Emerald Health Pharmaceuticals Presents Phase I Clinical Data and Preclinical Remyelination Data at ACTRIMS 2020 Conference

Emerald's lead product candidate, EHP-101, shows potential disease-modifying capabilities in multiple sclerosis, further supporting advancement into Phase II clinical development

SAN DIEGO, CA, Feb. 27, 2020 (GLOBE NEWSWIRE) --  Emerald Health Pharmaceuticals Inc. (EHP), a clinical-stage pharmaceutical company developing medicines based on cannabinoid science, presents new clinical and preclinical data on its lead oral product candidate, EHP-101, at the ACTRIMS Forum 2020, a prestigious scientific conference focused on multiple sclerosis (MS), in West Palm Beach, Florida, February 27-29, 2020.

In the Phase I study, EHP-101 was well tolerated, with plasma concentrations within the anticipated therapeutic dose range, and preliminary biomarker analyses indicating drug-related effects on various physiological functions that support its novel multi-pronged mechanism of action. New preclinical data also demonstrated the ability of EHP-101 to promote the remyelination of nerve cells in the brain.

"The profile of EHP-101 observed in our large first-in-human study is consistent with the extensive preclinical data we have generated to date," said Jim DeMesa, MD, Chief Executive Officer of EHP. "This Phase I study, along with the remyelination of axons demonstrated in our nonclinical studies, provides the rationale for us to advance EHP-101 into Phase II development for people living with MS.  We have already initiated a Phase IIa study of EHP-101 for systemic sclerosis."

The first EHP presentation on February 27, 2020 (Poster P061), titled "First-in-human Study with EHP-101 Oral Solution of a Synthetic Cannabidiol Derivative Enables the Initiation of a Phase II Study in Multiple Sclerosis," provided safety, pharmacokinetic and preliminary biomarker data in a Phase I clinical study in healthy volunteers.

The study was conducted between September 2018 and September 2019, studying 104 subjects at 12 different dose levels. A total of 48 subjects (6 subjects each) received a single dose of either 0.91 mg, 3 mg, 9 mg, 20 mg, 25 mg (fasted and fed), 50 mg, 100 mg or 185 mg of EHP-101. Another 32 subjects (8 subjects each) received daily repeated doses for 7 days of either 20 mg once per day (QD), 25 mg twice per day (BID), 51.9 mg QD, or 50 mg BID of EHP-101. Twenty-four (24) subjects received placebo (2 subjects at each tested dose level in the total of 12 cohorts studied.

The most common side effects reported in some subjects included mild-to-moderate headache, paresthesia (a feeling of pins and needles in the limbs), mild blurred vision as well as mild abdominal pain at the highest dose only. Similar side effects were observed with placebo treatments and no maximum tolerated dose was reached. There were no clinically significant abnormalities in vital signs, physical examination, echocardiograms, clinical laboratory parameters, or ophthalmological assessments.

The half-life of a 25 mg single dose was approximately 2 hours during fasted state and 7 hours during fed state. A mean increase of 1.5-fold in the maximum plasma concentration (C_max) and area under the curve (AUC, which represents the cumulative plasma concentration over time) was observed post-administration with food.  No drug accumulation in blood was observed with QD dosing and minimal accumulation was observed with BID dosing for 7 days.

The C_max for a predicted anticipated therapeutic dose (ATD) was reached with a 20 mg single dose and the targeted drug exposure based on AUC was approached with a 50 mg single dose and 25 mg BID multiple dosing for 7 days, thus helping the selection of the dosing and treatment regimen for Phase II studies.

Preliminary drug-related biomarker analysis in plasma on Day 7 supports the mechanism of action of EHP-101 related to the effects on the hypoxia inducible factor (HIF) pathway, peroxisome proliferator-activated gamma (PPARg) and cannabinoid type 2 (CB₂) receptors. Some proteins were upregulated (increased concentrations post-dosing) related to vascular endothelial cell function (HIF pathway activation), lipid metabolism and control of inflammation whereas other proteins related to CB₂ and PPARγ activation (inflammation and immunomodulation) were downregulated (decreased concentrations post-dosing). Further quantitative analyses by other techniques are ongoing to assess multiple specific proteins.

The second EHP presentation, on February 28, 2020 (Poster 289), titled "Oral Administration of EHP-101 Promotes Remyelination in the Cuprizone/Rapamycin Mouse Model of Multiple Sclerosis," reported positive preclinical proof-of-concept data specifically related to the remyelination of neurons.

EHP-101 previously demonstrated the prevention of demyelination in different murine models of MS and was recently shown to induce remyelination in both white and gray matter in a mouse cuprizone model. The potential of oral administration of EHP-101 to promote remyelination was further evaluated in a cuprizone/rapamycin (C/R) mouse model ("augmented cuprizone model"), a more aggressive demyelination model since the concomitant administration of rapamycin with cuprizone for 12 weeks reduces spontaneous myelin production by blocking differentiation of oligodendrocyte progenitor cells.

In the study, oral administration of EHP-101 once daily at 5, 10, and 20 mg/kg for 6 weeks induced statistically significant, dose-dependent remyelination of demyelinated axons in the white matter (corpus callosum) at 10 mg/kg (p < 0.005) and 20 mg/kg (p < 0.001) versus vehicle-treated controls as shown by the enhanced density of myelinated axons. Unlike in the previous cuprizone study, a statistically significant difference in remyelination in gray matter (hippocampus and cerebral cortex) was not achieved with treatment versus vehicle-treated controls in this study at 6 weeks. This is possibly due to the more rapid and extensive spontaneous remyelination occurring in the gray matter lesions, as levels of myelinated axons had returned to almost the same (normal) levels found in age-matched control animals at 6 weeks post-treatment.

The posters can be found on the ACTRIMS website and the EHP website.

About ACTRIMS

The ACTRIMS (Americas Committee for Treatment and Research in Multiple Sclerosis) Forum is a translational science meeting highlighting novel and rigorous scientific discoveries made in multiple sclerosis (MS) that advance the understanding of research and clinical care of MS patients. EHP-101 is an oral formulation of a novel, patented cannabidiol (CBD)-derivative in clinical-stage development for both MS and systemic sclerosis, a severe form of scleroderma.

About EHP-101

EHP-101 is an oral formulation of a patented fully synthetic aminoquinone derivative of CBD (VCE-004.8), which through rational drug design, has dual peroxisome proliferator-activated receptor gamma (PPARɣ) and cannabinoid receptor type 2 (CB₂) agonist activity; both receptors are therapeutic targets for anti-inflammation and neuroprotection in multiple sclerosis (MS) and systemic sclerosis (SSc). EHP-101 also targets the hypoxia inducible factor (HIF) pathway, expanding the rationale for its development as a novel drug since the HIF pathway has effects on myelination (for MS) and neo-vascularization (for SSc). EHP has received Orphan Drug Designation for EHP-101 in systemic sclerosis, a form of scleroderma, from both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

About Emerald Health Pharmaceuticals Inc.

Emerald Health Pharmaceuticals is developing product candidates derived from cannabinoids for the treatment of CNS, autoimmune, and other diseases. The Company has two families of new chemical entities, derived from synthetic cannabidiol (CBD) and cannabigerol (CBG), that it has modified through rational drug design to affect validated receptors and pathways pertinent to targeted diseases. Its first drug candidate, EHP-101, has completed a Phase I clinical study and is being developed for the treatment of multiple sclerosis and systemic sclerosis. Its second product candidate, EHP-102, is at preclinical stage and is focused on treating Huntington's disease and Parkinson's disease. For more information, visit http://www.emeraldpharma.life or contact: info@emeraldpharma.life.

To the extent statements contained in this news release are not descriptions of historical facts regarding Emerald Health Pharmaceuticals Inc. they should be considered "forward-looking statements," as described in the private securities litigation reform act of 1995, that reflect management's current beliefs and expectations. You can identify forward-looking statements by words such as "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "hope," "hypothesis," "intend," "may," "plan," "potential," "predict," "project," "should," "strategy," "will," "would," or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes. Forward-looking statements contained in this news release include, but are not limited to, statements regarding: (i) the success and timing of our product development activities and clinical trials; (ii) our ability to develop our product candidates; (iii) our plans to research, discover, evaluate and develop additional potential product, technology and business candidates and opportunities; (iv) the anticipated timing of clinical data availability; (v) our ability to meet our milestones; and (vi) our expectations regarding our ability to obtain and maintain intellectual property protection. Forward-looking statements are subject to known and unknown factors, risks and uncertainties that may cause actual results to differ materially from those expressed or implied by such forward-looking statements. Undue reliance should not be placed on forward-looking statements. We undertake no obligation to update any forward-looking statements. Emerald Health Pharmaceuticals' investigational drug products have not been approved or cleared by the FDA.