Can we avoid TeGenero-like scenarios and be better prepared rather than waiting for dangerous and disastrous outcomes to happen in the clinical phase?
Immundnz can generate more critical information on drug immune safety in the preclinical phase that could be essential in the success of the drug. Our unique service COMPIT, Comprehensive in vitro human Immune Testing, has been designed to enable preclinical in vitro testing of drugs for an in depth immunogenicity analysis – currently which is not offered by other established analytical systems. The system is based on the central dogma of immunology and the immune response against ‘Tissue Damage’. It merges cutting-edge immune response testing, 3D tissue models and ultrasensitive analytical assays. COMPIT outperforms current immune response testing and is complementary to current information obtained from preclinical studies.
Much more than just antigenicity and ADAs
Contrary to the current perception of immunogenicity of drugs, Immundnz brings a disruptive method in the understanding and practice of the term. Conventionally, with the testing of ADAs the definition and perception of Immunogenicity in the drug industry is limited to the ‘antigenicity’ of a drug only. Immunogenicity is a much more complex issue. In current immunology, the ‘self and non-self’ is a redundant issue and anything that can cause an immune response is immunogenic. A drug can be immunogenic by causing tissue damage and providing grounds for immunity against the tissue rather than the drug. This is most likely the underlying mechanism of most drugs that cause autoimmunity and other secondary diseases. Conventional toxicology testing takes into account acute toxic damage and ignores moderate immune responses that might have pathological impact through progressive and chronic development.
Drug Induced Secondary Pathology
There are many drugs in the market that are known to cause secondary disease. In many cases it is not known why the secondary adverse effect happens. The use of these drugs, in some cases on a wide scale, is due to their greater benefit of curing a life threatening condition. Autoimmunity is a common secondary pathology, and drug induced lupus (DIL) accounts for 10% of all lupus incidences. A few examples of drug side effects are given here:
- Penicillin – autoimmune haemolytic anaemia
- Amiodarone – interstitial lung disease
- Adalimumab – DIL, vasculitis
- Erythropoietin – red blood cell aplasia, ADA
- Pegferon- hyperthyroidism
- Carbamezepine – DIL
What COMPIT Does
COMPIT is a system of biological and analytical assays that combines novel cell lines, 3D scaffolds and primary cells to deliver an in vitro human cell-based immune system that recapitulates the in vivo human microenvironment. It can be used during preclinical development to assess drug-induced tissue damage and immunogenicity and to predict the human immune response as a result of a drug and drug-induced tissue damage. COMPIT fits into the current scheme of preclinical studies.
Please contact us for more information.
The COMPIT Process
The COMPIT process begins with assessing drug-induced tissue damage in various human tissue models. Sequentially the system analyses various specific markers associated with the immune response against tissue damage and combines the immune maturation analysis to obtain a comprehensive immune response profile. COMPIT incorporates a mathematical system to score immunological risk and predict secondary pathology.
COMPIT can be applied to:
- Small molecule drugs
- Large molecule drugs
- Generics and biosimilars
Particularly the research and development of large molecules is evolving and expanding worldwide and requires a better and more in-depth insight into the human immune response.
COMPIT has several benefits:
- Prediction of immune-mediated adverse drug reaction and avoiding risk in clinical phase
- Better translation from preclinical studies to humans
- Reduction of the number of animal tests
- A more robust and comprehensive immunologic profile: improved safety and risk prediction thus reducing human health hazard risk
- Drug development can be terminated before costly advanced stages of drug development: reduced investments in non-viable drugs and reduced attrition rate
- Potential to improve drugs, generate blocking agents against immune effectors and make non-viable drugs accessible to patients
- Meeting changes to expected regulatory requirements on safety