How Asthma went from general to personalized approaches

1. Ahmed Abouelnour
Asthma Drug Developments
From Generalized to Personalized

2. Ahmed Abouelnour
Topics
1. Asthma overview & Pathophysiology.
2. Generalized Targets.
3. Generalized Targets Developments Strategies.
4. Limitations to Generalized Targets.
5. Asthma Pathophysiology Development (TH2).
6. First Degree Personalization.
7. Second Degree Personalization
8. Conclusion.

3. Ahmed Abouelnour
1-Asthma Overview &
Pathophysiology.
• Chronic inflammatory disorder of the causes symptoms which are
usually associated with widespread, but variable, airflow obstruction
that is often reversible either spontaneously or with treatment. causes
wheeze, cough, chest tightness, and breathlessness (dyspnoea) (1)
• Affected about 235 m people around the world.
• Intrinsic (Non Allergic) or Extrinsic (Allergic).
• Pathophysiological Pathway discovery developed over last decades
advancing the targets and strategies of drug discovery.

4. Ahmed Abouelnour
2- Generalized Targets
• Based on simple asthma pathophysiological mechanism of mast
cells degranulation.
Binds to Degranulation
Histamine & Arachedonic Acid
Lipoxyginase
Leukotrienes
Bronchoconstriction
1- Mast cell Stabilizers (Cromoglycate).
2-Anti Histaminic.(Loratidine)
3- (5) Lipoxiginase inhibitors.(Zeluton)
4-Leukotrienes Receptors Antagonists.(Motelukast)
5-Bronchodilators.(B Agonists-Methylxanthine Der.-Anticholinergics)
6-Glucocorticoids (Bechlomethasone-Fluticasone)

5. Ahmed Abouelnour
2- Generalized Targets
Bronchodilators
Muscarinic
Antagonists
B2 Agonists
Methylxanthine
derivatives

6. Ahmed Abouelnour
2- Generalized Targets
6-Glucocorticoids (Bechlomethasone-Fluticasone)

7. Ahmed Abouelnour
3- Generalized Targets
Developments Strategies
No Strategy Example
1 Increase duration of action for
the same target
-B2 Agonists from short acting to long
acting.(Bambuterol-Salmetrol-
Fenoterol)
2 Increase Selectivity to
receptor
-Muscarinic M3 antagonists
(Ipratropium to Tiotropium)
3 Targeted Formulations
(decrease side effects)
-Inhaled Glucocorticoids.
-B2 Agonists Inhalations
4 Combinations products B2 Agonists & Glucocorticoids
(Salmetrol+Fluticasone)

8. Ahmed Abouelnour
4-Limitations to Generalized
Targets
FCMR734 Researching Contemporary Issues in Complementary Medicine
• Possible Side effects (Corticosteroid)
• Response Variability &Heterogeneity. (Genetic Environmental&
Character).
• Pathophysiology Mechanism Developments.

9. Ahmed Abouelnour
5-Asthma Pathophysiology
Development (TH2).
1- What’s
developed?
2-Where to
target?
3-Heterogenity?

10. Ahmed Abouelnour
6-First Degree Personalization
Omalizumab (Xolair®) :
1-IgE monoclonal antibody.
2- ↓ Asthma exacerbations greater when subanalyzed by type 2–high
phenotypes (↑ FENO levels, blood eosinophil counts, or serum periostin
levels)-Biomarker.

11. Ahmed Abouelnour
7-Second Degree Personalization
Lebrikizumab :
1-IL 13 monoclonal antibody.
2- ↑ FEV1; greatest clinical benefit when subanalyzed by type 2–high
phenotypes (↑ periostin and sputum IL-131).

12. Ahmed Abouelnour
7-Second Degree Personalization
• Other monoclonal Ab are being developed targeting:
1. IL-5 (mepolizumab) .
2. IL-4 (pitrakinra)
3. Thymic stromal lymphopoietin.
• Biomarker Identification & Regulatory Challenges for IVD and
product approval.

13. Ahmed Abouelnour
8-Conclusion
• Generalized ttt of Asthma is moving to personalized.
• Heterogeneous concept of Asthma is widely being recognized.
• Th2 cycle targets is under vigorous investigation via many
Monoclonal Ab.
• Biomarkers identification & Validation remain a challenge.
• Companies Strategies.

14. Ahmed Abouelnour
Thank You.
Q&A

15. Ahmed Abouelnour
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