Medical cannabis companies developing pharmaceuticals have largely focused on using purified cannabinoids as monotherapies to treat neurological diseases. This year, for example, Cambridge, U.K.-based GW Pharma plc gained FDA approval for Epidiolex (cannabidiol) to treat two rare pediatric epilepsies, Dravet syndrome and Lennox-Gastaut syndrome, and others are on GW's heels, developing drugs for epilepsy and pain indications. (See BioWorld Insight, Oct. 17, 2016.)
But now companies are starting to branch out into other diseases, using a strategy of combining cannabinoids, the active compounds in cannabis, to increase the efficacy.
Last week, researchers at Stanford University announced the launch of Toronto-based Katexco Pharmaceuticals Corp. The company was founded by two serial entrepreneurs, Jonathan Rothbard, who will act as CEO and chief scientific officer, and Lawrence Steinman, the chairman.
The research goes back a decade, when the two discovered that multiple sclerosis patients had excessive alphaB crystalline in their brains. Knockout mice got paralysis, and in model systems, giving animals alphaB crystalline helped them recover.
Rothbard, a medical chemist, discovered that the alphaB crystalline formed amyloids, and other amyloids, such as amyloid beta, tau and prion, were all able to suppress inflammation.
"A lot of people would chide us, 'Are you going to give amyloids to patients?'" Steinman recalled.
Instead the two figured out the target of the amyloids, alpha-7 nicotinic acetylcholine receptor (alpha7 NAChR), which is expressed on immune cells, publishing the results in a Proceedings of the National Academy of Sciences article June.
Katexco licensed the intellectual property from Stanford and set out to find agonists of the alpha7 NAChR.
The plan is to combine the agonist with cannabidiol to try and get a synergistic effect. "The signaling pathways converge through nodes," Steinman explained. Specifically both pathways activate signal transducer and activator of transcription 3 (STAT3).
While the company has offices in the San Francisco Bay Area, to be in proximity to Stanford, Katexco is headquartered in Toronto to make clinical trials with cannabinoids easier given the recent national approval in Canada. Many of the seed round investors were also located in Toronto.
Katexco has outsourced the screening of compounds to contract research organization Evotec AG with hopes of identifying its lead compound by the end of this year, which would put it on track to run toxicology studies next year, eventually testing the combination in inflammatory diseases such as Crohn's disease, gout and multiple sclerosis.
In the meantime, Katexco is considering running a proof-of-concept study with a known agonist of alpha7 NAChR, looking at immunological biomarkers.
There's also the possibility of a near-term IPO. Questioning whether the company would really go from seed round straight to an IPO, Steinman replied, "It sounds audacious, but the answer to that is yes."
The Canadian headquarters open the possibility for listing in Canada, which can have lower minimum requirements compared to the U.S. exchanges. "Canadian exchange could offer significant opportunities," Steinman said, noting that he's also "not adverse to a U.S. exchange."
Last week, FSD Pharma Inc., of Toronto, said it plans to acquire Therapix Biosciences Ltd., of Givatayim, Israel, for $48 million of FSD stock, representing nearly 10 percent of FSD.
"We have been actively seeking additional technologies that are complementary and synergize with our existing cannabinoid scientific research programs that are focused on irritable bowel syndrome," Raza Bokhari, chairman of FSD, told BioWorld Insight.
In addition to researching pharmaceuticals, FSD, which has an indoor facility to grow pharmaceutical-grade cannabis, will also continue to sell cannabis products. "There are currently more than two dozen countries worldwide where medical cannabis is legal, and FSD intends to be a primary supplier to these markets," Bokhari said.
In the deal, FSD will get Therapix's programs combining cannabinoid with palmitoylethanolamide (PEA) to treat disease such as Tourette's syndrome, obstructive sleep apnea and chronic pain, among others.
The lead compound THX-110 combines dronabinol (purified THC), which is approved to treat loss of appetite in people with AIDS and nausea and vomiting caused by cancer chemotherapy, with PEA, a cannabinoid mimetic lipid molecule.
Therapix has said it believes that there may be an "entourage effect" where PEA may indirectly stimulate the cannabinoid receptors by potentiating the affinity of other compounds for the receptor or by inhibiting their metabolic degradation, which, in turn, might increase the absorption of cannabinoid compounds such as THC.
In a study of 16 patients with Tourette's syndrome, THX-110 reduced the average Yale Global Tic Severity Scale Total Tic Score by 21 percent. The drug is now in a phase IIb study for Tourette's syndrome, which is scheduled to be completed in the second half of 2020.
Therapix is also studying THX-110 in a phase IIa study in obstructive sleep apnea, which is scheduled to be completed in the second half of 2019, and plans to start a phase IIa in chronic pain next year.
In addition to THX-110, Therapix has a preclinical pipeline, including THX-130, an ultra-low-dose THC it's developing for cognitive impairment, which has demonstrated efficacy in a traumatic brain injury in a rat model.
And Therapix is also testing THC with an antibacterial agent and possibly PEA as a treatment of multidrug-resistant bacteria. Preclinical data show the drug, dubbed THX-150, was better at eradicating resistant bacterial strains than antibiotics alone.
"It's important to note that we are utilizing already approved cannabinoid-based drugs in our clinical and preclinical programs. There is substantial data supporting the safety and potential of synthetic cannabinoids to treat central nervous system disorders," Bokhari concluded.