The epilepsy project CG01

CG01 is an AAV-based gene therapy with the potential to improve the quality of life for patients with drug-resistant focal epilepsy for whom there is currently no effective treatment. On October 12, 2021, CombiGene and Spark Therapeutics entered a collaboration and licensing agreement, which gives Spark the exclusive global right to develop, manufacture and commercialize CG01. 

Collaboration and licensing agreement with Spark Therapeutics

CombiGene and Spark are now working together to complete the remaining parts of the preclinical program. Once the preclinical phase is finalized, Spark will take over full responsibility for CG01.

Under the terms of agreement, CombiGene is eligible to receive up to USD 328.5 million excluding royalties, with USD 8.5 million upon signing, up to USD 50 million at preclinical and clinical milestones, and payments based on net sales milestones. CombiGene will also be reimbursed for certain authorized R&D expenses.

About Spark Therapeutics

Spark Therapeutics works to discover, develop, and deliver gene therapies. Spark Therapeutics, founded in March 2013, is based on the technology and know-how that accumulated over two decades at the Children’s Hospital of Philadelphia (CHOP). Spark is a member of the Roche-Group.

About CG01

CG01 is an AAV-based gene therapy with the potential to improve the quality of life for patients with drug-resistant focal epilepsy for whom there is currently no effective treatment. The therapy candidate CG01 uses a gene therapy vector to administer a combination of neuropeptide Y (NPY) and its receptor Y2 directly to the part of the brain which triggers the epileptic seizures.

CombiGene has in recent years conducted a number of preclinical studies which step by step have moved CG01 forward and the project is now in the final phase of preclinical development where the next step is to carry out the toxicology and biodistribution studies to support start of the first in human study.

Continuous progress in the preclinical program

Since 2017, CombiGene has conducted a number of successful preclinical studies:
  • Dose response study. In 2017, a preclinical dose response study was conducted that gave the company valuable knowledge of the drug candidate’s dose-dependent properties.

  • Proof-of-concept study. After completing the dose response study in 2017, CombiGene initiated a concept verification study of CG01 in a model of chronic epilepsy. The results of the study show that CG01 has clear antiepileptic effects.

  • Human expression study. In 2017, CombiGene also conducted a study on brain tissue donated in conjunction with resective epilepsy surgery from patients with confirmed pharmacoresistance. Data from the study show that CG01 can be expressed in human epileptic brain tissue and thus confirms that the technique of administering genes using CG01 works as intended.

  • Pharmacokinetic study. The preclinical pharmacokinetic study concluded in 2020 provides further evidence that an injection into brain tissue can create long-term expression of the active substances NPY and Y2.

  • Learning and memory study. NPY is associated with a number of physiological processes, including memory and learning ability. The learning and memory study shows that CG01 has no adverse impact on either learning or memory.

  • Cell tropism study. CG01 is intended to reach the neurons in hippocampus that trigger the epileptic seizures. CombiGene’s tropism study shows that CG01 is taken up into the neurons of the hippocampus.

Scalable production platform

In the autumn of 2020, CombiGene completed the extensive work to establish a production platform for CG01 in collaboration with its CDMO-partners CGT Catapult, Cobra Biologics, and Viralgen. The platform consists of three parts: production of quality assured starting material (plasmids), quality control methods and a scalable suspension-based production process which makes it possible to produce both limited volumes for preclinical and clinical studies as well as large-scale volumes for future commercial needs.

Toxicology and biodistribution studies

In 2021, CombiGene began toxicology and biodistribution studies in small animals together with Northern Biomedical Research (NBR) in Michigan, USA.

In mid-2021, CombiGene produced its first GMP material of CG01 for use in the toxicology and biodistribution studies in large animals.

Overview of the epilepsy project CG01

CombiGene’s epilepsy project is now approaching the final stage of the preclinical phase. The remaining preclinical work is done in collaboration with Spark Therapeutics.



First screening study conducted.

Selection of a candidate drug.


Data from the dose-response study indicate a dose-dependent anti-epileptic effect.

The proof-of-concept study in a chronic epilepsy model is initiated.

Studies in human epileptic brain tissue from patients with pharmacoresistant epilepsy confirm that CG01 is expressed in human cells.


Final data from the preclinical proof-of-concept study confirm positive treatment results in the form of significantly fewer and shorter seizures.

CombiGene enters into collaboration with British Cell and Gene Therapy Catapult to develop a GMP manufacturing method for CG01.

Horizon 2020, the EU frame-work program for research and development, allocates EUR 3.36 million for the development and commercialization of CG01.


Acquisition of Panion Animal Health gives CombiGene full control over the company’s intangible assets in the CG01 project.

Agreement with CRO Northern Biomedical Research (NBR), which specializes in preclinical studies in the central nervous system (CNS). The agreement covers assessment of the candidate drug, CG01, in a smaller pilot study, a biodistribution study and a safety study, a so-called toxicity study.

CombiGene signs an agreement with the CDMO, Cobra Biologics, regarding production of plasmids for GMP manufacturing of CG01.


Preclinical pharmacokinetic study completed with positive results. The study confirms that CG01 creates long-term expression of the active substances NPY and Y2.

The preclinical learning and memory study shows that NPY and Y2 have no significant negative effect on cognitive functions.

Successful pilot study performed with suspension production method. 

Positive results in tropism study.

Agreement on GMP production with Cobra for plasmids for CG01.

Analytical methods for quality control of the production of CG01 developed in collaboration with CGT Catapult.

Manufacturing agreement with Viralgen for the production of CG01.

Agreement with the British company Neurochase regarding the development of optimized administration of CG01.  

First large-scale production of CG01 at the Spanish gene therapy manufacturer Viralgen.


The material from the first large-scale production of CG01 released for use in the final parts of the preclinical program.

The CG01 project initiates preclinical biodistribution and toxicology studies in small animals.

GMP-produced plasmids (starting material for the production of CG01) released for GMP production of CG01.

GMP production of CG01 for the concluding preclinical studies planned to enable First In Human study.

CG01 gets patents in the U.S. and Russia.

Global and exclusive cooperation and licensing agreement with Spark Therapeutics.

European Union’s Horizon 2020

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