The CG01 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 uses an adeno-associated viral vector (AAV) to administer a combination of neuropeptide Y (NPY) and its receptor Y2 directly to the part of the brain where the epileptic seizure begins. The most important preclinical effect studies have been concluded with positive results and the next step will be the compulsory safety studies. Given a positive outcome from the safety studies and successful GMP production of CG01, studies in humans can begin.

CombiGene’s epilepsy project reaches milestones according to plan

In early 2017 a successful dose-response study was concluded, giving CombiGene new and valuable information. Gene therapy is unique compared to other drugs, since the patient receives medication only once or a few times, after which the body’s own cells continue to produce the genes that have been introduced. It is therefore important to understand how much NPY and Y2 the body will itself produce after a given dose of CG01. In the dose-response study several different doses of the candidate drug, CG01, were tested. This gave a clear indication of which dose is needed to produce a good effect in the treatment of patients with epileptic seizures.


Successful proof-of-concept study in a chronic epilepsy model

After completing the dose-response study, CombiGene began a proof-of-concept-study of CG01 in a chronic epilepsy model under the direction of Professor Merab Kokaia, one of CombiGene’s scientific founders. The applied test model resembles the progression and the symptoms of human temporal lobe epilepsy, and also 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. The final results from the study, presented in early 2018, show that CombiGene’s candidate drug, CG01, has clear antiepileptic effects.

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. The study was done with human epileptic brain tissue donated after resective surgery, a procedure whereby the part of the brain that causes the seizures is surgically removed. Data from the study indicate that CG01 is expressed in human epileptic brain tissue, i.e., that the cells take up and express the genes when the candidate drug is administered. The study thereby confirms that the technique of administering genes via the candidate drug functions in human tissue. The human tissue used in the study 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.


Preparations for biodistribution and safety studies

During autumn 2019 CombiGene signed two important agreements: for production of candidate drug CG01 and for implementation of biodistribution and safety studies, so-called toxicity studies. The process of identifying the most suitable companies was very thorough and many companies were assessed. The Swedish-British company Cobra Biologics was selected as the CDMO partner and US-based Northern Biomedical Research (NBR) was chosen as the CRO partner.

Cobra began working with production of the plasmids required for production of CG01 during autumn 2019. Concurrently, a broad transfer of technology and methodology from CGT Catapult, CombiGene’s partner in the development of a manufacturing method for CG01, began. The next important stage is a so-called Engineering Run, whereby the entire production process is tested before initial GMP manufacturing can begin.

We will now conduct a smaller pilot study together with NBR. This is necessary to give material to our collaborators that will develop the bioanalytical tools to be able to evaluate the effect of CG01. The full-scale biodistribution and toxicity studies will be carried out with material produced by Cobra according to the process which will subsequently be used for GMP manufacturing. 

Collaborating partners

Cobra Biologics is a leading international contract development and manufacturing organisation (CDMO) providing biologics and pharmaceuticals for pre-clinical, clinical and commercial supply. Cobra has broad expertise in areas including production of DNA, viral vectors, microbiota and proteins. Cobra’s work is always guided by customer’s specific requirements.

Northern Biomedical Research is a contract research organization that has worked with clients in research, the pharmaceutical industry and biomedicine for more than 25 years. The company specializes in pharmacology, toxicology, biodistribution and pharmacokinetics (the branch of pharmacology concerned with the movement of drugs within the body). The company is based in Spring Lake, Michigan, USA.

CombiGene’s lead project CG01 has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 823282

About CombiGene

CombiGene’s vision is to provide patients affected by severe life-altering diseases with the prospect of a better life through novel gene therapies. CombiGene’s business concept is to develop effective gene therapies for severe life-altering diseases where adequate treatment is currently lacking. Development assets are sourced from an external research network and developed to achieve clinical proof of concept. Drug candidates for common diseases will be co-developed and commercialized through strategic partnerships, while the company may manage this process on its own for drugs targeting niched patient populations. The company is public and listed on the Swedish marketplace Nasdaq First North Growth Market and the company’s Certified Advisor is FNCA Sweden AB, +46 (0)852 80 03 99


Combigene AB, Medicon Village, SE-223-81 Lund, Visiting adress: Scheelevägen 2, Lund, Sweden

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