The pain program COZY
– a unique opportunity for a breakthrough in pain treatment

The pain program COZY is being developed together with the Danish company Zyneyro with the goal of developing an effective treatment for severe chronic pain, a common and often difficult-to-treat condition. The program consists of two projects – a peptide treatment and a gene therapy treatment, both of which are based on a new biological mechanism of action that is expected to be without many of the debilitating side effects that current treatments often give rise to.

Pain is a major global problem

About 20-25 percent of the world’s adult population suffers from some form of chronic pain and between six and eight percent of the population suffers from severe chronic pain. Conventional treatment consists mainly of anti-inflammatory drugs, antidepressants, anticonvulsant drugs and opioids (a group of substances with a morphine-like mechanism of action).

The problem with these treatments is that they are not specifically developed to treat chronic pain. The pain relief that is achieved therefore often has a number of debilitating side effects such as substance abuse problems, depression, anxiety, fatigue, reduced physical and mental ability. In the United States, an estimated 700,000 people have died due to opioid abuse in the past 20 years. [1] 

One program – two projects

The program consists of two projects: a peptide treatment (COZY01) and a gene therapy treatment (COZY02), which expresses the active part of the peptide from COZY01, with potential lifelong effect.

In severe chronic pain, the intention is to administer the peptide directly to the patient on one or more occasions to achieve effective pain relief.

In severe chronic pain where the possibilities for spontaneous reduction of the pain are considered excluded or unlikely and which with conventional treatment requires daily medication, the intention is to achieve pain relief by treating the patient with an AAV vector that makes the body produce the pain-relieving peptide itself. In this way, long-term pain relief can be achieved without daily medication. Since the AAV vector encodes the peptide, the mechanism of action and thus the expected effect are the same as in direct administration of the peptide.

Independent evaluation by the National Institutes of Health

An independent evaluation of the potential of COZY01 as a future pain treatment is underway at the National Institutes of Health (NIH) in the US, in a government-funded program (Preclinical Screening Platform for Pain, PSPP) aimed at finding pain management alternatives that are not opioid-based and that are not addictive or result in tolerance development. COZY01 has passed the first level of three and has been selected to move on to the next level where the substance will be tested in a behavioral model and in different pain models. 

[1] Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults — United States, 2016; CDC; Morbidity and Mortality Weekly Report Weekly / Vol. 67 / No. 36 September 14, 2018.


Peptide treatment of severe chronic pain

The peptide treatment has shown positive effects in various preclinical models. The continued development will focus 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 in humans with COZY01.
COZY01 Roadmap


Gene therapy treatment of severe chronic pain where the possibility of spontaneous reduction of pain is considered excluded

A prototype of the AAV vector that acts as a carrier of the genetic material in gene therapy 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 studies in humans. AAV is the vector type that CombiGene has extensive experience of from our other projects. When the vector is optimized, preclinical studies will follow to investigate and characterize distribution, protein expression, efficacy, dose-response and toxicology. In parallel with the preclinical development, we will develop a process for manufacturing the selected vector for preclinical studies and for future clinical trials. Data from this work will form the basis for seeking permission to conduct a clinical trial on patients with severe chronic pain.
COZY02 Roadmap