Ethicann Pharmaceuticals’ lead product is EPI-002, for the treatment of spasticity resulting from multiple sclerosis (MS Spasticity). Spasticity refers to a feeling of stiffness and a range of uncontrollable muscle spasms/contractions of arms and legs, which can be painful. There are existing treatments for MS Spasticity, which afflicts 2.2 million persons worldwide, and the market globally is $2.2 billion. Three drugs have been approved by the FDA, Baclofen in 1971, Botulinum toxin in 1990 and trizanadine in 1996 … these three drugs constitute 55% of the global market, as other drugs – including a THC/CBD drug (Sativex®) are used off-label in the US.
The problem in this market is that the approved drugs are only marginally effective and have known safety issues. Sativex, an oral spray approved in more than 25 countries, has enjoyed some success in this market, but it is a mixture of different active compounds (including other cannabinoids and terpenes, etc.) suspended in 50% (by volume) alcohol – potentially causing oral pain, oral inflammation, tooth discoloration, and patients complain that it just tastes bad.
Ethicann’s solution is reformulation of the Sativex THC and CBD dosages into a proprietary Zydis® oral rapid dissolving tablet (ODT). Zydis is a proprietary ODT technology owned by Catalent, Inc., a global world leader in pharmaceutical development technologies and services (https://www.youtube.com/watch?v=95yfcw0aZ48).
EPI-002 Zydis tablets, for which a THC 2.7 mg: CBD 2.5 mg dose formulation and manufacturing process have been developed, contain no ethanol, have a strawberry flavoring, and dissolve within seconds, assuring rapid absorption in the oral tissue and delivery of therapeutic effect. Absorption by the oral tissue provides rapid delivery to the brain and bypasses the “liver first pass effect” which removes 30-45% of the cannabinoids in the blood absorbed through the stomach.
Ethicann’s Zydis EPI-002 formulation is covered by Catalent’s extensive world patent portfolio. Ethicann intends to file IP jointly with Catalent on the new formulations developed for the different indications.
Achievements to Date
To date, Ethicann has developed reliable sources of cGMP-compliant active pharmaceutical ingredients (APIs), CBD and THC, both synthetic and botanical. Our partner Catalent has successfully formulated synthetic CBD and THC into Zydis tablets, as described above, to match the dosage of the existing and approved Sativex formulation.
Ethicann has performed an exploratory non-GLP pharmacokinetic (PK) study, in dogs. This study was to demonstrated that blood levels of the active ingredients, over time, between Sativex and EPI-002 – administered to dogs – were substantially equivalent. Ethicann will include in their clinical program PK and clinical safety comparisons to the Sativex spray.
Regulatory Plan Going Forward
It is Ethicann’s intention to first register this product in Canada, using the abbreviated Submission Relying on Third-Party Data (SRTD) NDA pathway. In this case, we will conduct a short “pilot variability” study in humans to determine parameters and numbers of patients for a “full BE” study in humans, in order to show that pharmacokinetic (PK) parameters are essentially equivalent between Sativex and EPI-002. Concurrently, we will provide comparative human safety data to Health Canada, in the form of a short “Phase 2” safety study. The safety data will be used in the labeling of EPI-002. We expect that these studies can be completed during the second half of 2024 and that an SRTD submission to Health Canada for approval in Canada can be made during Q1-Q2, 2025. The Canadian data can be used for concurrent submissions in the UK, which will use the Canadian dossier as a basis for their approval, and in Germany, which has indicated to Ethicann that Canadian data can be used for an approval against the European Sativex drug.
In the United States, Ethicann intends to bring EPI-002 to market, where Sativex is not approved. Ethicann already understands that FDA will require a Phase 2 dose-ranging study, to confirm the optimum therapeutic dose ratio of THC:CBD, before it can progress into a pivotal study. Ethicann plans to use the abbreviated 505(b)(2) New Drug Application (NDA) pathway and believes it can obtain expedited FDA for the MS spasticity indication.
Manufacturing Plan Going Forward
Based on the successful dog pharmacokinetic (PK) study of EPI-002 verses Sativex, Ethicann has authorized Catalent to initiate GMP scale-up of its manufacturing process for EPI-002. Secondary packaging will be decided after consultation with Health Canada.
Ethicann does not plan to become a fully-integrated pharmaceutical company. The company has begun to identify interested companies in Canada, United Kingdom and Germany, who may license the EPI-002 product and be responsible for sales and distribution in their geographical markets.
In the US, Ethicann will initiate the Phase 2 dose-ranging study, but also seek a partner to in-license the drug and possibly fund the pivotal study. Depending on the amount raised in the Series A round, Ethicann believes it can expedite development in the US and reach the market within a few years.
Revenue Projections for EPI-002
As noted above, the existing annual market for MS Spasticity drugs is USD $2.2 billion. Ethicann plans, through its licensing partners, to be entering the Canadian market in 2025, the EU market in 2026 and the US market in 2028. Shown below are cumulative revenue (sales) projections (in USD $million) for the period 2025-2030 in all three markets. In these partner revenue projections, we assume a conservative 40% total addressable market of all MS spasticity patients, and a market penetration, by 2030, of a bit less than 10% in all markets. It is anticipated; however, that there will be licensing partners in certain Asian and Latin Markets, and that there may be off-label use for the much larger general spasticity market – but such is not included here.