20 slides from Protalix Biotherapeutics, Inc. (de)'s technical presentation, Nov 23, 2015
Slide 1: PRX-102 - A Novel Enzyme Replacement Therapy for Fabry Disease
PRX - 102 prh - Galactosidase - A Novel Enzyme Replacement Therapy for the Treatment of Patients with Fabry Disease 1 11/23/2015 1
Slide 2: Note Regarding Forward-Looking Statements
This presentation contains forward - looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward - looking statements including, among others, statements regarding expectations as to r
Slide 3: PRX-102: A Chemically Modified Plant Derived Human α-galactosidase-A Enzyme
PRX - 102: A Chemically Modified Plant Derived Human α - galactosidase - A Enzyme • PRX - 102 ( prh - alpha - GAL - A) is a chemically modified, recombinant DNA derived protein expressed from tobacco plant cells in suspension • The enzyme is: – Designed to be potentially superior to the currently ap
Slide 4: Unique Clinical Benefits Shown in Patients
Unique Clinical Benefits Shown in Patients ( ~15 patients’ years) 1. PRX - 102 has enhanced pharmacokinetic properties including a half - life (T½) of approximately 60 hours and a substantially higher AUC 2. PRX - 102 is well tolerated with favorable safety profile • The majority of adverse events b
Slide 5: Additional Efficacy Results
Additional Efficacy Results • A favorable trend was observed in Gastrointestinal Symptoms Assessment using the Gastrointestinal Symptoms Assessment questionnaire (GSA) – Severity and frequency of abdominal pain – Frequency of diarrhea • All patients exhibited stable cardiac function (LVM, LVMI and E
Slide 6: Enhanced Pharmacokinetics
0.001 0.010 0.100 1.000 10.000 100.000 0 5000 10000 15000 20000 Concentration ( ug /ml) Time (min) PRX - 102 2mg/Kg 1mg/Kg 0.2mg/Kg Algasidase beta time frame ~14 days Enhanced Pharmacokinetics 0 5000 10000 15000 20000 25000 30000 35000 40000 45000 PRX-102 (0.2mg/Kg) PRX-102 (1mg/Kg) PRX-102 (2mg/Kg
Slide 7: Favorable Safety Profile: Very Low Formation of Antibodies
Favorable Safety Profile: Very Low Formation of Antibodies • Adverse Events: ( ~15 patients’ years) – 98% AEs mild and moderate – 2% severe, 1% was treatment related – 27% were considered related or possibly related – 2 serious AE: 1 treatment related • Antibodies: – Low incidence with low titers of
Slide 8: Immune Tolerance
Immune Tolerance – PRX - 102 unique and enhanced PK properties potentially contributing to an immune tolerance phenomenon – Transient and reversible shift of overall drug availability in antibody positive patients – Low incidence of antibody formation with low titers which are reduced by 1 year of t
Slide 9: Immune Tolerance: Representative PK Profiles
Representative of PK of antibody negative patients Representative PK of ADA positive patients 10 100 1,000 10,000 0 50 100 150 200 250 300 350 400 Concentration (ng/mL) Time (hr) Subject 51 - F102; 0.2 mg/kg Day 1 3 Months 6 Months 12 Months 10 100 1,000 10,000 0 20 40 60 80 100 120 Concentration (n
Slide 10: Reversal in eGFR Slope Achieved Suggesting Improvement in Kidney Function
Population Annualized Rate of Estimated GFR Change (mL/min/1.73 m 2 /year) (95% Confidence Interval) ( Rombach et al., ( 2014 ) Untreated Males, GFR>60 - 3.00 ( - 3.20 , - 2.80 ) ERT Treated Males, GFR>60 - 2.57 ( - 3.21, - 1.93) PRX - 102 Phase 1 / 2 PRX - 102 treated males GFR>60 (0.2mg/kg) 0.16 (
Slide 11: Development Plan: Clear Path for BLA Submission
PRX - 102 Development Plan Clear Path for BLA submission – Phase 1 / 2 - Interim reports to date – FDA - End of phase II meeting held, minutes received – Plan to submit SPA for final study design in December 2015 Outlines are developed with lead KOLs including : D. Warnock, D. Hughes, R. Schiffmann
Slide 12: The Need for Alternative Treatments for Fabry Disease
The Need for Alternative Treatments for Fabry Disease Prof. Raphael Schiffmann Metabolic Disease, Baylor Research Institute, Dallas 12 11/23/2015 12
Slide 13: Specific Therapy for Fabry Disease
Specific Therapy for Fabry Disease • Currently only one enzyme replacement therapy (ERT), Fabrazyme ® (Genzyme), is approved in the US • A second one, Replagal® (Shire), is approved outside the US • Randomized controlled trials of either product have not shown a clinical effect
Slide 14: Limited Benefit of Current ERTs for Fabry Disease
Limited Benefit of Current ERTs for Fabry Disease Cumulative evidence from open l abel s tudies of approved ERTs in adults has shown a limited effect to date • Limited effect in slowing progression of renal disease • Decreases gastrointestinal symptoms • Possibly some stabilization of the peripheral
Slide 15: Shortfalls of Current ERT
Shortfalls of Current ERT • Not given often enough – patient not protected in the second week due to short half - life • High incidence of Neutralizing antibodies • ERT does not gain access to all cells in all relevant organs in sufficient amount • ERT likely initiated too late in life
Slide 16: Potential Benefits and Improvements for Fabry Treatment
Potential Benefits and Improvements of PRX - 102 for Fabry Treatment • Unique PK profile suggesting a better two week coverage to patients and potentially better penetration to target organs • Excellent safety profile couple with very limited formation of antibodies • Very promising results across a
Slide 17: Potential Benefits to Patients Derived from Unique Characteristics
0.001 0.010 0.100 1.000 10.000 100.000 0 5000 10000 15000 20000 Concentration ( ug /ml) Time (min) PRX - 102 2mg/Kg 1mg/Kg 0.2mg/Kg Algasidase beta time frame ~14 days ~1/2 day 10 100 1,000 10,000 0 20 40 60 80 100 120 Concentration (ng/mL) Time (hr) Subject 17 - F105; 0.2 mg/kg Day 1 3 Months 6 Mon
Slide 18: Phase III Clinical Trials - Attractive to Patients and Physicians
Phase III Clinical Trials – Attractive to Patients and Physicians • Favorable safety and efficacy profile from results to date will encourage patients and doctors to participate • For naïve study, relatively short - term trial of up to 6 months with a commitment to all patients to be on PRX - 102 th
Slide 19: Summary
Summary • There is a clear need for a better ERT for Fabry patients • PRX - 102 seems to have the potential to meet such demand based on its unique enzyme characteristics including PK profile and clinical results to date • The company has a clear path forward to support full approval
Slide 20: Conclusion
Conclusion • Superiority profile of PRX 102 is being built over time in number of layers: – Favorable Safety Profile with limited need for pre medication – Excellent immunogenicity profile with limited formation of antibodies – Favorable trend in kidney function – Immune tolerance phenomena is being