Kiniksa Pharmaceuticals International, Plc · NASDAQ:KNSA
Kiniksa Pharmaceuticals International — Technical Presentation (2024)
18 slides from Kiniksa Pharmaceuticals International's technical presentation, Nov 21, 2024
Slide 1: Efficacy, Safety, Pharmacokinetics of Anti-CD40 Antibody Abiprubart in Rheumatoid Arthritis
Efficacy, Safety, Pharmacokinetics of Anti- CD40 Antibody Abiprubart in Patients with Rheumatoid Arthritis: a Phase 2, Randomized, Placebo-Controlled 12-week- treatment Proof-of-Concept Study Eric Jenkins1, Ingrid Louw2, Attila Balog3, Elsa Van Duuren4, Diane Horowitz5, Janusz Jaworski6, Alan Kivitz
Slide 2: Disclosure
Disclosure I have the following relevant financial relationship to disclose: o Shareholder and employee of Kiniksa Pharmaceuticals In accordance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education, ACR has implemented mechanisms prior to the planning and impl
Slide 3: Learning Topics
Learning Topics By the end of this presentation, audience members will be able to: • Understand the mechanism of action for abiprubart • Describe the study design and enrolled population of the phase 2 trial of abiprubart in rheumatoid arthritis • Understand the clinical efficacy of abiprubart in rh
Slide 4: Mechanism of Action and Phase 1 Evidence
Mechanism of Action and Phase 1 Evidence
Slide 5: CD40/CD154 Interaction: Essential Immune Pathway for T-Cell Priming and B-Cell Responses
CD40/CD154 Interaction: Essential Immune Pathway for T-Cell Priming and T-Cell Dependent B-Cell Responses • CD40/CD154 interaction is implicated in a range of autoimmune diseases • Abiprubart (KPL-404): o Humanized monoclonal IgG4 antibody o Stabilized/functionally-silent Fc region o Binds to CD40 a
Slide 6: Abiprubart Demonstrated Prolonged TDAR Suppression in Phase 1
Abiprubart Demonstrated Prolonged TDAR Suppression in Phase 1 • Phase 1 SAD study in healthy participants1 o Abiprubart was well tolerated o Dose-dependent duration of full CD40 target engagement o Sustained dose-dependent TDAR suppression with both SC and IV administration • High-concentration liqu
Slide 7: Abiprubart Phase 2 Rheumatoid Arthritis Study Design
Abiprubart Phase 2 Rheumatoid Arthritis Study Design
Slide 8: Global Phase 2 Trial of Abiprubart in Rheumatoid Arthritis
Global Phase 2 Trial of Abiprubart in Rheumatoid Arthritis PATIENT POPULATION: PHARMACOKINETICS (PK) LEAD-IN PROOF-OF-CONCEPT • Active RA; bDMARD Cohort 3 AND/OR JAKi therapy for Abiprubart Cohort 4 ≥ 3 months with 5 mg/kg SC qwk inadequate response or Cohort 2 Abiprubart discontinued due to 400 mg
Slide 9: Results of Abiprubart Phase 2 Rheumatoid Arthritis Trial
Results of Abiprubart Phase 2 Rheumatoid Arthritis Trial
Slide 10: Select Baseline Demographics And Disease Characteristics
Select Baseline Demographics And Disease Characteristics Cohort 31 Cohort 41 Abiprubart Abiprubart Placebo Abiprubart Placebo 5 mg/kg SC qwk 5 mg/kg SC q2wk 400 mg SC q4wk (n=27) (n=25) (n=26) (n=31) (n=20) Baseline Demographics Mean Age, years 58.5 (9.7) 60.0 (10.1) 57.6 (9.9) 58.8 (9.5) 58.3 (11.8
Slide 11: Phase 2 Trial of Abiprubart in RA Met Primary Efficacy Endpoint
Phase 2 Trial of Abiprubart in RA Met Primary Efficacy Endpoint Change from Baseline in DAS28-CRP vs Placebo at Week 12 Cohort 1 & 2 Cohort 3 Cohort 4 DAS28-CRP Mean Change from Baseline1* DAS28-CRP LS Mean Change from Baseline1,2* DAS28-CRP LS Mean Change from Baseline1,2* 0.5 0.5 0.5 LS Mean Chang
Slide 12: Pharmacodynamics & Pharmacokinetics: Similar Reductions in Rheumatoid Factor at all SC Dose Intervals
Pharmacodynamics & Pharmacokinetics: Statistically Significant Similar Magnitude Reductions in Rheumatoid Factor at all SC Dose Intervals RF is primarily an IgM autoantibody which not only serves as a disease marker but also provides a mechanism-related PD marker of anti-CD40 target engagement Abipr
Slide 13: Pooled Analysis: Abiprubart Significantly Reduced DAS28-CRP Over Time
Pooled Analysis: Abiprubart Significantly Reduced DAS28-CRP Over Time Pooled Cohorts 3 & 4 DAS28-CRP LS Mean Change from Baseline1 0.5 LS Mean Change DAS28-CRP (±SE) 0.0 Pooled abiprubart (n=83) Pooled PBO (n=46) -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 On Treatment Washout -4.5 0 2 4 8 12 14 16 20 2
Slide 14: Abiprubart was Well-Tolerated - No Dose-related Adverse Experiences
Abiprubart was Well-Tolerated - No Dose-related Adverse Experiences Cohort 31 Cohort 41 Category2 Abiprubart Abiprubart Placebo Abiprubart Placebo 5 mg/kg SC qwk 5 mg/kg SC q2wk 400mg SC q4wk (n=27) (n=25) (n=26) (n=31) (n=20) Treatment Emergent Adverse Events 44.4 (n=12) 24.0 (n=6) 30.8 (n=8) 29.0
Slide 15: Ongoing Phase 2b Study in Sjögren's Disease
Ongoing Phase 2b Study in Sjögren’s Disease
Slide 16: The CD40/CD154 axis may play a central role mediating SJD pathology
The CD40/CD154 axis may play a central role mediating SJD pathology Abiprubart is likely to disrupt co-stimulation and the disease supporting role of salivary gland stromal cells SJD pathogenesis involves multiple factors1-3 • Autoreactive B and T cells escape regulatory suppression • Salivary epith
Slide 17: Ongoing Phase 2 Trial of Abiprubart in Sjögren's Disease
Ongoing Phase 2 Trial of Abiprubart in Sjögren’s Disease PATIENT POPULATION • Diagnosis of Sjögren's Disease according to 2016 ACR-EULAR Classification Criteria • ESSDAI value ≥ 5, counting only the biological, hematological, articular, cutaneous, glandular, lymphadenopathy, and constitutional organ
Slide 18: Key Takeaways
Key Takeaways • Phase 2 RA study met its primary efficacy endpoint o In refractory RA patients, abiprubart treatment resulted in a statistically significant reduction in DAS28-CRP at Week 12 vs. placebo in the 5mg/kg SC weekly dosing group • Comparable activity across weekly, biweekly, and monthly d
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