Inovio Pharmaceuticals, Inc. has reported preliminary results of a phase II clinical trial to treat leukaemia with a WT1 DNA vaccine delivered with Inovio's proprietary electroporation delivery system showed robust vaccine-specific antibody responses in all vaccinated subjects evaluated to date. Furthermore, T cell immune responses, including those of the "killer T cells," were detected. Antibody and T cell responses are strong signals of the DNA vaccine's potential to treat the disease.

The data was presented at an international conference, DNA Vaccines 2012, in San Diego, by Dr Christian H Ottensmeier, MD, PhD, the trial's principal investigator and Professor of Experimental Cancer Research at the University of Southampton, UK.

These interim results, from eight patients, are part of a phase II trial that will enroll 31 patients in its chronic myelogenous leukaemia (CML) arm. To date, 14 CML patients have been enrolled while another 13 unvaccinated CML patients have been enrolled to serve as a control group. The vaccine has been shown to be safe overall and well-tolerated in the trial subjects. A detailed analysis of T cell immune responses as well as the impact of the vaccination on the molecular marker, BCR-ABL, which is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) disease, will be performed.

As a result of the favourable safety and immunogenicity profiles observed in the CML vaccinated group, the trial is now open to enroll the acute myeloid leukaemia (AML) clinical trial arm, with a total target of 37 subjects in each of the vaccinated and control groups.

This open-label, multi-centre phase II clinical trial is evaluating a DNA vaccine-based immune therapy to treat these two types of leukaemia. The DNA vaccine, developed by the University of Southampton, is delivered using Inovio's proprietary electroporation technology. Financial support for the trial is being provided by the UK research charity Leukaemia and Lymphoma Research (LLR) and the Efficacy and Mechanisms Evaluation (EME) programme (which is funded by the UK Medical Research Council and managed by the UK National Institute for Health Research).

Leukaemia is a cancer of the bone marrow and blood that accounts for at least 300,000 new cases and 222,000 deaths worldwide each year - a very high death rate. Wilms' Tumour gene 1 (WT1) is highly associated with these types of cancer. Preclinical data from mice showed strong induction of antigen-specific CD8+ T cells and the ability to kill human tumour cells expressing WT1. This is the first study to combine DNA vaccination with electroporation delivery of WT1 antigens with the goal of stimulating high and durable levels of immune responses, in particular T cells, which are considered critical for improving clinical outcomes for this disease.

The principal investigator of this study, Dr Ottensmeier, said, "These preliminary data show strong vaccine-induced immune responses in vaccinated subjects in the CML arm. We are looking forward to enrolling and testing the vaccine's impact in AML patients, who currently have limited treatment options and a low rate of progression free survival."

In this ongoing phase II trial, all participants initially receive six doses of two DNA vaccines (called p.DOM-WT1-37 and p.DOM-WT1-126) delivered at four week intervals. Vaccine responders may continue with booster vaccinations every three months out to 24 months. An additional 60-75 AML/CML patients are being enrolled across the two arms as non-vaccinated controls for comparison. The primary endpoints are molecular responses to a disease marker called BCR-ABL in CML patients and time to disease progression in AML patients. The study is also monitoring WT1 transcript levels, immune responses to the WT1 antigen, time to progression and overall survival, and two-year survival in the AML group. The trial is taking place at hospitals in Southampton, London and Exeter. Regulatory approval to start this clinical study was provided by the UK Medicines and Healthcare Products Regulatory Authority (MHRA) and Gene Technology Advisory Committee (GTAC).

Inovio's CEO, Dr J Joseph Kim, said, "We are encouraged by preliminary phase II data showing the WT1 DNA vaccine's potential, administered with our novel delivery technology, to generate T cells and robust antibodies to treat leukemia. These results follow on our recent scientific breakthrough represented by our human data showing the powerful killing effect of T cells generated by our cervical dysplasia therapeutic vaccine.

Leukaemia is a malignant disease (cancer) of the bone marrow and blood characterized by the uncontrolled accumulation of blood cells. This high ratio of deaths-to-cases (74 per cent) reflects the poor prognosis of leukemia in many parts of the world, where the somewhat complex treatment regimes are not available.

There are five types of leukaemia based on rate of development and types of blood cells affected. Two of these are being evaluated in the study discussed in this release: AML, a cancer of the myeloid line of blood cells, is characterized by rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults and its incidence increases with age and CML is a type of cancer that causes the body to produce large numbers of immature and mature white blood cells (myelocytes).

The University of Southampton is a leading UK teaching and research institution with a global reputation for leading-edge research and scholarship across a wide range of subjects in engineering, science, social sciences, health and humanities.

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