Inovio announces regulatory approval for Phase 2 trial to treat leukemia using new vaccine delivery device

Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today the regulatory approval of a Phase 2 clinical trial (WIN Trial) to treat leukemia utilizing Inovio's new ELGEN 1000 automated vaccine delivery device. This open-label, multi-center clinical trial being run by the University of Southampton is evaluating a DNA vaccine to treat chronic myeloid leukemia and acute myeloid leukemia. 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.

Leukemia 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' Tumor gene 1 (WT1) is highly associated with these types of cancer, which led the University of Southampton to design its leukemia 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 tumor 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' Tumor gene 1 has emerged as one of the most promising targets for immunotherapy of blood malignancies including chronic myeloid leukemia (CML) and acute myeloid leukemia (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 take the next logical step into clinical testing. The trial has undergone extensive international peer review and we are delighted to see this trial in leukemia go ahead. We believe that this vaccine has real promise to improve outcomes in patients with leukemia."

The single dose level, Phase 2 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 patients 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 leukemia 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."