OPKO Health, Inc. · NASDAQ:OPK
OPKO Health — Merger or Acquisition (July 2013)
28 slides from OPKO Health's merger presentation, Jul 3, 2013
Slide 1: MOD-5014 - A Long Acting FVIIa
MOD - 5014 - A Long Acting FVIIa NYSE Amex: PBTH Non - Confidential
Slide 2: Disclosures
Presentation includes discussion of the following off - label use of a drug or medical device: N/A Disclosures of: GILI HART Employment PROLOR BIOTECH Research support No conflict of interest to disclose Scientific advisory board No conflict of interest to disclose Consultancy No conflict of interes
Slide 3: PROLOR Biotech: biobetter drugs with enhanced longevity
3 PROLOR BIOTECH Confidential Generation of biobetter drugs by enhancing the longevity of proteins, peptides and small molecules which require frequent injections
Slide 4: CTP Technology Created By Nature During Evolution
D B C A Two fertility hormones hCG – maintains pregnancy and requires long T 1 / 2 hLH – stimulates ovulation on a pulse mode requiring a short T 1 / 2 Amino acid sequence of hCG & hLH is almost identical E The 28 amino acid C - terminal peptide (CTP) of hCG with its 4 O - glycans does not exist in
Slide 5: CTP Increases Proteins Circulation Time
CTP Increases Proteins Circulation Time + = Any Short - Lasting Protein CTP Long - Lasting Protein CTP – A Natural Sequence Created During Evolution to Enhance Longevity of the hCG Hormone 5
Slide 6: CTP Competitive Advantages - Best Of Breed Combination
CTP PEGylation Protein Fusion DNA Mutations • Add sugar chains • Increase negative charge • Increase size • Slow enzymatic cleavage • Increase size • Slow enzymatic cleavage - FcR x Increase size x Slow enzymatic cleavage x Add sugar chains x Increase negative charge CTP Competitive Advantages - Bes
Slide 7: CTP: Clinically Validated Technology
CTP: Clinically Validated Technology Merck ’s long - acting FSH - CTP (Elonva®) received EU marketing authorization in 2010 Single FSH - CTP injection replaces 7 daily FSH injections in fertility treatment Extended immunogenicity studies PROLOR completed 4 clinical studies with its long acti
Slide 8: FVIIa-CTP Product Description
FVIIa - CTP (MOD - 5014) Product Description 8 Light Chain s s Catalytic Domain (HC) FVII - CTP is a single chain FVII directly linked to CTP peptide . The protein is expressed in CHO cells A FVIIa - CTP (MOD - 5014 ) specific purification and activation process was developed . CTP
Slide 9: Long Acting FVIIa-CTP – IV Administration
Long Acting FVIIa - CTP – IV Administration □ PK - PD rats □ Warfarin induced bleeding in rats □ Prothrombin time (PT) □ Bleeding Challenge □ Hemophilic Mice □ PK - PD □ TG □ Survival Study
Slide 10: FVIIa-CTP PK-PD Profile Following a Single IV Injection
10 FVIIa - CTP ( MOD - 5014 ) PK - PD Profile Following a Single IV Injection ( 189 µg/Kg) PK Parameters NovoSeven ® MOD - 5014 Half - life 1.31 6.49 AUC (U*hr/ml) 850.423 2551.7 MRT (hr) 1.2 3.3
Slide 11: Warfarin Model - FVII Transient Deficiency
Warfarin Model - FVII Transient Deficiency Male SD rats received Warfarin 24 hours pretreatment (orally) according to Diness et al. 1990 . Reduction of Vit . K dependent coagulation factors was accompanied by prolongation of PT and aPTT was measured . 11 0.00 20.00 40.00 60.00 80.00 100.00 120.0
Slide 12: Warfarin Model - Acute Effect (PT)
12 Warfarin Model - Acute Effect (PT) 12 Warfarin 24hr PT ( 15 min) IV injection NS/MOD - 5014 PT (sec)
Slide 13: Warfarin Model - Long Term Effect
Warfarin Model - Long Term Effect SD Rats were given Warfarin orally In - parallel to Warfarin, Novo Seven or MOD - 5014 were administered. PT was measured at designated time points and compared to placebo post treatment . 24hr 24 hr PT (24hr) IV injection NS/MOD - 5014 + Warfarin treatment PT
Slide 14: Warfarin Model - Long Term Effect (PT) - 1000 µg/Kg
Warfarin Model - Long Term Effect (PT) - 1000 µg/Kg 14 Placebo NS MOD - 5014 pre dose 10.87 10.93 11.60 10hr 21.37 10.50 8.45 24hr 40.48 37.60 17.37 36hr 79.05 73.30 32.00 48hr 80.5 78.00 42.00 PT (24hr) 24hr Warfarin treatment + IV injection NS/MOD - 5014 PT (36hr) 24 hr PT (48hr) 0.00 10.00 20.00
Slide 15: Warfarin Induced Bleeding Model - Long Term Effect (Tail Clip Model)
Warfarin Induced Bleeding Model - Long Term Effect (Tail Clip Model) SD Rats were given Warfarin orally Rats were anaesthetized and Novo Seven or MOD - 5014 were administered in - parallel to Warfarin ( 1000 µg/Kg) Full transection of the tail tip was made and bleeding intensity was measured f
Slide 16: Warfarin Induced Bleeding Model - Long Term Effect - IV (Tail Clip Model)
Warfarin Induced Bleeding Model - Long Term Effect - IV (Tail Clip Model) 16 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 0 1 2 3 4 5 6 7 8 blood loss (g) Group data point Average Naïve Vehicle NS MOD - 5014 NS MOD - 5014 NS MOD - 5014 15 min 24 h 48 h
Slide 17: PK-PD Profile Following a Single IV Injection to FVIII-/- Mice
17 MOD - 5014 PK - PD Profile Following a Single IV Injection to FVIII - / - Mice PK Parameters NovoSeven MOD - 5014 Half - life 0.96 5.1 AUC (U*hr/ml) 103.08 496 Recovery 12.1% 39% 20 0 50 100 Thrombin (nM IIa) Time after injection (h) Maximal Amount of Thrombin Per Time Point NS FVIIa-CTP 1.0 10.0
Slide 18: TVT (Tail Vein Transection) Study design
TVT (Tail Vein Transection ) Study design FVIII - / - mice were administered IV with 4mg FVIIa /Kg of NS or MOD - 5014. 24 hr post dosing the tail vein was cut . Animals survival and clinical condition was evaluated for the next 12 hr . NS/ MOD - 5014 injection TVT 24 hr Post dosing Overall %S
Slide 19: TVT Study Results – 24hr post injection
19 TVT Study Results – 24hr post injection 19 0 10 20 30 40 50 60 70 80 6HR 10HR 12HR % of Surviving mice Time Post TVT (hours) NovoSevem MOD-5014 0 20 40 60 80 100 120 0 2 4 6 8 10 12 % of Surviving animals Time post TVT (hours) MOD-5014 (24h) NovoSeven (24h) Overall % Survival – TVT 24 hr post Inj
Slide 20: PK-PD Profile Following Single SC Injection to Rats
MOD - 5014 PK - PD Profile Following Single SC Injection to Rats (360µg/Kg) 1.0 10.0 100.0 1000.0 10000.0 100000.0 0 10 20 30 40 50 60 Activity (mU/ml) Time (hr) NS SC MOD-5014 Unit base IVR ( 2 X) Bioavailability ( 2.5 x) Half life
Slide 21: Warfarin Model - Long Term Effect (PT) - SC 2000 µg/Kg
21 Warfarin Model - Long Term Effect (PT ) - SC 2000 µg/Kg 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00 90.00 pre dose 10hr 24hr 36hr 48hr PT (sec) Time post injection Buffer NS MOD5014 PT ( 24 hr) 24hr Warfarin treatment + IV injection NS/MOD - 5014 PT ( 36 hr) 24hr PT ( 48 hr) Buffer NS MO
Slide 22: Warfarin Induced Bleeding Model - Long Term Effect (Tail Clip Model) – SC
22 Warfarin Induced Bleeding Model - Long Term Effect (Tail Clip Model ) – SC 1000µg/Kg 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 Vehicle NovoSeven MOD-5014 blood loss (g) 2h 24h 40h 48h
Slide 23: TVT Following SC Administration Study Design
TVT Following SC Administration Study Design FVIII - / - mice were administered SC with MOD - 5014 or NovoSeven ( 4 mg/Kg) Five mice were injected with 100 ul of vehicle as control 12 hr post dosing the tail vein was cut Animals survival and clinical condition was evaluated for the next 12 h
Slide 24: FVIIa-CTP Has a Profound Survival Effect Compared to NovoSeven Following SC
24 FVIIa - CTP has a Profound Survival Effect as Compared to NovoSeven following SC Administration 24 0 10 20 30 40 50 60 FVIIa-CTP NovoSeven TVT Survival 12 h Following SC in FVIII - / - mice 11 % 55% MOD - 5014 %Survival Rate
Slide 25: Program - IV Administration: Summary & Perspectives
MOD - 5014 Program - IV Administration : Summary & Perspectives Protein In – vitro Characterization Similar in - vitro Thrombin Generation (TG) performance as compared to NovoSeven Similar in - vitro coagulation efficiency compared to NovoSeven as evaluated in Thrombelastography (TEG) MOD -
Slide 26: Program Status
MOD - 5014 Program Status Manufacturing Manufacturing process performance is comparable to NovoSeven large scale GMP manufacturing process High concentration Liquid formulation (Supports SC) Non – Viscous □ Pre - Clinical x Pharmacological studies – completed x Toxicological program - On g
Slide 27: Immunogenicity Testing
27 Immunogenicity Testing Test Specimen Negative Positive Subject is positive for Neutralizing antibodies For MOD - 5014 or/and hFVII Subject is positive for Binding antibodies Screening Assay Titer Assay Confirmatory Assay with MOD – 5014 Immunocompetition Reactive Negative Nab Positive Nab Negativ
Slide 28: Thank You
28 Thank You gili@prolor - biotech.com