Nabilone

TGR-63, being developed to target amyloid-beta plaques, has shown preclinical potential in reducing Alzheimer’s-related anxiety. Credits: AtlasStudio/Shutterstock.com With positive preclinical data for its Alzheimer’s disease drug candidate TGR-63, IGC Pharma has announced that it plans to advance this small molecule into early clinical development in the course of 2024. TGR-63 is an amyloid beta peptide-targeting drug designed to decrease plaque aggregation by preventing the misfolding and aggregation of amyloid-beta peptides. In the preclinical mouse models designed to assess behavioural responses in transgenic mice, subjects treated with TGR-63 demonstrated statistically significant reductions (43%) in overall movement as determined by an Open-Field behavioural test. As per the 1 February press release, the data reinforces “its [TGR-63] potential as a promising treatment” for reducing levels of anxiety and improving emotional wellbeing. The Timonium, Maryland-based pharmaceutical company is also actively evaluating its cannabinoid-based lead candidate IGC-AD1 as a treatment for Alzheimer’s dementia-associated agitation in a Phase IIb study (NCT05543681). In December 2023, the company announced a partnership with Los Andes University’s Center for Research and Training in Artificial Intelligence (CINFONIA) to incorporate generative AI analyses into the Phase II trial. IGC Pharma is in the process of training algorithms with the goal of identifying clues for reducing misdiagnoses and false negatives, which is important as misdiagnoses and false negatives tend to be high in the Alzheimer’s indication, CEO Ram Mukunda told Pharmaceutical Technology . By addressing these issues, the company aims to improve trial success rates and ultimately accelerate the development and delivery of economic, effective treatments for Alzheimer’s patients, he adds. See Also: Sanofi backs development of Graviton’s treatments for serious diseases Tyra Biosciences’ TYRA-300 gains FDA rare paediatric disease status Despite making headway with its lead pipeline candidate, IGC Pharma has faced difficulties in trial enrolment and finances for IGC-AD1 due to its active ingredient being the psychoactive substance tetrahydrocannabinol (THC). THC is federally regulated and therefore the study or use of it requires a special permit as it is not covered by a DEA license that could be used for a drug like morphine, Mukunda explained. While Otsuka Pharmaceuticals’ Rexulti (brexpiprazole), an atypical antipsychotic, is the only FDA-approved medication for Alzheimer’s-associated agitation, other small molecules are in clinical development for Alzheimer’s agitation. Otsuka is evaluating AVP-786, a dextromethorphan/quinidine combination treatment for Alzheimer’s agitation, in multiple global Phase III studies. Similar to IGC Pharma, Sunnybrook Health Sciences Centre is also conducting a Phase III trial (NCT04516057) of cannabinoid based Nabilone for the treatment of agitation. GlobalData forecasts Rexulti to bring $3.9 billion in sales in 2028. GlobalData is the parent company of Pharmaceutical Technology .

In a conversation at CPHI Barcelona last week, global market development manager Athanasia Kanli and manager marketing communication Céline Zuber explained how the company is tackling this mission. Some of the substances derived from the cannabis plant are famous for their mind-altering effects - like tetrahydrocannabinol (THC), whose recreational use is illegal in many countries. However, the medical applications of cannabis, particularly those linked to active ingredients in the plant, are gaining increasing interest. For example, the US Food and Drug Administration (FDA) has greenlit synthetic cannabis-related drug products including dronabinol and nabilone. The agency also made history in 2018 by approving Epidiolex, the first treatment based on purified CBD derived from marijuana. Epidiolex, which is marketed for two rare forms of epilepsy, consists of an oral solution of the non-psychoactive ingredient CBD. Zuber explained that the emerging CBD market is “developing in a favorable direction” at the moment and there are myriad potential applications, especially in mental health conditions and pain management. Nonetheless, she cautioned that there are multiple challenges for biotech companies developing CBD-based treatments such as difficulties in formulating the compound into solid oral dosage forms, the low bioavailability of the active ingredient, and complex regulations across the globe. In tandem with partner company Brains Bioceutical, dsm-firmenich is developing a platform to guide biotech and pharma customers through the complex development and manufacturing of their CBD treatment candidate treatments. “There’s the product but there's also the regulatory expertise, being able to design clinical trials, all the way to scanning the right pathway to enter the market,” said Zuber. “We can facilitate all of that together with Brains Bioceutical.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); Teaming up with Bod Science ​ One CBD innovator working with dsm-firmenich is the Australian company Bod Science. The companies joined forces last month to fuel the development of what could become the world’s first CBD-based treatment for insomnia. According to the release ​​, Bod Science is soon due to publish full results from a phase 2b trial of the treatment and deploy dsm-firmenich and Brains Bioceutical’s manufacturing and development expertise to fuel the next stage of commercialization. Prior to the partnership, Kanli saw Bod Science as a forward-looking company with a strong scientific perspective on the drug development process. “We were in conversations for a while and then at some point, we got to the conclusion that this was the right partnership for both of us,” she said. In addition to manufacturing support, dsm-firmenich and Bod Science plan to collaborate in at least two therapeutic areas and grow the partnership towards new formulations and new formats, said Kanli. She added that more information would be released in the coming months. Solid progress​ One obstacle for formulating CBD is that the compound is hard to dissolve in water and is typically delivered in oil or alcohol as soft-gel capsules, a liquid solution, sublingual drops, or an oromucosal spray. In the case of Epidiolex, CBD is mixed in oil and delivered orally via a measuring syringe. “If you have to administer [CBD] to a child with epilepsy, you might have to give them a tablespoon of oil twice a day,” said Kanli. “I don't want to try to give that to a three-year-old; it's not the most pleasant thing you can do.” To tackle this challenge, dsm-firmenich is developing a solid CBD formulation that could be delivered in a range of forms including a chewable pill or powder. Compared with current formulations, this formulation could be easier for patients to receive, improve absorption of CBD through the gut and reduce side effects. “The liver is going to be better, the stomach is going to be better, and there will be fewer drug-drug interactions,” said Kanli, adding that this could also improve patient compliance with dosage regimes. The company plans to trial the novel formulation in humans next year. While there are other solid CBD formulations in development at other companies, dsm-firmenich was the first to demonstrate improved CBD bioavailability in the solid form, Kanli said. As dsm-firmenich continues to design and develop new formulations, its mission has become easier with the merger that formed dsm-firmenich this year. The DSM side has all of the formulation expertise whereas the Firmenich side – specializing in flavorings and fragrances – can make CBD products more appealing to patients. “Let's assume you have a film under the tongue: you want it to taste good, right?” said Kanli. “It's really exciting.”