Phase 1 approval for lead chronic pain drug
Oxford Cannabinoid Technologies (OCT) develops non-opioid, non-addictive pain pharmaceuticals. Its lead product OCT461201 (“201”) is an oral product to relieve peripheral nerve pain caused by cancer chemotherapy (CIPN) and irritable bowel syndrome (IBS). Management estimate that the global CIPN market is worth around £1.7bn with 6.4% CAGR forecast, and the current IBS market around £2.1bn. OCT is aiming to develop a range of pain-related products to capture a section of the £59.9bn global market.
OCT announced in May that the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) and the Wales Research Ethics Committee (REC2) have given approval to commence phase 1 human study trial of 201. This is the first phase 1 in-human trial of 201, and is being conducted by Simbec-Orion. It will determine safety, tolerability and pharmacokinetics of 201 in healthy volunteers. Additional drugs, a second generation cannabinoid receptor type 2 agonist and a cannabinoid receptor type 1 agonist, are being developed for indications such as inflammation, chronic pains and cancers.
The company announced in March the renewal of its Home Office Licence for the fifth consecutive year which allows it to continue to supply schedule 1 drugs for clinical research purposes. Additionally, Clarissa Sowemimo-Coker — appointed in December as interim CEO — was appointed permanent CEO in April, having been at the company for four years and delivering its first submissions to MHRA and REC 2.
Recruitment to start immediately on company's first human trial
OCT reported an H1 cash balance of £4.9mln as at 31 October 2022. This is a decrease from £9.2mln on 30 April 2022, in most part due to the preclinical work for its lead candidate, OCT-201, which continued into H223. The fiscal year-end is 30 April.
The company expects to receive a tax credit cash payment of about £750k in H2 FY23. The next major expense will be the phase 1 study for 201, which can now start following MHRA and REC2 approval. OCT has stated that it has enough cash to last until Q1 2024, but it also acknowledges that additional funding will be needed to enable the phase 2 study of 201 to go ahead as planned, following the delay in approval of phase 1.
The market capitalisation of about £10.8mln reflects the current market for earlier-stage biotechnology stocks and the need for more funding. The share price has risen by about 82% since Clarissa Sowemimo-Coker's appointment as interim CEO 22 December 2023.
Financial position
Year end Apr 30 · 2020 · 2021
Operating profit (£,000s) · (3,346) · (5,503)
Net Cash · 14,630.0 · 9,266.0
Following regulatory approval from MHRA and REC 2, the phase 1 trial will test 201 for its safety and tolerability in preparation for phase 2 studies in designated indications. It is a cannabinoid-based pain reliever that has been shown to help patients suffering CIPN as well as IBS. The study is being conducted by an arm of Simbec-Orion.
Recruitment of participants will start immediately and management expects phase 1 to be completed in Q3 2023.
Exhibit 1 - 201 preclinical
Source: OCT
Exhibit 1 shows rat data and indicates a possible human dose of 3mg/kg according to OCT. The baseline is the untreated rat. The vehicle means the rats had paclitaxel chemotherapy, so had a fast pain response. Pregabalin (Lyrica) is an anti-epileptic drug also indicated for peripheral and central neuropathic pain. In this experiment it is given at a very high dose.
CIPN affects an estimated 60% of people undergoing chemotherapy after 3 months. The hallmarks of CIPN are pain, numbness and tingling in the extremities. CIPN can be progressive, enduring, often irreversible, leading to many years of debilitation and suffering. 201 activates the Cannabinoid Receptor 2 (CB2), which is found throughout the body. It exploits the same receptor targeted by some natural cannabis extracts, but it is chemically modified to ensure that it effectively and exclusively binds to the key receptor (CB2) in the nerves and immune cells that contribute to controlling the pain response, and it will do this in the same way every time a patient takes it. 201 has no psychoactive effects.
Other OCT drugs include OCT130401 (“401”) which is a combination of synthetic cannabis molecules that includes THC and CBD in a 1:1 ratio. The mixture is delivered to the deep lung using an off-the-shelf, metered-dose, pressurized inhaler for fast absorption. It aims to provide quick pain relief from the sudden onset of stabbing pain in TN. Preclinical work has now been completed and the project put on hold to improve cash flow and focus on OCT's lead drug 201. Programmes 3 and 4 cannabinoid derivatives will also cease further work once at pre-clinical and lead stages.
In our opinion, OCT is an interesting opportunity since its major lead project, 201, is expected to enter the clinic by the end of 2023. The CIPN indication has no effective current treatment. With clinical data, this novel product aiming for an underserved and accessible market could be an attractive partnering opportunity.
Exhibit 2 - 401
Source: OCT
201 trial
The 201 study is titled “First-in-human, randomised, double-blind, placebo-controlled, single ascending oral dose safety, tolerability and pharmacokinetics study of OCT461201 in Healthy Volunteers”. The trial will be run by a Wales-based CRO. The phase 1 uses a single ascending dose format and will assess dose and safety. The design is for 4 cohorts of 8 volunteers to assess dose and safety. The initial dose is very low. The next cohort, if no safety issues, gets a higher dose. Dosing usually rises in log scale increments (1, 3, 10) up to the highest equivalent dose tested in preclinical toxicology (not yet disclosed). The data recorded is safety and any minor side effects plus important blood measurements of the drug blood level over time and its metabolite levels. These are crucial to determine the doses and frequency for phase 2.
Phase 2 could start in H2 2023 after the full data set from phase 1 is available. This trial could lead to a partnering deal to fund the longer and larger set of phase 3 studies needed for approval and reimbursement. At least one of these will need to be in the US for marketing reasons and so would be expensive.
Phase 2 studies test efficacy in patients and are inherently more costly than phase 1 studies which test safety. Typically, a phase 2 will be a blinded, placebo-controlled study. This trial could lead to a partnering deal to fund the longer and larger set of phase 3 studies needed for approval and reimbursement.
Exhibit 3 - Estimated clinical timeline
Source: OCT