Algernon Pharmaceuticals Inc. (CSE:AGN, OTCQB:AGNPF) said its subsidiary Algernon NeuroScience (AGN Neuro) has added a new clinical research program for the treatment of Traumatic Brain Injury (TBI) with AP-188 (N,N-Dimethyltryptamine or DMT).
The company said AGN Neuro plans to be the first company globally to investigate DMT, a known psychedelic compound that is part of the tryptamine family, for TBI in humans and is planning to begin a Phase 2 clinical trial in the fourth quarter of 2023.
AGN Neuro has an active stroke research program underway and is currently conducting a Phase 1 DMT study in the Netherlands at the Centre for Human Drug Research, Algernon said, adding that it recently announced that it had completed dosing subjects in the first cohort of the study and that the safety review committee has approved moving the study forward with the next cohort at an escalated dose after observing no safety or tolerability issues.
READ: Algernon Pharma says unit completes dosing of first cohort in its Phase 1 clinical study of an intravenous formulation of DMT
The company said AGN Neuro’s clinical plan is to use the data from the Phase 1 Study of DMT currently underway, to accelerate directly into a Phase 2 TBI study in the fall of 2023. AGN Neuro, in consultation with its TBI advisors, may plan and conduct certain preclinical research to help better guide the planned Phase 2 clinical study.
AGN Neuro’s decision to investigate DMT for TBI is based on several factors, specifically:
- There are many commonalities between stroke and TBI where DMT has demonstrated benefits in several preclinical studies, including neuroinflammation, mitochondrial dysfunction, reactive oxygen species, excitotoxicity, and spreading depolarizations;
- DMT is an agonist of sigma-1, a part of the body’s natural defense against physiological stresses, which is elevated following TBI. DMT increases brain-derived neurotropic factor (BDNF), a protein which plays a key role in neuroplasticity. Natural levels of BDNF in the brain are decreased following TBI; however, expression of TrkB mRNA, the receptor to which BDNF binds, is increased as the brain seeks to compensate for the injury. Studies have shown that exercise-induced increases in BDNF generally improve recovery following TBI and that blocking the effects of BDNF attenuates the improvement. Furthermore, increased levels of BDNF following TBI are correlated with improved cognitive function;
- On-going symptoms of TBI are often psychological and cognitive; several psychedelic drugs, including DMT, have already shown therapeutic potential in clinical trials in some of these conditions; and
- In TBI, classified as mild according to the Glasgow coma scale, up to 50% of TBI patients have symptoms that have not resolved after 6 months. Millions of mild TBIs occur each year, and that number is expanding with increased access to motor vehicles in the developing world and the associated increase in accidents. There are currently no drugs approved for the treatment of TBI of any severity.
AGN Neuro also announced that it has appointed global TBI expert Dr Andrew Maas as a scientific and medical advisor to help guide its TBI research program. The company said it has also filed claims for combination therapy of DMT and Constraint Induced Movement Therapy (CIMT).
“We welcome Dr Maas as our first TBI program advisor,” Algernon CEO Christopher Moreau said in a statement. “After discussing key elements of the TBI program during our planning stages, Dr Maas, along with multiple other global TBI experts, voiced their support for AGN Neuro moving forward to investigate DMT as a potential new TBI therapy.”
The company noted that Dr Maas is an emeritus professor of neurosurgery at the Antwerp University Hospital and the University of Antwerp. He holds positions as past chairman of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies (WFNS) and the International Neurotrauma Society and is co-chairman of the European Brain Injury Consortium. He has a vast experience as a general neurosurgeon and has specific research interests in traumatic brain injury and neuro-intensive care.
Dr Maas was also the principal investigator of the IMPACT study group (International Mission on Prognosis and Clinical Trial Design in TBI), which was awarded an NIH grant (2003-2011) and resulted in over 55 publications and recommendations for improved trial design.
Currently, together with Professor David Menon, University of Cambridge, he coordinates the large-scale collaborative project CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI, supported by the FP7 program of the European Union. He received an honorary doctoral degree from the Burdenko Institute of Neurosurgery in Moscow in 2013 and Lifetime Achievement Award for his work on traumatic brain injury from the International Brain Injury Association in 2016.
Dr Maas is a member of various editorial boards, and review committees and is a reviewer for over 35 international journals. In total he has authored over 250 publications in peer-reviewed international journals, Algernon added.
“There is a great need to improve the recovery potential in patients after TBI, and the role of neuroplasticity is a promising target, for which DMT holds potential,” Dr Maas said.
AGN Neuro is a private equity subsidiary of Algernon Pharma and has been created to advance the company’s DMT stroke research program. AGN Neuro has filed a Form 1-A offering statement with the US Securities and Exchange Commission, seeking qualification to raise up to USD $10 million for AGN Neuro by offering up to 37.5% of its common shares, (including the maximum amount of bonus shares) with majority ownership residing with AGN Pharma, under a Tier II Regulation A+ offering.
Algernon Pharma is a Canadian clinical-stage drug development and repurposing company investigating multiple drugs for unmet global medical needs. It also has active research programs for IPF with chronic cough, and chronic kidney disease.
Contact the author at stephen.gunnion@proactiveinvestors.com