Kalvista Pharmaceuticals, Inc. · NASDAQ:KALV
Kalvista Pharmaceuticals — Bradykinin Symposium 2024
13 slides from Kalvista Pharmaceuticals's conference presentation, September 2024
Slide 1: A specific, sensitive assay measuring patient sample plasma kallikrein activity
A specific, sensitive assay measuring patient sample plasma kallikrein activity D. Lee1, A. Ghannam2, N. Murugesan1, D. Vincent3, 1KalVista Pharmaceuticals, Cambridge, United States of America A. Mogg4, M. Smith1, S. Hampton4, E. Feener1a 2KininBio, Grenoble, France 3Université de Montpellier, Montp
Slide 2: Disclosures
Disclosures • Daniel Lee is a full-time employee of KalVista Pharmaceuticals • This study was funded by KalVista Pharmaceuticals 2
Slide 3: Study Overview
Study Overview Background • PKa activity: • Is a primary cause for HAE and has been implicated in other KKS-mediated diseases • Is increased in plasma of patients with HAE1-4 • Could be a biomarker for other KKS associated diseases Bradykinin • Exogenous substrates commonly used in PKa assays can be
Slide 4: Measuring sPKa Activity in Plasma
Measuring sPKa Activity in Plasma PKa activity was measured in citrated plasma • Healthy controls (n=57) • HAE type I/II (n=25) samples obtained during Demographics the intercritical period (and the participants were Sex (%) not on HAE therapies) as a pre-dose sample in Age range the open-label phar
Slide 5: Cold Exposure Increases Amidolytic Activity in Plasma
Cold Exposure Increases Amidolytic Activity in Plasma Healthy HAE type I/II n=25 n=12 150 150 • Exposure of plasma to cold (4°C) has been shown to increase PKa activity1 Vmax (nmol/min/mL) Vmax (nmol/min/mL) Amidolytic activity Amidolytic activity 100 100 • PKa activity in plasma of healthy controls
Slide 6: Using a Specific PKa Inhibitor Is Essential to Establishing Assay Specificity
Using a Specific PKa inhibitor Is Essential to Establishing Assay Specificity Healthy patient samples 8 KV01HR67 • To quantify the amidolytic activity driven by PKa, the Vmax (nmol/min/mL) KV01NI85 Amidolytic activity 6 % Inhibition KALV1073 specific inhibitor KV999272 was introduced 22% 93% KALV107
Slide 7: Measuring sPKa Activity Improves Assay Sensitivity
Measuring sPKa Activity Improves Assay Sensitivity 425 Mean activity • Total amidolytic activity and sPKa activity 25.9 24.5 (inhibitable by a PKa inhibitor) were measured in Vmax (nmol/min/mL) 225 Amidolytic activity 25 plasma after 6 hours of cold exposure 20 • In healthy plasma, sPKa activity acc
Slide 8: Plasma Samples From Healthy Individuals and Those With HAE
sPKa Activity in Plasma Samples From Healthy Individuals and Those With HAE 425 ROC curve Healthy 100 225 Specific PKa activity Vmax (nmol/min/mL) HAE type I/II 25 80 (%) 20 Sensitivity% sPKa activity at 6 hours Sensitivity 60 15 AUC 0.98 10 40 P value <0.0001 5 Healthy Healthysample sample(6 hours)
Slide 9: Plasma Samples From Women and Men
sPKa Activity in Plasma Samples From Women and Men Women Men 425 Mean age: 44 Mean age: 37 425 Mean age: 44 Mean age: 39 Range: 25-65 Range: 19-61 Healthy Range: 23-65 Range: 25-68 Healthy 225 225 Specific PKa activity Specific PKa activity Vmax (nmol/min/mL) Vmax (nmol/min/mL) HAE type I/II HAE typ
Slide 10: HAE-nC1INH: Case Study
sPKa Activity in HAE-nC1INH: Case Study 1 15 • Background Specific PKa activity Vmax (nmol/min/mL) Intercritical o 22-year-old woman 10 o Diagnosed with presumptive HAE-nC1INH by physician o History of subcutaneous and facial oedema 5 o Treated with tranexamic acid (prophylaxis) Healthy Healthy samp
Slide 11: HAE-nC1INH: Case Study
sPKa Activity in HAE-nC1INH: Case Study 2 Attack • Background 400 o 45-year-old woman Specific PKa activity Vmax (nmol/min/mL) 300 o Diagnosed with presumptive HAE-nC1INH 200 by physician Intercritical o Responsive to on-demand treatment with 100 tranexamic acid and Berinert 10 o History of subcutan
Slide 12: Conclusions
Conclusions • Results from current amidolytic activity assays for PKa can be confounded by enzymes other than PKa. Quantifying PKa specifically can be enhanced by using a PKa inhibitor • The sPKa activity assay can differentiate HAE type I/II plasma collected during the intercritical period and that
Slide 13: Authors Affiliations
Authors Affiliations 1KalVista Pharmaceuticals, Cambridge, United States Daniel K. Lee1 Arije Ghannam, MD, PhD2 of America Nivetha Murugesan, PhD1 2KininBio, Grenoble, France Denis Vincent, MD, PhD3 3Université de Montpellier, Montpellier, France Adrian Mogg, PhD4 4KalVista Pharmaceuticals, Salisbur