PermetrexTMDespite its potential as an effective therapeutic, as...

PermetrexTM

Despite its potential as an effective therapeutic, as outlined above, cannabidiol has very low oral bioavailability, meaning that very little of the drug is absorbed by the body if taken in tablet, capsule or other oral delivery forms. As a result, development of new therapies containing the active pharmaceutical ingredient cannabidiol is challenging.One possible solution to the challenges of achieving sufficient levels of the drug in the body, is to deliver it transdermally, or directly through the skin to the target organs in the layers of the skin (or even into systemic circulation). Transdermal delivery avoids the 'first-pass' effect of liver metabolism and potentially enables lower dosage levels of active pharmaceutical ingredients to be rapidly and reliably absorbed with high bioavailability.Dr Cooper, a consultant of Botanix Pharmaceuticals, has developed a drug delivery technology known as PermetrexTM, which is designed to deliver pharmaceuticals into and through the skin more effectively than the manyPage 41For personal use onlyskin penetrating technologies available today. PermetrexTM is differentiated from other approaches in thati) it does not utilise chemicals which have a tendency to irritate the skin and are considered undesirable for diseases such as acne, psoriasis and atopic dermatitis;(ii) it generates substantial kinetic energy when applied to the skin, which facilitates the rapid delivery of active pharmaceutical ingredients into the skin; and(iii) it can accommodate other chemicals which can selectively leave parts of the formulation on the skin in a protective coating, for extended absorption and/or protection of the skin.Graphic representation of PermetrexTM skin delivery systemThe use of PermetrexTM is viewed as a significant competitive advantage as it solves a number of the challenges of delivering cannabidiol efficiently to the organs in the skin that are targeted for the treatment of various skin diseases.
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Dr Cooper has licensed the use of PermetrexTM to Botanix Pharmaceuticals pursuant to the PermetrexTM Licence Agreement, which provides Botanix Pharmaceuticals with exclusive rights to utilise PermetrexTM for the skin delivery of all cannabinoids,

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A summary of the key terms of the PermetrexTM Licence Agreement is contained in Section 10.2(a).(d) BTX1503 – the first proposed Botanix Pharmaceuticals product for acne Acne lesions are believed to result from an interaction of four primarypathogenic factorsi) the excessive production of sebum or lipids by sebaceous glands in the skin; Page 42For personal use only(ii) hyper-proliferation of sebocytes (highly specialised, sebum- producing epithelial cells) that contribute to clogging of pores through which sebum is normally released to the skin surface;(iii) colonisation of the area in and around the sebaceous gland by bacteria; and(iv) inflammation, often associated with colonisation by bacteria and their breakdown of sebum into irritating breakdown products.In the Existing Directors and Proposed Directors' view, no topical treatments are currently available which target all of the above pathogenic factors. While systemic therapies (such as isotretinoin) may inhibit sebum production, their use is limited by significant systemic side effects. Also, an unmet need remains for effective therapies that are not associated with antibiotic resistance or treatment-limiting side effects, particularly therapies with novel mechanisms of action. As a result, Botanix Pharmaceuticals believes there is an unmet need for a topical treatment that targets the four primary pathogenic factors.Overview of dominant acne treatments with potential activity of BTX1503 forecast, subject to successful development and approvalsBotanix Pharmaceuticals' proposed BTX1530 product aims to address these unmet needs.BTX1503 is a formulation of synthetic cannabidiol and other chemicals, which comprise the PermetrexTM drug delivery system. It is designed to deliver a consistent dose of cannabidiol to directly impact cutaneous cell growth and differentiation, provide anti-inflammatory effects and regulate sebum production. It is considered that cannabidioli) normalises excessive lipid synthesis of human sebocytes (the cells from the oil producing sebaceous glands in the skin which disintegrate and release their oil content);(ii) decreases proliferation (but not the viability) of these human sebocytes;(iii) exerts universal anti-inflammatory actions; and(iv) may have anti-bacterial effects. Page 43For personal use only