Kalytera Therapeutics, Inc. (TSX VENTURE: KLY and OTCQB: KALTF) (the “Company” or “Kalytera”) today provided an update on its lead product development program evaluating cannabidiol (“CBD”) for the prevention of acute graft versus host disease (“GVHD”).
Phase 2 Clinical Study (“Study KAL-05”)
To date, the results of Kalytera’s Phase 2 clinical study have been positive and encouraging. No patients in the first (low dose) cohort developed grades 3 or 4 acute GVHD while receiving oral CBD treatment, and only one patient developed grade 2 acute GVHD. Patients in the low dose cohort received doses of 75 mg of CBD administered twice daily.
The Company is currently completing enrollment of the second (medium dose) cohort, and, to date, no patients in the medium dose cohort have developed acute GVHD of any grade. Patients in the medium dose cohort are receiving doses of 150 mg of CBD administered twice daily. The Company expects to complete enrollment of the second cohort next month.
“We are very encouraged by the results we are seeing,” stated Robert Farrell, President and CEO of Kalytera. “We did not anticipate that the results for the low dose cohort would be as positive as they were, and now the interim results for the medium dose cohort are even better. These results will leave little or no room for improvement with the high dose of 300 mg of CBD administered twice daily.”
The results of Study KAL-05 to date are in line with data from the two previous Phase 2a clinical studies that were completed by Dr. Moshe Yeshurun, Kalytera’s Chief Medical Officer, at the Institute of Hematology, Davidoff Center, Rabin Medical Center, Petah Tikva, Israel.
The results from the first of these previous clinical studies were published in Biology of Blood and Marrow Transplantation (Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study, M. Yeshurun et al. / Biology Blood Marrow Transplant 21 (2015) 1770 – 1775). The 48 patients in this study received daily doses of 150 mg of CBD administered twice daily for 7 days prior to their bone marrow transplant procedure and for 30 days after, and, as previously announced, none of these patients developed acute GVHD while being treated with CBD.
Food Effect and QTc Study (“Study KAL-07”)
Kalytera also announced today that it expects to complete Study KAL-07, the Food Effect and QTc Study, early next month. Kalytera is conducting this study pursuant to written guidance received from the U.S. Food and Drug Administration (the “FDA”). The FDA required that the Company complete a study in healthy volunteers to assess the effect of food intake on the absorption of oral CBD, prior to the initiation of the Phase 3 registration study. The completion of Study KAL-07 will satisfy this FDA requirement.
Study KAL-07, is a double blind, randomized, two period, two treatment, fixed sequence, crossover (fed versus fasted) study that is evaluating the effect of food on the pharmacokinetics of CBD in 32 healthy volunteers. This study is being conducted at a single site in Melbourne, Australia.
FDA guidelines also require that a proposed new drug be evaluated for its effects on cardiac rhythm. This evaluation is typically done in a separate study known as a QT or QTc study. To save time and expense, Kalytera included a robust ECG evaluation of each subject enrolled in Study KAL-07. By including this evaluation in the design of Study KAL-07, the Company will be able to complete the collection of this critical data, without having to initiate a separate QT or QTc study for this purpose.
Drug-Drug Interaction Study (“Study KAL-08”)
Study KAL-08, the Drug-Drug Interaction Study, is a second healthy volunteer study that has been requested by the FDA. This study will measure the effect of certain anti-fungal drugs upon metabolism of CBD, and the Company anticipates that it will complete Study KAL-08 during the fourth quarter this year. This study is also being conducted at a single site in Melbourne, Australia.
Patients receiving bone marrow transplants are at high risk of developing acute GVHD, a life-threatening complication that occurs when the transplanted donor cells attack the patient’s organs, including the skin, GI tract, liver, lungs, and eyes. It is estimated that up to 50% of patients who undergo a bone marrow transplant from a sibling donor, and up to 70% of patients who undergo a bone marrow transplant from an unrelated donor, will develop some level of GVHD. There are currently no FDA approved therapies for either the prevention or treatment of acute GVHD.
Kalytera’s Novel, Proprietary CBD Formulation for Prevention of GVHD
The CBD drug product that Kalytera is evaluating for prevention of GVHD is a novel and proprietary formulation designed to overcome issues of poor oral bioavailability and stability.
One of challenges seen in development of CBD as an orally administered pharmaceutical is the issue of poor oral bioavailability caused by first pass metabolism. First pass metabolism occurs when CBD is absorbed from the GI tract and is then delivered to the liver by the portal vein. A significant fraction of CBD is then metabolized in the liver before it reaches systemic circulation, thereby reducing the oral bioavailability of the drug.
To overcome this issue, Kalytera has developed a formulation of CBD that is intended to by-pass first pass liver metabolism. Kalytera’s formulation is designed to allow CBD to be absorbed directly into the circulatory system through the ileum intestine, without first passing through the liver, thereby greatly enhancing the oral bioavailability of this CBD formulation.
CBD is also known to be unstable, leading to drug degradation over time. Stability is a critical quality attribute directly linked to potency, purity and safety, and therefore it was important that Kalytera find a way to overcome the instability of CBD during storage. The company’s novel formulation is designed to overcome this important issue, and this has been successfully demonstrated in stability studies conducted by the Company.
CBD is a non-psychotropic ingredient of cannabis that does not cause euphoria or cognitive effects. Kalytera is the exclusive licensee of two issued U.S. patents covering the use of CBD in the prevention and treatment of GVHD, and is also the exclusive licensee of pending patent applications in other jurisdictions for the use of CBD in the prevention and treatment of GVHD.
Kalytera Therapeutics, Inc. is pioneering the development of CBD therapeutics. Through its proven leadership, drug development expertise, and intellectual property portfolio, Kalytera seeks to establish a leading position in the development of CBD medicines for a range of important unmet medical needs, with an initial focus on GVHD and treatment of acute and chronic pain.
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