Kalytera Therapeutics (TSX-V:KALY) has put its bone repair and osteoporosis research programs on the back burner in order to focus on the development of a new cannabidiol (CBD) therapeutic for the treatment of acute Graft versus Host Disease (GvHD).
“We conducted a portfolio review this past summer and concluded that we had to broaden the scope of our activities into other disease indications and pursue an opportunity to acquire a closely held Israeli company, Talent Biotechs, which is advancing a clinical program in the use of CBD to treat and prevent GvHD,” Dr. Andrew Salzman, CEO and CMO of Kalytera, says in an interview with BioTuesdays.
“While this review was going on, we had a research program underway at my lab in northern Israel and we have now generated a pipeline of six prodrugs, or derivatives of CBD, for six different indications,” he adds. Kalytera completed the acquisition of Talent last week.
All of Kalytera’s GvHD and prodrug molecules consist of the synthetic form of CBD. “We have shied away from using botanical CBD because of regulatory and legal complexities,” Dr. Salzman contends. “We are not a medical marijuana company.”
GvHD is an orphan condition that can arise following stem cell or bone marrow transplants. GvHD occurs when the transplanted cells attack a patient’s organs, leading to acute and chronic illness and infections, disability, reduced quality of life, and death.
In January, Kalytera announced preliminary results of Talent’s 12-patient Phase 2a study evaluating the safety and efficacy of prolonged use of CBD in the prevention of GvHD. Final results of the trial will be announced on Feb. 22.
Preliminary results of the study demonstrated that only 15% of patients in the CBD treatment group developed Grade 2-4 GvHD, compared with a 60% to 70% incidence predicted by historical data used as a control.
“These results are outstanding, and mark a major milestone in the potential prevention of this serious and disabling disorder following allogeneic hematopoietic cell transplantation,” Dr. Salzman contends. “The acquisition of Talent is a game changer for Kalytera.”
According to Dr. Salzman cannabis, or marijuana, has over 80 chemical constituents, known as cannabinoids, which alter the release of neurotransmitters from the brain. Two of the most active and studied constituents of cannabis are tetrahydrocannabinol (THC) and CBD. THC is the major psychoactive component of cannabis, while CBD acts on many of the same receptors as THC, but without the psychoactive side effects.
“Cannabidiol has significant homeostatic properties to reset inflammation and immune activation in a way that is potentially useful across a number of serious unmet medical conditions,” he adds.
In addition, he points out that CBD has an established history of use in more than 80 clinical trials, “giving us an extensive safety database and reassurance that its use will be well tolerated in humans. So we have a molecule that is potent, active against a number of important targets and most likely safe. That’s an exciting combination.”
Dr. Salzman notes that Talent Biotechs has conducted four successful Phase 2 clinical trials with its CBD molecule for the treatment and prevention of GvHD. “Our focus is to move forward with a definitive proof-of-concept study for the treatment of acute GvHD,” he says, adding that other GvHD conditions, such as the prevention of acute and chronic GvHD, and the treatment of chronic GvHD, will be pursued at a later date. “We have promising preliminary data in these additional conditions.”
Prior to beginning the proof-of-concept study, hopefully in the fourth quarter this year, Dr. Salzman says, Kalytera plans to conduct a short study to measure and obtain data on pharmacokinetics of its molecule.
The proof-of-concept study, which effectively is a Phase 2b trial and will enroll some 160 patients, will be conducted at clinics in Israel, Australia, New Zealand, the U.S., Canada, and parts of the EU. “Our intent is to seek FDA approval that if this trial is successful, we can move immediately to a registration trial,” he adds.
In addition to GvHD, Dr. Salzman says Kalytera’s pipeline of six CBD prodrugs are indicated for acute renal failure, traumatic brain injury, inflammatory bowel disease, congestive heart failure, adult respiratory distress syndrome, and a topical for acne.
“These prodrugs have been constructed either to change the physical and chemical properties of CBD and make them more amenable to different routes of administration or to combine two active molecules with distinct mechanisms of action into a single combination molecule,” he adds. The company has filed patent applications on the new chemical entities.