Kalvista Pharmaceuticals, Inc. · NASDAQ:KALV
Kalvista Pharmaceuticals — Investor Presentation (July 2018)
36 slides from Kalvista Pharmaceuticals's investor presentation, Jul 31, 2018
Slide 1: Corporate Presentation July 2018
Corporate Presentation July 2018 Exhibit 99.2
Slide 2: Forward-looking statements
This presentation and the accompanying oral presentation contain “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan,"
Slide 3: Company Highlights
Company Highlights Discovery and development of small molecule protease inhibitors, with leading expertise on plasma kallikrein role in disease mechanisms Creating a portfolio of oral plasma kallikrein inhibitors to treat orphan disease hereditary angioedema (HAE) and diabetic macular edema (DME) HA
Slide 4: Product Portfolio
HAE Franchise KVD900 Target: Plasma Kallikrein KVD818 Target: Plasma Kallikrein KVDXXX Target: Plasma Kallikrein DME Franchise KVD001* Target: Plasma Kallikrein Oral Program* Target: Plasma Kallikrein Other Targets Additional Proteases Target: Undisclosed Oral Route Preclinical Phase 1 Phase 2 Statu
Slide 5: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE)
Slide 6: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) Rare, genetic condition causing painful and dramatic swelling in various parts of the body Orphan disease: incidence 1 in 10,000 to 1 in 50,0001 Driven by uncontrolled plasma kallikrein activity leading to excessive bradykinin release; primarily caused by defect in C1 inh
Slide 7: Diverse HAE Market – Opportunities in Prophylaxis and Acute
Diverse HAE Market – Opportunities in Prophylaxis and Acute 1Nordenfelt P et al. Acta Derm Venereol 2016; 96: 540–545 PMID: 26540175 Patient Attacks per Year 1 Patient treatment preference is influenced by attack frequency Percentage of patients
Slide 8: Oral Acute Therapy Meets Unmet Patient Needs
Oral Acute Therapy Meets Unmet Patient Needs On-Demand ($M)1,2 Prophylaxis ($M)1 A safe, oral therapy for acute attacks could help patients with less frequent attacks effectively manage their disease on-demand All patients would have the option of a convenient, effective oral treatment in lieu of an
Slide 9: Requirements for Best-In-Class Treatment of Acute Attacks
Requirements for Best-In-Class Treatment of Acute Attacks Well Tolerated; Pain Free Oral tablet formulation Promotes Earlier Intervention KVD900 Prevents progression of Attacks Rapid effect Stable AT room temperature
Slide 10: KVD900 Phase 1 Overview
KVD900 Phase 1 Overview Double-blind, randomized investigation of oral KVD900 in healthy, male volunteers Single ascending dose with cross-over to tablet formulation 8 cohorts assessed up to 600 mg Safety and tolerability AEs, laboratory measurements and clinical outcomes Pharmacokinetics PK profile
Slide 11: KVD900 Safety Profile to Date
KVD900 Safety Profile to Date No SAEs reported Twelve AEs reported, 10 mild and 2 moderate One mild AE (light headedness) considered possibly related (in the 5 mg/placebo cohort) All other reported AEs unrelated/unlikely related No AEs reported in 300 mg or 600 mg dose cohorts No subjects withdrew f
Slide 12: KVD900 Rapidly and Highly Absorbed at All Doses
KVD900 Rapidly and Highly Absorbed at All Doses Mean Tmax around 1 hour Mean Cmax up to 3500 ng/ml
Slide 13: KVD900 Phase 1 Study – Single Dose PK
KVD900 Phase 1 Study – Single Dose PK Dose-dependent increase in exposure of both Cmax and AUC Confident control of exposure with dose Tablet formulation shows even faster absorption than capsule
Slide 14: KVD900 Phase 1 Study – Single Dose PK/PD
KVD900 Phase 1 Study – Single Dose PK/PD Strong inhibition of plasma kallikrein activity 160 mg and 600 mg dose cohort shown Plasma activated by the addition of dextran sulfate Plasma kallikrein activity monitored using a fluorescent substrate Rapid onset of inhibition KVD900 exposure delivers poten
Slide 15: KVD900 Blocks Kininogen Cleavage
KVD900 Blocks Kininogen Cleavage Plasma kallikrein cleaves kininogen to release the hormone bradykinin – the mediator of edema in HAE Plasma kallikrein was activated in whole plasma by the addition of dextran sulfate KVD900 protects kininogen in both normal and HAE plasma Plasma samples from subject
Slide 16: KVD900 Potency Compares Favorably to Berinert
KVD900 Potency Compares Favorably to Berinert C1 inhibitor potency IC50 in whole plasma is 1700nM KVD900 is 90nM Berinert Following administration of the approved dose of 20IU/kg Cmax »3000nM (0.32mg/ml) reached within 48 minutes of dosing Maximal concentration is »2x IC50 Comparing to approved, acu
Slide 17: KVD900 Displays Rapid Uptake
KVD900 Displays Rapid Uptake Multiple dose levels achieve sufficient plasma kallikrein inhibition Based on clinically efficacious doses of C1-INH 600 mg – exceeds 100x IC50 and maintains 2x IC50 for 12+ hours 160 mg – exceeds 50x IC50 and maintains 2x IC50 for 10 hours Onset is important for acute e
Slide 18: KVD900: On-Demand Treatment of Acute HAE Attacks
KVD900: On-Demand Treatment of Acute HAE Attacks Data suggests an ideal fit with best-in-class treatment for acute oral therapy Rapid absorption leads to effective concentrations in 30 minutes or less, which is equivalent to injected Systemic levels above effective concentration maintained for up to
Slide 19: Early Treatment Dramatically Reduces Attack Duration
Early Treatment Dramatically Reduces Attack Duration… Attack duration (hrs) n=40 n=25 n=62 n=80 Icatibant Outcome Survey (IOS) – Attack duration by time of treatment initiation (n=207 attacks)1 Source: (1) Maurer M et al. PLoS ONE 8(2): e53773. doi:10.1371/journal.pone.0053773 Delaying treatment dra
Slide 20: But Majority of Patients Do Not Treat Early Enough
…But Majority of Patients Do Not Treat Early Enough >60% of patients administer their therapy more than one hour after the beginning of an attack, per IOS Key reasons why treatment is delayed: Inconvenient – many therapies require medical professional training Painful – both during and after adminis
Slide 21: KVD900 Supports Earlier Treatment and Faster Attack Resolution
KVD900 Supports Earlier Treatment and Faster Attack Resolution Convenience and tolerability of KVD900 compared to other therapies will encourage earlier dosing Rapid absorption of KVD900 yields high exposures which compare favorably to injectable therapies Combination of these attributes will lead t
Slide 22: Opportunity: Share Capture and Growth of $2B Market
12017 Revenues from Shire full-year results, February 14, 2018 Previously Untreated Patients PROPHYLAXIS FIRAZYR® $663 M KALBITOR® $67 M Berinert ® $248 M ACUTE RUCONEST® $13M Patient Switches CINRYZE® $699 M Tx Naive Breakthrough KVD900 NEW PATIENTS Opportunity: Share Capture and Growth of $2B Mark
Slide 23: KVD900 Next Steps
KVD900 Next Steps Food effect cohort will be completed before we begin the Phase 2 Moving into single dose Phase 2 efficacy study Investigation of PK/PD in HAE patients and efficacy in acute treatment of attacks Anticipated to begin recruitment before YE 2018 Expected completion mid-2019 Enables reg
Slide 24: Continued Focus on Our Portfolio Strategy
Continued Focus on Our Portfolio Strategy KalVista remains focused on delivering oral plasma kallikrein inhibitors for: prophylactic treatment of HAE DME Formulation development suggests that it is feasible to modulate the release profile of KVD900 for potential prophylactic use Dosing of delayed re
Slide 25: Diabetic Macular Edema (DME)
Diabetic Macular Edema (DME)
Slide 26: Diabetic Macular Edema: Over $1 Billion Market
Diabetic Macular Edema: Over $1 Billion Market Retinal swelling due to leaky blood vessels in the macula – a leading cause of blindness Approximately 900,000 patients in the United States have active DME and are at serious risk of vision loss – affects over 16% of diabetes patients1 Standard of care
Slide 27: 40% of Anti-VEGF Patients Not Adequately Treated
Protocol I analysis of ranibizumab treated eyes (n=340 at 12 wks) 40% anti-VEGF Patients Not Adequately Treated Large well controlled trial (DRCR Protocol I) of anti-VEGF treatment in DME patients evaluated 854 eyes 40% of eyes showed -0.3 letters of improvement in mean BCVA after 3 injections Gonza
Slide 28: KalVista Offers a Novel Therapeutic Approach
DME Diabetic Retinopathy Retina ischemia CURRENT TREATMENT Anti-VEGF Therapies (Lucentis, Eylea) VEGF NOVEL TREATMENT KalVista Pkal Inhibitor: Intravitreal KVD001 and oral program Retinal vessel leakage and hemorrhage Plasma Kallikrein TREATMENT KalVista KalVista Offers a Novel Therapeutic Approach
Slide 29: Plasma Kallikrein Elevated in DME Vitreous
Plasma Kallikrein Elevated in DME Vitreous Vitreous samples from patients with DME show increased Pkal levels Significant population has elevated Pkal and low VEGF Patients who may respond well to Pkal inhibition and poorly to anti-VEGF treatment Clear medical need Presence of Pkal in addition to VE
Slide 30: Plasma Kallikrein-Mediated Retinal Edema
Clermont et al, Diabetes 2011 Kita et al, Diabetes 2015 Injection of Pkal into vitreous causes retinal edema Effect of Pkal is enhanced in diabetic animals Diabetes sensitizes eye to effect of Pkal Induction of diabetes in animals increases retinal leakage Knock-out of Pkal is strongly protective ag
Slide 31: KVD001 Preclinical Profile
KVD001 Preclinical Profile KVD001 is a potent inhibitor of human plasma kallikrein with a Ki of 9 nM Highly selective against related proteases Selective against a broad panel of other enzymes IVT administration to rabbits at clinically relevant doses Highest exposure in the retina Exposure maintain
Slide 32: Phase 1 Trial Results KVD001
Phase 1 Trial Results KVD001: IVT first-in-class plasma kallikrein inhibitor for DME Open label, single ascending dose Phase 1 trial in 14 DME patients complete All patients had previously received anti-VEGF treatment Well tolerated Signal of improved visual acuity following single dose Duration of
Slide 33: Option Agreement With Merck on DME Programs
Option Agreement With Merck on DME Programs In October 2017, KalVista and Merck announced a collaboration for KVD001, KalVista’s intravitreal DME program, as well as future orally-delivered plasma kallikrein inhibitors for DME developed by KalVista Merck has two options, to acquire KVD001 and/or ora
Slide 34: KVD001 Phase 2 Enrollment on Track
KVD001 Phase 2 Enrollment on Track Approximately 123 patients who have discontinued treatment with anti-VEGF therapy and who still have significant edema and reduced visual acuity Sham-controlled, double-masked clinical trial will evaluate two doses Efficacy endpoints include best corrected visual a
Slide 35: Company Achievements and Milestones
HAE portfolio update KVD001 enrollment update KVD900 Phase 2 clinical trial initiates Late 2018 KVDXXX regulatory filing YE 2018 KVD900 Phase 2 completed Mid-2019 KVD001 Phase 2 data H2 2019 2H 2017 P P Company Achievements and Milestones
Slide 36: KalVista Pharmaceuticals
KalVista Pharmaceuticals NASDAQ: KALV
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