cell-based assays as well as ex vivo in SK explant studies. DermBiont’s Phase 2 proof-of-concept, adaptive open-label trial tested SM-020 gel 0.1% and 1.0%, enrolling 35 subjects with 4 SK target lesions across seven treatment cohorts. SKs were classified based on Physician’s Lesion Assessment (PLA) scores as follows: PLA 3 (thick: a visible, elevated SK lesion (thickness >1mm), PLA 2 (thin: a visible, elevated SK lesion (thickness ≤1mm), PLA 1 (near clear: a visible, not elevated SK lesion with a surface appearance different from the surrounding skin), and PLA 0 (no visible SK lesion with a surface appearance no different from the surrounding skin). In the clinical trial only PLA 2 and 3 SKs were treated.

All seven cohorts saw improvement and clearance of SKs, with the effect being most pronounced in the second of seven cohorts of subjects treated with SM-020 gel 1% applied BID for 28 days, with 100% (n=14) of SKs achieving a one-point or greater drop in PLA score and 57% (n=8) of SKs with a PLA score of 0 (complete clearance) as of last follow-up visit on Day 98. SM-020 was also very well tolerated with no drug-related adverse events and only rare local tolerability reactions, most commonly erythema and pruritis that were nearly exclusively mild in severity and transient in duration.

“The results of this trial have defined a highly effective, and very well tolerated treatment regimen that we will now advance to a larger, vehicle-controlled trial,” says Karl Beutner, M.D., Ph.D., and CEO of DermBiont, in a news release. “The current standard of care for treatment of patients’ SKs involves painful and destructive surgical procedures, including cryosurgery that carries a risk of both scarring and post-inflammatory hyperpigmentation and hypopigmentation. We believe that SM-020 has the potential to provide patients with a safe, well-tolerated, and easy to apply product to treat their SK lesions at home, and we look forward to continuing development of this product.”

SM-020 Gel 1% 14- and 28-day BID Results (Cohorts 1, 2, 3 and 5)

• 36% (n=20/55) of SK lesions treated for 28 days cleared completely, reaching a PLA score of PLA 0.
• 64% (n=35/55) of SK lesions treated for 28 days were clear or nearly clear, reaching a PLA score of PLA 1 or PLA 0.
• 80% (n=44/55) of SK lesions treated for 28 days experienced at least a one-point drop in their PLA score.
• All treatment arms were well tolerated with no drug-related adverse events or serious adverse events.
• There were rare and almost exclusively mild (only one moderate) transient application site reactions across patient-reported and investigator-measured reactions, including: pain, pruritus, erythema, edema, and scabbing. No subjects ended treatment due to tolerability