After initially collaborating in November 2006 to develop a cannabis-derived drug candidate, Cannasat Therapeutics Inc. and IntelGenx Corp. expanded their collaboration to include a second compound.

Under the agreement, St. Laurent, Quebec-based IntelGenx will develop and apply drug delivery technologies to the two preclinical cannabinoid-based products. IntelGenx also will manufacture the products and provide input regarding the design of the trials, which will be funded and managed by Toronto-based Cannasat.

Terms of the collaboration were not disclosed, but IntelGenx President and CEO Horst Zerbe said the agreement is "milestone-based" and that IntelGenx will share in any eventual royalties.

The cannabinoid receptors, CB1 in the brain and liver and CB2 in immune cells, are the targets of many drugs in development. The CB1-blocker Acomplia (rimonabant, Sanofi-Aventis Group) already has gained approval in Europe and is up for its second try at a U.S. approval later this year. Competitors Pfizer Inc. and Merck and Co. Inc. are both conducting Phase III trials with their own CB1-blockers for obesity, and Sanofi is looking at Acomplia in other indications including diabetes, cardiovascular disease, dyslipidemia and metabolic syndrome.

But Cannasat's drugs are designed to agonize rather than antagonize the cannabinoid receptors. The company plans to begin clinical trials in the third or fourth quarter with lead drug CAT 310, a treatment for chemotherapy-induced nausea based on tetrahydrocannabinol (THC), the active ingredient in cannabis. Following it into the clinic next year will be CAT 320, a non-THC-based drug for anxiety and depression.

Several cannabinoid agonists already are available on the market. Some countries, along with certain states within the U.S., allow doctors to prescribe medical marijuana in certain indications. Marinol, a synthetic version of THC, has long been approved for nausea in chemotherapy patients and as an appetite stimulant for AIDS patients.

Valeant Pharmaceuticals International markets a similar drug, Cesamet (nabilone), for chemotherapy-induced nausea and vomiting. And GW Pharmaceuticals plc's oral spray version of THC, Sativex, is approved for certain types of pain in Canada and is in Phase III trials in the United States and Europe. (See BioWorld Today, May 6, 2005.)

Yet metabolism poses a problem for THC and similar drugs, according to Cannasat's Chief Scientific Officer Umar Syed.

THC is converted into a psychoactive ingredient in the stomach and small intestine, resulting in the "stoned feeling" associated with its use, Syed said. By using novel formulations and drug delivery for CAT 310, Cannasat hopes to avoid this issue.

Beyond THC, Cannasat also is researching the other 59 cannabinoids that occur naturally in the cannabis plant and interact with CB1 and CB2 receptors.

"We know the cannabinoid molecules work and are not toxic," Syed said, citing data from years of cannabis use in medicinal settings. "From a safety and efficacy standpoint, we are way ahead." He added that Cannasat has built its intellectual property portfolio around novel formulations and delivery of the cannabinoids. Even for cannabinoids that don't metabolize into psychoactive substances, such as CAT 320, formulation and delivery are important to prevent degradation in the liver.

Cannasat plans to conduct its initial clinical trials with CAT 310 and CAT 320 in Canada. In the United States, cannabis is classified as a Schedule 1 drug, which would make the process of applying for licenses and exemptions "much more onerous," Syed said.

In Canada, Cannasat has obtained a Narcotic Dealer's License from Health Canada and aligned itself with Prairie Plant Systems Inc., the only government-licensed grower and distributor of medicinal cannabis in Canada.