Study explores synthetic cannabinoid for cancer-related anorexia

Anyone who’s had to watch a loved one deal with a cancer diagnosis—or has suffered from the disease themselves—knows loss of weight, body mass, appetite, and other problems are frequent effects. Artelo Biosciences recently received the go-ahead to test its unique cannabinoid to treat cancer-associated anorexia in a trial, potentially giving hope to cancer patients.

Artelo’s drug reportedly serves as a full agonist to the endocannabinoid system’s CB1 and CB2 receptors in the endocannabinoid system. While the drug is more potent than THC, it steers clear of the brain and does not lead to the euphoria associated with natural cannabis; instead, it targets the receptors found in the gut.

Outsourcing-Pharma spoke with Saoirse O'Sullivan, scientific advisor to Artelo Biosciences, about the benefits of synthetic cannabinoids, the properties and capabilities of the candidate, and what lies ahead.

OSP: Could you please share an ‘elevator presentation’ description of Artelo?​

SO: Artelo Biosciences is a San Diego, California-headquartered pharmaceutical company dedicated to the development and commercialization of proprietary therapeutics targeting endogenous lipid signaling pathways, including the endocannabinoid system. The company operates three subsidiaries: in the UK, Ireland, and Canada.

Artelo is rapidly advancing a portfolio of broadly applicable candidates designed to address significant unmet needs in multiple diseases and conditions, including anorexia, cancer, pain, and inflammation. Led by proven biopharmaceutical executives collaborating with highly respected researchers and technology experts, the company applies leading-edge scientific, regulatory, and commercial discipline to develop high-impact therapies.

OSP: Please share an overview of how research into and use of synthetic cannabinoids for the treatment of various conditions has emerged and evolved in recent years.​

SO: Hundreds of molecules are derived in nature that can modulate the endocannabinoid system, including the phytocannabinoids (plant-derived) and endocannabinoids (made in our bodies). Medical research tells us that these compounds can be very useful in treating a broad range of diseases and disorders from epilepsy to pain to cancer.

However, these molecules are not optimized; many are very insoluble and poorly absorbed in the body, some are not very potent, many are found in tiny quantities in nature. Producing these molecules synthetically or in the laboratory to improve their physical, chemical, and biological properties through medicinal chemistry programs allows us to harness the best of what nature provided; commercially, this also allows for the creation of intellectual property (IP) which is crucial to attracting investment for the expensive development of new medicines.

 A synthetic version of THC (Dronabinol) and a synthetic analog of THC (Nabilone) have been FDA approved since the 1980s for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting (Dronabinol) and chemotherapy-induced nausea/vomiting (Nabilone). Across the world, these medicines also have approvals in various countries for the relief of chronic pain, cancer pain, palliative care, MS spasticity, glaucoma, and AIDS.

Although not licensed in these indications, positive clinical trials have been conducted with these synthetic THC medicines in headaches, Fibromyalgia, Parkinson’s, Huntington’s, PTSD, and Obstructive Sleep Apnea.

OSP: Please tell us a bit about the synthetic cannabinoid you’re working on within the CAReS study.​

SO: ART27.13, the lead clinical program at Artelo Biosciences, is a development stage CB1/CB2 receptor agonist with reduced brain penetration. ART27.13 was originally evaluated (by AstraZeneca, previously called AZD1940). Development of the drug by AZ was terminated because it was not effective as a pain medication in patients who had had a molar extraction. In otherwise healthy subjects who participated in a Phase 1 pain study, it was observed that low doses of ART27.13 rapidly increased body weight of more than 3% that was not explained by fluid retention and without serious or persistent side effects.

Together with the knowledge that activation of the CB1 receptor in the peripheral can increase appetite and weight loss, we hypothesized that ART27.13 represents a novel therapeutic strategy to stimulate appetite and weight gain known to arise from CB1 receptor activation that could significantly benefit patients with cancer-associated anorexia without CNS side effects. In 2018, Artelo licensed ART27.13 for worldwide, exclusive development and commercialization.

OSP: Could you please explain the endocannabinoid system?​

SO: The endocannabinoid system (ECS) is a relatively recently (since the late 1980s) discovered system of endogenous cannabinoids (called endocannabinoids), the receptors they activate, and the enzymes involved in their degradation and synthesis. Endocannabinoids are important signaling messengers that are produced on demand and regulate many biological functions as diverse as neuronal function, pain, gastrointestinal function, and vascular function.

The receptors cannabinoids act at are called the CB1 and CB2 receptors. CB1 is found in almost every cell in the body and is particularly highly expressed in the brain, liver, and gastrointestinal systems. CB2 is expressed at low levels in the brain and at high levels in tissues with immune functions, and this receptor is upregulated in cells at times of stress and inflammation.

The ECS is altered in many pathologies (usually upregulated but sometimes downregulated) and activation of cannabinoid receptors either directly or indirectly has positive effects in a wide range of diseases and disorders. This has led to a growing interest in pharmaceutical drugs that are designed to optimize this knowledge of the ECS.

OSP: Could you please share an overview of the risks to patients suffering from cancer-related anorexia, and why it’s a condition worth pursuing treatment options for?​

SO: Anorexia affects over 60% of late-stage cancer patients for which there is no recognized standard of care. Anorexia and the resulting weight loss in cancer patients can compromise health, weakening the immune system, causing discomfort and dehydration, ultimately reducing the patient’s prognosis and quality of life.

No medicines are currently approved for treating cancer anorexia, but Megace (Megestrol acetate), THC compounds (Dronabinol), and steroids (dexamethasone) are used off-label with limited efficacy and often intolerable side effects. According to ASCO Guidelines published in May 2020 on Cancer Anorexia/Cachexia, there is no recognized standard of care. Therefore, this remains a significant unmet need in a considerably vulnerable patient group.

OSP:  If this phase of your study yields favorable results, can you share any plans for the next phase?​

SO: We are currently working on our Phase III strategy and will base our plans for the next steps on the data from the emerging data from CAReS and ongoing discussions with development partners and regulatory agencies. The drug previously had an IND in the US and we are planning to expand the participating countries and sites as we move the program through the next stages of development.

OSP: What other opportunities might be associated with using this cannabinoid to modulate the ECS?​

SO: While anorexia and cancer supportive care is our main focus, there are many other indications for which a peripherally restricted CB1 agonist could be beneficial such as muscle spasticity, neuropathic pain, anti-cancer effects, and gastrointestinal disorders. ART27.13 is also a CB2 agonist, which is likely to bring about anti-inflammatory effects in the periphery.

OSP: Do you have anything else you’d like to add about the study, the cannabinoid, your company, etc.?​

SO: Artelo Biosciences is also developing two additional very differentiated and novel compounds. First, the company has developed a patented novel CBD composition called ART12.11. Artelo’s approach to achieving patent protection for ART12.11 was to create a cocrystal. Cocrystallization is a proven pharmaceutical development strategy and follows FDA guidance for chemicals with properties similar to CBD.

Second, Artelo’s research team is working with scientists at Stony Brook University, who are pioneers in developing fatty acid-binding protein (FABP) inhibitors, to advance the lipid signaling program towards first-in-human trials. At Artelo, this program is called ART26.12. This program covers a library of unique small molecules that have been designed to selectively and potently inhibit FABPs.

Preclinical studies have shown that molecules that specifically inhibit FABP5 show considerable promise in animal models of cancer, pain, inflammatory pain, and anxiety. Artelo is truly a full-spectrum endocannabinoid modulating company.