Announcement • Jul 15
Azitra Announces Breakthrough Repeat Dose And Anti-Wrinkle Ex Vivo Results For ATR-COSF Program Azitra announced promising results from two separate ex vivo human skin tissue studies. The studies evaluated the distribution and anti-wrinkle activity of Azitra's filaggrin domain containing supernatant in two separate experimental studies. ATR-COSF uses a supernatant based formulation containing an active recombinant human domain of the protein, filaggrin ("rHDfilaggrin"). This S. epidermis derived supernatant is in development as a high value cosmetic ingredient. Ex vivo data successfully showed controlled distribution of the rHDfilaggrin into the stratum granulosum in increased amounts over prior single dose experiments in human skin. Single dose ex vivo experiments established improvements in elasticity and reduced the appearance of new fine lines and wrinkles in human skin. The ATR-COSF program utilizes the supernatant from a strain of S. epidermidis engineered to secrete a functional unit of the human filaggrin protein. In the first study, ATR-COSF supernatant was found to provide a positive penetration and distribution profile for rHDfilaggrin in a multiple dose, ex vivo model. The study, which utilized fresh, healthy human skin explants, demonstrated a remarkable increase in rHDfilaggrin delivered through the stratum corneum and into the stratum granulosum layers, compared to single dose previous work. Additionally, improved concentration in the stratum corneum and stratum granulosum layers was seen with the formulated product in comparison to concentrated supernatant alone. The first ex vivo model offers a biologically relevant system for evaluating skin penetration while preserving the architecture of human skin. The healthy human skin explants were first stimulated with TH2 cytokines to reduce the levels of endogenous filaggrin in the samples. The study used a 2% lyophilized supernatant in a hydrogel formulation. rHDfilaggrin penetration in the middle to lower stratum corneum was detected following a single application of the 2% formulation. Increased amounts of rHDfilaggrin were observed with additional applications. Safety testing conducted in accordance with standardized guidelines demonstrated that the 2% supernatant formulation is non-irritating and non-corrosive to the skin and eyes. (A) depicts the explanted healthy human skin explant prior to any treatment. Native filaggrin as well as profilaggrin in keratohyalin granules (stained in green) are apparent in the stratum granulosum (SG) layer. (B) shows the skin sample after TH2 cytokine stimulation to reduce or eliminate native filaggrin in the stratum granulosum layer. Furthermore, TH2 cytokine stimulation markedly reduced the presence of keratohyalin granules, resulting in decreased endogenous filaggrin. This reduction facilitates the differentiation and detection of rHDfilaggrin following application. (C) shows penetration and distribution of rHDfilaggrin into the stratum granulosum layer after one application of the cell free supernatant. (D) shows penetration and distribution of rHDfilaggrin into the stratum granulosum layer after three applications of the lyophilized cell free supernatant in a hydrogel formulation. The second ex vivo model utilized defatted human skin explants to assess the effect of the lyophilized rHDfilaggrin supernatant in a hydrogel formulation on human skin elasticity. Concentrations of the supernatant in the hydrogel were varied from 0.0% to 7.5% (weight/weight or "w/w"). Elasticity was measured at 20 hours post application. Skin samples were incubated at 30ºC. The hydrogel alone results are shown in open circles and the active are in black squares. The hydrogel containing the lyophilized supernatant was active in increasing the elasticity of ex vivo human skin sections in a dose-dependent manner. Minimal and maximum effects in elasticity enhancement were observed in hydrogels containing 0.09% w/w (1.6-fold) and 7.5% w/w (4.4-fold) of active ingredient, respectively. Hydrogels containing 0.28% w/w of active ingredient restored ex vivo abdominoplasty skin elasticity to values historically observed in healthy skin. Pictures taken of skin samples after the incubation period treated with placebo or the 0.3% w/w supernatant hydrogel are shown below. The active treated sample showed approximately two times the elasticity compared to the placebo treated skin sample, highlighting the formulation's potential as a novel cosmetic ingredient for improving skin firmness and resilience. Board Change • Jul 01
Insufficient new directors No new directors have joined the board in the last 3 years. The company's board is composed of: No new directors. 9 experienced directors. No highly experienced directors. Independent Director Barbara Ryan was the last director to join the board, commencing their role in 2023. The following issues are considered to be risks according to the Simply Wall St Risk Model: Insufficient board refreshment. New Risk • May 14
New major risk - Financial position The company has less than a year of cash runway based on its current free cash flow trend. Free cash flow: -US$11m This is considered a major risk. With less than a year's worth of cash, the company will need to raise capital or take on debt unless its cash flows improve. This would dilute existing shareholders or increase balance sheet risk. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-US$11m free cash flow). Share price has been highly volatile over the past 3 months (23% average weekly change). Shareholders have been substantially diluted in the past year (over 5x increase in shares outstanding). Revenue is less than US$1m. Market cap is less than US$10m (US$3.51m market cap). Minor Risk Currently unprofitable and not forecast to become profitable over next 3 years (US$22m net loss in 3 years). 
