Cellerant Therapeutics Inc., a biotechnology company developing novel haematopoietic stem cell-based cellular and antibody therapies for blood disorders and cancer, announced the initiation of a phase I/II clinical trial of CLT-008 in patients receiving intensive post-remission chemotherapy for high-risk leukaemia or myelodysplasia. CLT-008, a first-in-class, allogeneic cell-based therapy, is under development to provide haematopoietic support following high-dose chemotherapy or radiation exposure, by shortening the time to neutrophil recovery and decreasing the risks of febrile neutropenia and infection.

The open-label, multi-centre, dose escalation trial will evaluate the safety and tolerability of CLT-008 in the setting of chemotherapy-induced neutropenia in approximately 30 evaluable patients with high-risk Acute Myelogenous Leukaemia, Acute Lymphoblastic Leukaemia (ALL/AML), Chronic Myelogenous Leukaemia (CML) or Myelodysplasia (MDS). The secondary objectives include efficacy-related endpoints such as time to neutrophil recovery, duration of severe neutropenia and thrombocytopenia, days of fever and incidence of infections and incidence and duration of hospitalization.

“The advancement of CLT-008 in a second clinical trial represents an important milestone for Cellerant and for patients receiving high-dose chemotherapy to treat their haematological malignancies,” said Ram Mandalam, PhD, president and CEO of Cellerant Therapeutics. “These patients often suffer significant complications from the intensive chemotherapy that limit the dose of chemotherapy administered. With CLT-008, these patients could have a better chance for survival by allowing them to receive their full course of intensive chemotherapy regimen needed to treat their life-threatening cancers.”

Febrile neutropenia is a significant dose-limiting toxicity of chemotherapy which requires hospitalization and treatment with broad-spectrum antibiotics. Occurrence of neutropenia typically requires dose reductions for chemotherapy regimens which can impact subsequent disease control and survival, especially in the treatment of acute leukaemia and high-risk MDS, where dose-intensive, myelo-suppressive induction and consolidation chemotherapy have demonstrated significant clinical benefit. Current treatment options include the administration of colony-stimulating factors to increase the production of neutrophils. However, in dose-intensive chemotherapy settings as required for more advanced-stage solid-tumour cancers and haematological malignancies, the risk and incidence of neutropenia is greater due to loss of the myeloid progenitor cells necessary to mature into neutrophils. CLT-008, a human Myeloid Progenitor Cell product, would provide the critical myeloid progenitor cellular support to rapidly produce neutrophils and to shorten the duration of severe neutropenia following such chemotherapy regimens.

Cellerant is also developing CLT-008 for the treatment of Acute Radiation Syndrome (ARS) under a United States Government contract awarded on September 1, 2010 and valued up to $153 million over five years with the Biomedical Advanced Research and Development Authority (BARDA) in the Office of the Assistant Secretary for Preparedness and Response of the Department of Health and Human Services.

In ARS applications, CLT-008 is intended to provide haematopoietic cellular support after exposure to ionizing radiation from a nuclear or radiological weapon, or from a nuclear accident. Cellerant has conducted various preclinical studies to indicate that a single administration of CLT-008 could provide effective treatment for ARS in an emergency situation, and could be administered up to five days post-exposure to radiation. CLT-008 is being developed under the US Food and Drug Administration's Animal Rule for ARS. This approval pathway is available when human efficacy studies are neither ethical nor feasible and requires demonstration of efficacy in representative and well-characterized animal models along with safety and pharmacokinetic testing in human clinical trials. There is currently no FDA-approved medical countermeasure to treat ARS. If licensed by the FDA, the federal government could purchase CLT-008 for the Strategic National Stockpile under Project Bioshield. Project Bioshield is designed to accelerate the research, development, purchase and availability of effective medical countermeasures for the Strategic National Stockpile.

CLT-008 is a unique, off-the-shelf, cryopreserved, cell-based therapy that contains human Myeloid Progenitor Cells derived from adult hematopoietic stem cells that have the ability to mature into functional granulocytes, platelets and red blood cells in vivo. In preclinical models, CLT-008 has been shown to be highly effective in providing protection from lethal radiation, preventing infection, facilitating stem cell engraftment and improving overall survival with a high degree of efficacy. Cellerant is developing CLT-008 as an effective treatment for chemotherapy-induced neutropenia, protection following exposure to acute radiation, and facilitating engraftment of cord blood transplantation.

CLT-008 is currently in a phase I study in patients undergoing cord blood transplants for the treatment of haematological malignancies. CLT-008 is intended to rapidly produce neutrophils and platelets in vivo and facilitate long-term engraftment in patients undergoing bone marrow or cord blood transplantation.

Cellerant Therapeutics is a clinical stage biotechnology company focused on the regulation of the hematopoietic (blood-forming) system. The Company is developing human stem cell and antibody therapies for oncology applications and blood-related disorders. Cellerant's lead product, CLT-008, is currently in two phase I clinical trials in patients with haematological malignancies. The Company also has a Cancer Stem Cell (CSC) antibody discovery programme focused on therapies for AML, multiple myeloma and myelodysplastic syndrome.