1. The immune response CRO
Founded in 2016
Location
BioHub at Alderley Park (UK)
Management Team
Dr. Ir. Robert-Jan Lamers
Dr. Masih Alam

2. OUR BUSINESS
A CRO offering specialised lab services in the field of immunology:
General immune and bio-analysis of drugs in discovery and research
Immunogenicity analysis - preclinical in vitro human
immune analysis of drugs
TARGET CLIENT GROUPS
Drug Discovery Companies
Research Institutions
CROs for drug analysis

3. General immune analysis
Immunity assays
Cytokines, growth factors or antigen-specific detection
Cell mediated immunity
FACS, ELISA
Molecular assays
Histopathology
Microscopy and imaging
Animal models and animal based immunology
Immune Modelling – experimental designs
Mass spectrometry

4. SCOPE – Immunogenicity of drugs
Translation from preclinical (animal) studies to humans (clinical trials) needs urgent improvement >> demands preclinical human systems
Immune response (immunogenicity) can be caused by a drug but also by drug-induced tissue damage
Any drug molecule has the potential to cause unwanted tissue damage
Current immunological risk (immunogenicity) assessment does not include immune response against tissue damage, causing unsafe drugs being tested in clinical studies or even being used in treatment
This is a gap in the market!
This is the scope for novel in vitro human immune analytical systems.

5. Drug Induced Secondary Disease
Common but currently outweighed due to benefits of ‘risk’ drugs:
Neuropathy (idiopathic neuropathy)
Interstitial Lung Disease (DI-ILD)
Vasculitis
Drug Induced Lupus (DIL)
Immune Thrombocytopaenia
Immune based demyelination
Myopathy
>300 drugs are reported to cause DI-ILD (example)
>2 million cases of adverse drug reactions in the US annually including 100,000 deaths
250,000 cases of hospital admissions in the UK annually
€430M could be saved in the Netherlands if side effects are reduced

6. Our approach: COMPIT – A NOVEL UNIQUE SYSTEM
In vitro human immune model
Cell culture systems adapted to test drug-induced damage
Focused on novel biomarkers for immune response due to (drug- induced) tissue damage using cutting edge analytics (patent foreseen)
Incorporates mathematical system to score immunological risk and predict secondary pathology (patent foreseen)
Fits in preclinical studies

7. Preclinical studies: where does COMPIT fit?
In vitro studies
In vivo studies
COMPIT
COMPIT
General Characterisation
Immune Response
against drug and drug-induced tissue damage
N O A E L
Toxicological
studies
Pharmacological
studies
Mid Dose
M T D
Receptor characterisation
Binding assays
Enzyme inhibition
Cytotoxic activity
Immunological Safety
Safety
Efficacy
Immunological Safety
(Potential)
Inhibition of Danger Signals
Dose conversion

8. Fields of application COMPIT can be applied to Small molecules
Large molecules
Generics and biosimilars
Potentially predictive (preclinical) of ADA development
Particularly the research and development of large molecules is evolving and expanding worldwide >> requiring more immune response analysis
Regulatory Bodies increasingly seeking/advising analysis of safety based on new immune markers – these are included in COMPIT

9. Diffuse Alveolar Damage
Example for drug induced interstitial lung disease
Non Target Tissue
Tissue Damage
Pathology
Disease
Amiodarone
Target tissue cardiac but ……..
ROS – oxidative stress
Metabolites – interference with tissue
Modification of cell biochemistry e.g. covalent binding
ATP depletion or Loss of Ca++ homeostasis
Damaged mitochondria – increased cell permeability
PNEUMOCYTES
Epithelial cells
via
Inhalation or
Circulation
Inflammation
Alveolar and Bronchial area
Dysfunction/Death of Cells
Apoptosis to Necrosis
Compromised Alveolar Wall
Hyaline + Protein rich Exudate in Alveolar Space
Diffuse Alveolar Damage or
Organising Pneumonia
Hyaline
FIBRIN
Reactive epithelial cells
Danger mediated
antigen processing
PROGRESSIVE
IMMUNE RESPONSE
Scarring
Immune mediated damage + phagocytosis
Maturation and immune response generated
More examples:
Bleomycin
Amphotericin B
Rituximab
Nitrofurantoin
Lung Fibrosis
DI ILD
COMPIT ANALYSIS OF DAMAGE AND IMMUNOGENICITY

10. Benefits – Unique Buying Points
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 and make non-viable drugs accessible to patients
Meeting changes to expected regulatory requirements on safety

11. Why?
FDA 2014 guideline for ‘Immunogenicity Assessment for Therapeutic Protein Products’ mentions issues related to tolerance to endogenous proteins and autoimmunity through immune response against endogenous proteins
Latest version of EMEA guideline on immunogenicity assessment of biolotechnology derived therapeutic proteins mentions “while most effort is usually focused on antibody detection and characterisation as this is often related to clinical safety and efficacy, cell-mediated responses are also important and their assessment may be considered by applicants”
EMEA meeting (January 2016) “…. a highly interesting and important platform for pharma and biotech companies that meets an urgent demand”
Experienced in immunology and analytical chemistry
Access to high-end facilities, professionals and network through location at BioHub campus

12. Projects for PhD placements
You can work in our lab in the COMPIT project through and 2018 if your experience fits the requirement of the post
3 month placement period
You will need to bring your own funding for living and travel
Work location is Alderley Park near Macclesfield. You will be in a large campus where there are many other companies (mostly discovery and CROs involved in the drug industry)

13. Project 1: Tissue Modelling
Purpose:
Develop and maintain 3D tissue systems, organoids
Use of hydrogels/matrigels and specialised tissue growing wells.
3 month duration
Period Sep – Nov 2017 or any other time
Location: BioHub, Alderley Park
Skills & Learning:
Cell culture, mammalian cells
2D and 3D systems, organoids
Primary and established cells, Stem cells, media preparation
Histology, microscopy and imaging

14. Project 2: Assay Development
Purpose:
To extract and measure immunogenic particles from damaged tissue in culture.
Use of Mass Spec and immunologic assays for analysis.
3 month duration
Period Sep – Nov 2017 or any time after that
Location: BioHub, Alderley Park
Skills & Learning:
Cell culture
Protein identification and quantification
Western blotting, ELISA, MS, RNA methods
Experimental designs

15. Project 3: Bio analysis Purpose: Skills & Learning:
Assess the immunologic events that follow the tissue damage leading to an immune activation
Use of biomolecular and immunologic assays for analysis.
3 month duration
Period Jun – Aug 2018
Location: BioHub, Alderley Park
Skills & Learning:
Cell culture, tissue, lymphocytes
Protein identification and quantification
Western blotting, ELISA, Flow Cytometry, immunohistochemistry
Experiment designs
Statistics

16. Project 4: Cell Interactions
Purpose:
Design and maintain experiments that allow interaction of lymphocytes with damaged tissue
Use of general and customised cell culture systems
3 month duration
Period Sep-Nov 2017 and periods in 2018
Location: BioHub, Alderley Park
Skills & Learning:
Cell culture, tissue, lymphocytes
Cell migrations
2D and 3D cells, organoids
Microscopy and imaging
Experiment designs

17. Project 5: Mathematical Model
Purpose:
Assimilating and analysing data from cell culture studies for determining immune response scores. This will be crucial to validating the COMPIT system for preclinical immune response analysis.
Use of mathematical model designed by Chester University for translating experimental data.
3 month duration
Period Jun – Aug 2018
Location: BioHub, Alderley Park
Skills & Learning:
Mathematical modelling in biological experiments
Statistics
Understanding of cell based biological experiments and cellular pathways.
Experimental designs
Overview of drug toxicology and preclinical studies

18. My Contact DR. MASIH ALAM IMMUNOSYS LTD IMMUNDNZ LTDE.