In early September, CombiGene chose Viralgen as the manufacturer after successful pilot production of CG01. The choice was driven by the fact that Viralgen offers a suspension production method based on the industry-leading manufacturing process for AAV viral vectors, the AskBios Pro10 platform. Thus, CombiGene abandoned the adherent production method, which worked excellently during early preclinical work, to move to the more scalable and cost-effective suspension-based production method.

With Viralgen’s suspension method, CombiGene can use the same process to produce materials for the CG01 project’s final preclinical studies, future clinical studies and when the product finally reaches the market and patients.

Large-scale production of CG01 begins

On September 28, the next milestone in the CG01 project was reached when CombiGene announced that Viralgen had begun the first large-scale production of CG01. According to CombiGene, the production will be a general rehearsal for the upcoming cGMP production (Current Good Manufacturing Practice) as CG01 will be produced for studies in humans. The production process will provide material for the preclinical safety and biodistribution studies that are planned to be carried out in 2021.

»The ability to scale up the volumes is particularly important for CG01, which, unlike many other gene therapies, targets a large patient population. The estimates we have made indicate that approximately 10,000 epilepsy patients a year could be treated with CG01« – Jan Nilsson, CEO of CombiGene

Several milestones in a short time

After CombiGene successfully completed pilot production of CG01 using Viralgen’s suspension method on August 10, on August 18 the company was able to announce that Cobra Biologics had completed the production of three master cell banks for the epilepsy project CG01. This was followed by a signed agreement on the production of CG01 with Viralgen on September 3.

One week later, an agreement was signed with Cobra Biologics to secure GMP production of plasmids involved in the production of CG01. Five days later, CombiGene and CGT Catapult completed the quality control analyses for clinical production of CG01. These milestones were thus followed up with the news that large-scale production of the primary drug candidate CG01 for future safety and biodistribution studies had begun with Viralgen.

Powered by these five milestones, CombiGene has, in just over a month, taken several important steps towards clinical studies with CG01 in drug-resistant focal epilepsy.

Market Analysts see high potential

On September 29, Aktiespararnas Analysguiden published a company-sponsored research analysis of CombiGene, stating that the market for gene therapies is expected to grow very sharply in the coming years. It is estimated that the market will grow from USD 581 million in 2017 to USD 5.7 billion in 2025, corresponding to an average annual growth of just over 30 per cent.

The analysis also states that the large pharmaceutical companies’ significant interest in the gene therapy area has resulted in a number of acquisitions and collaboration agreements in recent years and that deals between large pharmaceutical companies and smaller biotechnology companies have taken place both in the early clinical phase and in the preclinical phase. The analysts’ conclusion is thus that an investment in CombiGene provides a unique exposure to this rapidly growing field in drug development.

In terms of value, Analysguiden does not yet include the unlicensed project CTG2 against the metabolic disease lipidystrophy as the project is at a very early stage. The target price is set at SEK 1.55 in a base scenario given that CG01 is approaching clinical trials in humans, which gives a potential upside of over 85 per cent compared to the share’s closing price before the analysis was published. In a bear and bull scenario, Aktiespararna sets the price at SEK 0.54 and SEK 2.33, respectively, where the bull scenario gives a potential upside of 180 per cent. Read the full analysis here.

»There is really no single milestone that stands out. The important thing is the sum of the milestones, which means that we now have a future-proof production platform«

CEO comments

BioStock contacted CombiGene’s CEO Jan Nilsson for a comment on what the next steps will be for the company and CG01.

Jan, it has been two very news-intensive months in the company. Which milestone was the most critical to achieve and which do you think should receive the most attention?

– There is really no single milestone that stands out. The important thing is the sum of the milestones, which means that we now have a future-proof production platform. The master cell banks that Cobra has produced means that we have secured access to quality-assured plasmids that are the starting material for production CG01. The analysis methods that CGT Catapult has developed on our behalf means that we can produce CG01 according to the strict regulatory requirements.

– The agreement with Viralgen on manufacturing according to the suspension method means that we have a production platform that is easy to scale up to future commercial volumes. The ability to scale up the volumes is particularly important for CG01, which, unlike many other gene therapies, targets a large patient population. The estimates we have made indicate that approximately 10,000 epilepsy patients a year could be treated with CG01.

– I would also like to mention our successful subscription of series TO3, which was subscribed for just over 97 per cent and which provided the company with approximately 17.7 million SEK before issue costs.

What will be the next step in the development and what will be required in the future to be able to apply for study start with CG01 in 2022?

– We have some really exciting steps ahead of us. The first step, which we have already begun, is to produce materials for the biodistribution and safety studies. As stated above, this production is already underway and we expect to have analyzed and quality-assured material completed around the turn of the year 2021/2022.

– The next step will be to carry out those extensive biodistribution and safety studies in 2021. This work is relatively extensive in time, and we will need most of 2021 to carry out the studies ourselves and then analyze the results. Then, when the results are compiled and a formal report is written, we can go ahead and apply to start the first studies in humans, the so-called clinical studies.

– In 2021, we will also fully produce CG01 according to the cGMP standard to manufacture materials for the first clinical study that we intend to begin in 2022.