InMed's Research of Rare Cannabinoids

InMed is researching and developing rare cannabinoids as potential therapeutics for unmet medical needs. While the most prevalent cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), are widely used for a variety of reasons, evidence suggests there may be greater therapeutic potential in rare cannabinoids that are found in very small traces in the cannabis plant. Cannabinol, a rare cannabinoid, is the active pharmaceutical ingredient (API) in InMed’s two lead programs for dermatological and ocular diseases.

The potential of cannabinol (CBN)

Each cannabinoid has a specific chemical structure that confers unique physiological properties in humans. Evidence demonstrates that even slight differences in the structure of these compounds can result in profound differences in biological activity, safety and potential therapeutic effect in the human body.

Cannabinol (CBN) is one of several rare cannabinoids found in the cannabis plant at significantly lower levels relative to the more commonly known tetrahydrocannabinol (THC) and cannabidiol (CBD). Different cannabinoids have been observed to have distinct physiological properties, including therapeutic potential in specific diseases and unique safety profiles. InMed is specifically exploring these unique effects of CBN, as well as other rare cannabinoids, and their therapeutic potential to treat disease.

% Breakdown in Typical Cannabis Plant

Learn more about cannabinol (CBN)

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An optimized process to cannabinoid manufacturing

Cannabinol (CBN) is one of the many rare cannabinoids found in miniscule amounts in the cannabis plant. The limited availability of rare cannabinoids makes them economically impractical to extract directly from the plant for pharmaceutical use. InMed is developing IntegraSyn, a cannabinoid synthesis manufacturing system to develop rare cannabinoids that are bio-identical to the compound derived from the cannabis plant. Producing rare cannabinoids using synthetic methods allows for the consistent, high-quality, high-purity drug substance that is required for pharmaceutical use. InMed’s IntegraSynTM cannabinoid synthesis system holds the potential to produce rare cannabinoids for diseases with high unmet medical needs.

Learn more about InMed’s IntegraSynTM cannabinoid manufacturing system

InMed’s INM-755 under development to treat epidermolysis bullosa (EB)

InMed most advanced compound, INM-755, is a cannabinol topical cream under development for the treatment of epidermolysis bullosa. INM-755 is currently being tested in Phase 1 safety and pharmacokinetic (PK) studies in healthy volunteers. InMed is conducting two Phase 1 studies of INM-755, including treatment on intact skin and treatment on wounded skin, both in healthy volunteers.

The initial clinical trial, Study 755-101-HV, which recently completed, is a randomized, double-blind, vehicle-controlled, Phase 1 study designed to evaluate the local and systemic safety, tolerability, and pharmacokinetics of INM-755 applied daily on intact skin in healthy volunteers. Two strengths of INM-755 cream, plus vehicle-only, will be evaluated in 22 adult subjects over a 14-day treatment period.

A Clinical Trial Application (CTA) was recently submitted to begin the second Phase 1 clinical trial, Study 755-102-HV. The study involves testing INM-755 cream on open wounds of 8 healthy volunteers. 

A Phase 1-2 global, multi-center trial in epidermolysis bullosa patients is planned after Phase 1 safety studies, with anticipated regulatory filing in Q4 2020.

Learn more about epidermolysis bullosa.

INM-755 preclinical studies show potential in managing symptoms of EB and skin strengthening in a subset of EB

InMed has completed extensive safety pharmacology and toxicology studies of INM-755. These studies have demonstrated promising results and supported the further investigation of the compound in clinical trials.

In preclinical pharmacology studies, INM-755 demonstrated activity in reducing markers of inflammation and pain. It also upregulated expression of a type of keratin (keratin 15, or K15), which might lead to skin strengthening and reduced blister formation in EB simplex (EBS) patients with mutations of another keratin (keratin 14, or K14). Its anti-inflammatory activity may be beneficial in healing chronic wounds caused by prolonged inflammation.

Rare cannabinoid formulation for glaucoma

INM-088 is an ocular topical cannabinol (CBN) formulation being developed for the treatment of glaucoma. InMed is currently evaluating several formulations to deliver CBN into the eye to address major issues of dosing frequency, side effects and treatment penetration. INM-088 is being designed for topical delivery to the eye; this localized delivery results in very little drug being absorbed or migrating into the bloodstream, thus minimizing potential adverse side effects. There is considerable room for improvement of existing drugs in terms of efficacy, safety, delivery, and the development of tolerance over time.

Learn more about the role of cannabinoids in the treatment of glaucoma.

Source: Marinkovich Medicine EB Subtypes
INM-088 shows promise to reduce intraocular pressure and provide neuroprotection of the eye

Glaucoma is a chronic optic neuropathy that is typically characterized by high intraocular pressure (IOP). Inadequate or obstructed drainage of fluid increases pressure in the eye. The increased intraocular pressure affects the basal membrane of the retina, thinning the mesh-like tissue and damaging the head of the optic nerve.

Current glaucoma remedies work by lowering intraocular pressure either by reducing the fluid secretion by the ciliary epithelial cells, or by increasing fluid drainage through the trabecular meshwork.

InMed is developing INM-088 to provide a dual mechanism of action:

  • Reduce the intraocular pressure (IOP) in the affected eyes; and
  • Provide neuroprotection for the retinal ganglion cells (RGCs) and other optic nerve tissues in the affected eyes.

InMed has conducted a number of studies comparing CBN against other cannabinoids including tetrahydrocannabinol (THC) and cannabidiol (CBD); CBN outperformed these major cannabinoids as well as a panel of other rare cannabinoids in its potential to affect disease pathways in glaucoma. Preclinical studies have shown the potential of INM-088 to provide neuroprotection and to reduce intraocular pressure of the eye.

Learn more about InMed’s Glaucoma Program

INM-755 demonstrates an excellent safety profile

In its lead dermatology program for INM-755, InMed conducted several preclinical safety pharmacology and toxicology studies using CBN at very high doses that achieved systemic exposure (blood levels) hundreds of times higher than what would occur with topical dosing in humans. No adverse events were seen on central nervous system (CNS) function in a rigorous and extensive evaluation of CNS effects; 108 aspects of behavior posture, gait, and movement were assessed. In that study, the blood levels were more than 10,000 times what is expected to occur with topical dosing in humans. No adverse effects were observed even at the highest doses in preclinical studies where the drug was applied either as a cream (for local effects) or injected under the skin (for systemic effects) daily for 28 days.

In summary, the toxicology studies conducted to date support the initial clinical investigations in healthy volunteers with up to 14 days of topical application on the skin and will support a subsequent study in patients with EB in which creams will be applied for up to 28 days.

INM-755 is the first cannabinol formulation under therapeutic development to advance to clinical trials

There are more than 100 rare cannabinoids present in the cannabis plant in trace amounts. The active pharmaceutical ingredient (API) in INM-755 is cannabinol (CBN), a rare cannabinoid. INM-755 is the first CBN formulation under therapeutic development to advance to clinical trials. Evidence demonstrates that even slight differences in the structure of cannabinoid compounds can result in profound differences in activity, safety and potential therapeutic effect in the human body.

In preclinical studies, InMed investigated the safety and therapeutic potential of a number of different cannabinoids. Of the cannabinoids tested, which included widely known cannabidiol (CBD), only cannabinol (CBN) up-regulated keratin 15. Keratin 15 may be able to substitute for deficient or defective keratin 14 and that might lead to reduced blister formation in EB simplex (EBS) patients with mutations in keratin 14. Additionally, INM-755 was a strong candidate to reduce a number of symptoms that EB patients face on a daily basis, such as inflammation and pain.

Learn more about InMed’s epidermolysis bullosa (EB) program.