OR - CQS Virtual Meeting held on 17 June 2020

1. CoVid
&
Immuno-Suppresants
Understand well before
Administration
Life may never come back
What we know, What we don’t know &
How do we know

2. OR
Centre for Quality Sciences ET-WAP
Empirical Therapeutics in War Against Pandemic
Live talk on 17 June 2020, Wednesday in Urdu
10.30 to 11 PM followed by Q & A
What we know, What we don’t know
& How do we know

4. D PT

5. Attack Defense

6. Infection Immunity

7. Arthritis Immunity

8. Immuno-suppresant Drug
Toci-li-zu-mab
(TCZ)
Rheumatoid Arthritis
Systemic Juvenile Idiopathic Arthritis
Humanized MAB block cytokine (Interleukin 6)

9. Small Proteins … Cell Signaling
Includes Chemokines, Interferons,
Interleukins, Lymphokines, Tumor
Necrosis Factor
Produced by B & T lymphocyte
Mast cells, Endothelial cells, Fibroblasts,
Macrophages, Stromal cells
Cytokine

10. Immune response
• Autoimmune disease
• Multiple Myeloma
• Prostate Cancer
Cytokine

11. • Bone macrophogenetic protein to treat
bone related conditions
• Erythropoietin to treat anemia
• Granulocyte Colony Stimulating Factor
(GCSF) to treat neutropenia
• Granulocyte Macrophage Colony
Stimulating Factor (GmCSF) to treat
neutropenia & fungal infections in
cancer patientsCytokine Usage

12. • Interferon alpha used to treat Heaptitis
C & Multiple Sclerosis
• Interferon Gamma used to treat chronic
Granulomotus disease & Osteopetrosis
• Interferon beta used to treat Multiple
Sclerosis
Cytokine Usage

13. • Interleukin 2 used to treat cancer
• Interleukin 11 used to treat
thrombocytopenia in cancer patients
Cytokine Usage

14. Cytokine storm
Dangerous inflammatory immune
response can accelerate damage to
lungs & other organs
EUA – June 04, 2020

15. • WBCs, B cell, T cell, Natural Killer
cell, Macrophage cell, Dendritic cell,
Monocytes are activated and release
inflammatory cytokine
Cytokine Release Storm

16. Immunological &
Inflammatory Reactions
Drug binds IL-6 receptors, hinder
in its inflammatory effects
IL-6

17. 1997 – TCZ developed
2005 – Approved in Japan
2009 – Approved in EMA
2010 – Approved in US-FDA
IL-6 discovered in
Japan – 1980s

18. China used for 21 patients in March
Australia recommended for off-
label use
Italy used for few cases
Randomized studies started
CoVid - 19

19. For 330 patients around the world
… under trial
End point assessing clinical status,
mortality, mechanical ventilation &
ICU Variables in the patient
population
Trial COVACTA

20. Highest risk of upcoming
respiratory failure
IL-6 Elevated

21. Bind with
Soluble & Membrane bound
receptors
69% of 45 patients with life threatening
cytokine release syndrome resolved within
14 days of one or two doses
IL-6
Receptor Antagonist

22. Life threatening matter &
no treatment option
Infections, TB, Immune disorders
Benefit Risk Assessment

23. Serious infections leading to death
Tuberculosis, Bacterial, invasive
fungal, viral & opportunistic
infections
Latent TB test is mandatory
Warning

24. • Patients with chronic or recurrent
infections
• Who have been exposed to TB
• With a history of serious or
opportunistic infections
• Who have resided or traveled in an area
of endemic TB or mycosis
• With underline conditions that may
predispose them to infectionsWeigh the Risk for

25. • Herpes zoster exacerbation observed in
clinical studies
• Uncertainty prevails for hepatitis
patients
Viral Reactivation

26. • Malignancy was observed in clinical
studies
Malignancy

27. • Highly uncertain due to immunological
cross-response
• Dangerous for use of live vaccine
Vaccination

28. B cell chronic lymphocytic
leukemia & RA
Over secretion of Cytokine triggers a
dangerous cytokine storm
6 patients in Phase 1 Trial
London, Parexell , 2006
500 times lower dose safe in animals
Systemic Organ Failure
TGN-1412 – Theralizumab

29. Dexamethasone ……… Another News …. CoVid 19

30. Dexamethasone ……… Another News …. CoVid 19

31. Dexamethasone ……… Another News …. CoVid 19

32. What can be prevented?
From Ventilator From Oxygen
1 out of 8 1 out of 25

33. Thanks