INM-088 for the Treatment of Glaucoma


Glaucoma is a chronic optic neuropathy that is typically caused by high intraocular pressure, or IOP. Inadequate or obstructed drainage of the aqueous humor through the trabecular mesh, which is the pathophysiology of glaucoma, increases the fluid pressure within the anterior chamber, subsequently propagating into the posterior chamber of the eye, according to Weinreb et al.’s, 2014 article “The pathophysiology and treatment of glaucoma: a review”. The increased intraocular pressure exacts a toll on the basal membrane of the retina, thinning the mesh-like tissue in this region and damaging the head of the optic nerve. According to Quigley and Boman’s 2006 publication “The number of people with glaucoma worldwide in 2010 and 2020”, glaucoma is currently the second leading cause of blindness world-wide; it is estimated to affect a population close to 80 million by 2020.

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Science behind Glaucoma

Glaucoma is a group of eye diseases, which results in damage to the optic nerve and vision loss, according to the 2016 publication “Facts about Glaucoma” from the United States National Eye Institute. The most common type is open-angle glaucoma, or OAG, with less common types including closed-angle glaucoma, or CAG, and normal-tension glaucoma.

OAG develops slowly over time and there is no pain. If left untreated, however, side vision may begin to decrease followed by central vision, resulting in blindness if not treated. CAG can present gradually or suddenly, according to Mantravadi & Vadhar’s 2015 article titled “Glaucoma” in the “Primary Care” publication. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye and nausea. Vision loss from glaucoma, once it has occurred, is permanent.

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Drawing on epidemiology information from previously cited sources, total open-angle glaucoma prevalence worldwide is estimated at 1.96% of the population, of which 75% is OAG. As of 2010, there were 44.7 million people in the world with OAG of which 2.8 million were in the United States. By 2020, the prevalence is projected to increase to 80 million worldwide and 3.4 million the United States. It occurs more commonly among older people. CAG is more common in women. Both internationally and in the United States glaucoma is the second-leading cause of blindness.

Cannabinoids for the Treatment of Glaucoma

Although the role of cannabinoids in treating glaucoma is thought to be very well understood, according to the 2004 publication from Tomida, et al., entitled “Cannabinoids and glaucoma”, no such products are currently approved for this disease. The neuroprotective role of cannabinoids has not been utilized as a therapeutic strategy, primarily due to great difficulties associated with the targeted delivery of cannabinoids to intraocular tissues. This class of compound is also relatively poorly bioavailable due to low aqueous solubility.

Previously reported attempts for topical delivery of cannabinoids to the ocular tissues used formulations based on mineral oil (see Jay et al.’s 1983 article “Multiple-drop study of topically applied 1% delta 9-tetrahydrocannabinol in human eyes”) and cyclodextrins (according to multiple references).

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InMed’s Proprietary Hydrogel Formulation for Once-a-Day Eye Drops

INM-088 (formerly INM-085) utilizes a once-a-day hydrogel formulation to address the major issues of non-compliance (dosing frequency, side effects and adherence).

Preclinical animal data evidenced enhanced penetration of cannabinoid molecules through the cornea and lens compared to control.

Cannabinoids are lipophilic in nature, and InMed currently believes that with a novel delivery system, the reduction of IOP in glaucoma patients by topical (eye drop) application of cannabinoids will hold significant promise as a new therapy.

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Current limitations of existing eye drop formulations include:

  • Wiping away of the drops immediately after administration by blinking, which leads to
  • Inadequate drug exposure time to the surface of the eye, which, in turn, leads to
  • Significant reduction in the amount of drug reaching its target.

Thus, the end result is the need for multiple administrations of the drug over the course of the day. Improvements are needed in drug delivery / formulations to address this.

As reported by Gaudana, et al. in their 2009 publication “Recent perspectives in ocular drug delivery”, colloidal dosage forms have been widely studied and employed in the field of ocular drug delivery. These dosage forms include liposomes, nanoparticles, microemulsions and nanoemulsions, etc. Barriers to ocular drug delivery have already been described earlier in the context of structure and function of various ocular tissues and how each tissue can act as a barrier. The chronic nature of many ocular diseases necessitates frequent drug administration.

Advantages of colloidal dosage forms include:

  • sustained and controlled release of the drug at the targeted site;
  • reduced frequency of administration;
  • ability to overcome blood–ocular barriers; and
  • efflux-related issues associated with the parent drug.

Further, these carriers can also bypass or overcome various stability-related problems of drug molecules, e.g., proteins and peptides.

Designing an ideal delivery system for any ocular disease depends on molecular properties of the drug such as size, charge, and affinity towards various ocular tissues and pigments.

InMed is developing a stimulus-responsive, nanoparticle-laden hydrogel vehicle for spatiotemporal and dosage-controlled release of cannabinoids into the aqueous humor of the eye. This hydrogel is envisioned to be packaged as a liquid and is intended for application as a once-per-day eye drop administered immediately prior to the patient’s bedtime. The liquid forms a gel when it reaches body temperature. Formulation of the product as a liquid permits easy dosing and simplifies the path towards development of a regulated, industrial-scale manufacturing process.

Key design criteria for InMed’s nanoparticle hydrogel include:

  • Biocompatibility and biodegradability;
  • Viscous fluid behavior while inside the container (to facilitate ease of manufacturing, handling and dosing);
  • 4-6 hour drug release, absorption and subsequent carrier degradation;
  • Triggered gel formation on the surface of the eye (to enhance pre-corneal residence time);
  • Modulate the interplay between temperature-dependent rheopexy (becoming a thicker gel if influenced by temperature) and thixotrophy (becoming thinner liquid if a force is exerted, such as blinking);
  • Optimized particle size and surface charge to avoid scratchy feelings inside the eye, enhance shelf-life, and to facilitate ocular penetration; and
  • Muco-adhesive properties.


Current Treatments

Current treatments for glaucoma include medication, laser treatment and surgery. According to Mantravadi & Vadhar’s 2015 article titled “Glaucoma” in the “Primary Care” publication, the goals of glaucoma management are to avoid glaucomatous damage and nerve damage, and preserve visual field and total quality of life for patients, with minimal side effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although intraocular pressure is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment.

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