Inovio Pharmaceuticals, Inc. a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases announced the regulatory approval of a phase II clinical trial (WIN Trial) to treat leukaemia utilizing Inovio's new Elgen 1000 automated vaccine delivery device. This open-label, multi-centre clinical trial being run by the University of Southampton is evaluating a DNA vaccine to treat chronic myeloid leukaemia and acute myeloid leukaemia.

Financial support for the trial is being provided by the UK research charity Leukaemia and Lymphoma Research (LLR) and by 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). The DNA vaccine was developed at the University of Southampton with funding from LLR and the charity Cancer Research UK.

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, which led the University of Southampton to design its leukaemia DNA vaccine to target this antigen. Preclinical data from mice showed strong induction of antigen-specific CD8+ T cells and the ability to kill human tumour cells expressing WT1.

There have been several prior clinical studies in humans using parts of the WT1 gene, notably as peptide vaccine candidates, demonstrating the production of modest levels of CD8+ T-cell responses and measurable clinical responses, although both effects were transient. This will be 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, critical for improving clinical outcomes.

The principal investigator of this study, Dr. Christian H. Ottensmeier, MD, PhD, Professor of Experimental Cancer Research at the University of Southampton, said, “Wilms' Tumour gene 1 has emerged as one of the most promising targets for immunotherapy of blood malignancies including Chronic Myeloid Leukaemia (CML) and Acute Myeloid Leukaemia (AML). We previously reported strong immune responses in our prostate cancer vaccine trial using a similar DNA-electroporation approach.

In that trial, patients with relapsed prostate cancer showed vaccine-induced immune responses that persisted to the end of the trial follow-up at 18 months. We are excited to extend this promising vaccine approach to CML and AML, for which better treatment options are sorely needed. This trial will evaluate the WT1 DNA vaccine in two parallel settings with the purpose of identifying the most promising path forward for a pivotal Phase 3 clinical trial."

Dr David Grant, Scientific Director of Leukaemia and Lymphoma Research said: “It is an important step for us to see the laboratory work on DNA vaccines that LLR has supported takes the next logical step into clinical testing. The trial has undergone extensive international peer review and we are delighted to see this trial in leukaemia go ahead. We believe that this vaccine has real promise to improve outcomes in patients with leukaemia.”

The single dose level, phase II study, called “WT1 immunity via DNA fusion gene vaccination in haematological malignancies by intramuscular injection followed by intramuscular electroporation,” led by Professor Ottensmeier and Dr Katy Rezvani of Imperial College London and Hammersmith Hospital, London, is designed to recruit two patient groups. One group is planned to recruit up to 37 CML patients and the other up to 37 AML patients. All participants will 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 100-110 AML/CML patient will be enrolled across the two arms as non-vaccinated controls for comparison.

The primary endpoints will be molecular response to a disease marker called BCR-ABL in CML patients and time to disease progression in AML patients. The study will also monitor 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 will take place at hospitals in Southampton, London and Exeter over the next two years. 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).

This is the first clinical trial using Inovio's new ELGEN-1000 automated device, which is based on its proprietary electroporation delivery platform. The device's needle electrodes automate vaccine delivery at the push of a button and co-locate subsequent controlled, millisecond electrical pulses that increase cell membrane permeability and dramatically improve cellular uptake of the vaccine. Inovio's electroporation systems have been shown to increase levels of gene expression (production of the antigen coded by the DNA vaccine) up to 1000-fold and increase immune responses to the antigen up to 100-fold.

Inovio's CEO, Dr. J. Joseph Kim, said, “This leukaemia study expands Inovio's long-standing relationship with the University of Southampton into an important disease area and moves our first fully automated injection-electroporation delivery product into human studies. This program could further validate the ability of Inovio's DNA vaccines and delivery platform to generate clinically relevant immune responses and effects. We are proud that Inovio will make a significant contribution to this Phase 2 trial for these cancers with clear unmet medical needs.”

Leukaemia is a malignant disease (cancer) of the bone marrow and blood characterized by the uncontrolled accumulation of blood cells. It accounts for at least 300,000 new cases and 222,000 deaths worldwide each year. This high ratio of deaths-to-cases (74%) reflects the poor prognosis of leukaemiain many parts of the world, where the somewhat complex treatment regimes are not available. Approximately 45,000 new cases of leukaemia were diagnosed in 2008 in the US, with 20,000 deaths. This represents 3% of all cancers in the United States, and 30.4% of all blood cancers. It is estimated that approximately $3 billion is spent in the United States each year to treat leukaemia.

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: Acute Myeloid Leukaemia (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 leukaemia affecting adults and its incidence increases with age. Only about one-third of those between ages 18-60 who are diagnosed with AML can be cured. With conventional chemotherapy 70% of the patients in the group under study will relapse within 2 years and current therapy is devastating in older adults.

Chronic Myeloid Leukaemia (CML) is a type of cancer that causes the body to produce large numbers of immature and mature white blood cells (myelocytes). Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. Ultimately, in the absence of curative treatment, the disease progresses to an accelerated phase where median survival is around 3-5 years. Chronic myeloid leukaemia can occur at any age, but it more commonly affects middle-aged and older people.

Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. These SynCon vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses. Inovio's clinical programs include HPV/cervical dysplasia and cancer (therapeutic), avian flu (preventive), and HIV vaccines (both preventive and therapeutic).

Inovio is developing universal influenza and other vaccines in collaboration with scientists from the University of Pennsylvania. Other partners and collaborators include Merck, National Cancer Institute, US Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, and PATH Malaria Vaccine Initiative.

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.

Imperial College Healthcare NHS Trust comprises Charing Cross, Hammersmith Hospital, Queen Charlotte's & Chelsea, St Mary's and Western Eye hospitals. It is one of the largest Trusts in the country, and in partnership with Imperial College London, is the UK's first Academic Health Science Centre (AHSC). The AHSC was created to take the research discoveries it makes and translate them into new and improved treatments and techniques to directly benefit patients throughout the Trust and beyond.

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research. The charity's groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public. It has been at the heart of the progress that has already seen survival rates double in the last forty years. It also supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.

Leukaemia and Lymphoma Research is the only national UK charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin's lymphoma and other lymphomas, myeloma and the related blood disorders. Leukaemia and Lymphoma Research receives no government grants and urgently needs to raise over 100 million pounds in the next five years to commit to new research. From basic laboratory research to clinical trials with patients, Leukaemia and Lymphoma Research is committed to saving lives by funding high quality, carefully selected research throughout the UK.

Leukaemia and Lymphoma Research currently supports 30 Specialist Programmes in which the groups undertake long-term intensive research into relevant areas of leukaemia and the related diseases, often working closely with diagnosis and treatment; more than 200 project grants, which provides short-term funding, usually two-three years, for work on a specific problem; 25 clinical fellowships for the training of outstanding junior doctors in both the treatment and research of leukaemia and more than 20 studentships, lectureships and senior fellowships. Further information, including patient information booklets, is available from www.beatbloodcancers.org/ or on 020 7405 0101.

The Efficacy and Mechanism Evaluation programme supports later-phase “science-driven” clinical trials and evaluative studies, which seek to determine whether a health intervention (e.g. a drug, diagnostic technique or device) works and in some cases how or why it works.

The NIHR provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training.