Home Interviews Chronic pain in focus for CombiGeneĀ“s new collaboration

Chronic pain in focus for CombiGeneĀ“s new collaboration

Chronic pain in focus for CombiGeneĀ“s new collaboration

11 January, 2023

CombiGene has entered into a collaboration agreement with Danish Zyneyro regarding the continued development of treatments for chronic pain conditions ā€“ a peptide with short-term benefits and a gene therapy with potentially lifelong effects. To find out more about what sparked CombiGene’s interest in Zyneyro and their projects in temporary and chronic pain conditions, BioStock contacted CombiGene’s CEO Jan Nilsson.

The gene therapy company CombiGene’s pipeline consists of CG01, which is being developed for the treatment of drug-resistant epilepsy, and CGT2, which is being developed for the treatment of lipodystrophy. Last year, CombiGene signed an exclusive collaboration and licensing agreement worth up to USD 328.5 million with US-based Spark Therapeutics for the development of CG01. Since the agreement was signed, CombiGene has increased its efforts to find more partners, and on January 9, the company entered into a collaboration with the Danish company Zyneyro.

Focus on pain treatments

Today’s treatments for pain have several shortcomings. Although approximately one in five individuals suffers from chronic pain, there is no specific treatment that addresses the underlying problem. Instead, patients rely on therapies that cause a wide range of side effects or increase the risk of addiction, such as opioids.

It is within this medical vacuum that Zyneyro have niched themselves. The company was founded by researchers from the Department of Neuroscience at the University of Copenhagen and a group of entrepreneurs. The company’s researchers have extensive experience in research on the brain and nervous system and on modulation of neuronal interaction. The company’s focus is to develop drug candidates based on a new biological mechanism of action to offer effective pain relief without the side effects that today’s therapies are accompanied by.

CombiGeneā€™s/Zyneyro’s pipeline in the field of pain consists of two drug candidates: a peptide-based treatment for short-term benefits and a gene therapy with potentially lifelong effects. In severe temporal pain conditions, the intention is to administer the peptide directly to the patient on one or more occasions to achieve effective pain relief.

According to the parties, this concept could potentially also offer an opportunity to check that a patient responds well to treatment with the peptide before proceeding with the more costly gene therapy solution. By screening potential patients prior to treatment, the company believes it could increase the accuracy of the gene therapy.

CombiGene’s CEO comments on the collaboration

Jan Nilsson, CEO CombiGene

To find out more about the collaboration with Zyneyro, BioStock contacted CombiGene’s CEO Jan Nilsson.

Jan, what specifically made you interested in Zyneyro’s approach?

ā€“ A lot of things! First, pain is a gigantic problem. Estimates show that between 15-25 per cent of the adult population in Europe and the United States suffers from ongoing pain problems and that about 7 per cent have severe chronic pain. The need for new and effective therapies is thus enormous. The fact that the pain programme includes two separate forms of treatment, a peptide treatment and a gene therapy treatment, is also extremely interesting.

How do you see the potential to use a gene therapy based on an AAV vector that teaches the body to create a pain-relieving mechanism itself?

ā€“ CombiGene has extensive experience working with AAV vectors, and the fact that Zyneyro’s gene therapy concept is based on this particular vector was one of the things that made us especially interested. Chronic pain is a very large medical problem where good and effective treatments are lacking for large patient groups. Existing drugs often have severe side effects. The need for new forms of treatment is thus dramatic and it would be absolutely fantastic if CombiGene in collaboration with Zyneyro could offer an effective gene therapy. The CombiGene/Zyneyro pain programme has extensive scientific support, including data from preclinical pain models.

Can you elaborate on what the strategy looks like in terms of developing two types of pain treatments where one is the screening method for the other?

ā€“ The pain programme, just as you say, consists of two separate forms of treatment, a peptide treatment and a gene therapy treatment. The peptide therapy is being developed to treat severe temporary pain conditions while the gene therapy is being developed to potentially cure severe chronic pain. They are thereby two separate treatments aimed at different patient groups. This is the primary ambition of the pain programme. Potentially, we will also be able to use the less costly peptide treatment to screen patients with chronic pain in advance to determine how well they will respond to a gene therapy treatment. The reason that this is interesting is that the gene therapy will be considerably more costly than the peptide therapy and to get an indication in advance of how effective a gene therapy treatment is very interesting.

What will the collaboration look like in terms of the process of taking the candidates to the clinical phase?

ā€“ The agreement with Zyneyro is a cooperation agreement which means that Zyneyro and CombiGene share the project’s costs and revenues equally. According to the agreement, CombiGene will pay Zyneyro an upfront payment of DKK 5 million in connection with the signing of the agreement. CombiGene has also undertaken to pay an additional maximum of DKK 11.4 million in continued development support towards clinical phase 1. The peptide-based treatment is expected to be ready for first dosing in humans in 2025, while the AAV-based treatment will need additional development time to reach the same point. From a practical point of view, Alvar Grƶnberg at CombiGene will be the project manager for the entire pain programme. CombiGene will primarily contribute with expertise in drug development. We are now facing a series of preclinical studies where we will work with external resources as well as with the researchers at Zyneyro.

Does the agreement with Zyneyro mean that you are now putting your efforts to find additional projects on hold?

ā€“ Not at all. This work will continue unabated. Our ambition is to build a broad portfolio of projects in several of the different phases of drug development, ranging from projects in the really early phase to projects in preclinical development and thereby contribute to gene therapies being put to clinical use.

The content of BioStockā€™s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

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