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
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.
On October 12, 2021, Spark Therapeutics licensed the epilepsy project CG01 from CombiGene. The benefits of this agreement are numerous. Firstly, the CG01 project is now jointly run by a company that has resources, knowhow and experience required to advance the CG01 project. Spark is a member of the Roche Group, and the first company to receive FDA approval of a gene therapy for a genetic disease. Secondly, CombiGene’s cash position was substantially enhanced by the upfront payment of USD 8.5 million with the potential of another USD 50 million in preclinical and clinical milestone payments. Spark also covers all costs associated with the preclinical development of CG01, external as well as internal CombiGene cost. Thirdly, the agreement rapidly transformed CombiGene into an internationally recognized
gene therapy company.
The scope of the preclinical and clinical phases has, as previously communicated, been expanded. The text below reiterates the terms of the agree-ment and the expansion of the preclinical and clinical programs.
The collaboration and licensing agreement between CombiGene and Spark is an exclusive worldwide licensing agreement, which gives Spark license to develop the CG01 project throughout the preclinical and clinical phases of the program, to manufacture CG01, and to commercialize CG01 to the global market.
The total potential value of the agreement amounts to USD 328.5 million, excluding royalties. The upfront payment, which was made in conjunction with the signing of the agreement, amounted to USD 8.5 million. Milestone payments through the preclinical and clinical phases amount, in total, to USD 50 million. Royalties on future sales of CG01 range from the mid-single digits up to low double-digits based on net sales. All milestone payments will be communicated through CombiGene press releases as they occur.
The remainder of the preclinical program is performed by Spark in collaboration with CombiGene. CombiGene continues to run certain aspects of the program while the overall design and execution of program is controlled by Spark. Since the agreement was signed, the preclinical program has been expanded into a cohesive plan to meet the needs of an extended clinical trial submission which includes clinical trials in the U.S. Studies initiated prior to the agreement with Spark have thereby been integrated in the new and larger program, and in some cases complemented with additional studies. Spark will cover all costs throughout the preclinical development program, including all CombiGene external and internal costs related to CG01.
Once the preclinical program is completed, Spark will assume responsibility for the design and execution of the clinical development. Since the agreement with Spark, the clinical development program has been extended to include the U.S. All results and knowhow from the preparatory work CombiGene made prior to the agreement has been transferred to Spark. As part of our current agreement, Spark will cover associated costs on any clinical development work.
Future updates regarding the CG01 program will be provided by Spark in line with their standard practice.
The agreement gives Spark license to develop the CG01 project throughout the preclinical and clinical phases of the program.
The agreement gives Spark license to manufacture CG01 for preclinical, clincal, and commercial use.
The agreement gives Spark license to commercialize CG01 to the global market.
CombiGene is eligible to receive up to USD 328.5 million, excluding royalties.
The upfront payment was made in conjunction with the signing of the agreement.
CombiGene is eligible to receive up to USD 50 million at preclinical and clinical milestones.
Upon commercialization, CombiGene is eligible for tiered royalties ranging from the mid-single digits up to low double-digits based on net sales.
All milestone payments will be communicated through CombiGene press releases as they occur in line with information rules of Nasdaq First North.
The remainder of the preclinical program is performed by Spark in collaboration with CombiGene.
Since the agreement was signed, the preclinical program has been expanded into a cohesive plan to meet the needs of an extended clinical trial submission which includes clinical trials in the U.S.
Studies initiated prior to the agreement with Spark have been integrated in the extended program.
Spark will cover all costs throughout the preclinical development program, including all CombiGene external and internal costs related to CG01.
Future updates regarding the CG01 program will be provided by Spark in line with their standard practice and in line with information rules of Nasdaq First North.
Once the preclinical program is completed, Spark will assume responsibility for the design and execution of the clinical development.
Since the agreement with Spark, the clinical development program has been extended to include the U.S.
All results and knowhow from the preparatory work CombiGene made prior to the agreement has been transferred to Spark.
As part of our current agreement, Spark will cover associated costs on any clinical development work.
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.
CombiGene’s lead project CG01 has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 823282