Oxford Cannabinoid Technologies: Clinical outlook for 2024
Year end Apr 30 · 2022 · 2023
Operating profit (£,000s) · (5,503) · (5,945)
Net Cash · 9,266.0 · 2,297.0
OCT has a pipeline of '201', plus three projects (Exhibit 1). OCT130401 is a synthetic cannabis mixture of THC and CBD delivered by a metered dose inhaler. It is aimed at rapid pain relief of trigeminal neuralgia (TN): acute onset facial pain. Programmes 3 and 4 are in earlier research stages. Programme 3 targets neuralgia, and any stabbing nerve pain; Programme 4 is an immuno-oncology project in the research phase. Exhibit 2 shows the development stages
Pipeline
Exhibit 1 - OCT's four programmes
Source: OCT Aug 2023 Presentation
Exhibit 2 - OCT 2024 pipeline
Source: OCT Website (Jan 2024)
OCT's lead drug 201, Programme 1, is a first-in-class cannabinoid receptor 2 (CB2) selective agonist. The first stage was completed in 2023 using a SAD format with 4 cohorts of 8 volunteers (32 people) to assess dose and safety. This is a solid basis for further development. However, It does not give any efficacy information. The trial (ISRCTN39003837) is registered on the ISRCTN database; this is not helpful as most details are redacted. The SAD study had a starting dose of 10mg and could have used up to 470 mg - the level reached has not been disclosed. The next step will be a MAD study. This could start, funding allowing, in mid-CY24 and have data by late CY24 or early CY25. Two dose arms (low and high) are likely with a short pause to evaluate safety. We expect doses of between 50mg and 150mg twice per day for 14 days will be selected.
201 phase I design: SAD done; MAD next stage
From 2025, a Phase 2 in patients with established CIPN could be run which could give some signs of efficacy; this could lead to partnering discussions. The mechanism is not fully understood as CB2 has received less study than the CB1 (the target of psychoactive THC).
Potential phase II
CIPN need and market
As shown in Exhibit 3, CIPN is caused by cancer chemotherapy damaging the nerves. A paper in 2022 (Lin et al) based on a sophisticated animal model supports the hypothesis in addition to OCT's own internal research. A 2021 paper by Yang et al (2021) reviewed the area. The general area of CB2 receptors was the subject of a special journal issue in 2022 (Smoum et al 2022)
Initially, 201 will be trialled in Phase 2 in patients who have completed a course of chemotherapy and developed CIPN which did not resolve after several months of recovery. Established CIPN provides a clearer baseline from which to assess efficacy in a patient group with a clear medical need. OCT puts this market at about $1.17bln. With good Phase 2 data, 201 could be an excellent candidate for partnering.
Exhibit 3 - CIPN - nerve damage due to cancer chemotherapy
Source: OCT
External CB2 developments
A Phase 2b trial of a promising CB2 agonist, olorinab (Pfizer) did not meet its endpoint in a study of irritable bowel syndrome (Chang et al 2023) emphasising that careful choice of indication is essential. Other companies that have targeted CB2 in clinical trials in the last five years include Corbus and Centrexion.
Programme 2: 401
The company's second programme OCT130401 (“401”) is a combination of cannabis molecules: synthetic THC (dronabinol (DBN)) and CBD a 1:1 ratio. The mixture is delivered to the deep lung using an off-the-shelf, metered-dose, pressurized inhaler (Exhibit 4) for fast absorption through the lung.OCT envisages that 401 can provide quick pain relief from the sudden onset of stabbing severe facial pain in trigeminal neuralgia (TN), Exhibit 5.
Exhibit 4 - 401 inhaler
Source: OCT presentation
Exhibit 5 - TN clinical facts
Source: OCT Aug 2023
Preclinical work has now been completed and the project put on hold to improve cash flow and focus on 201. The 401 project can be fast-tracked once funding is available. Phase 1 is planned to run in Australia probably due to the more sympathetic approach of the Therapeutic Goods Authority (the regulator) towards cannabinoid therapeutics. This would be an orphan drug market and could be worth, in OCT's estimate, about £1.8 billion.
Programes 3 and 4
OCT is expanding and diversifying its cannabinoid pipeline with programmes 3 & 4 utilising its extensive cannabinoid library. These candidates come from OCT’s cannabinoid library of 475 derivatives (Exhibit 6). The library includes 335 derivatives that the company has exclusive rights to use across THC, CBD and CBG derivatives, as well as 140 cannabinoid molecules through its collaboration with Canopy Growth Corporation (TSX:WEED, NYSE:CGC).
Programmes 3 and 4 cannabinoid derivatives will be paused once at pre-clinical and lead stages till funding allows.
Exhibit 6 - OCT pipeline mix
Source: OCT Investor Presentation
Programme 3 - on clinical entry pathway
Programme 3 is a novel analgesic for a rare pain condition. The candidate is a dual agonist of CB1 and CB2 receptors, which are part of the endocannabinoid system (ECS) that regulates pain and inflammation. The candidate has demonstrated superior pain relief than THC and fewer adverse effects in preclinical studies. The company has started the safety pharmacology package and is moving towards Phase I readiness. A patent application was filed in early 2024.
Programme 4 - intriguing oncology lead
Programme 4 is based on a novel cannabinoid derivative aimed at treating solid tumours. A possible mode of action in our view is that it might selectively block an endocannabinoid receptor. This receptor is also expressed by immune cells and plays a role in modulating inflammation. Overall, the aim seems to be to lower the natural limitations on the immune response to enable therapies like checkpoint inhibitors to work more effectively. Checkpoint inhibitors are infused antibodies whereas OCT's proposed agent is envisaged as an oral product based on data to date. A lead compound is expected to be designated in 2024. This will then need pre-clinical workup and evaluation so could be clinic-ready from 2026; these studies are not predictable as the compound has to meet strict criteria.
Interestingly, OCT has identified a research organisation that can supply matched tumour and white blood (immune) cell samples from individual patients. This is a useful test system since the immune cells (PBMCs; Peripheral Blood mononuclear Cells) from the patient have been programmed to tolerate the tumour cells. If the compounds being developed by OCT can overcome this tolerance, the PBMCs should attack and kill the tumour cells. This is the general basis of immune-oncology with products like Keytruda (pembrolizumab). However, these blockbuster products are monoclonal antibodies and expensive. The OCT programme 4 aims to find a smaller and cheaper orally available product with similar effects. Although we know little about this programme, we would expect it to be developed as an adjuvant product unless it shows dramatic efficacy. It is also worth noting that such anti-cancer drugs can have powerful and dangerous side effects by unleashing a poorly controlled immune response.
Outlook
OCT's ability to progress depends on funding in Q1CY24 from a low market capitalisation. With adequate funding in place, the MAD stage of the 201 development can progress and possibly b401 can enter the clinic. Of these two, 401 could progress faster as both THC and CBD are well understood pharmacologically and the metered dose system is again well understood from other respiratory products. Further, the TN indication could give a fast readout. The 401 programme is “Phase 1-ready”, TN is an unserved orphan market and could be a lucrative franchise.
Programmes 3 and 4 are in earlier development. Programme 3 targets the large and not well-served neuralgic pain market. Programme 4 seems more intriguing and speculative but could be a novel approach to a very large and lucrative cancer franchise. We suggest that this would need partnering fairly early if the data looks good.