27 March 2023 - - US-based clinical-stage biotechnology company DermBiont's Phase 2 adaptive design trial with of investigational drug SM-020 gel 1% met its primary endpoint of a one point improvement in Physician's lesion assessment score at last visit and safety via local tolerability, as well as key multiple secondary endpoints including complete clearance of treated lesions, the company said.

SM-020 is a selective and potent AKT inhibitor applied by patients at home to their seborrheic keratoses lesions. Dr. Karl Beutner, Co-Founder and chief executive officer of DermBiont, presented the trial results at the Late Breakers session of the American Academy of Dermatology annual meeting, taking place in New Orleans, LA from March 17-21, 2023.

SKs are the most common benign tumors of the skin, with estimates of at least 80 m Americans and a quarter of the global population impacted by them.

SKs are initiated by clonal mutations and sustained by activation of AKT which blocks normal timed cell death (apoptosis).

SKs are currently treated with ablative surgical procedures and there is currently no available topical therapy for these tumors.

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 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% of SKs achieving a one-point or greater drop in PLA score and 57% 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.

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 issues.

Based on the trial results DermBiont expects to file its Investigational New Drug application with the US Food and Drug Administration in Q2 2023, and subsequently initiate a Phase 2b trial in 2023.

SM-020 is an AKT kinase inhibitor. AKT kinase, also known as Protein Kinase B, is a central node in the tyrosine kinase/PI3K/AKT/mTOR and Ras/mitogen-activated protein kinase pathways, which are tumorigenesis/tumor suppression pathways.

AKT inhibits apoptotic mechanisms and is involved in cellular survival pathways, can promote protein synthesis, and is important in cellular pathways promoting tissue growth.

Apoptosis is the normal timed death of a cell and an increase in AKT activity can prevent apoptosis or normal cell death and promote tumor growth.

SKs are proliferations of benign tumor cells, which can be explained by increased AKT phosphorylation and activity, as well as a decrease in cell death. AKT inhibitors can therefore block AKT activity, enabling apoptosis and cell death of SK cells.

DermBiont's mission is to become the world's leading precision dermatology company developing and commercializing targeted topical therapeutics that treat, cure, and prevent diseases.

The company aims to impact the root causes of skin diseases through the development of targeted small molecule therapeutics with well-defined mechanisms of action and biotherapeutics that repair an imbalance of the microbiome.

The company's targeted topical therapeutics pipeline includes two lead assets: SM-020 for the treatment of seborrheic keratosis and SM-030 for the treatment of hyperpigmentation disorders of the skin.