Recently, gene therapy company CombiGene signed an exclusive global license agreement for their gene therapy candidate CG01 with Spark Therapeutics. The deal is potentially worth $328.5 million excluding royalties. Much has happened since CombiGene was formed and BioStock turned to the scientific founders Professor Merab Kokaia and Associate Professor David Woldbye, for a comment on the company’s development.
The foundation of CombiGene was laid over ten years ago. Prior to this, preclinical research had suggested that the production of neuropeptide Y (NPY) increases in the brain after an epileptic seizure. Professor Merab Kokaia, working at the Epilepsy Center at Lund University and Associate Professor David Woldbye, Department of Neuroscience at the University of Copenhagen, initiated a research collaboration across the strait, with the aim ofdeveloping new treatments for hard-to-treat epilepsy. The hypothesis was based on the assumption that NPY inhibits epileptic seizures, as a part of the body’s own defenses. Since then, this assumption has been confirmed in several studies.
A challenge to administer drugs to the brain
The researchers soon realised that by combining the neurotransmitter NPY with its receptor Y2, a better effect should be achieved, especially if the drug could exclusively target the area of the brain where the epileptic attack is being triggered. Now it was a question of developing a method of administering the drug to the brain. This is a challenge due to the blood-brain barrier that protects the brain, but at the same time constitutes an obstacle to the transportation of drugs to the brain.
The solution was to use a harmless, non-pathogenic virus whose own DNA was largely removed and replaced with functional DNA sequences of NPY and Y2 (AAV vectors) for injection directly into the damaged area of the brain. Thus, CombiGene’s gene therapy project with the candidate CG01 was born.
The culmination of a long development cycle
On October 12, 2021, CombiGene announced that it had entered into an exclusive collaboration and licensing agreement for the CG01 project with Spark Therapeutics, a gene therapy company that is part of the Roche Group. The deal amounts to 328.5 million USD excluding royalties. By Swedish standards it is a very substantial deal that Medicon Village-based CombiGene, a small company with limited internal resources, has signed with one of the biggest players in the industry.
Extensive work now remains in order to carry the CG01 project through the upcoming clinical studies together with Spark.
High price tag for exclusive rights
The agreement gives Spark the exclusive global right to develop, manufacture, and commercialise CG01. CombiGene will continue to conduct certain parts of the preclinical program in collaboration with Spark.
Under the terms of the agreement, CombiGene is eligible to receive up to 328.5 million USD excluding royalties of 8.5 million USD at the time of signing, and up to 50 million USD at preclinical and clinical milestones. CombiGene will also be reimbursed for agreed development costs. At the point of commercialisation, CombiGene is eligible for incremental royalties up to low double-digit percentages based on net sales.
Comment from the founders
BioStock reached out to CombiGene’s scientific founders, Professor Merab Kokaia and Associate Professor David Woldbye, for a comment.
After the agreement with Spark, it only feels right to start with the classic sports question, how do you feel?
“It feels great. Both us researchers and the team at CombiGene have put a lot of time and energy into getting to the point where clinical studies are possible so the agreement with Spark could not have come at a better time. Spark has the financial and intellectual resources to conduct the clinical studies with CG01 in patients with intractable epilepsy. Despite treatment with today’s medications, these patients suffer from uncontrolled epileptic seizures. If CG01 shows positive results in clinical studies, it represents a completely unique treatment option that can help these patients and significantly improve their quality of life.
“This is a great day for CombiGene and for me and Prof Kokaia”, says Assoc Prof Woldbye. “This is the culmination of preclinical work, dating as far back as 1996, showing that neuropeptide Y exerts seizure-suppressant effects. Through the deal with Spark, we now have ensured that this treatment can be tested in the clinic for temporal lobe epilepsy patients. Since many of these patients are drug resistant, there is a great need for developing novel treatments. It is my hope that with this deal, we can now get a great chance to help these patients”.
The deal is a clear sign of how Spark value the potential of CG01. How would you describe your hopes for further development, based on the data you have accumulated over the years?
– We have been working on the NPY/Y2 gene therapy project for many years and we have demonstrated – in various animal models as well as in human brain tissue from epilepsy patients – that it works and suppresses seizures. So, I am very optimistic that it will work in humans as well, but of course that remains to be seen. The agreement with Spark ensures that the clinical studies that will give us answers regarding what effect CG01 has on drug-resistant focal epilepsy, will be carried out.
”If we, in collaboration with Spark, can show that CombiGene’s gene therapy candidate works in a planned human drug-resistant epilepsy trial, it is my hope and prediction that this will pave the way for the use of gene therapy in other epilepsy patients as well. The reasoning behind this belief is that gene therapy has the potential to selectively treat the part of the brain where the seizure is located and may therefore also reduce the use of antiseizure drugs. In turn, that would also reduce the potential side effects of taking such drugs for extended periods of a patient’s life”, says Assoc Prof David Woldbye.
Finally, will you have close contacts with the research cluster behind Spark for the further development of CG01?
So far, we have had very good contact and discussions with the Spark team, and I am impressed by their knowledge and experience in the field of gene therapy. So, I am very positive about the future collaboration with Spark and hope for continued successful development of the CG01 project with the combined strengths from CombiGene and Spark.
Assoc Prof Woldbye adds “Yes, it is part of the deal between CombiGene and Spark that Prof. Kokaia and I will continue to be involved in driving the project forward together with Spark. Since this project is like a child to me and Prof Kokaia, we will be happy to maintain a role in the project in the future interaction with the very competent Spark team.”
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