CombiGene´s lead project CG01 has received funding from the European Union´s Horizon 2020 research and innovation programme

Epilepsy project

CombiGene is developing a breakthrough therapy with potential to dramatically improve the quality of life for a group of epilepsy patients for whom there is currently no effective treatment. CombiGene’s unique platform employs a gene-therapy vector to administer a combination of neuropeptide Y (NPY) and NPY receptors to the brain cells, which has been shown to suppress epileptic seizures in a series of preclinical studies.

CombiGene’s epilepsy project is reaching milestones according to plan
In early 2017 a successful dose-response study was concluded, giving the company valuable information. Gene therapy is unique compared to other drugs, since the patient receives medication only once, after which the body takes over treatment. It is therefore important for the company to know how much of the substance the body will itself produce after a given dose of gene therapy. In the dose-response study many different doses of the candidate drug, CG01, were tested. This gave a clear indication of which doses are needed to produce a clear effect in the treatment of patients with epileptic seizures.

Successful long-term study
After completing the dose-response study, CombiGene began a decisive preclinical proof-of-concept-study (the long-term study) of CG01 under the direction of Professor Merab Kokaia, one of CombiGene’s scientific founders. For the long-term study to produce relevant results it is important that the test models approximate the human disease as closely as possible. At Professor Merab Kokaia’s laboratory at Lund University there is a model that does precisely that. The model resembles the disease and the symptoms of human temporal lobe epilepsy, which makes it an ideal model for testing the anti-epileptic effects of CombiGene’s candidate drug. The model includes use of MR scanning (magnetic resonance) and EEG examinations (electroencephalography); i.e., exactly the same methods that are used for examining patients at a clinic. Preliminary results from the study, presented in the last quarter of 2017, show that CombiGene’s candidate drug, CG01, has clear antiepileptic effects with fewer seizures.

Human expression study confirms that human brain cells take up CombiGene’s candidate drug
During the final quarter of 2017 CombiGene, in collaboration with Associate Professor David Woldbye at the University of Copenhagen and Professor Merab Kokaia at Lund University, conducted a so-̊ called human expression study, i.e., a study in human epileptic brain tissue. Initial data from the study indicate that the therapeutic gene that is included in CG01 is expressed in human epileptic brain tissue, i.e., that the cells actually take up the gene when the candidate drug is administered. The study thereby confirms for the first time that the technique of administering genes via the candidate drug functions in human tissue. The human tissue used in the study is unique, since it comes from epilepsy patients who do not respond to conventional medication – precisely the patient group CombiGene initially intends to treat with CG01. The results are therefore extremely encouraging.

Agreement with Cell and Gene Therapy Catapult for development of a manufacturing method
After receiving positive initial results from both the long-term study and the human expression study CombiGene took the next important step in development towards an effective therapeutic treatment by signing an agreement with British Cell and Gene Therapy Catapult (CGT Catapult). Collaboration is aimed at developing a complete and finalized manufacturing method that will enable CombiGene to proceed with commercial GMP manufacturing and subsequent clinical trials.

CGT Catapult has high-level expertise within a range of key areas such as development of manufacturing processes and regulatory support. In addition, the organization offers partners the opportunity to sign on for each individual stage of development, one at a time, something that, from a financial perspective and a financing perspective, can be very important for a company of CombiGene’s size.