Gene Therapy

GeneQuine develops drugs that are based on gene therapy. The concept of gene therapy is to introduce genetic material into the patient's cells in the body. The cells then produce a therapeutic protein according to the template that the introduced genetic material (DNA) provides. Therefore, the patient's body itself produces the therapeutic protein. One of the major advantages of this approach is that therapeutic proteins can be produced over a long period of time as opposed to conventional drugs, which have to be administered frequently because they are metabolized or eliminated by the body. Gene therapy has proven to be safe and efficacious in a number of diseases and several products have received market authorization.

GeneQuine’s Gene Therapy Vector Technology

GeneQuine's gene therapy product candidates are based on a certain vector technology called helper-dependent adenoviral vectors (HDAd). HDAds are the newest generation of adenoviral gene therapy vectors, characterized by lower immunogenicity compared to earlier generation adenoviral vectors, and long-term gene expression, which has been demonstrated in numerous animal models by GeneQuine and other groups. HDAds have some important advantages compared to other commonly used gene therapy vector as HDAds exhibit high transduction efficiency in many tissues (in most cases significantly higher than adeno-associated viruses (AAV)), especially in joints and intervertebral discs. HDAds offer the additional advantage that they can carry up to 30 kilo base pairs of DNA (compare AAV with 2.5-5 kilo base pairs), which enables gene therapy with large genes and combinations of genes.

GeneQuine is working on expanding and modifying its HDAd platform as well as establishing an efficient, large-scale manufacturing process that enables cost-effective production with a low footprint for large markets such as osteoarthritis and intervertebral disc degeneration.

Osteoarthritis

Osteoarthritis is a chronic degenerative joint disorder characterized by cartilage loss, inflammation and pain. Osteoarthritis can affect various joints such as knee, hip, ankle, shoulder, hand and finger joints. GeneQuine is initially focused on patients with osteoarthritis of the knee, who experience joint pain as well as swelling and stiffness of the joints leading to limited joint functionality and impaired mobility. Knee osteoarthritis currently affects approximately 36 million people in the seven largest healthcare markets (USA, Germany, France, UK, Spain, Italy, Japan).

Gene Therapy for Osteoarthritis

Sufficiently high drug concentrations and long-term bioavailability within the joint are two of the major challenges for efficient treatment of osteoarthritis. Both attributes are requisite for sustained efficacy and a disease-modifying effect.

Currently used drugs to treat osteoarthritis as well as most of the investigational drug candidates used in clinical studies are typically chemical or biological substances administered either systemically or by a direct injection into the joint. However, if administered systemically, only small portions of the administered drug reach the joint space. When injected directly into the joint, most active compounds are relatively rapidly cleared from the joint by physiological mechanisms resulting in short dwell times in the joint. Frequently repeated joint injections, however, are not feasible in the long-term treatment of a chronic joint diseases such as osteoarthritis.

A single joint injection of GeneQuine’s gene therapy is expected to establish local long-term production of a therapeutic protein by the joint cells. This way, optimal drug concentrations and long-term bioavailability within the affected joint can be achieved, while exposure of the rest of the body to the drug is minimal. Thus, GeneQuine’s gene therapy is expected to have a sustained symptomatic and disease-modifying effect with a favorable systemic safety profile for the treatment of osteoarthritis.

Intervertebral Disc Degeneration

Chronic low back pain is one of the largest global disease burdens affecting approximately 100 million people in the EU and US. In approximately 34% of the cases, intervertebral disc degeneration is the cause for chronic low back pain, i.e. there are approximately 34 million intervertebral disc degeneration patients. Currently, there are only symptomatic drugs available to treat the pain associated with intervertebral disc degeneration, while end-stage disease often requires surgical interventions.

Gene Therapy for Intervertebral Disc Degeneration

As the intervertebral disc is an essentially avascular tissue, systemically administered drugs cannot efficiently reach the site of degeneration inside affected discs. Therefore, GeneQuine develops a gene therapy drug that is injected directly into affected discs (intradiscal injection). After entering the cells in the disc, these cells are expected to produce therapeutic proteins over a long period as they represent a very stable cell population. This way, the structure of the discs should be improved and pain associated with the degeneration should be alleviated while keeping levels of the therapeutic proteins minimal in the rest of the body.