American Thoracic Society - Sanofi Investor Call
sanofi
SAR 765: IL-13/TSLP bispecific shows potential to break
efficacy ceilings in type 2 Inflammation and beyond
Type 2 inflammation1-3
.
Mainly driven by IL-4, IL-5 and IL-13
Drives IgE synthesis, eosinophil recruitment, and
FeNO production, indicating nitrosative/oxidative
stress
NO❤
2022
2023
SAR'765 vs. PLACEBO
Phase 1b
•
Phase 1b-Proof of
mechanism in Asthma
Mild/moderate asthma
with elevated FeNO
Respiratory
epithelium
TSLP
-TARC
¡NOS*
Dendritic cell
Th2 cell
IL-5
IL-4, IL-13
Eosinophil
*INOS activation may also be driven by
non type 2 inflammation e.g. in sepsis
•
Single dose (400 mg vs
placebo) SC
•
N=36 (2:1)
Bispecific NanobodyⓇ VHH against both TSLP and IL-13
Potential to benefit from combined approach
- anti-TSLP therapy is effective in reducing exacerbations in
asthma with type 2 and non-type 2 inflammation4-7;
-
anti-IL-13 therapy has mixed effects on exacerbations, but
improves lung function and reduces fractional
exhaled nitric oxide8-12
1. Ziegler, S, et al. Nat Immunol. 2006;7:709-14;
2. Ricciardolo FL, et al. Allergol Immunopathol (Madr). 2015;43:609-16;
3. Munakata M. Allergol Int. 2012;61:365-72, 4. Gavreau GM, et al NEJM. 2014;370:2102-10; 5. Corren JC, et al. NEJM.
2017;377:936; 6. Menzies-Gow A, et al. NEJM. 2021;384:1800-09; 7. Weschler M, et al. Lancet Respir Med. 2022;10:650-60; 8. Corren JC, et al. NEJM. 2011;365:1088-98; 9. Austin CD, et al. Clin Exp Allergy. 2020;50:1342-51; 10. Hanania
NA, et al. Thorax. 2015;70:748-56; 11. Panettieri RA, et al. Lancet Respir Med. 2018;6:511-25; 12. Russell RJ, et al. Lancet Respir Med. 2018;6:499-510
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