Idorsia Ltd. · SIX:IDIA
Idorsia — Technical Presentation (December 2022)
43 slides from Idorsia's technical presentation, December 2022
Slide 1: Cenerimod investigated for the treatment of patients with systemic lupus erythematosus
Cenerimod investigated for the treatment of patients with systemic lupus erythematosus Investor webcast
Slide 2: Forward-looking statements
The following information contains certain “forward-looking statements”, relating to the company’s business, which can be identified by the use of forward-looking terminology such as “estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “will continue”, “should”, “would be”, “seeks”,
Slide 3: Cenerimod has the potential to modify several inflammatory pathways
“Cenerimod has the potential to modify several inflammatory pathways providing broad immune-modulatory coverage.” Martine Clozel Chief Scientific Officer 3 Phase 3 initiation investor webcast | December 2022
Slide 4: Cenerimod: high S1P1 selectivity and attenuated calcium response
Cenerimod Attenuated calcium response Cenerimod Ca2+ High S1P1 selectivity Selected for development due to unique combination of S1P1 targeting and attenuated calcium response Abbreviations: Ca2+ = calcium ion Cenerimod is investigational, in development and not approved or marketed in any country.
Slide 5: Systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE) 5 Phase 3 initiation investor webcast | December 2022
Slide 6: Symptoms of SLE
Symptoms of SLE Skin: rashes, Fatigue sensitivity to light Liver and Joint and • Tissue damage spleen: enlarged muscles: aches and pains across multiple organ systems Blood and circulation: Nervous • Severe organ swollen glands, poor circulation Lupus system: headaches, damage and in the fingers and
Slide 7: Epidemiology
Epidemiology 5 million people worldwide have a form of lupus 10% male More common in people of Afro-Caribbean and Asian origin compared to 90% Caucasians female Peak incidence between Lupus Foundation of America Center for Disease Control and Prevention 15 and 40 years 7 Phase 3 initiation investor
Slide 8: Lupus is characterized by autoreactive lymphocyte activation and persistent inflammation
Lupus is characterized by autoreactive lymphocyte activation and persistent inflammation T/B-CELL Genetic factors Triggers (e.g., viral) Susceptibility Spread of autoimmunity Autoreactive T and B cells Interferon-driven Asymptomatic Autoantibodies Symptoms Pathogenic inflammation autoantibodies Loss
Slide 9: Cenerimod
Cenerimod Cenerimod is investigational, in development and not approved or marketed in any country. 9 Phase 3 initiation investor webcast | December 2022
Slide 10: Cenerimod inhibits the egress of T and B lymphocytes into the circulation
Cenerimod inhibits the egress of T and B lymphocytes into the circulation S1P S1P1 receptor T/B-CELL Cenerimod T/B-CELL T/B-CELL T/B cells egress T/B-CELL T/B-CELL Lymph nodes Blood S1P gradient Cenerimod is investigational, in development and not approved or marketed in any country. 10 Phase 3 init
Slide 11: Cenerimod is active through several pathways
Cenerimod is active through several pathways T/B-CELL Genetic factors Triggers (e.g., viral) Susceptibility Spread of autoimmunity Autoreactive Interferon-driven T and B cells inflammation Pathogenic Asymptomatic Autoantibodies Symptoms autoantibodies Cenerimod Loss of tolerance QoL impact Organ dam
Slide 12: SLE mouse model
SLE mouse model …inflammation …autoantibodies T cell anti- MRL/lpr mouse IFN-α infiltration dsDNA Spontaneous development of lupus-like multi-organ syndrome. Similarities with human SLE. Model validated with standard of care agents: CTX, DEX, MTX. Increases in… Decreases in… Abbreviations: SLE, syst
Slide 13: Cenerimod treatment reduces T cell infiltration & auto-antibodies
Cenerimod treatment reduces T cell infiltration & auto-antibodies Plasma anti- dsDNA T cell infiltration into kidney antibodies MRL/lpr mouse model; 7 weeks old (n=15) (n=19) (n=14) (n=20) 2.5 at treatment start. Cenerimod 8,000 CD3+ T cell area in kidney tissue (mm2) ~ 20-40 mg/kg in food admix unt
Slide 14: Cenerimod treatment reduces tissue damage & maintains kidney function
Cenerimod treatment reduces tissue damage & maintains kidney function Renal Proteinuria histopathology MRL/lpr mouse model; 7 weeks old (n=14) (n=20) (n=17) (n=20) at treatment start. Cenerimod 1000 Ratio urine albumin/creatinine (mg/mg) ~ 20-40 mg/kg in food admix until pre- 5 defined study endpoin
Slide 15: Cenerimod treatment improves survival
Cenerimod treatment improves survival Survival 100 Cenerimod (n=20) ** 90 Percent survival Vehicle (n=20) Reduced tissue damage & reduced proteinuria 80 Decreased 70% 100% anti- dsDNA biomarkers 70 (14/20) (20/20) IFN-α 60 **p<0.01 (Mantel-Cox test) Improved survival 50 1 2 3 4 5 6 7 8 9 10 11 Treat
Slide 16: Cenerimod
Cenerimod T/B-CELL • Effective on multiple aspects of the lupus pathogenesis Autoreactive • Unique in tackling T cells, B cells, the T and B cells Interferon-driven inflammation IFN related inflammation, and Pathogenic autoantibodies autoantigen transport • Reduces circulating lymphocytes without st
Slide 17: A program designed to provide a more holistic view on patient response
“We have designed a program that has the potential to provide a more holistic view on patient response.” Alberto Gimona Head of Global Clinical Development 17 Phase 3 initiation investor webcast | December 2022
Slide 18: Phase program overview
Phase 1 Phase 2a Phase 2b Phase 3 program study study confirmatory study • Marked and 3 months of treatment: 12 months of treatment: 2 studies sustained lowering • Dose-dependent, sustained • Cenerimod 4 mg showed 1 dose of circulating reduction in circulating clinically meaningful 12 months of lymp
Slide 19: CARE: Phase 2b study
CARE: Phase 2b study Multicenter, randomized, double-blind, placebo- controlled, parallel-group study to evaluate the efficacy and safety of cenerimod for the treatment of adult patients with moderately to severely active, autoantibody-positive SLE Cenerimod is investigational, in development and no
Slide 20: CARE study objectives
CARE study objectives Primary Objective • Assess the efficacy (disease activity) of 6 months cenerimod treatment given at 4 different dose levels in subjects with moderate to severe SLE Secondary Objectives (at Month-6 and Month-12) • Safety and tolerability of cenerimod doses • Effect on quality of
Slide 21: CARE study design
CARE study design Randomization Re-randomization of 4 mg End-of- End-of- 5 groups (1:1:1:1:1) to placebo and 2 mg (1:1) treatment study Cenerimod 0.5 mg Cenerimod 0.5 mg Cenerimod 1 mg Cenerimod 1 mg Cenerimod 2 mg Cenerimod 2 mg Cenerimod 2 mg Cenerimod 4 mg Placebo Placebo Placebo V1 V2 V8 V14 V18
Slide 22: Baseline demographic and disease characteristics
Baseline demographic and disease characteristics Balanced across treatment groups Cenerimod Cenerimod Cenerimod Cenerimod Baseline characteristics 0.5 mg 1 mg 2 mg 4 mg Placebo n=85 n=85 n=86 n=85 n=86 Age, mean ± SD 42.8 ± 12.41 40.0 ± 12.77 42.2 ± 12.06 42.1 ± 10.44 41.0 ± 11.94 Female, n (%) 79 (
Slide 23: Cenerimod 4 mg reduced disease activity
Cenerimod 4 mg reduced disease activity Primary endpoint (reduction in mSLEDAI-2K* at Month 6) LS-Mean change from baseline in mSLEDAI-2K LSM change between cenerimod 4 mg and placebo at Month 6 (95% CI) (means +/- SE) -1.19 (-2.25, -0.12), Efficacy starts at month 2 P=0.0291 and increases over time
Slide 24: Treatment effect is increased in more severe patients
Treatment effect is increased in more severe patients Overall population Anti-dsDNA ≥ 30 IU/ml C4 < LLNR, 4mg only ≥ 10 SLEDAI-2K ≥ 7.5 mg OCS BILAG 1A and/or 2B Cenerimod is investigational, in development and not approved or marketed in any country. 24 Phase 3 initiation investor webcast | Decembe
Slide 25: 50% of CARE population had IFN-1 High status
50% of CARE population had IFN-1 High status CARE study IFN-1 gene expression signature 201 patients (49%) 207 patients (51%) IFN-1 HIGH • 408 patients out of 427 had evaluable IFN-1 status IFN-1 LOW • IFN-1 genes - IFI27 Number of patients - RSAD2 - HERC5 - IFIT1 IFN-1 gene expression score Cenerim
Slide 26: Cenerimod 4 mg reduced disease activity
Cenerimod 4 mg reduced disease activity Primary endpoint (reduction in mSLEDAI-2K* at Month 6) LS-Mean change from baseline in mSLEDAI-2K at 6 months 0 -2 -4 -2.85 -4.04 -6 -8 Δ = -1.19 Placebo Cenerimod 4 mg (n=77) (n=77) Overall population Cenerimod is investigational, in development and not appro
Slide 27: Cenerimod 4 mg reduced disease activity
Cenerimod 4 mg reduced disease activity Primary endpoint (reduction in mSLEDAI-2K* at Month 6) LS-Mean change from baseline LS-Mean change from baseline in mSLEDAI-2K at 6 months in mSLEDAI-2K at 6 months 0 0 -2 -2 -4 -2.85 -4 -2.62 -4.04 -6 -6 -5.41 -8 Δ = -1.19 -8 Δ = -2.79 Placebo Cenerimod 4 mg
Slide 28: SRI-4 response was consistent with mSLEDAI-2K
SRI-4 response was consistent with mSLEDAI-2K Secondary endpoint SRI-4 response at 6 months (%) 80 70 60 53.2 50 44.2 40 30 20 10 0 Placebo Cenerimod 4 mg (n=77) (n=77) Overall population SRI-4 response is defined as a response of all three components: • mSLEDAI-2K (reduction from baseline ≥4) BILAG
Slide 29: SRI-4 response was consistent with mSLEDAI-2K
SRI-4 response was consistent with mSLEDAI-2K Secondary endpoint SRI-4 response at 6 months (%) SRI-4 response at 6 months (%) 80 80 69.7 70 70 60 53.2 60 50 44.2 50 45.7 40 40 30 30 20 20 10 10 0 0 Placebo Cenerimod 4 mg Placebo Cenerimod 4 mg (n=77) (n=77) (n=35) (n=33) Overall population IFN-1 hi
Slide 30: Cenerimod reduced the SLE hallmark biomarker anti-dsDNA in blood
Cenerimod reduced the SLE hallmark biomarker anti-dsDNA in blood Cenerimod reduced blood anti-dsDNA levels (median% change to baseline) IFN-1 High IFN-1 Low 0 0 Median % change from baseline -10 -10 in anti-dsDNA (%) -20 -20 -30 -30 -40 -40 Baseline Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Ba
Slide 31: Overview of adverse events
Overview of adverse events Onset during 6-month treatment Cenerimod 0.5 mg Cenerimod 1 mg Cenerimod 2 mg Cenerimod 4 mg Placebo Subjects with at least one N=85 N=85 N=86 N=84 N=86 n (%) n (%) n (%) n (%) n (%) Adverse event (AE) 42 (49.4) 55 (64.7) 51 (59.3) 49 (58.3) 47 (54.7) AE leading to study d
Slide 32: Areas of special interest
Areas of special interest 6-month treatment • First dose effect: comparable to other S1P modulators but no need for up-titration − at 4 mg maximum average effect of ~ −9 bpm at 6 h post-dose − Two 2nd degree AV block (1 mg and 4 mg) – transient and no therapeutic intervention required • Opportunisti
Slide 33: Safety at 12 months
Safety at 12 months Cenerimod Cenerimod Cenerimod Cenerimod Ex- 4 mg 0.5 mg 1 mg 2 mg N=84 Placebo n=84* n=85 n=87* n (%) n=86 Treatment-emergent AEs, n (%) 53 (63.1) 70 (82.4) 68 (78.2) 66 (78.6) 61 (70.9) Treatment-emergent SAEs, n (%) 4 (4.8) 12 (14.1) 4 (4.6) 3 (3.5) 6 (7.0) AEs leading to study
Slide 34: CARE delivered according to promise
CARE delivered according to promise • Clinically meaningful improvement in disease 4 mg cenerimod activity selected for Phase 3 − Treatment effect increases over time Potential to be the − Treatment effect is increased in patients with greater disease severity and high IFN-1 gene first new generatio
Slide 35: OPUS: Phase 3 confirmatory program
OPUS: Phase 3 confirmatory program (Oral S1P1 Receptor ModUlation in SLE) Cenerimod is investigational, in development and not approved or marketed in any country. 35 Phase 3 initiation investor webcast | December 2022
Slide 36: OPUS: Confirmatory program design
OPUS: Confirmatory program design Two Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies to evaluate the efficacy, safety, and tolerability of cenerimod in adult patients with moderate-to-severe SLE on top of background therapy Open-label extension Randomizatio
Slide 37: Target patient population
Target patient population • Moderate-to severe SLE • Approximately 80% patients with IFN-1 high signature • Treatment allocation will be stratified by: − OCS therapy : < 10 mg/day or ≥ 10 mg/day prednisone (or equivalent) at Randomization, AND − IFN-1 gene expression signature : IFN-1 high or IFN-1
Slide 38: OPUS: Primary objective
OPUS: Primary objective To evaluate the effectiveness of cenerimod 4 mg at reducing disease activity compared to placebo Primary efficacy endpoint • Change from baseline to Month 12 in the mSLEDAI-2K score Secondary efficacy endpoint • Response on SRI-4 at Month 12 compared to baseline Cenerimod is
Slide 39: OPUS: Secondary objective
OPUS: Secondary objective To evaluate the effect of cenerimod 4 mg to control the disease compared to placebo Secondary endpoints • Time to first confirmation of a 4-month sustained mSLEDAI 2K response • Time to first confirmation of a 4-month sustained response in mucocutaneous manifestations (i.e.
Slide 40: Sustained mSLEDAI-2K response, exploratory endpoint
Sustained mSLEDAI-2K Exploratory endpoint IFN-1 high signature Time to first confirmation of a 4-month sustained response Probability of first sustained mSLEDAI-2K response up to Month 12. A sustained response being defined as 4 consecutive monthly assessments with a mSLEDAI-2K response (ie. Reducti
Slide 41: Integrating patient voices
Integrating patient voices Exploratory analysis • Phase 3 study design developed collaboratively with a council of 6 patients associations from the US, Europe, Asia, and Latin America • Treating symptoms that matter the most to patients: − Patient will indicate the symptom of most concern among myos
Slide 42: Alopecia – SLEDAI 2K
Alopecia – SLEDAI 2K Resolution of Alopecia at 6 months Responders at 6 months (%) • 70% of patients had alopecia at baseline Placebo (n=62) 11.30% • 3 times more patients treated with 4 mg had Cenerimod 4 mg (n=60) 31.70% resolution of alopecia compared to placebo Cenerimod is investigational, in d
Slide 43: Cenerimod for systemic lupus erythematosus
Cenerimod for systemic lupus erythematosus Selective sphingosine-1-phosphate 1 (S1P1) receptor modulator First oral immune-modulator active on both B and T cells could represent a novel approach to the treatment of SLE • CARE allowed us to define: − Patient population that benefits most − Most effec