Bone Fracture Healing (KAL436/9)

Therapeutic goal and molecular design Kalytera is investigating two compounds to assess their potential ability to improve bone fracture healing, including cannabidiol (“CBD”), a natural non-psychoactive cannabis constituent, and KAL436/9, a synthetic derivative of CBD that has been structurally modified to enhance solubility in water to improve potency.

Current pharmacology studies Kalytera is collaborating with Dr. Yankel Gabet, the Director of the Bone Research Laboratory at Tel Aviv University. In 2015 Dr. Gabet published a study showing that cannabidiol (“CBD”) increased collagen cross-linking and stabilization in rat femurs, increasing the maximal load and work-to-failure, but not the stiffness.

Unmet need Approximately one-third of all tibial and femoral shaft fractures have delayed rates of healing or non-healing. Patients with delayed union or non-union can expect poorer outcomes, including increased pain, loss of function, loss of quality of life, and delay in return to work. There are currently limited treatment options available for improving the rate of bone healing and bone fracture repair. Bone morphogenetic proteins (“BMPs”) and anabolic agents, including Teriparatide (“TPD”), are costly and may lack desired efficacy; improved therapeutic options are desired.

Osteoporosis (KAL671)

Therapeutic goal and molecular design KAL671 is a unique synthetic fatty acid amide and an endocannabinoid-like molecule that may restore bone in persons suffering from osteoporosis. Kalytera has obtained an exclusive license to KAL671 from Yissum Research Development Company, Hebrew University’s technology transfer arm.

Current pharmacology studies Studies in mice have shown that KAL671 increases bone volume density with a favorable side effect profile. Researchers used a mouse ovariectomy (“OVX”) model where mice ovaries were surgically removed at six weeks of age; the OVX model mimics osteoporosis in women post-menopause, when sex hormone levels are significantly altered. OVX mice were treated with daily doses of KAL671 and a control group of OVX mice were administered a solvent. The mice’s skeletons were analyzed for physical variations at weeks 1, 6, and 12; serum markers were tracked to identify bone remodeling patterns. Compared to controls, mice treated with KAL671 (0.5 mg/kg/day) recovered more than half of the OVX-attributed bone loss. No serious side effects observed as a result of KAL671 administration.

Unmet need Osteoporosis, the most common bone disease, is a chronic condition characterized by a weakening of the bone and an increased risk of fracture. Osteoporosis typically does not manifest until late in life, when bone loss begins due to bone breakdown and decreased levels of bone formation. Loss of bone mass leads to the development of structural abnormalities that make the skeleton more fragile. According to the National Osteoporosis Foundation (“NOF”), osteoporosis affects approximately 10.2 million adults in the U.S. alone. The NOF estimates that an additional 43.4 million U.S. adults may have low bone mass. Globally, one in five men and one in three women aged 50+ will experience osteoporotic fractures.