Kalytera Therapeutics, Inc. (TSX-V:KALY) (“Kalytera”) announced today that it has successfully completed the previously announced acquisition (the “Acquisition”) of Talent Biotechs Ltd. (“Talent”), strengthening Kalytera’s position as an emerging market leader in cannabidiol (“CBD”) pharmaceuticals. Talent is a privately held, Israeli-based company evaluating the use of CBD to prevent and treat Graft versus Host Disease (“GvHD”).
“We feel incredibly fortunate to be continuing Talent’s groundbreaking work in GvHD,” said Andrew Salzman, M.D., Kalytera’s Chief Executive Officer. “There are currently few options to prevent or treat persons with GvHD, a large and critically underserved market. The results of Talent’s Phase 2 clinical studies are unprecedented, and mark a major milestone in the potential prevention and treatment of this severe and life-threatening disease. We are encouraged by the data and seek to rapidly advance the GvHD program into FDA Phase 2b clinical studies.”
“This is a transformational transaction for Kalytera,” said Robert Farrell, President, COO, and CFO of Kalytera. “Multiple studies have demonstrated that CBD, a non-psychoactive cannabis constituent, possesses remarkable therapeutic potential across a broad range of diseases and disorders. The acquisition of Talent and its late-stage GvHD program significantly advances Kalytera’s position as an emerging leader in CBD pharmaceuticals. We expect our work in GvHD to be the first of many programs that seek to investigate and commercialize this important compound.”
Summary of Transaction Terms
As consideration for the Acquisition, Kalytera will provide a combination of cash, securities, and future contingent payments to Talent. To date, Kalytera has made cash payments to Talent totaling USD$10,000,000. In addition, Kalytera has issued 17,301,208 common shares to Talent, which securities will be subject to a contractual hold period expiring December 30, 2017. Subject to the completion of certain milestones in relation to the development and commercialization of the GvHD program, Kalytera will pay up to USD$20,000,000 in aggregate future contingent payments. Kalytera shall also issue to Talent an additional 2,883,535 common shares upon the completion of the first Phase 2b clinical study, and a further additional 2,883,535 common shares upon the issuance of the first patent by the USPTO or EU with respect to certain assets of Talent acquired in connection with the Acquisition. The shareholders of Talent shall also receive additional earn-out payments equal to 5% of the aggregate annual net sales of all products covered by patent rights included in the business of Talent. The Acquisition has been conditionally approved by the TSX Venture Exchange, but remains subject to final approval.
About Graft versus Host Disease
GvHD is an orphan disease that can arise following hematopoietic stem cell transplantation (“HCT”), a procedure where the stem cells of the bone marrow or peripheral blood of a healthy donor are transplanted into a new host after chemotherapy or radiation. HCT is a lifesaving procedure for many diseases of the blood and bone marrow including leukemia, Hodgkin and Non-Hodgkin lymphoma, multiple myeloma, sickle cell anemia, and thalassemia. There were over 8,000 HCT procedures in the U.S. in 20141 and the use of HCT procedures is expected to continue to increase. While HCT procedures can be lifesaving, they pose many dangerous side effects, including infection and GvHD.
GvHD is a multisystem disorder that occurs when the transplanted cells from a donor (“the graft”) recognize the transplant recipient (“the host”) as foreign. This interaction initiates an immune reaction that causes disease in the transplant recipient. This reaction can occur within days after the transplant (acute GvHD) or months to years after HCT (chronic GvHD).
GvHD can be mild, moderate, severe, and even life threatening. Patients with acute GvHD may suffer from rashes and blistering of the skin, nausea, vomiting, abdominal cramps accompanied by diarrhea, and jaundice. Generally, acute reactions are more severe and life threatening.
GvHD is a major cause of morbidity and mortality following HCT. Researchers estimate that even with intensive prophylaxis with immunosuppressive treatments, 30-50% of patients transplanted from fully matched sibling donors and 50-70% of patients transplanted from unrelated donors will develop some level of GvHD2. The GvHD market was valued at $295M across the six major markets in 2013, and is expected to grow to $544M by 2023, according to the research and consulting firm GlobalData3.
Standard of Care: Prevention and Treatment of GvHD
The first step in prevention of GvHD is the selection of donor cells that closely match the genetics of the immune system of the transplant recipient, ideally a sibling donor. From there, the patient relies on drugs that have been developed to prevent or treat GvHD. Medicinal prevention of acute GvHD is dependent on immunosuppression of the donor cells, either pharmacologically or through T cell depletion. Common drugs include methotrexate, cyclosporine tacrolimus, sirolimus, mycophenolate mofetil, and ATG. Preventive measures and clinical practices vary by institution4.
Treatment of GvHD involves pharmacologic suppression of the graft’s immune cell activation and reestablishment of donor-host immune-tolerance. Most patients are prescribed corticosteroids, which directly suppress the donor’s immune cell attack on host tissue, but also raise the risk of infection and cancer relapse. As with prevention, the optimal drug strategy for GvHD is not well defined. Only 30-50% of patients with moderate to severe GvHD respond to corticosteroids, putting many at risk for fatal outcomes5. Better treatment options are needed to improve the mortality and morbidity outcomes for transplant recipients.
CBD and GvHD
CBD is a major component of Cannabis sativa, commonly known as marijuana. CBD possesses potent anti-inflammatory and immunosuppressive properties. Unlike the other major component of cannabis, tetrahydrocannabinol (“THC”), CBD is non-psychoactive and is well tolerated by humans when taken over extended periods of time6. CBD has shown benefit in a number of models of inflammatory diseases including diabetes7, rheumatoid arthritis8, multiple sclerosis9, and inflammatory bowel disease10.
GvHD Clinical Research
In May 2015, Moshe Yeshurun, M.D., Chief Medical Officer of Talent and of the Head of the Bone Marrow Transplantation Department at the Rabin Medical Center in Israel, published the results of a Phase 2a study that followed adult recipients of HCT receiving standard GvHD prophylaxis11. Study participants were provided with daily doses of CBD for the seven days prior to transplantation and for 30 days after HCT. Participants were monitored for an average of 16 months following treatment. Talent researchers compared the trial results to historical data and reported that:
- No participants developed Acute GvHD while being treated with CBD
- The risk of developing Acute GvHD by day 100 was decreased
- Among those that did develop GvHD after HCT, the time to onset was significantly longer (60 days in the CBD group versus 20 days in the control group)
- Participants treated with CBD had fewer skin and gastrointestinal issues compared to the control group
- CBD treatment was found to be safe and well tolerated
Based on these promising results, Talent commenced a second phase 2a trial to evaluate the efficacy of a longer administration of CBD following HCT. As disclosed by Kalytera in its January 18, 2017 press release, in this study, which enrolled 12 patients, participants were provided daily doses of CBD 7 days prior to transplantation and for 100 days following the procedure. With a median follow up of 8.5 months following transplantation, preliminary results show that 85% of the patients did not develop significant (Grades 2-4) acute GvHD, although most of them received bone marrow from unrelated donors, and only 2 patients developed acute GVHD (being 15% of patients), versus the predicted incidence of 50-70% in the scientific literature.
Talent has completed additional pilot studies exploring the use of CBD in the treatment of GvHD. Kalytera plans to initiate placebo-controlled, double blind, randomized studies of CBD for both the prevention and treatment of GvHD. These clinical studies may support U.S. Food and Drug Administration (“FDA”) Breakthrough Therapy and Fast Track Designations, which could accelerate the regulatory approval process.
About Kalytera TherapeuticsKalytera (TSX-V:KALY) is pioneering the development of a next generation of cannabinoid therapeutics. Through its proven leadership, drug development expertise, and intellectual property portfolio, Kalytera seeks to establish a leading position in the development of novel cannabinoid medicines for a range of important unmet medical needs, with an initial focus on Graft versus Host Disease (“GvHD”).
Kalytera is focused first on developing a new class of proprietary cannabidiol (“CBD”) therapeutics. CBD is a remarkable compound that has shown activity against a number of pharmacological targets. However, there are limitations associated with natural CBD, including its poor oral bioavailability and short half-life. Kalytera is developing innovative CBD formulations and prodrugs in an effort to overcome these limitations, and to target specific disease sites within the body. Kalytera intends to file composition of matter and method of use patents covering its novel inventions, with the goal of limiting future competition.
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Cautionary NoteNeither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) has in any way passed upon the merits of the proposed Transaction and associated transactions and neither of the foregoing entities has in any way approved or disapproved of the contents of this press release.
Neither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this press release.
Forward-Looking Statement DisclosureThis news release contains “forward-looking information” within the meaning of applicable securities laws relating to the proposed Transaction including statements regarding the terms and conditions of the proposed Transaction, as well as information relating to Talent. The information about Talent contained in the press release has not been independently verified by Kalytera. Although Kalytera believes in light of the experience of its officers and directors, current conditions and expected future developments and other factors that have been considered appropriate, that the expectations reflected in this forward-looking information are reasonable, undue reliance should not be placed on them because Kalytera can give no assurance that they will prove to be correct. Readers are cautioned to not place undue reliance on forward-looking information. Actual results and developments may differ materially from those contemplated by these statements, depending on, among other things, the risks of failure to obtain final approval of the TSX Venture Exchange, failure of the results of the Phase 2a clinical trial to be consistent with the preliminary results of such trial, that the Phase 2a clinical trial results are not determinative of or consistent with the results of the results of future Phase 2 or other clinical studies, that the small number of patients in the Phase 2a clinical trial may contribute to the risk that future studies may be inconsistent with the results of the Phase 2a clinical trial, and that clinical trials are subject to a number of other health, safety, efficacy and regulatory risks. The statements in this press release are made as of the date of this release. Kalytera undertakes no obligation to comment on analyses, expectations or statements made by third-parties in respect of Kalytera, Talent, their securities, or their respective financial or operating results (as applicable). Kalytera disclaims any intent or obligation to update publicly any forward-looking information, whether as a result of new information, future events or results or otherwise, other than as required by applicable securities laws.
1 Center for International Blood and Marrow Transplant Research (CIBMTR) HCT Trends and Survival Data
2 Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
3 GlobalData Report (2015)
4 Ruutu T, Van biezen A, Hertenstein B, et al. Prophylaxis and treatment of GVHD after allogeneic haematopoietic SCT: a survey of centre strategies by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47(11):1459-64.
5 Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
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7 Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39(2):143-51.
8 Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 2000;97(17):9561-6.
9 Trojano M. Advances in the management of MS symptoms: real-life evidence. Neurodegener Dis Manag. 2015;5(6 Suppl):19-21.
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