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GvHD Program Overview

Kalytera is developing a clinical-stage cannabidiol (“CBD”) medicine to prevent and treat Graft versus Host Disease (“GvHD”). GvHD is a multisystem disorder that is a common, life-threatening complication of hematopoietic stem cell transplant (“HCT”) procedures. GvHD occurs when the transplanted donor cells attack the patient’s organs, including the skin, gastrointestinal tract, liver, lungs, and eyes. GvHD is associated with acute and chronic illness, infections, disability, reduced quality of life, and death.

Program Highlights
  • Demonstrated proof-of-concept1
  • Four Phase 2a clinical studies complete
  • Orphan Drug Designation (“ODD”) granted in the U.S. and Europe
  • Urgent unmet need; there are currently no FDA approved therapies for the prevention or treatment of GvHD

Program

Phase 1

Phase 2

Phase 3

Prevention

Related and Unrelated Donors

Advancing to Phase 2

60%

Treatment

Acute GvHD

Phase 2

50%

Treatment

Chronic GvHD

Phase 2

50%

Clinical Research

In a published Phase 2a study, researchers followed adult recipients of HCT receiving standard GvHD prophylaxis. Study participants were provided with daily doses of CBD for the seven days prior to transplantation and for 30 days after HCT (“CBD Treatment”). Participants were monitored for an average of 16 months following treatment. The researchers compared the trial results to historical data used as a control (“Historical Control”).

Developed Grade II-IV Acute GvHD
Developed Grade III-IV Acute GvHD

CBD Treatment

Historical Control

CBD Treatment

Historical Control

Phase 2a Study Highlights
  • No patients 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 group versus)
  • Patients treated with CBD had fewer skin and gastrointestinal issues compared to the control group
  • CBD treatment was safe and well tolerated

The preliminary results add to a growing body of evidence that supports the continued investigation of CBD for the prevention and treatment of GvHD. Existing and planned clinical studies may support U.S. Food and Drug Administration (“FDA”) Breakthrough Therapy and Fast Track Designations, which could accelerate the approval process.

GvHD Opportunity

About Graft versus Host Disease

A hematopoietic stem cell transplantation (“HCT”) is 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. This 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 20142 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).

Cases of Acute Graft versus Host Disease

Source: GlobalData; Jagasia et al., 2012; Pasquini and Wang, 2013

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 GvHD3. 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 research and consulting firm GlobalData4.

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 institution5.

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 outcomes6. 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 time7. CBD has shown benefit in a number of models of inflammatory diseases including diabetes8, rheumatoid arthritis9, multiple sclerosis10, and inflammatory bowel disease11.

Important Notice

Notice: We do not have approval from the U.S. Food and Drug Administration or any other governmental agency, whether in the U.S. or abroad, to sell or market any product to treat or cure any disease or condition, including our drug candidates that we hypothesize may, following further study, clinical trials and all required approvals, be used to treat Graft versus Host Disease. Our drug candidates have not completed the approval process (including, but not limited to clinical trials) that is required by the U.S. Food and Drug Administration. Our drug candidates have not been proven safe and effective and may not receive U.S. Food and Drug Administration approval. We do not currently sell any drug products or other treatments.

References

  1. Yeshurun M, Shpilberg O, Herscovici C, et al. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study. Biol Blood Marrow Transplant. 2015;21(10):1770-5.
  2. Center for International Blood and Marrow Transplant Research (CIBMTR) HCT Trends and Survival Data
  3. Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
  4. GlobalData Report (2015)
  5. 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.
  6. Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
  7. Mechoulam R, Peters M, Murillo-rodriguez E, Hanus LO. Cannabidiol–recent advances. Chem Biodivers. 2007;4(8):1678-92.
  8. Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39(2):143-51.
  9. 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.
  10. Trojano M. Advances in the management of MS symptoms: real-life evidence. Neurodegener Dis Manag. 2015;5(6 Suppl):19-21.
  11. Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89(3-4):149-55.

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