Kiniksa Pharmaceuticals International, Plc · NASDAQ:KNSA
Kiniksa Pharmaceuticals International — Investor Presentation (January 2019)
47 slides from Kiniksa Pharmaceuticals International's investor presentation, Jan 28, 2019
Slide 1: 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 2: Passionate Employees, Sequential Pipeline, Rare and Specialty Diseases
Passionate Employees Sequential Pipeline Rare and Specialty Diseases Strong Biologic Rationale or Validated Mechanisms Potential for Multiple Indications 3 | 28 January 2019
Slide 3: Building a fully-integrated global biopharmaceutical company
Building a fully-integrated global biopharmaceutical company Discovering, acquiring, developing and commercializing life-changing therapies for debilitating diseases B USI N E SS D EV EL O P M EN T 4 | 28 January 2019 DATA-DRIVEN CAPITAL ALLOCATION
Slide 4: Pipeline of product candidates across various stages of development
Pipeline of 5 Program & Target product candidates across various stages of development Status Rights Indication Preclinical Phase 1 Phase 2 Phase 3 IL-1α & IL-1β GM-CSFRα Prurigo Nodularis (PN) Chronic Idiopathic Pruritus, Chronic study in multiple diseases characterized by OSMRβ Psoriasis, Lichen S
Slide 5: Strong execution produced transformational 2018 and 2019 goals
Strong execution produced transformational 2018 2018 Goals Rilonacept Report interim Phase 2 data Start Phase 3 clinical trial 2019 Go2al0s19 Rilonacept Enroll in the pivotal Phase 3 clinical trial Present Phase 2 data at ACC Mavrilimumab Enroll in the global Phase 2 clinical trial (GCA) Announce ad
Slide 6: Rilonacept – Phase 3 (IL-1α and IL-1β cytokine trap)
1 Rilonacept – Phase 3 (IL-1α and IL-1β cytokine trap) Rilonacept Mavrilimumab KPL-716 KPL-045 KPL-404 ) 1) Brucato et al. JAMA. 2016, 316 (18): 1906-1912; Arcalyst Prescribing Information; 2) IQVIA PharMetrics Plus Claims Data 1/1/2013-3/31/2018; ClearView Analysis, UptoDate, Trinity Partners, Mayo
Slide 7: Recurrent pericarditis is a debilitating disease with no currently approved therapies
Recurrent pericarditis is a debilitating therapies disease with no currently approved Pericarditis is chest pain caused by pericardial inflammation Recurrent pericarditis causes significant impairment of quality of life constrictive pericarditis) but, when they occur, they can be life 8 | 28 January
Slide 8: Refractory patients are left with few treatment options
Refractory patients are left with few treatment options and rilonacept could mitigate the dangers of long-term steroid use 9 | 28 January 2019 Sources: UptoDate, Trinity Partners, Kiniksa Analysis 4th line Pericardiectomy Refractory patients: IL-1 Candidates 3rd line IVIG, Azathioprine, Methotrexate
Slide 9: Recurrent pericarditis prevalence and addressable opportunity in the U.S.
Recurrent pericarditis prevalence in the U.S. estimated to be ~40k patients* Addressable opportunity for rilonacept in the U.S. estimated to be ~14K patients* ~5k Steroid-Intolerant Patients Refractory to NSAIDs and Colchicine + + ~3k Refractory Patients ~6k Poorly-Controlled or Steroid-Dependent Pa
Slide 10: Recurrence burden significantly impacts morbidity and quality of life
Recurrence burden significantly impacts morbidity and impairs quality of life Refractory and steroid dependent patients have the highest recurrence burden, with ~30 – 40% of patients experiencing ≥2 annual episodes, significantly higher than the broad recurrent population Over the last two years, ~6
Slide 11: Open-label Phase 2 clinical trial of rilonacept in pericarditis populations
Open-label Phase 2 clinical trial of rilonacept in pericarditis populations Subjects 6 to 75 years old Distinct Trial Populations > 1mg/dL Confirmed L Screening Period Extension Period Open-Label Treatment Period pt (6 doses) > 1mg/dL 2nd 3rd Dose 160 mg 4th Dose 160 mg 5th Dose 160 mg Loading 6th D
Slide 12: Pericardial signs resolved during rilonacept 6-week base treatment period
Pericardial signs resolved during rilonacept 6-week base treatment period Pericardial Effusion PR Depression Widespread ST Pericardial Rub 14 | 28 January 2019 Note: Interim data from on-going study (Part1) as of Nov 1st, 2018 Number of Subjects Baseline (n= 12) 12End of Base Treatment Period (n= 10
Slide 13: Summary of adverse events
Summary of adverse events • • • • Rilonacept was generally well-tolerated 7/12 subjects experienced at least one treatment-related adverse event during the treatment period The most common adverse events were mild transient injection site reaction and gastrointestinal disorders One patient discontin
Slide 14: Pivotal Phase 3 clinical trial of rilonacept for recurrent pericarditis
Pivotal Phase 3 clinical trial of rilonacept for recurrent pericarditis Primary Efficacy Endpoint Time-to-First-Pericarditis-Recurrence Loading Dose 320 mg SC Randomization 1:1 End of Study (EOS) Stabilization and tapering of background pericarditis medications Clinical responders randomized 1:1 to
Slide 15: Mavrilimumab – Phase 2 (monoclonal antibody inhibitor targeting GM-CSFRα)
2 Mavrilimumab – Phase 2 (monoclonal antibody inhibitor targeting GM-CSFRα) Rilonacept Mavrilimumab KPL-716 KPL-045 KPL-404 Mechanistic rationale for focusing on high unmet need vasculitides & inflammatory cardiomyopathies 1) Sources: Wicks, Roberts, Nature Review Immunology, 2015; Hamilton, Expert
Slide 16: GCA is a serious condition characterized by inflammation of blood vessels
GCA is a serious condition characterized by inflammation of medium-large blood vessels; it can lead to bilateral blindness if left untreated “ “ “ 3 life threatening!” – Rheumatologist I hate steroids, the long –term side effects I definitely don’t want to go blind.” 18 | 28 January 2019 Sources: Me
Slide 17: Current treatment paradigm for GCA involves high-dose steroids
Current treatment paradigm for GCA involves high-dose steroids for all patients upon clinical suspicion st year after • Steroid dose is increased MTX, AZA, Actemra) Steroid sparing agents are prescribed to ~40-60% of patients after their first flare and to all patients with chronic flares experience
Slide 18: GCA prevalence in the U.S. estimated between 75k-150k patients
GCA prevalence in the U.S. estimated to be between 75k-150k patients patients to RA prevalence Key Considerations to Market Sizing Approach Sources: 1.) Medicare analysis conducted 1/2018 2.) Trinity Partner’s Quantitative Primary Market Research (n=74) 3.) Trinity Partner’s Quantitative Primary Mar
Slide 19: GM-CSF is a key growth factor involved in the pathology of GCA
GM-CSF is a key growth factor believed to be involved in the pathology of GCA Estimated U.S. prevalence of ~75k-150k1; ~50-70% of patients are refractory or steroid-dependent2 1 GM-CSF and GM-CSFRα are overexpressed in GCA lesions GCA Lesions are heavily comprised of giant cells & non-classical macr
Slide 20: High GM-CSF-Rα mRNA expression in GCA positive biopsies
High GM-CSF-Rα mRNA expression GCA Positive Biopsies via RNAscope in GCA positive biopsies GCA Negative Control Biopsy vs control ll Nucleus Red: GM-CSFRα Intima Media Multi-nucleated Giant Cell Elevated GM-CSFRα expression in all 3 layers of the artery (adventitia, media and intima) in GCA positive
Slide 21: High PU.1 mRNA expression via RNAscope in GCA positive biopsies
High PU.1 mRNA expression via RNAscope in GCA positive biopsies Blue: Cell Nucleus Red: PU.1 transcription factor GCA Positive Biopsies GCA Negative Control Biopsy Elevated expression of downstream transcription factor for colony stimulating factors in all 3 layers of the artery (adventitia, media a
Slide 22: Randomized, double-blind, placebo-controlled Phase 2 study of mavrilimumab in GCA
Randomized, double-blind, placebo-controlled Phase 2 study of mavrilimumab Washout Safety Follow-up (12 weeks) in GCA Double-Blind Treatment Period (26 weeks) R 3:2 Clinical Observation Prednisone as per Investigator R 3:2 Primary Efficacy Endpoint Time to Flare 24 | 28 January 2019 Control (n=12) P
Slide 23: KPL-716 – Phase 2 (monoclonal antibody inhibitor targeting OSMRβ)
KPL-716 – Phase 2 (monoclonal antibody inhibitor targeting OSMRβ) 3 Rilonacept Mavrilimumab KPL-716 KPL-045 KPL-404 Differentiated molecule with potential to treat variety of pruritic, inflammatory and fibrotic indications 1)Trinity Qualitative Interviews; 2) Trinity Consulting - HCUP/Medicare Data
Slide 24: Prurigo nodularis is characterized by pruritic lesions
Prurigo nodularis is characterized by pruritic lesions on patients’ extremities, which lead to significant distress and decreased quality of life “ – Dermatologist “ Some patients present with lesions that 26 | 28 January 2019 Lesions may have a ‘thickened’ appearance due to the patient scratching,
Slide 25: Prurigo nodularis treatment is usually unsuccessful initially
Prurigo nodularis is typically treated by dermatologists through a combination of medications and behavioral therapies; treatment is usually unsuccessful initially slot here Note: none of the above therapies are approved specifically for prurigo nodularis 27 | 28 January 2019 Sources: 1. Medscape, 2
Slide 26: Prevalence of prurigo nodularis is estimated at ~300K in the U.S.
The prevalence of prurigo nodularis is estimated at ~300K in the U.S. Ratio of PN to PsO In 2016, a PN-specific ICD-10 code was created, ICD10-L28.1 Quant Survey Quant Survey ~25% Medicare Split from HCUP ~1% of dermatologist visits are made by PN patients, Dantas 2015 CDC 2014 2017 Cowen Report CDC
Slide 27: IL-31 and OSM are implicated in the pathology of prurigo nodularis
IL-31 and OSM are implicated in the pathology of prurigo nodularis Dual-targeting of OSM and IL-31 though OSMRβ blockade has the potential to be disease modifying Quantitative Real-time PCR Analysis of IL-31 mRNA in Human Skin • IL-31 significantly overexpressed in pruritic skin vs. non-pruritic ski
Slide 28: KPL-716 inhibited IL-31 & OSM signaling through OSMRβ
KPL-716 inhibited IL-31 & OSM signaling through OSMRβ but avoided inhibiting signaling critical to hematopoiesis through OSM/LIFR in in vitro studies Many cell types OSM LIF LIFR Hematopoietic and many other cell types neurons 30 | 28 January 2019 IL-31Rα hematopoiesis and many other processes TH2Mϕ
Slide 29: KPL-716 showed potential efficacy in non-human primate models of pruritus
KPL-716 primate showed signs of potential efficacy in two validated non-human models of pruritus NHP Model of Pruritus* and inflammation after a single dose NHP Model of Inflammation* A single dose of KPL-716 at 3mg/kg inhibited pruritic response driven by supraphysiologic levels of IL-31 for over 2
Slide 30: KPL-716 single-ascending-dose Phase 1a/1b study design
KPL-716 placebo-controlled, single-ascending-dose Phase 1a/1b study design Phase 1a: Normal Healthy Volunteer (n=50) Dose Groups Phase 1b: Subjects with Atopic Dermatitis (n=32) Patient Experience d60 d0 d28 d90/d120 SV1 SV2 7d wash off of all prior therapies Primary endpoint: Safety and Tolerabilit
Slide 31: Baseline parameters were balanced overall
Baseline parameters were balanced overall KPL-716 recipients had more atopic dermatitis flares in the year prior to enrollment, suggesting more unstable disease at baseline compared with placebo 7.5 mg/kg IV Pooled IV Baseline is defined as the last measurement prior to dosing, AD = atopic dermatiti
Slide 32: KPL-716 was well-tolerated in single-dose Phase 1a/1b study
KPL-716 No Deaths No SAEs was well-tolerated in single-dose Phase 1a/1b study • • • • • • • • • No Thrombocytopenia No Peripheral Edema No Conjunctivitis Drug-Related Treatment Emergent Adverse Events (DR-TEAEs) infrequent and not related to dose All resolved without sequalae • No Discontinuations d
Slide 33: Exploratory efficacy endpoints and analysis plan
Exploratory efficacy endpoints and analysis plan Efficacy Endpoints • Pruritus: ̶ ̶ Weekly average of daily WI-NRS (worst itch in past 24 hours) collected by daily eDiary Pruritus Visual Analog Scale, a component of SCORAD (average itch in past 3 days) collected at study visits • Sleep loss VAS: ̶ A
Slide 34: Reduction in pruritus over the 28-day monotherapy period
Single doses in Phase 1a/1b provided early evidence indicative of target engagement and showed reduction in pruritus over the 28-day monotherapy period Pruritus Visual Analog Scale (VAS)* Weeks Weekly Average Worst Itch Numerical Rating Scale (WI-NRS) Weeks 0 1 2 3 4 0 1 2 3 4 0 0 -10.4% (n=10) -10
Slide 35: Maximum decrease in WI-NRS in KPL-716 recipients versus placebo
The maximum decrease in WI-NRS at day 28 in the absence of concomitant TCS was > 8-points in KPL-716 recipients compared to > 4-points in placebo WI-NRS Reduction from Baseline 8.0-8.9 pts 7.0-7.9 pts 6.0-6.9 pts 5.0-5.9 pts 4.0-4.9 pts Wk 1 Wk 2 Wk 3 Wk 4 Subjects were treated as non-responders aft
Slide 36: Reduction in sleep loss and disease severity over 28 days
Single doses in Phase 1a/1b showed reduction in sleep loss and disease severity over the 28-day monotherapy Sleep Loss VAS* Weeks period Eczema Area and Severity Index (EASI) Weeks 0 1 2 3 4 0 1 2 3 4 0 20 10 0 -10 -20 -30 -10 -2.3% (n=10) -20 -25% (n=10) -30 -40 -42.3% (n=10) -40 -50 -60 -70 -80 -5
Slide 37: PK/PD model predicts weekly SC dosing provides sufficient exposures
PK/PD model predicts that weekly SC dosing provides sufficient/high exposures for current POC studies as well as studying alternate dosing regimens in future dose-finding studies (e.g., q2w and/or qm) Phase 1b data used to build predictive PK/dosing model for currently ongoing multiple-dose studies
Slide 38: Planned KPL-716 adaptive Phase 2a/2b trial in prurigo nodularis
Planned KPL-716 adaptive Ph2a Proof-of-Concept (POC) Segment design Phase 2a/2b trial in prurigo nodularis Ph2b Dose Range-Finding Segment: • Objective: Define optimal KPL-716 dose/regimen on pruritus endpoint • Sample size: n=300 (anticipated) • Doses/Interval: TBD Treatment Period-16 weeks • Objec
Slide 39: Planned KPL-716 exploratory pilot study in chronic pruritus
Planned pruritus KPL-716 exploratory pilot study in multiple diseases characterized by chronic Pilot Study Rationale conventional therapies; ~15-20% treated with Xolair Subject Experience in Each Disease Cohort 720 mg SC loading dose followed by weekly 360 mg single SC administration yr; ~1-in-3 tre
Slide 40: KPL-716 repeated-single-dose Phase 1b study in atopic dermatitis
KPL-716 placebo-controlled repeated-single-dose Phase 1b study design in patients with moderate-to-severe atopic dermatitis SV2 D0 D77 D147 SV1 KPL-716 360 mg or placebo (1:1) via SC injection once weekly for 12 weeks 1 - 40 Days 7 Days 42 | 28 January 2019 Wash off TCS TCS as Rescue for Flare Only
Slide 41: KPL-045 – Preclinical (monoclonal antibody targeting CD30L)
KPL-045 – Preclinical (monoclonal antibody targeting CD30L) 4 Rilonacept Mavrilimumab KPL-716 KPL-045 KPL-404 Fully-human monoclonal antibody inhibitor of signaling between CD30 and CD30L • Involved in T-effector memory function, humoral response & TH2 immunity • CD30L is expressed at high levels on
Slide 42: KPL-404 – Preclinical (monoclonal antibody targeting CD40)
KPL-404 – Preclinical (monoclonal antibody targeting CD40) 5 Rilonacept Mavrilimumab KPL-716 KPL-045 KPL-404 Humanized monoclonal antibody inhibitor of signaling between CD40L and CD40 • CD40/CD40L interaction between B & T-cells are required for humoral responses • Antigen presenting cells express
Slide 43: Kiniksa at a glance
Kiniksa at a glance Financial Highlights Corporate Highlights Cash and Short-Term Investments* Shares Outstanding Capital Allocation to Highest Value Opportunities Across Existing Portfolio, Internal R&D and Business Development * As of September 30, 2018 45 | 28 January 2019 $490M Gross Proceeds Ra
Slide 44: Anticipated Achievements by Year-End 2019
clinical-stage programs 5 investigational indications 10 pivotal Phase 3 trial 1 Phase 2 trials 3 Anticipated Achievements by Year-End 2019 Phase 2 trial complete 1 Phase 1 trial complete 1 2 clinical data readouts multiple internal, discovery-stage projects 278 January 2019 46
Slide 45: Summary of anticipated corporate milestones for 2019-2020
Summary of anticipated corporate milestones for 2019-2020 47 | 28 January 2019 Program Milestone Anticipated Timing Rilonacept Present Phase 2 trial data in recurrent pericarditis at ACC 1H 2019 Top-line data from Phase 3 RHAPSODY trial in recurrent pericarditis 2H 2020 Mavrilimumab Top-line data fr
Slide 46: Relentless. Passionate. Focused.
TM Relentless. Passionate. Focused.
Slide 47: Kiniksa
i \ KINIKSA V7 Relentless. Passionate. Focused. ™
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