Periodic Reporting for period 1 - oils4cure (Oils4cure: finding an effective drug to alleviate Refractory Epilepsy, one of the most severe symptoms in the pathology of Tuberous Sclerosis)
Reporting period: 2023-12-01 to 2024-11-30
Tuberous sclerosis Complex (TSC) is an autosomal dominant disease manifesting with tumours in different organs (e.g. the brain), the symptoms of which vary depending on where the site of the tumours. However, 80% of patients develop epilepsy that is controlled with antiepileptic drugs, although only 6 paediatric antiepileptic agents exist. As many as 60% of TSC patients develop refractory epilepsy (RE) resistant to treatment and many of them are children, their seizures potentially provoking impaired cognitive development or injury, as well as causing distress and anxiety in their families. Hence, new drugs are needed to enhance the efficacy and tolerance of current antiepileptic treatments.
Epilepsy has been associated with dysfunction and altered endocannabinoid signalling, and cannabinoids may be potent alternative therapies. In particular, cannabidiol (CBD) is thought to have anti-convulsant and anti-inflammatory properties, although no clinical evidence of the efficacy of a full-spectrum cannabis extracts to treat RE from controlled clinical trials exists. Since many Cannabis varieties are available and there are concerns about the claims made for CBD products of unknown origin/uncontrolled compositions, there is an urgent need for a medicinal cannabis product approved under strict standards of production following Good Clinical Practices (GCP). Epidyolex, a broad spectrum cannabis extract, was recently introduced as to reduce the frequency of seizures in Dravet and Gastaut Lennox syndrome patients. While also approved for TSC, its side effects produce dissatisfaction among some clinicians/caregivers (e.g. diarrhoea, somnolence, aggressiveness and behavioural disorders), as does its pricing and efficacy.
OILS4CURE, a Spanish biotech company that develops medicinal products based on cannabis extract, recently developed a drug to manage RE associated with TSC, YCJ-01. This full spectrum cannabis sativa extract contains CBD and tetrahydrocannabinol (20:1 ratio), and other components, and it is produced under controlled GMP conditions. While its mechanism of action remains unclear, observational studies suggest YCJ-01 effectively treats RE with fewer side effects than current anti-epileptic drugs . Hence, YCJ-01 could offer significant gains in both patient and caregiver quality of life, also reducing the intellectual impairments associated with recurrent seizures. Indeed, the available evidence led the Spanish Medicinal Products and Medical Devices Agency (AEMPS) to fast track YCJ01 to a phase 3 clinical trial.
The aim of this project is to further develop YCJ-01 as a therapy for TSC, testing its efficacy in reducing seizures in a clinical trial. We expect similar superior efficacy to Epidyolex based on the 'entourage effect' that exploits synergies among the compounds in full-spectrum extracts. Efficacy will also be expected at lower doses, improving the profile of side-effects. YCJ-01 will be marketed at a lower price point than Epidyolex and it avoids the need of concomitant clabozam therapy, providing superior pharmacoeconomics.
Epilepsy has been associated with dysfunction and altered endocannabinoid signalling, and cannabinoids may be potent alternative therapies. In particular, cannabidiol (CBD) is thought to have anti-convulsant and anti-inflammatory properties, although no clinical evidence of the efficacy of a full-spectrum cannabis extracts to treat RE from controlled clinical trials exists. Since many Cannabis varieties are available and there are concerns about the claims made for CBD products of unknown origin/uncontrolled compositions, there is an urgent need for a medicinal cannabis product approved under strict standards of production following Good Clinical Practices (GCP). Epidyolex, a broad spectrum cannabis extract, was recently introduced as to reduce the frequency of seizures in Dravet and Gastaut Lennox syndrome patients. While also approved for TSC, its side effects produce dissatisfaction among some clinicians/caregivers (e.g. diarrhoea, somnolence, aggressiveness and behavioural disorders), as does its pricing and efficacy.
OILS4CURE, a Spanish biotech company that develops medicinal products based on cannabis extract, recently developed a drug to manage RE associated with TSC, YCJ-01. This full spectrum cannabis sativa extract contains CBD and tetrahydrocannabinol (20:1 ratio), and other components, and it is produced under controlled GMP conditions. While its mechanism of action remains unclear, observational studies suggest YCJ-01 effectively treats RE with fewer side effects than current anti-epileptic drugs . Hence, YCJ-01 could offer significant gains in both patient and caregiver quality of life, also reducing the intellectual impairments associated with recurrent seizures. Indeed, the available evidence led the Spanish Medicinal Products and Medical Devices Agency (AEMPS) to fast track YCJ01 to a phase 3 clinical trial.
The aim of this project is to further develop YCJ-01 as a therapy for TSC, testing its efficacy in reducing seizures in a clinical trial. We expect similar superior efficacy to Epidyolex based on the 'entourage effect' that exploits synergies among the compounds in full-spectrum extracts. Efficacy will also be expected at lower doses, improving the profile of side-effects. YCJ-01 will be marketed at a lower price point than Epidyolex and it avoids the need of concomitant clabozam therapy, providing superior pharmacoeconomics.
The clinical trial protocol has been updated and modified, contracts have been signed to govern the preparation of the starting material and the Investigational Medicinal Product (IMP - YCJ-01), and with both the hospitals that will participate in the clinical trial. The trial was promoted among professionals and patients/families at the Spanish Tuberous Sclerosis Association meeting.
Batches of the starting material have been transferred from “Cañamos Farmland” to “Medalchemy” to produce the IMP, which has then been delivered to the participating hospitals.
Patient recruitment was initiated and the first patient was enrolled on the trial, signalling its start. The first results of the drug’s effects indicate it produces a reduction in the number of epileptic crises, as well as cognitive and behavioural improvements in the patients, coupled to a good safety profile. The AEMPS has opened the possibility for compassionate use of the drug by patients who experienced fewer crises during the trial due to the drug administration, enabling them to continue to use the drug beyond their participation in the trial.
The queries of the European Patent Office were addressed to advance the protection of the drug, its production and its use. It is anticipated that full protection will be awarded towards the end of 2025.
Batches of the starting material have been transferred from “Cañamos Farmland” to “Medalchemy” to produce the IMP, which has then been delivered to the participating hospitals.
Patient recruitment was initiated and the first patient was enrolled on the trial, signalling its start. The first results of the drug’s effects indicate it produces a reduction in the number of epileptic crises, as well as cognitive and behavioural improvements in the patients, coupled to a good safety profile. The AEMPS has opened the possibility for compassionate use of the drug by patients who experienced fewer crises during the trial due to the drug administration, enabling them to continue to use the drug beyond their participation in the trial.
The queries of the European Patent Office were addressed to advance the protection of the drug, its production and its use. It is anticipated that full protection will be awarded towards the end of 2025.