Viatris Inc. · NASDAQ:VTRS
Viatris — Technical Presentation (May 2024)
17 slides from Viatris's technical presentation, May 2024
Slide 1: Cenerimod - SLE EULAR Presentation May 2024
DRAFT Cenerimod - SLE EULAR Presentation May 2024 For internal use, education and training purposes only. Do not duplicate, distribute or use when detailing. This document contains confidential and proprietary This document contains proprietary information of Viatris Inc. Unauthorized use, duplicati
Slide 2: Pharmacodynamic effects of the selective S1P1 receptor modulator cenerimod on the blood transcriptome of patients with SLE
Pharmacodynamic effects of the selective S1P1 receptor modulator cenerimod on the blood transcriptome of patients with SLE Daniel Strasser, Madeleine Suffiotti, Pijus Brazauskas, Aaron Hart, Marianne Martinic, Thomas Hoyler, Gustavo Seifer, Ouali Berkani, Peter Cornelisse, Mark Murphy Idorsia Pharma
Slide 3: Conflict of Interest declaration
Conflict of Interest declaration Daniel Strasser is an employee of Idorsia Pharmaceuticals Ltd.
Slide 4: SLE - a molecularly heterogeneous disease
SLE - a molecularly heterogeneous disease • SLE is a clinically and molecularly heterogeous autoimmune disease. • The IFN-1 molecular endotype is recognized as an important SLE patient subgroup. • IFN-1 high patients present with an increased incidence of clinical manifestations such as arthritis1,
Slide 5: Cenerimod: Next generation highly selective S1P1 receptor modulator with a novel MoA for SLE
Cenerimod: Next generation highly selective S1P1 receptor modulator with a novel MoA for SLE S1P via the S1P1 receptor regulates key pathogenic processes in SLE1 − T and B cell egress from lymphoid organs − Inflammatory response − Antigen transport into lymphoid organs References: 1Burg N, Nat Rev I
Slide 6: Phase 2b Clinical Study (CARE)
Phase 2b Clinical Study (CARE) Cenerimod 4 mg improved clinical score in patients Cenerimod decreased IFN-1 gene with SLE expression in IFN-1 high and low patients P < 0.001 P < 0.001 SRI-4 response(1) at 6 months (%) [change from baseline to 6 months] IFN-1 gene expression score IFN-1 status Refere
Slide 7: Objective
Objective Explore the pharmacodynamic effect of 2 mg and 4 mg cenerimod in the whole blood transcriptome in samples from the phase 2b clinical trial (CARE – NCT03742037) in adult subjects with moderate to severe SLE concurrently receiving background therapy.
Slide 8: Methods
Methods • Peripheral blood samples from patients with SLE participating in the CARE study were collected at baseline and after 6 months of treatment with cenerimod. • Gene expression was quantified by qPCR and total RNA sequencing (RNAseq). Baseline 6 months Placebo (n=86) Cenerimod 2 mg (n=86) Cene
Slide 9: IFN-1 score (RNAseq)
IFN-1 RNAseq score correlates with qPCR score (DxTerity) and protein IFN-a levels IFN-1 RNAseq score correlates with qPCR score (A) IFN-1 RNAseq score is significantly decreased in and IFN-a protein levels (B) the 4 mg cenerimod dose Placebo Cenerimod Cenerimod A) B) 2 mg 4 mg P < 0.001 IFN-1 score
Slide 10: IFN-g score (RNAseq)
Cenerimod 4 mg reduces IFN-g RNAseq score and IFN-g pathway protein levels Cenerimod 4 mg reduces the IFN-g Cenerimod 4 mg reduces protein IFN-g and downstream signature score target of IFN-g (IL12) particularly in IFN-1 high patients Placebo Cenerimod Cenerimod 2 mg 4 mg IFN-g Il12p70 [change from
Slide 11: Plasma cell xCell enrichment score
Cenerimod 4 mg shows the most pronounced reduction on plasma cells Cenerimod 4 mg reduces the plasma cell RNAseq Cenerimod 4 mg reduces the plasma cell score to a greater extent than 2 mg cenerimod inferred abundance Placebo Cenerimod Cenerimod 2 mg 4 mg Placebo Cenerimod Cenerimod P = 0.018 2 mg 4
Slide 12: xCell enrichment score
Cenerimod 4 mg shows the most pronounced reduction on inferred T cells abundance Total memory CD4+ T cells Naive CD8+ T cells Central memory CD8+ T cells Placebo Cenerimod Cenerimod Placebo Cenerimod Cenerimod Placebo Cenerimod Cenerimod 2 mg 4 mg 2 mg 4 mg 2 mg 4 mg P < 0.001 P < 0.001 P < 0.001 P
Slide 13: Cenerimod – Mechanism of Action
Cenerimod – Mechanism of Action Immunomodulation
Slide 14: Conclusion
Conclusion These results confirm the S1P1-dependent immunomodulatory properties of cenerimod and demonstrate that the 4 mg dose consistently reduced the investigated disease-relevant pathways. The efficacy and safety of 4 mg cenerimod is under evaluation in two Phase 3 clinical studies for SLE (OPUS
Slide 15: Acknowledgments
Acknowledgments • CARE study patients • Idorsia Pharmaceuticals Ltd. • Viatris Innovation GmbH For more information please visit: • Poster 1408 in session poster view VIII on Saturday – Targeting Key Components of SLE pathogenesis with the multifaceted Immunomodulatory properties of cenerimod • Boot
Slide 16: EULAR Poster May 2024
DRAFT Cenerimod - SLE EULAR Poster May 2024 For internal use, education and training purposes only. Do not duplicate, distribute or use when detailing. This document contains confidential and proprietary This document contains proprietary information of Viatris Inc. Unauthorized use, duplication, di
Slide 17: Targeting Key Components of SLE
Objectives Targeting Key We combine results from Methods A murine model of SLE (MRL/lpr mice) and a proof-of-mechanism murine model for antigen Results In rodent disease models, cenerimod reduced the migration of dendritic cells to the draining lymph preclinical and clinical studies node, which was