Introduction to Protalix Biotherapeutics. Overview of clinical trial findings. Overview of status with US FDA. Overview of three clinical trial programs.

1. pegunigalsidase alfa
a Novel Enzyme Replacement
Therapy for Fabry Disease
2018 FSIG Expert Fabry Conference
San Diego, February 9th -10th , 2018
Dr. Raul Chertkoff
VP Medical Affairs

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• Focused on the development of recombinant therapeutic
proteins with Potentially Clinically Improved Profiles
• Produced in a plant cell-based protein expression system
• Elelyso for Gaucher disease
• First plant based approved
therapeutic protein by the FDA and
world wide regulatory authorities

3. pegunigalsidase alfa:
Designed to Answer Un-met Clinical Needs
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Continuous presence of enzyme throughout the 2
weeks dosing interval
Extended stability in plasma and in target cells
Masking of enzyme parts which could be
recognized by the immune system  Potentially
reducing the immune response to the enzyme
pegunigalsidase
alfa
Un Met Clinical Needs:
• Continuous disease progression
• Immune response
• Infusion reactions
• Limited long-term efficacy
Stabilizing the molecule by a chemical modification – PEGylation
Relevant for all mutations

4. Concentration(ng/mL)
Time (hr)
Plasma pegunigalsidase alfa concentration vs. time
~14 days
10
100
1000
10000
100000
0 50 100 150 200 250 300 350
1mg/Kg
Available Enzyme Throughout 2-Week Interval
Phase 1/2 Study in Naïve FD Patients
Half life*  80 hours
*The period of time required for the amount of drug in the body to be reduced by one-half

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• Reduction of Gb3 in kidney biopsies
after 6 months
• Continuous reduction of biomarkers –
24 months
Efficacy

6. Efficacy – 24 months
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• Continuous stability of renal function
• Continuous stability in cardiac parameters
• No cardiac fibrosis
• Improvement in disease severity score (MSSI)
• Improvement in gastrointestinal symptoms

7. Safety – 24 months (906 infusions)
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* With accordance to the crurent regulatory guidelines, using sensitive and validated methods
81%
19%
Low titers
Immune tolerization
All 3 patients turned to be
negative after 12M of treatment
Neutralizing :
2 of 3 positive patients had
neutralizing activity in some
samples
Low Incidence of treatment induced
antibodies
3 out 16 patients
Favorable safety and tolerability observed with 98% of events being mild and moderate

8. PK:
pegunigalsidase has a longer half-
life and a substantially higher
AUC
 Available enzyme throughout
2-week infusion intervals
 Markedly extended circulatory
half-life compared with other
ERTs
Safety:
pegunigalsidase was found to
be well tolerated
 Majority of adverse events –
mild and moderate in severity
 Low incidence of treatment
induced ADA with reversible &
transient effect on PK
 ADA response was transient and
tolerization was observed
 ADA positivity had no observed
impact on safety and efficacy
Efficacy:
Demonstrated effectiveness, in
various disease endpoints including:
 Stable kidney and cardiac function
 Reduction of Gb3 inclusions in kidney
biopsies
 Continuous reduction of plasma Gb3
and Lyso-Gb3
 Improvement in Gastrointestinal
Symptoms- parameters
pegunigalsidase alfa – PEGylated covalently-linked recombinant alpha-GAL-A enzyme, stable homodimer,
produced in plant cells
(PRX-102)
Overall Conclusions- Interim 24 month

9. Considering two dosing regimens: potential for better efficacy and lower treatment burden
1mg/kg/2weeks 2mg/kg/4weeks
Potentially Superior ERT for
patients with progressive
disease
Potentially improved quality
of life by maintaining clinical
stability with 50% less
infusions
Dose and regimen will be based on physician assessment per individual patient
Dosing and Treatment Regimens

10. US FDA Fast Track designation for pegunigalsidase alfa –
Obtained- January 2018
 Fast Track designation based on presentation of non-clinical and clinical trial
data generated to date of medically plausible evidence demonstrating that
pegunigalsidase alfa has the potential to address an unmet medical need for
Fabry patients.
Potential Clinical Benefits
 Slow down of renal function decline and prevention of renal failure
 Improved survivability
 Positive impact on quality of life

11. Protalix Fabry Clinical Development Program
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• Monthly dosing of 2mg/kg
pegunigalsidase alpha (PRX-102)
• Patients with Fabry disease currently
treated with agalsidase alfa or agalsidase
beta
• Agalsidase beta
Fully enrolled
• Open for
agalsidase alfa
outside of US
• Every other week of 1 mg/kg
pegunigalsidase alpha (PRX-102)
• Patients with Fabry disease treated
with agalsidase beta and rapid
kidney deterioration
• Enrolling in US
• Every other week of 1 mg/kg
Pegunigalsidase alpha (PRX-102)
• Patients with Fabry disease treated
with agalsidase alpha
• Enrolling outside US
• Patients will be offered to continue on an extension study with pegunigalsidase alfa
• Home care and patient support are part of the program

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E-mail : raul@protalix.com