KaloBios Pharmaceuticals, Inc. a privately held biopharmaceutical company, announced treatment of the first patient in a phase I clinical trial of KB004, its first-in-class Humaneered monoclonal antibody, in EphA3-expressing haematologic malignancies.

EphA3 is an onco-fetal protein that is expressed in a range of cancers, including haematologic malignancies and possibly on leukaemic stem cells. A team of Australian collaborators, including Dr Martin Lackmann of Monash University, Melbourne; Dr Andrew Boyd of Queensland Institute of Medical Research and the University of Queensland, Brisbane, who originally isolated the KB004 precursor monoclonal antibody, IIIA4; and Dr Andrew Scott of Ludwig Institute for Cancer Research, Melbourne, realized the potential of EphA3 as an anti-cancer target and, in a series of animal studies, evaluated the IIIA4 antibody as an anti-cancer agent.

“We are excited to see progression of KB004 into the clinic, as we believe this antibody could provide significant benefit to patients with a broad array of cancer types, given its potential to kill tumours through several distinct mechanisms,” said Dr Lackmann.

“KB004's unique ability to target and activate EphA3 and its similarity to the human germ-line sequences could result in measurable efficacy and low immunogenicity,” said Dr Boyd. “As a haematologist, I am particularly pleased that the first trial is in patients with leukaemia.”

“KB004 is a patient-targeted, potentially disease-modifying antibody that has shown encouraging preclinical proof-of-concept results that we hope will translate into the clinical setting for leukaemias,” said Jeffrey E. Lancet, MD of Moffitt Cancer Centre of Tampa, Florida who treated the first patient. MD Anderson Cancer Centre of Houston, Texas is also participating in the study.

The multi-centre, open-label phase I trial is being conducted in patient populations with EphA3-positive haematologic malignancies, including chronic myelogenous leukaemia, acute myelogenous leukaemia, acute lymphocytic leukaemia, and myelodysplastic syndromes, who are refractory to, have failed, or have not received standard-of-care treatment. Patients older than age 65 who are not considered medically suitable for standard-of-care are also eligible. In the dose-escalation phase of the trial, up to 24 patients that have been prospectively screened for the presence of EphA3 will receive one of four dose levels, once weekly for three weeks for a maximum of 17 treatment cycles.

Once the escalation phase is complete, an expanded phase of the trial will be initiated with up to an additional 15 patients. The primary endpoint of the trial is the determination of the maximum tolerated dose; secondary endpoints include safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity.

KB004 is a first-in-class engineered IgG1? antibody targeting the EphA3 receptor tyrosine kinase. KaloBios has licensed this target from the Australian team who discovered EphA3, and has used its proprietary antibody Humaneering technology platform to develop an afucosylated recombinant human antibody with enhanced Antibody-Dependent Cytotoxic (ADCC) activity. KB004 also has variable regions that are very similar to human germ-line sequences, an attribute specifically enabled by KaloBios' Humaneering technology platform, providing the potential for low immunogenicity in patients.

KaloBios' Humaneering technology is a proprietary method for converting non-human antibodies into Humaneered antibodies. Humaneered antibodies are high affinity, but nearer to human germline sequence than is possible with other available antibody engineering methods, making them potentially well-suited for repeated use in the treatment of chronic or other therapies.

KaloBios Pharmaceuticals, Inc., is developing a proprietary portfolio of patient-targeted, first-in-class monoclonal Antibodies (mAb) designed to significantly improve the lives of seriously ill patients with difficult-to-treat diseases.