Pain is a global problem. Between six and eight percent of the world’s adult population suffers from severe chronic pain with enormous costs for society as a result. In the US alone, the cost to society is estimated at an unimaginable USD 636 billion annually, which is twice the cost of cardiovascular disease.[1]

There is a huge need for new options for pain relief
One thing that further complicates the picture is that there are no efficient treatment options. Today’s treatments consist mainly of anti-inflammatory, antidepressant and anticonvulsant drugs and opioids, i.e., a group of substances with a morphine-like mechanism of action.

The problem is that these treatments often have a number of debilitating side effects such as substance abuse problems, depression, anxiety, fatigue and reduced physical and mental ability. 

All in all, this means that there is an enormous need for new effective forms of treatment that do not have the side effects that current alternatives are associated with and that do not lead to tolerance development, i.e., that the patient over time needs increasingly higher doses to achieve effective pain relief.

The COZY program is based on a new biological mechanism of action
The pain program COZY, which CombiGene runs in collaboration with the Danish company Zyneyro, aims to develop alternatives for the treatment of chronic pain without addiction problems and without tolerance development. The pain program consists of two projects –  a peptide treatment (COZY01) and a gene therapy treatment (COZY02), both of which are based on a new biological mechanism of action. Both the peptide and the gene therapy are being developed for treatment of severe chronic pain conditions, where the gene therapy is reserved for patients where the possibility of spontaneous reduction of chronic pain is judged to be limited (or unlikely). 

The peptide project COZY01
The peptide treatment, which is the one of the two projects that has advanced furthest in its development, has shown good effects in various preclinical models. CombiGene and Zyneyro are now focusing on conducting the necessary preclinical studies as quickly and efficiently as possible to evaluate safety and toxicology and to produce clinical trial material in order to obtain approval from regulatory authorities to conduct the first clinical trials on humans with COZY01 within a few years.

The gene therapy COZY02
A prototype of the AAV vector that acts as a carrier of the genetic material has been developed by Zyneyro and tested in several preclinical models with very good and long-lasting effect. The upcoming work is focused on optimizing the genetic material that will be included in the vector so that we can administer this in future human studies. AAV is the vector type that CombiGene has extensive experience of from our other projects. When the vector is optimized, preclinical studies follow to investigate and characterize distribution, protein expression, efficacy, dose-response, and toxicology.

In parallel with the preclinical development, we will ensure that manufacturing of the selected vector takes place in an optimal way and that the necessary quality tests are in place for future clinical trials. This work will form the basis for seeking permission to conduct a clinical trial on patients with severe chronic pain

[1] Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Appendix C. The Economic Cost of Pain in the US. Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Washington (DC): National Academies Press (US); 2011