Kalvista Pharmaceuticals, Inc. · NASDAQ:KALV
Kalvista Pharmaceuticals — Technical Presentation (May 2023)
14 slides from Kalvista Pharmaceuticals's technical presentation, May 2023
Slide 1: Rationale for the Short-term Prophylaxis Regimen With Sebetralstat in KONFIDENT-S
13th C1 Inhibitor Deficiency and Angioedema Workshop, 4-7 May 2023 Budapest, Hungary Rationale for the Short-term Prophylaxis Regimen With Sebetralstat in KONFIDENT-S Matthew Iverson, Edward Duckworth, Erik Hansen, Sally L. Hampton, Michael D. Smith, Paul K. Audhya, Christopher M. Yea KalVista Pharm
Slide 2: Disclosures and Acknowledgments
Disclosures and Acknowledgments • Disclosures: All authors are employees of KalVista Pharmaceuticals • This study was performed by KalVista Pharmaceuticals Ltd. Medical writing assistance was provided under the direction of the authors by Katherine Stevens-Favorite, PhD, of Cadent, a Syneos Health G
Slide 3: Background
Background • HAE is a rare and potentially life-threatening genetic disease characterized by recurrent episodes of swelling; attacks can have a significant negative impact on patients’ quality of life1-3 ‒ For many patients with HAE, guidelines recommend the use of STP prior to medical or dental pro
Slide 4: KONFIDENT Trials
KONFIDENT Trials • Sebetralstat is a novel investigational oral plasma kallikrein inhibitor for the on-demand treatment of HAE attacks that showed a favorable PK and PD profile and positive efficacy and safety results in a recent phase 2 trial1,2 • The phase 3, randomized, double-blind, placebo-cont
Slide 5: KONFIDENT-S Includes Rollover Patients From KONFIDENT and Naïve Patients
KONFIDENT-S Includes Rollover Patients From KONFIDENT and Naïve Patients KONFIDENT-S (NCT05505916)1 End-of-Trial Rollover Visit Patients (Completed KONFIDENT2) N≈150 Enrollment Visita Treatment Period (0-24 Months) Naïve Monthly Quarterly Visits Visits (Months 6, 9, 12, 15, Patients In-clinic (Month
Slide 6: Evaluation of Short-term Prophylaxis in KONFIDENT-S Trial
Evaluation of Short-term Prophylaxis in KONFIDENT-S Trial • During KONFIDENT-S, participants may use sebetralstat for on-demand treatment or, on a case-by-case basis, after consultation with the investigator and the patient, as STP therapy for a surgical, medical, or dental procedure • To support th
Slide 7: Methods
Methods • This phase 1, double-blind, placebo-controlled, • Venous blood was collected for PK and PD multiple-dose, multiple-cohort study evaluated the measurements at prespecified intervals following the safety, tolerability, and PK of multiple doses of 600 mg first and third doses, up to 40 hours
Slide 8: Maximum Plasma Concentrations of Sebetralstat Were Similar After Dose 1
Maximum Plasma Concentrations of Sebetralstat Were Similar After Dose 1 Maximum Plasma Concentrations After Dose 1 and Dose 3 Dose 1 Dose 3 Cohort 1; q8h Geometric mean 3916 ng/mL 8838 ng/mL Cmax (CV%) (104.7%) (92.8%) (n=6) Cohort 2; q4h Geometric mean 4412 ng/mL 7136 ng/mL Cmax (CV%) (54.3%) (32.8
Slide 9: A Geometric Mean PKa Inhibition of >90% Was Achieved Within 30 Minutes of Dose 1
A Geometric Mean PKa Inhibition of >90% Was Achieved Within 30 Minutes of Dose 1 in All Cohorts 120 Cohort 1 (q8h) PKa Activity % of Predose Cohort 2 (q4h) 100 (geometric mean ± SD) Cohort 3/4 (q2h) 80 60 50% Inhibition 40 20 80% Inhibition 90% Inhibition 0 0 4 8 12 16 20 24 28 32 36 40 Time After I
Slide 10: Geometric Mean PKa Inhibition Was at >90% Then >80% Through 28 Hours After 3 Doses
Geometric Mean PKa Inhibition Was at >90% Through 24 Hours and Then >80% Through 28 Hours After 3 Doses of Sebetralstat in Cohort 1 (q8h) 600 mg Sebetralstat Dosed Every 8 Hours, 3 Doses (n=6) 17,500 Sebetralstat plasma 100 concentration 90 Sebetralstat PKa PKa Activity % of Predose 15,000 (geometri
Slide 11: Sebetralstat Was Well Tolerated in All Cohorts
Sebetralstat Was Well Tolerated in All Cohorts • Adverse events were mild and comparable between treatment groups receiving sebetralstat and placebo – No participants discontinued the trial because of an adverse event • No serious adverse events occurred during the trial, and all adverse events were
Slide 12: Administration of Sebetralstat for Short-term Prophylaxis in KONFIDENT-S
Administration of Sebetralstat for Short-term Prophylaxis in KONFIDENT-S Begins 1 Hour Prior to a Surgical, Medical, or Dental Procedure Medical or dental procedure start time A 6-hour interval was chosen to allow flexibility around sleep Approx Approx 6 hours 6 hours or other patient life events af
Slide 13: Conclusions
Conclusions • Three doses of sebetralstat within 24 hours were well tolerated and led to drug accumulation • Geometric mean PKa inhibition of >80% was maintained for 28 hours when dosing sebetralstat q8h • Based on these data, KONFIDENT-S will prospectively evaluate the effectiveness and safety of t
Slide 14: Thank You
Thank You
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