MGC Pharmaceuticals | 22 October 2018

The second study is an investigator-sponsored, 160-patient Phase II pilot study of dronabinol for

the treatment of agitation in AD (NCT02792257). The trial, which commenced in March 2017, is

expected to report top-line results in August 2020. Dronabinol (Marinol, AbbVie), a synthetic oral

formulation of THC, is FDA-approved for anorexia/weight loss in AIDS and for nausea/vomiting

associated with chemotherapy.

The successful nabilone study and the ongoing studies of dronabinol and Avidekel raise the

possibility that CogniCann could face competition from an established cannabinoid-based therapy

for dementia-related AD symptoms by the time MGC generates efficacy data for CogniCann for this

indication.

Other potential drugs for agitation in dementia on the horizon

Neither the FDA nor EMA has approved any drugs to treat neuropsychiatric symptoms such as

agitation in dementia patients. Non-pharmacological interventions are suggested as first-line

treatment, but are not effective for every patient. Currently, these symptoms are treated by off-label

use of psychotropic medications such as antipsychotics, antidepressants, benzodiazepine

sedatives and anti-convulsants. These drugs have modest efficacy and their use can produce

harmful side effects.

A number of candidate drugs are in Phase III development for the treatment of agitation in

dementia, including the antipsychotic brexpiprazole, the antidepressant citalopram, and the novel

compounds AVP-786 (deuterated-dextromethorphan/quinidine combination) and Lumateperone

(ITI-007).

These drugs could be potential competitors for CogniCann (if approved).

The Alzheimer’s disease and dementia market

A recent meta-analysis found that the prevalence of dementia worldwide for people aged 60 years

or older ranged from 5-7%; the prevalence in the US was 6.5% while in Western Europe it was

7.3%.

Dementia is estimated to affect 50 million people worldwide currently, with the number

expected to triple to 152 million by 2050. About two-thirds of dementia patients have AD; other

common dementia syndromes include vascular dementia, mixed dementia, Lewy body dementia or

frontotemporal degeneration.

Over 90% of people with dementia experience at least one neuropsychiatric symptom over the

course of their disease. Agitation, psychosis and mood disorders are the three main

neuropsychiatric syndromes of dementia. Agitation (including aggression and non-aggressive

agitation) occur in 20% of people with AD living in the community and in 40-60% of individuals with

dementia living in care facilities.

As we do not have data on the proportion of dementia patients living in care facilities, we

conservatively assume that the addressable market of patients with agitation or other

neuropsychiatric symptoms that are not adequately controlled by non-pharmacological interventions

represents 10% of dementia patients. This represents 550,000 patients in North America, 950,000

patients in Central and Western Europe and 40,000 patients in Australia.

The market research group EvaluatePharma estimated that the market for AD drugs was valued at

~US$2.4bn in 2018 and forecasts it to grow to US$5.7bn by 2024. The approved AD drugs fall into

two drug classes. Cholinesterase inhibitors, such as donepezil, galantamine and rivastigmine, slow

down the breakdown of the neurotransmitter acetyl choline, which is involved in memory and

Porsteinsson et al 2017. Expert Opinion on Pharmacotherapy, 18:6, 611-620

Prince et al 2013. Alzheimers Dement. Jan;9(1):63-75

World Alzheimer Report 2018

Ballard and Corbett 2010. CNS Drugs 2010; 24 (9): 729-739