Kiniksa Pharmaceuticals International, Plc · NASDAQ:KNSA
Kiniksa Pharmaceuticals International — Investor Presentation (May 2021)
120 slides from Kiniksa Pharmaceuticals International's investor presentation, May 2021
Slide 1: Every Second Counts! Corporate Presentation
Every Second Counts!™ Corporate Presentation May 2021
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation (together with any other statements or information that we may make in connection herewith) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 with respect to Kiniksa Pharmaceuticals, Ltd. (and i
Slide 3: Building Patient-Centric Leadership in Immune-Modulating Therapies
Building Patient-Centric Leadership in Immune-Modulating Therapies Leveraging internal & external expertise to drive growth 1 FDA Approved Drug: Targeting Debilitating Diseases ARCALYST®; with Unmet Medical Need 3 Clinical-Stage Assets Jill Pipeline-in-a-Molecule Validated Mechanisms or Potential Ac
Slide 4: Portfolio of Four Immune-Modulating Assets
Portfolio of Four Immune-Modulating Assets Program & Target Preclinical Phase 1 Phase 2 Phase 3 Commercial Commercial Rights Recurrent Pericarditis Worldwide (Excluding MENA) ARCALYST1 CAPS U.S. & Japan IL-1α & IL-1β DIRA U.S. & Japan Giant Cell Arteritis Worldwide Mavrilimumab 2 GM-CSFRα COVID-19 P
Slide 5: Lead Indications Based on Validated Mechanisms with Attractive Commercial Prospects
Lead Indications Based on Validated Mechanisms with Attractive Commercial Prospects Indication Validated Mechanism U.S. Current Prevalence U.S. Current Addressable ARCALYST Recurrent Pericarditis ~40k1 ~14-17k1 Mavrilimumab Giant Cell Arteritis ~75-150k2 ~45-65k3 Vixarelimab Prurigo Nodularis ~300k4
Slide 6: ARCALYST Rilonacept
ARCALYST® Rilonacept – Phase 3 IL-1α and IL-1β cytokine trap Disease Area: Recurrent pericarditis1; painful and debilitating auto-inflammatory cardiovascular disease Competition2: First and only FDA-approved therapy for recurrent pericarditis Regulatory: U.S. Orphan Drug designation in pericarditis;
Slide 7: Role of IL-1α and IL-1β in the Autoinflammatory Cycle of Recurrent Pericarditis
Role of IL-1α and IL-1β in the Autoinflammatory Cycle of Recurrent Pericarditis In addition to inflammatory cytokines such as IL-6, promotion and progression of the inflammatory process in pericarditis is due to IL-1α and IL-1β CRP, C-reactive protein; DAMPs, damage- associated molecular patterns; I
Slide 8: Recurrent Pericarditis Patients Currently Have Limited Treatment Options
Recurrent Pericarditis Patients Currently Have Limited Treatment Options Patients with pericarditis are deemed recurrent after symptom-free period of 4-6 weeks 1st Line NSAID +/- Colchicine Steroid-Sparing 2nd Line Systemic Corticosteroids Opportunity Recurrent Pericarditis 3rd Line IVIG, Azathiopri
Slide 9: Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive
Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive to Quality of Life “I cannot work, walk to the mailbox, or go up/down stairs without a great deal of pain and shortness of breath. Many referred visits to the ER because of pain, where ER docs accuse me of drug seeking for pain
Slide 10: Key Areas of Unmet Need in Patients with Recurrent Pericarditis
Key Areas of Unmet Need in Patients with Recurrent Pericarditis Recurrent pericarditis episodes: painful, debilitating and disruptive to quality of life Resolution of Prevention of Steroid-Sparing Episodes Future Episodes1 Disease Control Quality of Life ~50% Have Increased Rates of 50% Annual Unabl
Slide 11: ARCALYST Label
ARCALYST Label ARCALYST is a patient-administered once-weekly subcutaneous therapy ADULTS (18 years and older) ADOLESCENTS (12 to 17 years) Loading dose: Loading dose: 320 mg 4.4 mg/kg delivered as two 160 mg (2 mL) injections delivered up to a maximum of 320 mg, delivered as 1 or 2 injections (not
Slide 12: Pivotal Phase 3 Trial of ARCALYST in Recurrent Pericarditis
Pivotal Phase 3 Trial of ARCALYST in Recurrent Pericarditis Loading Dose Randomization Primary Efficacy Endpoint End of Study 320 mg SC 1:1 Time-to-First-Adjudicated Pericarditis-Recurrence (EOS) Screening Single-Blind Run-In Period Double-Blind, Placebo-Controlled, Randomized-Withdrawal (RW) Period
Slide 13: ARCALYST Initiation Resulted in Rapid Resolution of Pericarditis Episodes
ARCALYST Initiation Resulted in Rapid Resolution of Pericarditis Episodes Pivotal Phase 3 RHAPSODY Data Rapid and sustained reductions in both reported pain and inflammation as early as after the first dose of ARCALYST Median time to pain response = 5.0 days; Median time to CRP normalization = 7.0 d
Slide 14: ARCALYST demonstrated a steroid-sparing treatment effect
ARCALYST demonstrated a steroid-sparing treatment effect Pivotal Phase 3 RHAPSODY Data Patients treated with ARCALYST discontinued corticosteroids Each patient treated with corticosteroids at In the run-in period of the Phase 3 baseline achieved clinical response with trial RHAPSODY, patients receiv
Slide 15: 96% Reduction in Risk of Pericarditis Recurrence
96% Reduction in Risk of Pericarditis Recurrence Pivotal Phase 3 RHAPSODY Data ARCALYST reduced the risk of pericarditis recurrence The primary efficacy endpoint was time to first adjudicated pericarditis recurrence in the randomized withdrawal period. The median time to recurrence on ARCALYST could
Slide 16: 92% of Trial Days of No/Minimal Pain
92% of Trial Days of No/Minimal Pain Pivotal Phase 3 RHAPSODY Data Patients on ARCALYST had significantly more trial days with no/minimal pain vs placebo Secondary efficacy endpoint was assessed during the randomized withdrawal period of days At Week 16 of the randomized withdrawal period: Patients
Slide 17: Most common ARCALYST adverse reactions
Most common ARCALYST adverse reactions: Injection-site reactions and upper respiratory tract infections Adverse experiences in RHAPSODY 17 *Patients with multiple events were counted once in each appropriate category †Counted once, according to the maximum severity of the adverse event. ‡Cancer was
Slide 18: ARCALYST Use in Clinical Practice
ARCALYST Use in Clinical Practice Average Duration of Recurrent Pericarditis is 2 Years1 • The presence of certain baseline characteristics may identify patients who may benefit from longer-term treatment • The mean duration of disease in RHAPSODY in patients prior to enrollment was 2.4 years Median
Slide 19: ARCALYST: First and Only FDA-Approved Therapy for Recurrent Pericarditis
ARCALYST: First and Only FDA-Approved Therapy for Recurrent Pericarditis Third indication for ARCALYST underscores utility in IL-1 mediated diseases 2008 2020 2021 CAPS DIRA Recurrent Pericarditis FDA Approved FDA Approved FDA Approved 19 CAPS = cryopyrin-associated periodic syndromes ; DIRA = defic
Slide 20: Collaborative Field Force to Drive Awareness and Overcome Access Barriers
Collaborative Field Force to Drive Awareness, Overcome Access Barriers and Help Ensure Positive Patient and Physician Experience Clinical Sales Specialists • Focus: ~2500 HCPs across ~800 accounts • Responsibility: Physician accounts, disease Sales education, Arcalyst promotion, account and territor
Slide 21: Pericarditis Epidemiology
Pericarditis Epidemiology Approximately 14,000 recurrent pericarditis patients suffer from persistent underlying disease, with multiple recurrences and inadequate response to conventional therapy1 ~ 160,000: Epidemiological analysis using large national surveillance databases to calculate the pooled
Slide 22: Recurrent Pericarditis U.S. Prevalence Estimated to be ~40K Patients
Recurrent Pericarditis U.S. Prevalence Estimated to be ~40K Patients ~14K patients with inadequate response to conventional therapy and persistent underlying disease Clear Call to Action: ~14K Patients Potential to Broaden Utilization Over Time ~8K ~5K ~1K ~3K First Multiple Steroid- Refractory1,2 R
Slide 23: Specialty Cardiology Salesforce Expected to Reach ~70% of Patients
Specialty Cardiology Salesforce Expected to Reach ~70% of U.S. Recurrent Pericarditis Patients Estimated Recurrent Pericarditis Patients by Account Focused & Targeted Sales Execution Strategy Targeting National Territory Level Initial launch focus on top tier accounts ~45% of RP patients First 3 mon
Slide 24: COVID-19: Strategic Response and Tools to Help Ensure a Successful Launch
COVID-19: Strategic Response and Tools to Help Ensure a Successful Launch Enabled Tools to Support Effective Remote Detailing • Support convenient, impactful and compliant virtual content sharing • Mitigate COVID-19 risk of physical access restriction Representative-Triggered Approved Emails • Impro
Slide 25: Building to and Supporting a Successful Launch
Building to and Supporting a Successful Launch Disease Educational Programs • Whatispericarditis.com; co-created with patients to provide support and self-advocacy including doctor discussion guides • Heartofinflammation.com; targeted for healthcare professional disease knowledge • Webcast series fo
Slide 26: Pricing, Access and Distribution Considerations
Pricing, Access and Distribution Considerations Pricing Access Distribution • Kiniksa maintains the already established list • Kiniksa’s goal is to enable rapid and broad access • ARCALYST is distributed through a closed price for ARCALYST of $20,000 per month to ARCALYST for patients with Recurrent
Slide 27: Comprehensive Support for Patients Through Kiniksa One Connect
Comprehensive Support for Patients Through Kiniksa One Connect The Patient Access Lead provides one-on-one support, including: Insurance coverage determination Explanation of benefits verification Assistance with prior authorizations and appeals Virtual or hybrid model injection training sup
Slide 28: Summary of ARCALYST Profit Share Arrangement with Regeneron
Summary of ARCALYST Profit Share Arrangement with Regeneron1 • Upfront payment: $5 million ARCALYST Net Sales (CAPS + DIRA + Recurrent Pericarditis)2 • Regulatory milestones: $27.5 million in aggregate Minus 100% of Cost of Goods Sold3 • Kiniksa covers 100% of development expenses related to approva
Slide 29: Mavrilimumab
Mavrilimumab Rilonacept – Phase 3 Monoclonal antibody inhibitor targeting GM-CSFRα Disease Areas: Giant Cell Arteritis (GCA): chronic inflammatory disease of medium-to-large arteries; COVID-19 Pneumonia and Hyperinflammation Competition1: Only one FDA-approved therapy for GCA, but unmet needs remain
Slide 30: Phase 2 Clinical Trial of Mavrilimumab in GCA
Phase 2 Clinical Trial of Mavrilimumab in GCA Key Inclusion Criteria: GCA Flare Definition (Adjudicated): • Age > 50 to 85 years • Re-increase of CRP from normal to • Diagnosis of new-onset or ≥1mg/dL and/or of ESR from <20 relapsing/refractory GCA event mm to ≥30 mm within 6 wks prior to randomizat
Slide 31: Primary Efficacy Endpoint: Time-to-First Adjudicated GCA Flare by Week 26
Primary Efficacy Endpoint: Time-to-First Adjudicated GCA Flare by Week 26 Mavrilimumab Phase 2 Giant Cell Arteritis Data 100 80 HR = 0.38 Sustained Remission (%) Mavrilimumab Risk Reduction = 62% Placebo p=0.0263 Probability of 60 40 Mavrilimumab Placebo (N=42) (N=28) Patients with Flare 8 (19) 13 (
Slide 32: Unmet Need and Commercial Opportunity for Safe and Effective GCA Therapies
Unmet Need and Commercial Opportunity for Safe and Effective GCA Therapies Mavrilimumab Phase 2 giant cell arteritis data1 Relapsing/Refractory Cohort Patients With Flare by Week 26 Remaining Unmet Need Sustained Remission at Week 26 HR = 0.43 p=0.0668 p=0.1231 • Cumulative U.S. GCA prevalence expec
Slide 33: Mavrilimumab: Potential Treatment of COVID-19 Pneumonia and Hyperinflammation
Mavrilimumab: Potential Treatment of COVID-19 Pneumonia and Hyperinflammation • GM-CSF is a key growth factor and cytokine in autoinflammation and autoimmunity1 Mechanism • Mavrilimumab is a monoclonal antibody inhibitor targeting GM-CSFRα • GM-CSF is implicated in the mechanism of excessive and abe
Slide 34: Phase 2/3 Clinical Trial of Mavrilimumab in Severe COVID-19
Phase 2/3 Clinical Trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation Key Inclusion Criteria: • Positive COVID-19 test within 14 days prior to randomization • Hospitalized for COVID-19 • Bilateral pneumonia on chest x- ray or computed tomography • Active fever or recently docum
Slide 35: Data from Phase 2 Portion of Phase 2/3 Trial in Severe COVID-19
Data from Phase 2 Portion of the Phase 2/3 trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation The Phase 2/3 trial is a global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of mavrilimumab treatment in adults hospitalized with s
Slide 36: Baseline Demographics and Baseline Characteristics
Baseline Demographics and Baseline Characteristics Phase 2 Portion of Phase 2/3 trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation Median time to randomization from diagnosis was 7 days Sex (% of Patients) Randomized Number of Patients by Country2 Baseline Demographics were Bal
Slide 37: Reduction in Mechanical Ventilation and Death at Day 29
Non-Mechanically Ventilated Patients Treated with Mavrilimumab Demonstrated a Reduction in Mechanical Ventilation and Death at Day 29 Pooled Across Dose Levels Phase 2 Portion of Phase 2/3 trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation Primary Endpoint: Proportion of Patien
Slide 38: Mavrilimumab Reduced the Risk of Mechanical Ventilation or Death by 65%
Mavrilimumab Reduced the Risk of Mechanical Ventilation or Death by 65% Versus Placebo Phase 2 Portion of Phase 2/3 trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation HR = 0.35 p-value = 0.0175 38
Slide 39: Mavrilimumab was Well-Tolerated and Exhibited a Favorable Safety Profile
Mavrilimumab was Well-Tolerated and Exhibited a Favorable Safety Profile Phase 2 Portion of Phase 2/3 trial of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation 1 39 1) AESIs include: Hepatic Function Abnormality / induced Liver Injury, Acute and Delayed, Hypersensitivity Reactions, Ne
Slide 40: Potential Broad Utility Mavrilimumab
Potential Broad Utility Mavrilimumab Next steps for development of mavrilimumab expected in 1H 2021 Mavrilimumab Data Across 3 Indications: Rheumatoid Severe COVID-19 Arthritis Giant Cell Arteritis Pneumonia and Mavrilimumab was dosed in Phase 2 trial of mavrilimumab Hyperinflammation over 550 patie
Slide 41: Vixarelimab
Vixarelimab Rilonacept – Phase 3 Monoclonal antibody inhibitor targeting OSMRβ Disease Area: Prurigo Nodularis (PN); chronic inflammatory skin disease with pruritic nodules Competition1: No FDA-approved therapies for PN Regulatory: U.S. Breakthrough Therapy designation for the treatment of pruritus
Slide 42: Vixarelimab Phase 2a Study in Prurigo Nodularis
Vixarelimab Phase 2a Study in Prurigo Nodularis Phase 2a Proof-of-Concept Objective: Assess pruritus reduction Dose: 720 mg SC loading dose --> 360 mg single SC QW thereafter Primary Efficacy Endpoint : % change from baseline in weekly average Worst Itch-Numeric Rating Scale (WI-NRS) Treatment Perio
Slide 43: Dual Mechanism Offers Potential Pruritus Relief and Nodule Improvement
Dual Mechanism Offers Potential Pruritus Relief and Nodule Improvement Vixarelimab Phase 2a prurigo nodularis data Vixarelimab is the only mAb targeting OSMRβ, which mediates signaling of key cytokines (IL-31 & OSM) Primary Efficacy Endpoint Secondary Efficacy Endpoint Mean change in weekly-average
Slide 44: Vixarelimab Phase 2b Dose-Ranging Study in Prurigo Nodularis
Vixarelimab Phase 2b Dose-Ranging Study in Prurigo Nodularis Enrollment and dosing of patients commenced in Q4 2020 Expected to enroll approximately 180 patients Primary Efficacy Endpoint (Week 16): • Moderate-to-severe prurigo nodularis experiencing • WI-NRS (% change from baseline in weekly averag
Slide 45: Vixarelimab Dose-Ranging Phase 2b Study: Pharmacokinetic Simulation
Vixarelimab Dose-Ranging Phase 2b Study in Prurigo Nodularis Pharmacokinetic Simulation Supraphysiologic doses of IL-31 in a non-human primate IL-31 challenge model suggest a Ceff of 5-8ug/ml Data from studies of vixarelimab in prurigo nodularis and chronic pruritic diseases support a potential Ceff
Slide 46: KPL-404
KPL-404 Rilonacept – Phase 3 Monoclonal antibody inhibitor interaction between CD40 and CD40L Disease Area: External proof-of-concept previously established in broad range of autoimmune diseases: Sjogren’s disease, systemic lupus, rheumatoid arthritis, solid organ transplant and Graves’ disease1 Sci
Slide 47: CD40/CD40L is an Essential Immune Pathway for T-Cell Priming
CD40/CD40L is an Essential Immune Pathway for T-Cell Priming and T-Cell Dependent B-Cell Responses • CD40 is expressed on the surface of • CD40 ligation on DCs induces cell maturation by promoting dendritic cells, B-cells, antigen-presenting antigen presentation and enhancing their costimulatory act
Slide 48: KPL-404 Single-Ascending-Dose Phase 1 Study
KPL-404 Single-Ascending-Dose Phase 1 Study First-in-human study to provide safety data and pharmacokinetics as well as receptor occupancy and TDAR Part A (Single IV dose) Part B (Single SC Dose) KLH Challenge Groups* 10 mg/kg KLH Challenge d0 d4 d29 3 mg/kg 5 mg/kg 404 KLH KLH Weekly sampling for a
Slide 49: Final Data from KPL-404 Single-Ascending-Dose Phase 1 Study
Final Data from KPL-404 Single-Ascending-Dose Phase 1 Study The randomized, double-blind, placebo-controlled first-in-human (FIH) study is designed to investigate the safety, tolerability, PK and PD properties of single-ascending intravenous (IV) and subcutaneous (SC) doses of KPL-404 in healthy sub
Slide 50: RO and TDAR Suppression Shown Through Day 29 at 3mg/kg IV
RO and TDAR Suppression Shown Through Day 29 at 3mg/kg IV Preliminary KPL-404 Phase 1 data Preliminary data support subsequent study in patients, including potential monthly intravenous or subcutaneous administration Final data from all cohorts expected in 1H 2021 50 1) Free CD40R = inverse of recep
Slide 51: KPL-404 Plasma Concentration
Final Data from KPL-404 Single-Ascending-Dose Phase 1 Study Pharmacokinetic profiles for KPL-404 KPL-404 Plasma Concentration Geometric mean ± SD (ng/mL) ≥ 90% RO ≥ 90% RO ≥ 90% RO LLQ 51 Visit Day
Slide 52: KLH-Specific IgG Level
Final Data from KPL-404 Single-Ascending-Dose Phase 1 Study T-Cell Dependent Antibody Response (TDAR) for KLH antigen challenge Primary KLH Challenge Secondary KLH Challenge for IV Cohorts KLH-Specific IgG Level Mean ± SE PBO (units/mL) 1 mg/kg 3 mg/kg 10 mg/kg Visit Day 52 KLH = keyhole limpet hemo
Slide 53: Potential for Evaluation of KPL-404 in a Broad Range of Autoimmune Diseases
Potential for Evaluation of KPL-404 in a Broad Range of Autoimmune Diseases Indications with Immune Thrombocytopenic Purpura* Published Data1 Kidney Transplant Myasthenia Gravis Sjogren’s Syndrome* Systemic Lupus Erythematosus Psoriasis Graves’ Disease Indication Selection Criteria Rheumatoid Arthri
Slide 54: Building Value at Kiniksa: 2021 Corporate Priorities
Building Value at Kiniksa 2021 Corporate Priorities ARCALYST Commercial launch in recurrent pericarditis (April 2021) Mavrilimumab COVID-19 data (April 2021) and next steps for program (expected Q2 2021) Vixarelimab Phase 2b study in PN evaluating a range of once- monthly dose regimens KPL-404 Final
Slide 55: Appendix
Every Second Counts!™ Appendix
Slide 56: Appendix – ARCALYST (rilonacept)
Appendix – ARCALYST (rilonacept) Every Second Counts!TM 56
Slide 57: Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive
Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive to Quality of Life “I cannot work, walk to the mailbox, or go up or down stairs without a great deal of Symptoms during most recent pericarditis episode pain and shortness of breath. Many referred visits to the ER because of pa
Slide 58: Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive
Recurrent Pericarditis Episodes are Painful, Debilitating and Disruptive to Quality of Life “I have gained a great deal of weight from steroids and inactivity. Exercise sets off more events, so am afraid to exercise. Pain is there constantly, just not as intense as it is during and event. [My] quali
Slide 59: Addressable U.S. Opportunity of ARCALYST Estimated to be ~14K Patients
Addressable U.S. Opportunity of ARCALYST Estimated to be ~14K Patients ~7K new patients with multiple recurrences enter target pool annually Year -4 -3 -2 -1 0 Incident case of acute pericarditis (1st episode)1 117K 117K 117K 117K 117K Incidence of initial RP patients Annual pericarditis 26K 26K 26K
Slide 60: Design of Pivotal Phase 3 Trial of Rilonacept
Design of Pivotal Phase 3 Trial of Rilonacept in Recurrent Pericarditis Loading Dose Randomization Primary Efficacy Endpoint End of Study 320 mg SC 1:1 Time-to-First-Adjudicated Pericarditis-Recurrence (EOS) Screening Single-Blind Run-In Period Double-Blind, Placebo-Controlled, Randomized-Withdrawal
Slide 61: Baseline Demographics and Clinical Characteristics
Baseline Demographics and Clinical Characteristics Pivotal Phase 3 Rilonacept Data Baseline Demographics (n=86) Prior Pericarditis History at Baseline (n=86) Qualifying Episode CRP & NRS (n=86) Sex 10 10 Male 43% Idiopathic 85% Female 57% Post-Pericardiotomy 6.18 6.2 0 100 Syndrome 14% CRP Level % o
Slide 62: Subject Disposition
Subject Disposition Pivotal Phase 3 Rilonacept Data SCREENED Median time to Monotherapy rilonacept = 7.9 weeks (7.0, 8.1) n = 141 Median time to Pain Response2 = 5.0 days (4.0, 6.0) Median time to CRP Normalization3 = 7.0 days (5.0, 8.0) Median time to Treatment Response4 = 5.0 days (4.0, 7.0) ENROL
Slide 63: Rilonacept Initiation Resulted in Rapid and Sustained Reductions
Rilonacept Initiation Resulted in [Rapid and Sustained Reductions in Reported Pain and Inflammation] Pivotal Phase 3 Rilonacept Data 10 10 CRP (mg/dL) mean (±SE)a Pain NRS mean (±SE)a 8 Median (95% CI) Time to Pain Response: 5.0 (4.0, 6.0) days 8 Median (95% CI) Time to CRP Normalization:2 7.0 (5.0,
Slide 64: Rilonacept Resulted in a 96% Reduction in Risk of Recurrence
Rilonacept Resulted in a 96% Reduction in Risk of Pericarditis Recurrence Pivotal Phase 3 Rilonacept Data 100 Probability of No Pericarditis Recurrence (%) 90 80 70 rilonacept placebo Number of Patients Number of Weeks 60 with Recurrence1 to Recurrence1 n (%) Median (95% CI) 50 HR = 0.04 p-value < 0
Slide 65: Rilonacept Resulted in 98% of Trial Days of No/Minimal Pain
Rilonacept Resulted in 98% of Trial Days of No/Minimal Pain Pivotal Phase 3 Rilonacept Data Proportion of Subjects with Absent/Minimal Pericarditis Percent of Days with No or Minimal Pain in First 16 Weeks Proportion of Subjects Who Maintained Clinical Response 1 Symptoms based on the 7-point PGIPS
Slide 66: Rilonacept Was Well-Tolerated in Clinical Trials
Rilonacept Was Well-Tolerated in Clinical Trials Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Ri
Slide 67: Summary of Adverse Events
Summary of Adverse Events Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Rilonacept Bailout Rilona
Slide 68: Summary of Adverse Events
Summary of Adverse Events Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Rilonacept Bailout Rilona
Slide 69: Summary of Adverse Events
Summary of Adverse Events Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Rilonacept Bailout Rilona
Slide 70: Summary of Adverse Events
Summary of Adverse Events Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Rilonacept Bailout Rilona
Slide 71: Summary of Adverse Events
Summary of Adverse Events Pivotal Phase 3 Rilonacept Data Run-In Period Randomized Withdrawal Period Run-In Period Randomized Withdrawal Period Rilonacept Including Placebo Only Before Rilonacept Including Placebo Only Before Rilonacept Rilonacept Bailout Rilonacept Bailout Rilonacept Bailout Rilona
Slide 72: Appendix – Mavrilimumab
Appendix – Mavrilimumab Every Second Counts!TM 72
Slide 73: Central Role of GM-CSF in Pathophysiology of Giant Cell Arteritis
Central Role of GM-CSF in Pathophysiology of Giant Cell Arteritis ↑ Vascular SMC Medial proliferation7,8 remodeling1 9 Arterial wall Aortic aneurysms2 weakening2 Recruitment of Macrophages1 Arterial Ischemic injury3,8 1,6,7 ↑ Matrix metallo- Intimal occlusion4,7 proteinases1,2 hyperplasia1,2 1 • vis
Slide 74: Preclinical Data Support the Mechanistic Rationale of Targeting GM-CSF in GCA
Preclinical Data Support the Mechanistic Rationale of Targeting GM-CSF in GCA GM-CSF and its receptor, GM-CSFRα, shown to be Mavrilimumab reduced arterial inflammation compared elevated in GCA biopsies compared to control1 to control in an in vivo model of vasculitis2 GM-CSF 1) Poster presentation a
Slide 75: Phase 2b Rheumatoid Arthritis Study: Mavrilimumab Reduced CRP and IL-6
In Phase 2b Rheumatoid Arthritis Study Mavrilimumab Reduced CRP and IL-6, Key Markers of Disease Activity for Giant Cell Arteritis Indicative of potential broad utility across spectrum of indications with similar biomarker profiles C-reactive Protein (CRP)1 Interleukin-6 (IL-6)2 75 1) Burmester GR,
Slide 76: GCA is a Serious Condition Characterized by Inflammation of Arteries
GCA is a Serious Condition Characterized by Inflammation of Medium-to-Large Arteries 1 Chronic inflammation of medium-to-large arteries • GCA is characterized by inflammation of medium-to-large arteries with predisposition for the cranial branches of the carotid artery and is typically found “There
Slide 77: Current Treatment Paradigm for GCA Involves High-Dose Steroids
Current Treatment Paradigm for GCA Involves High-Dose Steroids Upon Clinical Suspicion High Dose Steroids Treatment Approach: • All treated patients receive high-dose Low Dose Steroids steroids, which are effective at preventing Patient Experiences Disease Flare disease related complications; howeve
Slide 78: GCA U.S. Prevalence Estimated to be ~75-150k Patients
GCA U.S. Prevalence Estimated to be ~75-150k Patients Literature Sources HCUP/Medicare Data Quantitative Survey Data ~8K – 20K ~45K Avg. GCA patients: ~22 Incident GCA patients Medicare GCA patients1 Avg. RA patients: ~3903 ~65K – 220K5 ~61% GCA Applied ratio of RA prevalence: ~1.3M4 Prevalent GCA p
Slide 79: Mavrilimumab Phase 2 Study in Giant Cell Arteritis
Mavrilimumab Phase 2 Study in Giant Cell Arteritis Primary and Secondary Endpoints Statistically Significant The randomized, double-blind, placebo-controlled, global Phase 2 trial consists of a 6-week screening period, a 26-week double-blind placebo-controlled treatment period, and a 12-week washout
Slide 80: Baseline Demographics and Clinical Characteristics
Baseline Demographics and Clinical Characteristics Mavrilimumab Phase 2 Giant Cell Arteritis Data Baseline Demographics (n=70) Randomization Strata Baseline Disease Characteristics (n=70) 40 GCA Type Sex 35 35 Cranial 76 Male 29% 35 Extracranial 21 Female 71% 30 11 Both 3 0 % of Patients 100 25 17 0
Slide 81: Secondary Efficacy Endpoint: Sustained Remission at Week 26
Secondary Efficacy Endpoint: Sustained Remission at Week 26 Mavrilimumab Phase 2 Giant Cell Arteritis Data Sustained Remission at Week 26 p=0.0038 100% 90% 83.2% 80% % of Patients 70% 60% 49.9% 50% 40% 30% 20% 10% 0% Mavrilimumab Placebo N = 42 N = 28 The sustained remission rate at Week 26 was 33.3
Slide 82: Consistent Trend of Efficacy Across New Onset and Relapsing/Refractory Cohorts
Consistent Trend of Efficacy Across the New Onset and Relapsing/Refractory Cohorts Mavrilimumab Phase 2 Giant Cell Arteritis Data New-Onset GCA Relapsing/Refractory GCA Patients With Flare by Week 26 Sustained Remission at Week 26 Patients With Flare by Week 26 Sustained Remission at Week 26 HR = 0.
Slide 83: Time to Flare and Sustained Remission at Week 26
Time to Flare and Sustained Remission at Week 26 Mavrilimumab Phase 2 Giant Cell Arteritis Data . NE = Not estimable. [1] Kaplan-Meier method used to estimate the survival functions for each treatment arm. [2] Calculated based on a Cox proportional-hazards model with treatment as covariate and strat
Slide 84: Summary of Adverse Events
Summary of Adverse Events Mavrilimumab Phase 2 Giant Cell Arteritis Data Mavrilimumab 150mg Placebo (N=42) (N=28) n (%) n (%) Treatment Emergent Adverse Events 33 (78.6) 25 (89.3) By Maximum Severity [1] Mild 18 (42.9) 13 (46.4) Moderate 14 (33.3) 11 (39.3) Severe 1 (2.4) 1 (3.6) Related to Mavrilim
Slide 85: Escalating Phases of Disease Progression with COVID-19
Escalating Phases of Disease Progression with COVID-19 Source: Hasan K. Siddiqi MD, MSCR , Mandeep R. Mehra MD, MSc , COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal, Journal of Heart and Lung Transplantation (2020), doi: https://doi.org/10.1016/j.heal
Slide 86: Mavrilimumab Treatment Protocol in COVID-19 Pneumonia and Hyperinflammation
Mavrilimumab Treatment Protocol in COVID-19 Pneumonia and Hyperinflammation Improved clinical outcomes compared to matched contemporaneous controls, including earlier weaning from supplemental oxygen, shorter hospitalizations, and no deaths The mavrilimumab open-label treatment protocol was a prospe
Slide 87: Mavrilimumab Treatment Protocol Showed Improved Clinical Outcomes
Mavrilimumab Treatment Protocol in Patients with COVID-19 Pneumonia & Hyperinflammation Showed Improved Clinical Outcomes Compared to Matched Contemporaneous Controls1 100 + 100 + Probability of Failure (%) Probability of Failure (%) Mechanical Ventilation Cumulative Survival (%) 80 Free Survival (%
Slide 88: Representative Patients Showed Improvement in Lung Opacification on CT
Representative mavrilimumab-treated patients showed significant improvement in lung opacification on computerized tomography (CT) scans, consistent with the overall improvement in their clinical status Baseline CT Discharge CT Patient A: 58 year old male. • At day 0: febrile, receiving O2 through a
Slide 89: Data from U.S. Investigator-Initiated Study in Severe COVID-19
Data from U.S. Investigator-Initiated Study of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation The investigator-initiated study was a randomized, double-blind, placebo-controlled study across a consortium of U.S. academic sites designed to evaluate the efficacy and safety of mavrilim
Slide 90: Baseline Demographics and Baseline Characteristics
Baseline Demographics and Baseline Characteristics U.S. investigator-initiated study in patients with severe COVID-19 pneumonia and hyperinflammation Mean Age (years): 56.1 Hospitalized on Time of Onset to Supplemental O2 Hospitalization Age Range (years): 22.6 - 82.9 100 14 12 Sex (% of Patients) 7
Slide 91: Encouraging Trends toward Reduced Mortality and Duration of Mechanical Ventilation
Encouraging Trends toward Reduced Mortality and Duration of Mechanical Ventilation U.S. investigator-initiated study in patients with severe COVID-19 pneumonia and hyperinflammation Primary Endpoint: Proportion of Patients Alive and off Supplemental Oxygen at Day 14 Percentage of Patients who Progre
Slide 92: Cytokine Cascade Amplification System in the Pathophysiology of ARDS
Cytokine Cascade Amplification System in the Pathophysiology of ARDS Pathophysiology of ARDS (Exudative Phase) 1 2 • Inflammatory insults, either locally • Resident alveolar macrophages secrete from the lungs or systemically from proinflammatory cytokines, leading to extra-pulmonary sites, affect ne
Slide 93: Role of Mavrilimumab Throughout the Immune System
The Role of Mavrilimumab Throughout the Immune System and its Potential to Treat COVID-19 Pneumonia and ARDS More Broadly Mechanisms driving ARDS Targetable by Targetable by Targetable by Mavrilimumab pathophysiology Mavrilimumab(4-14) anti-IL-6(15-20) anti-IL-1β(21-26) Recruitment of neutrophils √
Slide 94: 300k to 860k Cases of Adult ARDS in the U.S. Every Year
There are between 300k and 860k Cases of Adult ARDS in the U.S. Every Year; Significant Unmet Need Remains in These Populations Clinician-recognized Adult ARDS All Adult ARDS Patients • Excludes ARDS associated with COVID-19 US Population 318,498,5001 US Population 318,498,5001 • Pediatric ARDS occu
Slide 95: Viral Infections Causing ARDS Have an Inflammatory Pathophysiology
Viral Infections Causing ARDS (i.e., influenza, H1N1, RSV, COVID-19, etc.) Have an Inflammatory Pathophysiology, Primarily Precipitated by Cytokine Storm • Uncontrolled pro-inflammatory response, originating from the focal infected area, spreading through Under-diagnosis of viral infections circulat
Slide 96: Appendix – Vixarelimab (KPL-716)
Appendix – Vixarelimab (KPL-716) Every Second Counts!TM 96
Slide 97: Vixarelimab Inhibits IL-31 & OSM Signaling Through OSMRβ
Vixarelimab Inhibits IL-31 & OSM Signaling Through OSMRβ but Avoids Inhibiting Signaling Critical to Hematopoiesis Through OSM/LIFR in vitro Studies Many cell types TH2 Mϕ T-cell PMN mast cell OSM OSM LIF IL-31 Vixarelimab Vixarelimab IL-31Rα LIFR sensory sensory mesenchymal keratinocytes epithelial
Slide 98: Prurigo Nodularis U.S. Prevalence Estimated to be ~300K Patients
Prurigo Nodularis U.S. Prevalence Estimated to be ~300K Patients HCUP/Medicare Data Literature Sources Quantitative Survey Data ~1:3.8 ~2% of patients seeing Ratio of PN to PsO Derms have PN Quant Survey Quant Survey In 2016, a PN- specific ICD- 10 ~27.5M ~1.2M ~23K ~27.5M code was created, Dermatol
Slide 99: Prurigo Nodularis is Typically Treated by Dermatologists; Treatment Usually Unsuccessful
Prurigo Nodularis is Typically Treated by Dermatologists Through a Combination of Medications and Behavioral Therapies; Treatment is Usually Unsuccessful Emollients + Antipruritic Creams + 1st Line ~100% Topical Corticosteroids + Antihistamines Vixarelimab may Diagnosis of 2nd Line ~60-70% Low-Dose
Slide 100: Vixarelimab Phase 2a Study Prurigo Nodularis
Vixarelimab Phase 2a Study Prurigo Nodularis Statistically significant primary efficacy endpoint of reduction in weekly-average WI-NRS at Week 8 Enrolled and treated 49 patients with moderate-to-severe prurigo nodularis (mean PN- IGA of 3.4) experiencing moderate-to-severe pruritus (mean WI-NRS scor
Slide 101: Vixarelimab Phase 2a Data in Prurigo Nodularis
Vixarelimab Phase 2a Data in Prurigo Nodularis LS-Mean % Change in % of Vixarelimab Subjects with a PN-IGA Score of 0 or 1 Weekly Average WI-NRS Clinically Meaningful Response in WI-NRS 52.2% -29.4% 30.4%, p = 0.032 -50.6% P=0.035 7.7% Statistically Significant Primary Efficacy Majority of Vixarelim
Slide 102: Statistically Significant Primary Efficacy Endpoint of Reduction in WI-NRS
Vixarelimab Phase 2a Study in Prurigo Nodularis: Statistically Significant Primary Efficacy Endpoint of Reduction in Weekly-Average WI-NRS at Week 8 Median change from baseline in weekly-average WI-NRS at Week 8 was -69.8% LS-Mean % Change in Weekly Average WI-NRS Median % Change in Weekly Average W
Slide 103: Majority Showed Clinically Meaningful ≥4-Point WI-NRS Reduction
Vixarelimab Phase 2a Study in Prurigo Nodularis: Majority of Vixarelimab Recipients Showed a Clinically Meaningful ≥4-Point Weekly-Average WI-NRS Reduction at Week 8 52.2% 30.8% Vixarelimab = KPL-716 103 WI-NRS = Worst-Itch Numeric Rating Scale
Slide 104: More Vixarelimab Recipients Attained Clear/Almost Clear Lesion Score
Vixarelimab Phase 2a Study in Prurigo Nodularis: Significantly More Vixarelimab Recipients Attained A Clear/Almost Clear Lesion Score by Week 8 PN-IGA Score of 0 or 1 ≥1 Point Change in PN-IGA 30.4%, p = 0.032 7.7% 104 Vixarelimab = KPL-716; PN-IGA = prurigo nodularis-investigator’s global assessmen
Slide 105: Concordant Activity of Vixarelimab on PN-IGA and Pruritus
Vixarelimab Phase 2a Study in Prurigo Nodularis: Concordant Activity of Vixarelimab on PN-IGA and Pruritus % of IGA 0-1 Subjects with ≥4 Point Change in WI-NRS % of Subjects with ≥4 Point Change in WI-NRS and an IGA of 0-1 n=7 n=2 n=12 n=8 85.7% of the subjects who achieved 0-1 on the PN- 50% of the
Slide 106: Representative Images of Nodule Resolution at Week 8
Vixarelimab Phase 2a Study in Prurigo Nodularis: Representative Images of Nodule Resolution at Week 8 in Vixarelimab-Treated Subjects Day 1 Week 8 Subject 1 WI-NRS = 8.43 WI-NRS = 1.67 PN-IGA = 4 PN-IGA = 1 Subject 2 WI-NRS = 9.29 WI-NRS = 0 PN-IGA = 4 PN-IGA = 2 106
Slide 107: Vixarelimab Phase 2a Study: Baseline Characteristics
Vixarelimab Phase 2a Study in Prurigo Nodularis: Baseline Characteristics General Vixarelimab Placebo Total Characteristics* (n=23) (n=26) (n=49) Age (Mean Years) 52 64 58 Sex (Male/Female) 10/13 10/16 20/29 Race White (n) 65.2% (15) 80.8% (21) 73.5% (36) Black or African 21.7% (5) 11.5% (3) 16.3% (
Slide 108: Vixarelimab was Well-Tolerated in Prurigo Nodularis Phase 2a Study
Vixarelimab was Well-Tolerated in Prurigo Nodularis Phase 2a Study Vixarelimab Placebo Summary of Adverse Events (n=23) (n=26) Any AE (n) 82.6% (19) 65.4% (17) TEAE (n) 82.6% (19) 65.4% (17) Drug-Related TEAE (n) 39.1% (9) 30.8% (8) Serious TEAE 0 0 Drug-Related Serious TEAE 0 0 TEAE Leading to Trea
Slide 109: Vixarelimab was Well-Tolerated in Prurigo Nodularis Phase 2a Study
Vixarelimab was Well-Tolerated in Prurigo Nodularis Phase 2a Study Vixarelimab Placebo System Organ Class Preferred Term (n=23) (n=26) Infections and Infestations (n) 30.4% (7) 46.2% (12) Upper Respiratory Tract Infection (n) 17.4% (4) 3.8% (1) Nasopharyngitis (n) 4.3% (1) 7.7% (2) Gastroenteritis V
Slide 110: Vixarelimab Exploratory Phase 2 Study in Chronic Pruritus
Vixarelimab Exploratory Phase 2 Study in Diseases Characterized by Chronic Pruritus Pilot Study Rationale 1 Investigate presence of IL-31 & OSM signature in multiple diseases characterized by chronic pruritus 2 In diseases where IL-31 is present (based on post-hoc biopsy analysis) link inhibition
Slide 111: Vixarelimab Exploratory Phase 2 Study: Plaque Psoriasis Cohort Results
Vixarelimab Exploratory Phase 2 Study in Diseases Characterized by Chronic Pruritus Plaque psoriasis cohort achieved statistically significant reduction in weekly-average WI-NRS at Week 8 Enrolled patients experiencing moderate-to-severe pruritus and assigned them to one of the following cohorts bas
Slide 112: Reduction in Weekly-Average WI-NRS at Week 8
Vixarelimab Exploratory Phase 2 Study in Diseases Characterized by Chronic Pruritus: Reduction in Weekly-Average WI-NRS at Week 8 Plaque psoriasis cohort achieved statistically significant reduction in weekly-average WI-NRS at Week 8 Plaque Psoriasis Chronic Idiopathic Pruritus LS-Mean % Change in W
Slide 113: ≥4-Point Weekly-Average WI-NRS Reduction at Week 8
Vixarelimab Exploratory Phase 2 Study in Diseases Characterized by Chronic Pruritus: ≥ 4-Point Weekly-Average WI-NRS Reduction at Week 8 71.4% of vixarelimab recipients in plaque psoriasis cohort showed a clinically meaningful ≥ 4-point reduction Plaque Psoriasis Chronic Idiopathic Pruritus 71.4% 66
Slide 114: Chronic Pruritus Study: Baseline Characteristics
Vixarelimab Exploratory Phase 2 Study in Diseases Characterized by Chronic Pruritus: Baseline Characteristics General Characteristics* Vixarelimab Placebo Total Plaque Psoriasis (n=14) (n=7) (n=21) Clinical Findings at Baseline: WI-NRS Age (Mean Years) 49 53 50 Sex (Male/Female) 5/9 3/4 8/13 Race 10
Slide 115: Appendix – KPL-404
Appendix – KPL-404 Every Second Counts!TM 115
Slide 116: Preliminary Data from KPL-404 Single-Ascending-Dose Phase 1 Study
Preliminary Data from KPL-404 Single-Ascending-Dose Phase 1 Study The randomized, double-blind, placebo-controlled first-in-human (FIH) study is designed to investigate the safety, tolerability, PK and PD properties of single-ascending intravenous (IV) and subcutaneous (SC) doses of KPL-404 in healt
Slide 117: KPL-404 Showed Encouraging Results in a Non-Human Primate Model of TDAR
KPL-404 Showed Encouraging Results in a Non-Human Primate Model of TDAR Mean KPL-404 PK Mean KPL-404 Receptor Occupancy (RO) Mean KLH IgG (Intravenous Dosing) 150 a n t i- K L H ( Ig G ) 0 m g/kg 1 m g/kg a n t i- K L H Ig G ( u g /m l) 5 m g/kg 10 m g/kg 100 50 0 P r e -d o se 7 14 21 28 T im e (d
Slide 118: Preliminary Data from KPL-404 Phase 1 Study: Pharmacokinetic Summary
Preliminary Data from KPL-404 Single-Ascending-Dose Phase 1 Study Pharmacokinetic summary 118
Slide 119: Receptor Occupancy and KLH Antigen Challenge TDAR Summary
Preliminary Data from KPL-404 Single-Ascending-Dose Phase 1 Study Receptor occupancy and KLH antigen challenge TDAR summary 119 1) Free CD40R = inverse of receptor occupancy; KLH = keyhole limpet hemocyanin; TDAR = T-cell dependent antibody response
Slide 120: Every Second Counts!
Every Second Counts!™
Kiniksa Pharmaceuticals — Investor Presentation (May 2021) on 6ix