The start of CombiGene’s epilepsy project
- Professor Merab Kokaia and Associate Professor David Woldbye initiated Swedish-Danish collaborative research to develop new forms of treatment of difficult-to-treat epilepsy.
- Several academic studies had indicated that production of NPY increases in key areas of the brain after an epileptic seizure. One hypothesis was that NPY is part of the body’s own defence for preventing epileptic seizures.
- Woldbye and Kokaia succeeded in demonstrating that a more pronounced anti-seizure effect is achieved if an increased level of NPY is combined with an increased level of the receptor Y2.
2006 – 2013
CombiGene is established, research intensifies.
- A priority application for what subsequently became candidate drug CG01 was submitted to the Swedish Patent and Registration Office, PRV.
- Successes are achieved in the gene therapy field and so-called AAV vectors gain acceptance as an appropriate method of introducing therapeutic genes into human nerve cells.
- Together with entrepreneur and financier Lars Thunberg, Merab Kokaia and David Woldbye formed the company CombiGene AB to pursue development and commercialization of the discovery.
- Priority applications for what subsequently became candidate drug CG01 were submitted to patent offices in Europe and the USA.
- Woldbye and Kokaia’s academic research project in the epilepsy area continued in parallel with the development of the company and a large number of articles were published in recognized scientific journals.
2014 – 2015
CombiGene takes shape
- Priority applications for what subsequently became candidate drug CG01 were approved in Europe and the USA.
- CombiGene becomes a public limited company.
- The company’s registered head office and premises were relocated to Medicon Village in Lund, Sweden.
- A heavily oversubscribed offering yielded MSEK 12.5 before issuing expenses.
- Listing on Spotlight Stock Market as of 25 May 2015.
- The subsidiary CombiGene Vet AB was established.
- Screening to find the optimal gene vector commences.
- The first round of screening studies is conducted according to plan.
- The candidate drug was selected in the summer of 2016. The candidate drug was named CG01.
- Preclinical studies with CG01 begin.
- A new patent application for CG01 is submitted.
- The subsidiary CombiGene Vet AB was distributed to shareholders. The independent company is named Panion Animal Health AB
Continued preclinical studies, Seal of Excellence from Horizon 2020
- Data from a dose-response study confirms that CG01 has the intended antiepileptic effect. The study was conducted by an external CRO.
- CombiGene completes a preference share issue. The rights issue is oversubscribed and the company raises MSEK 14.2 before issuing expenses.
- CombiGene begins a proof-of-concept study of CG01 in a chronic epilepsy model.
- CombiGene is awarded the “Seal of Excellence” by the EU Horizon 2020 framework programme and receives 500,000 kronor from Vinnova.
- Human expression study confirms that human brain cells can express CombiGene’s candidate drug, CG01.
Development of a manufacturing method
- The proof-of-concept study of CG01 in a chronic epilepsy model is concluded and demonstrates “proof of concept” in the form fewer seizures.
- CombiGene and Cell and Gene Therapy Catapult sign an agreement for development of a manufacturing method.
- Horizon 2020, the EU framework programme for research and development, invests 3.36 million euros in CombiGene’s ongoing development and commercialization of the company’s gene therapy project focussing on difficult-to-treat epilepsy.
- CombiGene carries out a preferential rights issue which raises about 31 million kronor before issuing expenses.
- On December 19th 2018 CombiGene is listed on Nasdaq First North Growth Market.
CombiGene takes on an additional development project, acquires Panion Animal Health and selects CDMO and CRO partners for CG01.
- CombiGene acquires a majority interest in Panion Animal Health. Among other things, the purpose of the acquisition was to take advantage of synergies between the two companies and gain overall control over all intellectual property rights.
- CombiGene signs an 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 British-Swedish CDMO Cobra Biologics for production of plasmids for the manufacturing of the drug candidate CG01.
- CombiGene acquires a project from Lipigon Pharmaceutical AB for gene-therapeutic treatment of the rare disease lipodystrophy.
The epilepsy project – CG01
- Preclinical pharmacokinetic study completed withpositive results. The study confirms that CG01 creates long-term expression of the activesubstances NPY and Y2
- The preclinical learning and memory study show that NPY and Y2 have no significant negative effect on cognitive functions.
- Delivery of all three plasmids needed to produce CG01.
- Delivery of master cell banks for the three plasmids.
- Successful pilot study performed with suspension production method
- Framgångsrik pilotstudie av suspension som produktionsmetod.
- 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 epilepsy project – CG01
- 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 first human study.
- CG01 gets patents in the U.S. and Russia.
CombiGene’s lead project CG01 has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 823282
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 firstname.lastname@example.org.