Presentation to J.P. Morgan 33rd Annual Healthcare Conference. Moshe Manor President and CEO January 15, 2015

Transcription

1 Presentation to J.P. Morgan 33rd Annual Healthcare Conference Moshe Manor President and CEO January 15,

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 regulatory approvals, market opportunity for, and potential sales of, the Company s product and product candidates, goals as to product candidate development and timing of the Company s clinical trials, are based on the Company s current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company s filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today s date. The Company undertakes no obligation to update or revise the information contained in this presentation whether as a result of new information, future events or circumstances or otherwise. 2

3 Protalix is proud of its success First company to gain FDA approval for plant based production of a protein Platform can manufacture complex proteins, antibodies and vaccines Ability to orally deliver certain therapeutic proteins as demonstrated in animal models Scalable and capital efficient production 3

4 Moving forward, Protalix will continue to leverage multiple unique advantages of the proprietary plant based platform Biologic optimization IP Drivers Internal capabilities developed to improved biologic dynamics (e.g., glycosylation, half life) of a protein Success in leveraging these capabilities in current pipeline Potential workaround manufacturing IP for certain proteins Difficult to Express Cost Time to clinical material Oral delivery Ability to express certain proteins that are difficult to express in other systems Lower cost of scale up (CapEX) and production (COGS, animal free virus inactivation) Ability to more rapidly develop clinical material for testing versus other protein platforms Protein protected inside plant cell enabling oral delivery demonstrated in animal models 4

5 Protalix Vision To become a fully integrated biopharmaceutical company leveraging Protalix s unique technology platform advantages 5

6 Evolution of the Protalix strategy 6

7 Strategy highlights Work with Pfizer to continue to drive penetration and share capture including launch in new territories Maximize opportunity in single payer markets especially Brazil Drive clinical development of BioBetter product for Fabry s Disease Accelerate early clinical validation of oral anti-tnf and DNase products Improve oral GCD formulation to provide a higher effective dose Focus early stage pipeline on BioBetter opportunities 7

8 Overview of the visible BioBetter pipeline PRX 102 for Fabry s Disease PI/II results PIII initiation Filing PRX 106 Oral anti-tnf Initiate Non- IND Clinical POC Non IND Clinical POC results PRX 110 Dnase AIR for CF Initiate Non- IND Clinical POC Non IND Clinical POC results PRX 112 Oral GCD New formulation 8

9 Overview of PRX-102 for Fabry s Disease Market overview 8,000 diagnosed patients; 4,500 treated Fabrazyme (Genzyme), Replagal (Shire, Ex-US only); Market ~$ 1 billion High unmet need: efficacy and safety Improved pharmacokinetics Protalix program profile PRX Potential for clinically superior enzyme replacement therapy through chemical modification Development plan - PRX Phase I/II results by year end Phase III to be initiated early 2016 Protalix to fund development through phase III AUC (ug/ml*min) Area Under the Curve (AUC) 4200 PRX-102 (0.2mg/Kg) PRX-102 (1mg/Kg) 575 Fabrazyme (1mg/Kg) 9

10 Phase I/II for PRX-102 in Fabry s Disease by the numbers Total patients treated to date (6 at 0.2 mg/kg; 6 at 1 mg/kg; 1 at 2 mg/kg) Patients included in interim safety analysis at 0.2 and 1 mg/kg dosage Patients included in interim efficacy analysis at 0.2 mg/kg dosage month efficacy follow-up Patients being screened for inclusion at 2 mg/kg 10

11 Unmet needs remain in the treatment of Fabry s Disease The potential to treat patients with an improved alternative of enzyme replacement therapy would be a significant advance in the treatment of Fabry disease. Professor Raphael Schiffmann, Director, Institute of Metabolic Disease at the Baylor Research Institute, Dallas, Texas Principal investigator in the PRX-102 clinical trial Disease continues to progress even for patients on long term ERT therapy 2013 Rombach et al Antibodies developed by 50-88% of Fabry patients treated with ERT Impact of IgG positivity on long term outcomes are unclear 2004 Linthorst et al Safe to switch from agalsidase-β between agalsidase-α 2014 Tsuboi et al 11

12 Meaningful Kidney Gb3 reductions after 6 months of treatment Capillary Gb3 scores using semi quantitative method Capillary mean Gb3 scores using quantitative BLISS method n=5 0.2mg/kg Abnormal capillary score* 56% 17% 69.6% 0.2mg/kg % % Normal capillary score** 44% Baseline 83% 6 months 88.6% % Baseline 6 months Baseline 6 months Baseline 6 months Overall Male Female n= 5 n=3 n=2 * Abnormal capillary score defined as sum greater than on a scale of 0-3 indicating capillary damage in >300 capillaries per biopsy ** Normal capillary score defined as sum less than 0.5 on a scale of 0-3 capillary damage >300 capillaries per biopsy sample 12

13 Dramatic Pain Improvement These interim results provide very encouraging efficacy and safety data with PRX- 102 Of particular note are the meaningful reductions in pain and renal Gb3 levels and favorable safety Brief Pain Inventory (BPI) scale n=6 0.2mg/kg -100% -78.8% Dr. Derralynn Hughes Lysosomal Storage Disease Unit, Institute of Immunity and Transplantation, Royal Free London NHS Foundation Trust, London, UK Principal investigator in the PRX- 102 clinical trial Worst pain * Mean Interference ** * Mean score of most intense pain within a 24 hour period * * Impact or interference with daily functioning,(eg. walking ability, work, mood, enjoyment of life, relations with others) 13

14 Stability across all disease parameters Stable cardiac function n=6 6 mos. 0.2mg/kg Parameter BL (mean) 6M (mean) LVM LVMI Mean Change EF Stable kidney function n=6 6 mos. 0.2mg/kg Mean egfr Mean Urine Protein

15 Favorable safety and tolerability Safety analysis for adverse events represents a total of 6.7 patient years PRX-102 was well tolerated, with the majority of events being mild and moderate Only one of the 12 patients evaluated for safety experienced hypersensitivity Of eight patients evaluated for antibody formation, only two patients, or 33% of the 0.2 mg/kg dose cohort, developed antibodies 15

16 PRX 102 for Fabry s Disease Phase I/II Positive data consistent across all clinical parameters Interim Results Improved pharmacokinetics compared to the currently marketed ERTs Meaningful Kidney Gb3 reductions Dramatic pain improvement Improvement or stability across all disease parameters Favorable safety and tolerability Limited development of antibodies observed thus far Upcoming milestones Q3 2015: Interim efficacy and safety results for the 1 mg/kg dose Q4 2015: Final efficacy and safety results for the 0.2mg,1 mg and 2mg/kg doses 16

17 Overview of PRX-106 Oral Anti-tumor Necrosis Factor Alpha (anti TNF α) for Inflammatory Diseases Market overview Market for anti TNFα >$20B Multiple players including Humira (Abbvie), Remicade (J&J) Unmet need for improved efficacy, SE and delivery IBD animal model Protalix program profile P=0.001 Orally delivered anti TNFα Potential to deliver higher doses locally with fewer side effects in a convenient dosage form Development plan Pre-clinical safety and efficacy models Planning non-ind safety and efficacy clinical study in 2015 with results in early 2016 Non-diseased control 17

18 Overview of PRX-110 AIR (Actin Inhibition Resistant) DNase for Cystic Fibrosis Market overview 70,000 patients globally Market ~$600 million; Pulmozyme (Genentech) High clinical unmet needs remain to future improve airway clearance and reduce infection Protalix program profile PRX 110 AIR Designed to be clinically superior than Pulmozyme Less inhibited by the presence of actin Delivery by existing nebulizers or advanced ones Development plan - PRX AIR Rheology Data Analysis in in human sputum samples Stress as compared to control (%) Pre-clinical safety and efficacy models Planning non-ind safety and efficacy clinical study in 2015 with results in early 2016 N=6 PRX 110 AIR PRX-110 Pulmozyme 18

19 Overview of PRX-112 Oral Enzyme Replacement Therapy for Gaucher s Disease Market overview 12,000 diagnosed patients with 6,000 treated Market ~$1.4 billion; Cerezyme Cerdelga (Genzyme), VPRIV (Shire), Elelyso(Protalix/Pfizer) Opportunity to improve patient convenience with an oral alternative to infusion GCD levels in Leukocytes Following Orally Delivered prgcd in humans Protalix program profile PRX Stability in switch from IV ERT treated patients Oral delivery of drug Development plan - PRX First wave of pre-clinical safety and efficacy models complete as well as a Phase I. Phase IIa on-going Focusing efforts on improving formulation 19

20 Financial Overview ~ 93.5M shares outstanding, as of December 31, 2014 US, Israeli and EU institutional holders Dual listed on NYSE MKT and TASE Strong cash position: ~$54 M in Cash, as of December 31, 2014 $69M convertible note due by September years of tax exemption after using NOL (currently ~ $120M) 20

21 Protalix has an exciting road ahead Promising results for flagship product for Fabry s Disease 2015 includes three molecules in clinical development Clinical stage pipeline targeting markets that are >$5 billion R&D focus to fill early pipeline with attractive BioBetter opportunities 21

22 and multiple near term catalysts Initiate POC study for PRX 106 (oral anti TNF) Initiate POC study for PRX 110 AIR DNase (CF) Report interim results on the 1mg/kg dose from the ongoing Ph I/II trial for PRX 102 (Fabry) Report final results from ongoing Ph I/II trial for PRX 102 (Fabry) Report results from POC for PRX 106 (oral anti TNF) Report results from POC for PRX 110AIR DNase (CF) Initiate Phase III trial for PRX 102 (Fabry) 22

23 Moshe Manor President and CEO Protalix Biotherapeutics 23