Slide 1: Vectus Biosystems: VIP Technology
For personal use only Vectus Biosystems Vasoactive Intestinal Peptide (VIP) TECHNOLOGY 1
Slide 2: Oral VIP Agonists: A Platform Technology for Fibrotic Diseases
For personal use only Oral VIP Agonists A Platform Technology for the Management of Fibrotic Diseases 2
Slide 3: VIP Agonists for Hypertension, Cardiovascular and Renal Disease
For personal use only VIP AGONISTS FOR THE MANAGEMENT OF HYPERTENSION, CARDIOVASCULAR AND RENAL DISEASE 3
Slide 4: Background
4 For personal use only Background
Slide 5: 21st Century Health Challenges
21st Century Health Challenges For personal use only • Hypertension affects 40% of the adult population worldwide, less than 25% of patients achieve target blood pressure, it is a major risk factor for – heart failure – kidney failure – stroke – dementia • Heart failure – affects 5% of those >50 yrs
Slide 6: Vasoactive Intestinal Peptide (VIP)
Vasoactive Intestinal Peptide (VIP) For personal use only • First isolated by Said and Mutt in 1970 • 28 amino acid peptide • Amino acid sequence identical across all mammalian species except the guinea pig • Described as “the most potent vasodilator known” • Participates in sodium homeostasis as a
Slide 7: VIP Reverses Fibrosis – Models
VIP Reverses Fibrosis – 3 Models For personal use only a normotensive rats on 4.4% salt diet treated with VIP a (5pmol/kg/min) or control vehicle infusion for 4 weeks b rats on 4.4% salt diet plus L-NAME (10mg/kg/day) treated with VIP (5 pmol/kg/min) or vehicle control infusion for 4 weeks c fibrosi
Slide 8: Systolic Blood Pressure Effects
For personal use only Systolic Blood Pressure Effects 8
Slide 9: Systolic Blood Pressure
Systolic Blood Pressure For personal use only 30 30 50 Change in SBP (mmHg) VIPAG1b 20 B Decrease in SBP (mmHg) B Decrease in SBP (mmHg) 40 10 20 B J 30 B 0 JB B -10 J 20 B 10 enalapril -20 10 B R2=0.9553 R2=0.9347 -30 0 0 0 2 4 1 10 100 1000 10000 0 2 4 6 8 10 Time (weeks) Dose (pmol/kg/min) Time (
Slide 10: Anti-Fibrotic Actions
For personal use only Anti-Fibrotic Actions 10
Slide 11: Myocardial Fibrosis
Myocardial Fibrosis For personal use only 25 • Upper Panel: Myocardial fibrosis after 4 weeks treatment with VIP (5pmol/kg/min) or enalapril (dose adjusted to Myocardial Fibrosis (% surface area) # 20 maintain the same BP reduction as VIP average dose 705 p<0.0005 pmol/kg/min). * p<0.005, ** p<0.001
Slide 12: Cardiac Histology
Cardiac Histology For personal use only Heart sections stained with Masson trichrome, Control 14 weeks Control 18 Weeks 18 Weeks 5% EtOH fibrous tissue appears blue-cyano in colour. Upper Panels: 14 week control fibrosis is predominantly around blood vessels with some interstitial extension 18 week
Slide 13: Effects on Kidney Fibrosis
Effects on Kidney Fibrosis For personal use only 30 # • Renal Interstitial Fibrosis (% surface area) p<0.0005 In humans increasing interstitial fibrosis in the kidney parallels the decline in renal function leading to dialysis 20 ## • Upper panel shows results from 14 week old SHR on 2.2% salt diet
Slide 14: Renal Histology
Renal Histology For personal use only Kidney sections stained with Masson trichrome, fibrous tissue appears blue in Control 14 weeks Control 18 Weeks 18 Weeks 5% EtOH colour Upper Panels: 14 week control: fibrosis surrounds some but not all tubules 18 week vehicle control: marked increase in interst
Slide 15: VB0004 Data Summary
VB0004 Data Summary For personal use only VB0004 in SHR animal term: – decreased BP in a dose dependent manner in the SHR animal model – BP reduction via both direct and endothelium dependent mechanisms – more effective than enalapril on SBP treatment (greater reduction at lower dose) – reversed fib
Slide 16: VB0004 ADME and Toxicology
For personal use only VB0004 ADME and Toxicology 16
Slide 17: ADME Toxicology - Summary
ADME Toxicology - Summary For personal use only • No behavioural evidence of toxic effects in rats • No effect on cardiac rate or evidence of cardiac arrhythmias • No residual effects after cessation • No significant inhibition of Cytochrome P450’s in therapeutic range • No mutagenic effect i.e. neg
Slide 18: Current Status
Current Status For personal use only • GMP synthesis almost complete • Animal toxicology and pharmacokinetic studies commenced • Tendering process for Phase1 underway 18
Slide 19: VIP Agonists for Fibrotic Disease in the Liver
For personal use only VIP AGONISTS FOR THE MANAGEMENT OF FIBROTIC DISEASE IN THE LIVER 19
Slide 20: Hepatic Cirrhosis (Liver Fibrosis)
Hepatic Cirrhosis (Liver Fibrosis) For personal use only • Causes – genetic – infectious (Hep A, B, C) – alcohol related – diabetic – due to obesity – cryptogenic (no discernible cause) • Prevalence – varies to >40% of the population in countries such as India, Cambodia, Vietnam and China due to end
Slide 21: Current Therapies
Current Therapies For personal use only • vaccination Hep A, Hep B for preventionn • abstinence to prevent further damage • weight loss • diabetes management • symptom relief (albumin infusion, ascites removal) • Sofosbuvir and related agents for Hepatitis C (note this treats the infection but does
Slide 22: A32 – Liver
A32 – Liver For personal use only 20 Week Control A32 20 Weeks 150 140 AST (Iu/L) 130 p<0.05 120 110 100 Control A32 10 Liver p<0.005 Treatment with A32 for 6 weeks in a rat model 8 Hepatic Fibrosis (% surface area) of liver cirrhosis resulted in significant 6 improvement in liver function (above ri
Slide 23: A32 – Other Organs
A32 – Other Organs For personal use only 15 Myocardial Fibrosis (% surface area) p<0.0005 Cardiac (upper panel) and renal (lower panel) fibrosis in SHR on a 10 p<0.005 5 2.2% salt diet after 4 weeks treatment with A32 at 500pmol/kg/ 0 min. In the heart A32 reversed Control 14 weeks A32 Control 18 We
Slide 24: Intellectual Property
For personal use only Intellectual Property 24
Slide 25: IP Position
IP Position For personal use only • VIP patents for heart, kidney and aortic fibrosis - granted most jurisdictions • VIP fragment patents compositions and methods of use for hypertension, cardiac, renal and aortic fibrosis – granted most jurisdictions • VB0004 compositions and methods of use for hyp
Slide 26: IP Position (cont)
IP Position (cont) For personal use only • P5 and library of related compounds compositions and methods of use for treatment of renal cell death, renal fibrosis and hepatic fibrosis - PCT application • GMP method of synthesis VB0004 - PCT application • A79 and related compounds compositions and use
Slide 27: VIP Agonists: the benchmark in anti-fibrotics
For personal use only VIP Agonists: the benchmark in anti-fibrotics 27
Slide 28: www.vectusbiosystems.com.au
For personal use only www.vectusbiosystems.com.au 28