Protalix BioTherapeutics, Inc. (de) · AMEX:PLX

Protalix BioTherapeutics, Inc. (de) — Technical Presentation (2014)

18 slides from Protalix BioTherapeutics, Inc. (de)'s technical presentation, Aug 2, 2014

1. Slide 1: Phase I Clinical Study: Oral Delivery of prGCD for Gaucher Disease

   Phase I Clinical Study Oral Delivery of prGCD (plant recombinant human glucocerebrosidase) for the Treatment of Gaucher Disease Ari Zimran Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel

2. Slide 2: Disclosures

   Disclosures Protalix Biotherapeutics -Receives consultancy fees -Has options -Member of Scientific Advisory Board Genzyme/Sanofi -Support for participation in the ICGG Registry (to institution) -Honoraria Shire -Support for participation in the Gaucher Outcomes Registry (to institution) -Honoraria P

3. Slide 3: Oral Administration of Therapeutic Proteins

   Oral Administration of Therapeutic Proteins The challenge of oral delivery of therapeutic proteins  Long-time goal of the biopharmaceutical industry  Stability, enzymatic degradation and ineffective absorption  Currently only very limited success Plant cells – Oral Delivery Platform  Natural cap

4. Slide 4: PRX-112 Oral ERT for Gaucher Disease

   PRX-112 Oral ERT for Gaucher Disease  Edible carrot cells expressing recombinant human glucocerebrosidase (prGCD)  Produced by the same cells as the approved drug taliglucerase alfa  Carrot cells contain “ready to use” enzyme  Once in blood, enzyme is expected to act like IV administered taliglu

5. Slide 5: Biodistribution of Active prGCD Following Oral Administration (animal studies)

   Biodistribution of Active prGCD Following Oral Administration (animal studies) 60 prGCD in pig plasma prGCD in Rat plasma % addition of GCD activity 50 Over baseline 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 Time post feeding (hours) 4 prGCD in rat target organs GCD activity mg/gr 4 3 liver 3 spleen tissue

6. Slide 6: PRX-112 Phase I Study

   PRX-112 Phase I Study An exploratory, open-label study to evaluate the safety of PRX-112 and pharmacokinetics of oral prGCD (plant recombinant human glucocerebrosidase) in Gaucher patients Design Primary Objective:  Adult Gaucher patients  To evaluate the safety of oral PRX- 112 in Gaucher patient

7. Slide 7: Patient Population

   Patient Population Main Inclusion Criteria Main Exclusion Criteria  Males and females, 18 years or older.  Presence of any GIT disease or symptomatology  Confirmed Gaucher disease by low leukocyte GCD activity level  Subjects with any history of allergic response to drugs or other allergies  Pl

8. Slide 8: Phase I Results - Safety

   Phase I Results - Safety  Drug was well tolerated  No drug related serious adverse reactions reported  No patient discontinued the study prematurely  No treatment induced antibodies

9. Slide 9: Safety

   Safety Severity # of AEs AEs (# of patients) % of total Adverse events 11 (7) Mild or moderate 11 (7) 100.0% Severe or very severe 0 (0) 0.0% No. of AEs (No. of % of Relatedness Patients) TotalAEs AE (#patients) Not related to 7 (5) 63.6% treatment Possibly related to 3 (2) 27.3% Mild dizziness (1)

10. Slide 10: Evaluation of prGCD Delivery in Leukocytes - Introduction

    Evaluation of prGCD Delivery in Leukocytes- Introduction  GD diagnosis is commonly performed in leukocytes  Monocytes represent a surrogate of GD target cells S. S. RAGHAVAN,1 J. TOPOL,2 AND E. H. KOLODNY' Am J Hum Genet 32:158- 173, 1980

11. Slide 11: Results: GCD Activity in Leukocytes Following Orally Delivered prGCD

    Results: GCD Activity in Leukocytes Following Orally Delivered prGCD 1.40 1.40 Baseline Day 1 1.20 1.20 Day 3 1.00 1.00 Cmax (ng/mL) Cmax (ng/mL) 0.80 0.80 0.60 0.60 0.40 0.40 0.20 0.20 0.00 0.00 0 1 Baseline 2 1 Day 3 3 Day 4

12. Slide 12: Representative PK Profiles

    Representative PK Profiles Subject A02-005 (~500U) Subject A01-007 (~500U) Subject A01-008 (~500U) 0.90 Concentration GCD/TSP (ng/mg) 1.20 1.20 0.80 1.00 1.00 0.70 0.60 0.80 0.80 0.50 0.60 0.60 0.40 0.30 0.40 0.40 0.20 0.20 0.20 0.10 0.00 0.00 0.00 8 13 18 23 28 8 13 18 23 28 8 13 18 23 28 Time (hr)

13. Slide 13: PK Summary of Oral Delivered prGCD

    PK Summary of Oral Delivered prGCD  Active enzyme was detected in patients' blood circulation following oral administration  The observed increase in Cmax and the AUC values of active GCD in leukocytes constitute evidence of absorption of prGCD after oral administration of PRX- 112  PK profile is

14. Slide 14: Oral treatment

    PTX ww 'nxioin Tm LE NIn'90 - ANAI7IONA :NNAoYN NINN dyn 19/10/1980 sat yen YSS Abi- Full Name Units 25/10/2012 09/04/2013 3010472013 01/05/2013 08/05/2013 20/08/2013 02/09/2013 11/09/2013 ioe 10:27 10:53 10:36 08:56 10:24 09:49 09:55 880688 238250 254475 256414 260813 339913 349780 356313 iC Popula

15. Slide 15: Effect of Oral prGCD on Thrombocytopenia

    Effect of Oral prGCD on Thrombocytopenia Platelet Platelet levels levels end of Change in plt % change in Patient ID Gender Dose (U) baseline study level plt levels (103/ml) (10 /ml) 3 A01-001 M ~250 60,000 61,000 1,000 1.67 A01-002 M ~250 95,000 130,000 35,000 36.84 A01-003 F ~250 81,000 142,000 61

16. Slide 16: Overall Conclusions

    Overall Conclusions  Presence of an active enzyme was detected in patients' blood circulation following oral administration  Oral GCD was found to be safe and well tolerated in all 16 patients across all of the three doses tested  Some of the patients with thrombocytopenia demonstrated an unexpec

17. Slide 17: Clinical Investigators and Contributors

    Clinical Investigators and Contributors Ari Zimran1, Hanna Rosenbaum3, Myriam Golembo2, Svetlana Velitski2, Raul Chertkoff2, Einat Almon2, Yoseph Shaaltiel2 Affiliations: 1Shaare Zedek Medical Center, Jerusalem; 2Protalix Biotherapeutics, Carmiel, 3Rambam Medical Center, Haifa, Israel.

18. Slide 18: Special thanks

    Special thanks to the patient and the hospital staff: nurses, coordinators, MDs and pharmacists [email protected]

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