UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 2, 2007
Protalix BioTherapeutics, Inc.
(Exact name of registrant as specified in its charter)
Florida
(State or other jurisdiction of incorporation)
| 000-27836 (Commission File Number) |
65-0643773 (IRS Employer Identification No.) |
|
| 2 Snunit Street Science Park POB 455 Carmiel, Israel (Address of principal executive offices) |
20100 (Zip Code) |
+972-4-988-9488
Registrant’s telephone number, including area code:
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| o | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |
| o | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |
| o | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |
| o | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Item 7.01. |
Regulation FD Disclosure |
On November 2, 2007, Protalix BioTherapeutics, Inc. (the “Company”) issued a press release announcing that the Company would present at the CIBC World Markets 18th Annual Healthcare Conference being held at the Waldorf-Astoria Hotel in New York City on Monday, November 5, 2007 at 3:00 p.m. EST. The full text of the press release is set forth in Exhibit 99.1 to this Report.
A copy of the Company’s presentation materials for the conference, appearing in Exhibit 99.2, is furnished and not filed pursuant to Regulation FD.
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Item 9.01. |
Financial Statements and Exhibits |
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(d) |
Exhibits |
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99.1 |
Press release dated November 2, 2007, titled “Protalix BioTherapeutics to Present at CIBC World Markets 18th Annual Healthcare Conference.” |
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99.2 |
Slide Presentation to be used at the CIBC World Markets 18th Annual Healthcare Conference on November 5, 2007. |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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PROTALIX BIOTHERAPEUTICS, INC. | ||
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Date: November 2, 2007 |
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By: |
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Name: |
David Aviezer, Ph.D. | |
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Title: |
President and |
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Exhibit 99.1
Protalix BioTherapeutics to Present at
CIBC World Markets 18th Annual Healthcare Conference
CARMIEL, Israel – November 2, 2007 – Protalix BioTherapeutics, Inc. (Amex: PLX), today announced that Dr. David Aviezer, Ph.D., its President and Chief Executive Officer, will present at the CIBC World Markets 18th Annual Healthcare Conference. Dr. Aviezer’s presentation will take place at 3:00 EST on Monday, November 5th at the Waldorf-Astoria Hotel in New York City.
Dr. Aviezer's presentation may be heard live via a simulcast link at http://www.veracast.com/webcasts/cibcwm/healthcare07/84112115.cfm. Following the live presentation, the archived webcast will be available for a period of 90 days after the presentation.
About Protalix BioTherapeutics, Inc.
Protalix is a biopharmaceutical company. Its goal is to become a fully integrated biopharmaceutical company focused on the development and commercialization of proprietary recombinant therapeutic proteins to be expressed through its proprietary plant cell based expression system. Protalix’s ProCellExTM presents a proprietary method for the expression of recombinant proteins that Protalix believes is safe and scalable and will allow for the cost-effective, industrial-scale production of recombinant therapeutic proteins. Protalix has initiated enrollment and treatment of patients in its pivotal phase III clinical trial in the United States of its lead product candidate, prGCD, for its enzyme replacement therapy for Gaucher disease, a lysosomal storage disorder in humans, and has reached an agreement with the United States Food and Drug Administration on the final design of the pivotal phase III clinical trial through the FDA’s Special Protocol Assessment (SPA) process. Protalix is also advancing additional recombinant biopharmaceutical drug development programs.
To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to attract and retain partners for our technologies and products under development, the identification of lead compounds, the successful preclinical development of our products, the completion of clinical trials, the review process of the FDA, foreign regulatory bodies and other governmental regulation, and other factors described in our filings with the Securities and Exchange Commission. The statements are valid only as of the date hereof and we disclaim any obligation to update this information.
For additional information, contact Protalix BioTherapeutics at:
investors@protalix.com
AMEX IR Alliance for Protalix BioTherapeutics
Lee Roth / David Burke
212-896-1209 / 1258
lroth@kcsa.com / dburke@kcsa.com
CIBC Healthcare Conference
November 5th
, 2007
Dr. David Aviezer
President and CEO
2
Safe Harbor Statement
To the extent that statements in this press release are not strictly historical, all such statements are forward-
looking, and are made pursuant to the safe-harbor provisions of the Private Securities
Litigation Reform Act
of 1995. These forward-looking statements are subject to known and unknown risks and uncertainties that
may cause actual future experience and results to differ materially from the statements made. These
statements are based
on our current beliefs and expectations as to such future outcomes. Drug discovery and
development involve a high degree of risk. Factors that might cause such a material difference include,
among others, the inherent risks and uncertainties in developing
drug platforms and products of the type we
are developing; delays in our preparation and filing of applications for regulatory approval; delays in the
approval or potential rejection of any applications we file with the FDA, or other health regulatory
authorities; lack of progress of our research and development (including the results of clinical trials being
conducted by us); obtaining on a timely basis sufficient patient enrollment in our clinical trials; the impact of
development of competing
therapies and/or technologies by other companies; our ability to obtain additional
financings required to fund our research programs; our ability to establish and maintain strategic license,
collaboration and distribution arrangements and to manage
our relationships with collaborators,
distributors and partners; potential product liability risks and risks of securing adequate levels of product
liability and clinical trial insurance coverage; the possible disruption of our operations due to terrorist
activities and armed conflict, including as a result of the disruption of our subsidiary, our manufacturing
facilities, collaborative partners, licensees, and clinical trial sites; and other factors described in our filings
with the Securities and
Exchange Commission. The statements are accurate only as of the date hereof and we
disclaim any obligation to update this information, except as required by law.
3
Company Highlights
Lead product candidate targeting a large, growing market
Similar to Cerezyme, the only approved enzyme replacement therapy
Currently in Phase III trials under SPA for treating Gaucher Disease
Gaucher Disease , a growing $1 billion market, is a severe and
chronic condition
prGCD for
Gaucher Disease
Proprietary Protein
Expression System
Proprietary ProCellEx™ plant cell-based expression system offers
significant advantages over existing expression systems
New paradigm for developing recombinant proteins with equivalent activity and
structure to their naturally-produced human counterparts
Enables penetration of patent-protected markets
Greater cost-effectiveness and Safety
Biologically equivalent of superior versions of proteins with known
biological mechanisms of action, validated markets and clearer
regulatory path
Substantially less development and regulatory risk
Pipeline focused on complex therapeutic proteins, including Fabry disease and
female infertility disorders and other novel and biogeneric indications
Targeting Commercially
Viable Proteins
World Class
Management & Board
Experienced board and management team
Mr. Eli Hurvitz, Chairman of the Board, Chairman of the Teva
Dr. Phillip Frost, former Chairman and CEO of IVAX
Dr. David Aviezer, Director, President and CEO
4
Experienced Management and World
Class Board and Advisors
Advisor
Prof. Ari Zimran
Advisor
Prof. Gad Galili
Director of the Gaucher clinic, Shaarei Zedek Medical Center, Jerusalem.
World opinion leader in
Gaucher Disease
Advisor
Prof. Aaron
Ciechanover
Chairman, Dept. of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA.
World leader in
Hematology and genetic diseases
Advisor
Prof. Ernest Beutler
SCIENTIFIC ADVISORY BOARD
Ivax, DVM Pharmaceuticals
Director
Dr. Jane Hsiao
TEVA, Chairman and former CEO of Ivax, Ladenburg Thalman, Key Pharmaceuticals
Director
Dr. Phillip Frost
Chairman and former CEO of TEVA, former director Bank Leumi
Chairman
Mr. Eli Hurvitz
KEY BOARD MEMBERS
Taro Pharmaceutical Industries, M.Sc. in Biotechnology and Food Engineering
VP, Operations
Iftah Katz
Biogenics, Ph.D. in molecular biology of cancer research
VP, Product Dev
Dr. Einat Almon
MIGAL Technological Center, Rutgers U, Berkley U., Biological Center of IDF, Ph.D. in Plant Biochemistry
Executive VP, R&D
Dr. Yoseph Shaaltiel
Colbar LifeScience, Way2Call Communications, C.P.A., M.B.A
CFO
Yossi Maimon
KEY MANAGEMENT
President & CEO
Title
ProChon Biotech, American Cyanamid, Ph.D. in Molecular Biology and Biochemistry, M.B.A
Dr. David Aviezer
Experience
Name
Director of the Institute for Research in Medical Sciences at the Technion, Israel.
Laureate of the
Nobel Prize in Chemistry. World opinion leader in the field of protein
trafficking.
Chairman, Dept. of Plant Biology, Weizmann Institute of Science, Israel.
Scientific opinion leader
in the field of plant molecular and cell biology
5
Company Snapshot
Proprietary ProCellEx™ protein expression system based on plant cell-based expression
technology
Lead product prGCD - plant expressed Glucocerebrosidase for Gaucher Disease
currently in Phase III clinical trials
Deep pipeline focused on complex therapeutic proteins for novel and biogeneric
indications
Publicly traded PLX: AMEX.
Executive offices, R&D and manufacturing facility in Carmiel, Israel
Collaboration agreement with TEVA for the development of two biological drugs
90 employees of which 40% earned Ph.D., M.D. or M.Sc. Degrees
Approved Enterprise status granting 0% tax for a period of 10 years
Advanced clinical stage biopharmaceutical company focused on development
and commercialization of recombinant therapeutic proteins
Technology Demonstration
7
ProCellEx™ Protein
Expression System
Technology Platform
Proprietary plant cell-based protein expression system
Comprehensive set of technologies and capabilities for the development of
recombinant proteins from initial nucleotide cloning to large scale protein
production
Enables expression of proteins with similar amino acid, glycan and three
dimensional structure as compared to their naturally-produced human counterparts
Demonstrated feasibility through expression of many complex therapeutic proteins
belonging to different drug classes:
Enzymes, cytokines, monoclonal antibodies, hormones, vaccines.
Have shown biological and structural equivalence to the naturally-produced
human protein
8
Key Advantages of the
ProCellEx System
Avoids infringing on the method-based patents of other proteins
developed with mammalian cell-based expression systems,
allowing penetration of certain patent-protected markets.
Expect to obtain method-based patent protection for proteins
developed using our ProCellEx system and in some cases, will
seek composition patents as well.
Enables Penetration
of Patent Protected
Markets
Flexible polyethylene bioreactors entail low initial capital
investment.
Rapidly scalable at low cost in compliance with cGMP.
Requires less costly hands-on maintenance.
Cost
Effectiveness
and Scalability
Significant
Advantages Over
Mammalian Cell-
based Systems
Excellent safety profile – No risk of mammalian viral transmission or
infection.
Substantial cost benefits.
Uniform glycosilation patterns result in greater effectiveness and
potency.
Longer half life and superior cell uptake (in prGCD).
9
Gaucher Disease:
A genetically inherited disorder
Macrophages
Bone
Bone Marrow
Liver
Lung
Spleen
Source: Beutler and Grabowski, The Metabolic and Molecular Bases of Inherited Disease 2001
Skeletal pathology
Pulmonary hypertension/
infiltration
Hepatomegaly
Anemia
Thrombocytopenia
Splenomegaly
Outcome: Death - Poor quality of life
10
HO CH2 CH CH CH = CH (CH2)12
CH3
OH
O
O
OH
HO
OH
OH
O
OH
OH
HO
OH
O=C CH2 CH2
CH2 (CH2)
n
CH3
N OH
CH2 CH
CH CH = CH (CH2
)12
CH3
O=C CH2 CH2
CH2 (CH2)
n
CH3
N OH
Acid -Glucosidase
Glucocerebrosidase
Glucose
Ceramide
Glucosyl
Ceramide
+
The Enzymatic Defect in
Gaucher Disease
11
Gaucher Disease: Attractive
Market Characteristics
No cure for Gaucher, ongoing chronic therapeutic treatment
Treatment cost of ~$200,000 p.a.,
Less than 5,000 treated patients
Relatively concentrated group of prescribing physicians
Cerezyme ® (Genzyme) : The only recombinant GCD on the market
with ~100%
share
Zavesca ®
- (Actelion): Small molecule drug - Usage extremely
limited due to significant
side effects
Historic annual market growth of approx 10-15%
Estimated global market penetration of ~50%
Future penetration to be driven by patient education and
screening
Only player in the market has annual revenues of > $1bn
Approx. 10,000 patients (treated and untreated) globally
Enzyme replacement therapy is gold standard treatment
Comment
Characteristic
Cerezyme ® Growth ($m)
CAGR: 12.7%
Large
Market
Size
Attractive
Patient
Profile
Steady
Growth
Prospects
Competition
12
prGCD: Equal to Superior
Biological Activity
prGCD has equal to superior enzymatic activity degrading the
natural substrate when compared to Cerezyme® :
Cerezyme and prGCD cellular
uptake
-0.05
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0 u/ml
1.6 u/ml
3.2 u/ml
6.4 u/ml
Enzyme concentration
Cerezyme
prGCD
Enhanced uptake
of prGCD
by mouse macrophages
compared to Cerezyme® :
Gaucher patients macrophages model:
prGCD demonstrates superior uptake vs.
Cerezyme®
following 24 and 48 hours
of incubation
13
3-D crystal structure of prGCD solved by a team of world renowned scientists from the Weizmann Institute of Science and compared to Cerezyme® structure.
Similar three Dimensional structure
14
Technology Animation
15
Glucocerebrosidase Binds to its Target
Cells via the Mannose Receptor
Macrophage
Mannose
receptor
Mannose
residues
GCD
16
Protalix plant cell
technology produces a
“ready to use” bioactive
enzyme:
Mammalian technology requires
multiple post-expression modifications:
Active - Mannose exposed
glycan structure
Mannose
GlcNAc
Fucose
Xylose
Galactose
Sialic acid
Protalix technology does not require
additional glycan processing
Non Active
17
Batch to Batch Consistency of Glycoforms
produced by the ProCellEx™
system
18
Successful Phase I Clinical Study
Design
Single-center, non-randomized, open label performed at Hadassah Medical Center,
Jerusalem
Study performed under FDA IND approval.
Objectives
Primary: To evaluate the safety of three escalating doses of human prGCD in healthy
volunteers
Secondary: To determine the pharmacokinetics of prGCD in human subjects
Results
prGCD was well tolerated.
Highly satisfactory safety laboratory results.
No anti prGCD antibodies
No immune reaction against prGCD.
Pharmacology – prolonged half life of drug in serum
19
Pharmacokinetic data:
prGCD vs. Cerezyme
(IV
administration)
Preclinical –Primate
data
Human data
prGCD data:
T1/2 13-20 minutes
T1/2 10.5-14.5
minutes
Cerezyme
(published
data)
T1/2 6.8-8 minutes
T1/2 ~
3.6-10.4
minutes
20
prGCD Phase III Trial – Launched Aug 07
Multi-center world wide study
Efficacy and safety in 30 untreated patients with significant
symptoms of Gaucher disease treated with prGCD for 9 months
Special Protocol Assessment approved by FDA in July 2007
Randomized, double blind, parallel groups, dose-ranging study
Primary End Point
Mean decrease of 20% in spleen volume would represent a clinically
relevant improvement
Three Major Secondary Endpoints
decrease in liver volume , increase in Hemoglobin concentration,
increase in platelet count
21
prGCD Clinical Development Timeline
2007
2008
2009
Initiated Phase III
Clinical
Trials
NDA
Submission
Phase III
Efficacy Data
Drug Approval
22
prGCD for Gaucher Disease
prGCD
Plant cell expressed recombinant GCD for enzyme replacement therapy
Enzyme replacement therapy is gold standard of care
Substantially similar amino acid, glycan and three dimensional structure
compared to Cerezyme
Major proof of concept for ProCellEx™ Protein Expression System
Clear Clinical Path
Following clinical protocol similar to Cerezyme
Clinical data demonstrated increased half-life and increased in vitro and uptake efficacy
Implies potential for more potent and effective drug
Demonstrated safety and no immunological responses in intensive animal studies or Phase I human study
Initiated 30 patient Phase III clinical trial in August 2007 under SPA
An Effective and Cost Efficient Treatment
Low production costs result from:
Lower initial set-up investment and ongoing growth media, labor and monitoring costs
Absence of post-expression glycosilation modification which are needed for Cerezyme
23
Leveraging our Platform into
Attractive Market Opportunities
R & D,
Animal Studies
R & D,
Animal Studies
Phase III
in progress
Phase of
Development
Follicle Stimulating
Hormone for Female
Infertility
Biodefense and
organophosphate
poisoning
Enzyme replacement
therapy for Gaucher
Disease
Indication
>$1,200 mm
~ $500 mm
>$1 B
Market
Opportunity
Unmet medical need in rapidly growing
biodefense market
Vast potential of civilian applications
Acetyl-
Cholinesterase
Currently three meaningful products
and only two recombinant hormone
market players
PRX-111
FSH
Currently only one meaningful market
player - Genzyme
Incurable disease, ongoing chronic
treatment
prGCD
Market Dynamic
Pipeline
Candidate
One product in US and another in EU
and Rest of World
Rapidly growing market
Enzyme replacement therapy is
standard of care
>$500 mm
R & D,
Animal Studies
Enzyme replacement
therapy for Fabry
Disease
PRX-102
Fabry
Disease
24
IgG1-CHO
IgG4-Protalix
IgG1-Protalix
Control
Heavy Chain
Light Chain
Human IgG
Standard
Recombinant
IgG produced by
Protalix’s plant
culture system
Monoclonal Antibodies Expression
Protalix system represents an
alternative platform for hard-to-
express proteins in mammalian
systems, including monoclonal
antibodies
Binding to Jurkat Leukemia cells
25
Strategic Collaborations
In addition to internal, proprietary development, Protalix also seeks to
share risk and enter into partnerships for the early-stage
co-development
for biotherapeutic proteins
Framework agreement for R&D collaboration on two proteins using ProCellEx
system
TEVA to be granted license to commercialize the developed products
Protalix will receive milestone and royalties and retain exclusive manufacturing
rights
Licensed technology from Weizmann to design next generation of GCD for Gaucher
Based on a 3-D crystal structure of prGCD technology provides methodology for
rational design for an improved drug
Protalix pays fixed research budget and some royalties for any commercialized
products
Agreement with Hebrew University and Boyce Thompson of Cornell University
to license the technology underlying the developed acetylcholinesterase and its
molecular variants
for the use in several therapeutic and prophylactic indications,
as well as in a biodefense program
Protalix pays some royalties for any commercialized products
26
Strong Intellectual Property Protection:
50+ Patents & Applications
6 patent families in the
in house portfolio
Cell & tissue culturing
device, system
and method
Expression of
lysosomal
Enzymes in
plant cells
Large scale
bioreactor system
delivering
proteins through
oral administration
Expression of
antibodies
in plant cells
Expression of FSH
variant protein in
plant cells
27
Company Highlights
Lead product candidate targeting a large, growing market
Similar to Cerezyme, the only approved enzyme replacement therapy
Currently in Phase III trials under SPA for treating Gaucher Disease
Gaucher Disease , a growing $1 billion market, is a severe and
chronic condition
prGCD for
Gaucher Disease
Proprietary Protein
Expression System
Proprietary ProCellEx™ plant cell-based expression system offers
significant advantages over existing expression systems
New paradigm for developing recombinant proteins with equivalent activity and
structure to their naturally-produced human counterparts
Enables penetration of patent-protected markets
Greater cost-effectiveness and Safety
Biologically equivalent versions of proteins with known biological
mechanisms of action, validated markets and clearer regulatory path
Substantially less development and regulatory risk
Pipeline focused on complex therapeutic proteins, including Fabry disease
and female infertility disorders and other novel and biogeneric indications
Targeting Commercially
Viable Proteins
World Class
Management & Board
Experienced board and management team
Mr. Eli Hurvitz, Chairman of the Board, Chairman of the Teva
Dr. Phillip Frost, former Chairman and CEO of IVAX
Dr. David Aviezer, Director, President and CEO
Contact:
Dr. David Aviezer
President & CEO
david@protalix.com