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. 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.

Project status

On October 12, 2021, Spark Therapeutics licensed the epilepsy project CG01 from CombiGene. In conjunction with the outlicensing, CombiGene received an upfront
payment of USD 8.5 million. Since October 2021, Spark Therapeutics has covered all development costs of CG01 and generated new preclinical data through several different studies.

The collaboration agreement gave Spark a global exclusive license to develop, manufacture, and commercialize CG01. Under the terms of the agreement, CombiGene was entitled to receive milestone payments and royalties. During the collaboration, CombiGene has also been compensated for agreed development costs.

Termination of the agreement

On October 14, 2023, CombiGene announced that Spark Therapeutics, as a result of a strategic decision, had decided to terminate the collaboration agreement for the epilepsy project. CombiGene thus have regained the global rights for the project.

The agreement with Spark Therapeutics has demonstrated CombiGene’s ability to increase the value of the project in an early-stage development phase so that it attracts a pharmaceutical company for in-licensing. This is our business concept, and this is how we generate our revenue.

Careful evaluation

CombiGene will now carefully evaluate the situation that has arisen and investigate how the handover should be carried out in order to terminate the collaboration. The company will, of course, inform the market as soon as it has analyzed the future conditions for the project.

CombiGene is not liable

CombiGene is not liable for any of the payments received by the company from Spark Therapeutics, totaling USD 8,5 million excluding development costs, but is also not entitled to any future milestone payments or royalties.

Milestones

2016

First screening study conducted.

Selection of a candidate drug.

2017

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.

2018

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.

2019

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.

2020

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.

2021

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.

2023

Spark Therapeutics terminates the collaboration agreement for CG01.

CombiGene initiates a thorough evaluation of the future conditions for the project.

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