Protalix BioTherapeutics

{{Infobox company

| name = Protalix BioTherapeutics Inc.

| logo = Protalix logo.jpg

| type = Public

| traded_as = {{AMEX|PLX}}
{{TASE|PLX}}

| fate =

| successor =

| foundation = {{Start date|1993}}

| founder = Yoseph Shaaltiel

| defunct =

| location_city = Karmiel

| location_country = Israel

| location =

| locations =

| area_served =

| key_people = Shlomo Yanai (Interim Chairman)
Moshe Manor {{small|(CEO)}}

| industry = Biotechnology

| products = Elelyso

| services =

| revenue = {{Decrease}} $11.51 million (2013)[http://phx.corporate-ir.net/phoenix.zhtml?c=101161&p=irol-fundBalanceA "Fundamentals"], Protalix BioTherapeutics. Retrieved 23 March 2014.

| operating_income =

| net_income =

| assets = {{Increase}} $113.33 million (2013)

| equity =

| owner =

| num_employees = 266 (2013)

| parent =

| divisions =

| subsid =

| homepage = {{Url|protalix.com}}

| footnotes = [https://online.wsj.com/article/BT-CO-20111206-710412.html FDA Extends Review Of Protalix's Rare-Disease Drug]

}}

Protalix BioTherapeutics is an Israeli pharmaceutical company that manufactures a plant-based enzyme, taliglucerase alfa, which has received U.S. Food and Drug Administration approval for the treatment of Gaucher disease.

Corporate history

Protalix BioTherapeutics was established in 1993.[http://phx.corporate-ir.net/phoenix.zhtml?c=101161&p=irol-faq_pf#40212 Investor FAQ] It was founded by Yoseph Shaaltiel, who received his Ph.D. in Plant Biochemistry from the Weizmann Institute in Israel and served in the Biology Department of the Israel Defense Forces' Biological and Chemical Center.{{cite web|title=Yoseph Shaaltiel Ph.D.|url=http://investing.businessweek.com/research/stocks/people/person.asp?personId=941525&ticker=PLX:US|archive-url=https://archive.today/20120719080109/http://investing.businessweek.com/research/stocks/people/person.asp?personId=941525&ticker=PLX:US|url-status=dead|archive-date=July 19, 2012|work=Bloomberg Businessweek|access-date=3 May 2012}} One of the earliest and largest investors in the company was Phillip Frost.{{cite news|last=Tsipori|first=Tali|title=With Protalix worth $801m, chairman Frost cuts stake|url=http://www.globes.co.il/serveen/globes/docview.asp?did=1000617866&fid=1725|access-date=4 May 2012|newspaper=Globes|date=24 January 2011}} Protalix has two Nobel Prize winners (Chemistry) in its Scientific Advisory Board, Roger Kornberg Ph.D and Prof. MD. Aaron Ciechanover.

In its early days Protalix operated out of a warehouse in the town of Qiryat Shemona in northern Israel.{{cite news|last=Korenfeld|first=Tomer|script-title=he:'מי שלא מאמין שיצליח, אין לו מה לחפש במקצוע הזה. נתחיל למכור את התרופה למחלת הגושה כבר בתוך מספר שבועות'|url=http://www.bizportal.co.il/shukhahon/biznews02.shtml?mid=317096&p_id=&maavar=1|access-date=3 May 2012|newspaper=Bizportal|date=2 May 2012|language=Hebrew|trans-title='Whoever doesn't believe he'll succeed has nothing to look for in this field. We'll begin selling the treatment for Gaucher's disease within a few weeks'|quote=בעקבות האישור, מנכ"ל פרוטליקס דוד אביעזר התראיין ל-Bizportal על הדרך שעברה חברת הביומד הקטנה שהחלה במוסך בקרית שמונה ועד האישור המיוחל.}} On July 19, 2005, Protalix Biotherapeutics announced the closing of a $5.3 million private placement of its series C preferred stock.{{cite web |url=http://origin-www.lexisnexis.com/ap/auth/ |title= Protalix raises $ 5.3M in private financing}} Protalix entered into a partnership agreement with Teva Pharmaceutical Industries in 2006 for the development of two proteins{{cite journal|title=Teva, Protalix collaborate on two biopharmaceuticals|journal=Drug Discovery News|date=November 2006|publisher=Old River Publications|location=Rocky River, Ohio|quote=Teva Pharmaceutical Industries Ltd. and Protalix Biotherapeutics Ltd. have signed a collaboration and licensing agreement for the development of two proteins, using Protalix’s plant cell culture platform.}} and in 2009 signed a collaboration agreement with Pfizer for the development and commercialization of its taliglucerase alfa treatment.{{cite news|last=Loftus|first=Peter|title=Pfizer-Protalix Deal Bolsters Competition For Genzyme|url=https://www.wsj.com/articles/SB10001424052748704107104574569530771644554|access-date=3 May 2012|newspaper=The Wall Street Journal|date=2 December 2009}} Also in 2009, Protalix reported that Frost & Sullivan presented the company with its 2009 European Orphan Diseases

Market Product Innovation of the Year Award.{{cite news|title=Frost & Sullivan Presents Protalix Biotherapeutics with its 2009 European Orphan Diseases Market Product Innovation of the Year Award|url=https://www.bloomberg.com/apps/news?pid=conewsstory&tkr=PBD:GR&sid=aX77eP00CGCg|access-date=4 May 2012|newspaper=Bloomberg|date=4 June 2009|agency=Business Wire}} In 2011 Protalix announced that the U.S. Food and Drug Administration had approved the company's manufacturing facility in Karmiel.{{cite news|last=Gorodisher|first=Jonathan|title=פרוטליקס חושפת: ה-FDA ביקר כבר במפעל בכרמיאל 'מעלה את הסיכוי לאישור'|url=http://www.bizportal.co.il/shukhahon/biznews02.shtml?mid=264113|access-date=3 May 2012|newspaper=Bizportal|date=24 February 2011|language=Hebrew|trans-title=Protalix reveals: the FDA already visited the plant in Karmiel 'increases the probability of approval'|quote=מפעל הייצור של חברת פרוטליקס בכרמיאל אושר על ידי מנהל המזון והתרופות האמריקני (FDA) בביקורת שנערכה החודש, כך עולה מהדו"חות השנתיים שפרסמה חברת הביומד הבוקר (ה').}}

Protalix initially became a public company through a reverse merger process with Orthodontix, a company which was at the time traded "over the counter" on the NASDAQ.{{cite book|url=https://books.google.com/books?id=jUVlxEkjy7oC&q=protalix&pg=PA465|title=Plant Biotechnology and Agriculture: Prospects for the 21st Century|first=Arie|last=Altman|pages=465–466|isbn=978-0-12-381466-1|publisher=Academic Press|year=2011}} This merger was completed on December 31, 2006, and is notable as one of the largest reverse mergers executed, valuing the joint entity at almost $1 billion.{{cite book|url=https://books.google.com/books?id=UJP9wzee4jwC&q=protalix&pg=PA286|title=The Issuer's Guide to PIPEs: New Markets, Deal Structures, and Global Opportunities for Private Investments in Public Equity|first=Steven|last=Dresner|page=286|isbn=978-0-470-88349-5|year=2010|publisher=John Wiley & Sons}} It subsequently applied for a listing on the AMEX, and sold 10 million shares in a public offering.

Products

Protalix has been using cultured plant cells to manufacture biopharmaceuticals. As of 2017, Protalix has one FDA approved product sold by Pfizer in the U.S. and currently developing four products:

Taliglucerase alfa (Elelyso) – a recombinant glucocerebrosidase enzyme produced from transgenic carrot cell cultures.{{cite book|url=https://books.google.com/books?id=biGwUBUpTZMC&q=protalix&pg=PA60|title=Molecular Farming in Plants: Recent Advances and Future Prospects|first=Aiming |last=Wang|page=60|isbn=978-94-007-2216-3|year=2011|publisher=Springer}} Known also as Elelyso, taliglucerase won approval from the U.S. Food and Drug Administration in May 2012 as an orphan drug for the treatment of Type 1 Gaucher's disease. Protalix has licensed global development and commercialization rights for Elelyso to Pfizer, except for Brazil, where Protalix retains full rights. Brazil has the third largest number of Gaucher patients identified worldwide, after the U.S. and Israel.{{Cite web|url=https://gaucherdiseasenews.com/2016/12/15/protalix-announces-brazilian-plans-to-buy-gaucher-treatment-alfataliglicerase/|title=Gaucher Therapy, Alfataliglicerase, Being Purchased by Brazil|date=2016-12-15|website=Gaucher Disease News|access-date=2017-05-23}} The Brazilian National Health Surveillance Agency, known as ANVISA, granted regulatory approval for Elelyso (Uplyso) to treat adults with Gaucher disease in March 2013, and extended that approval to children in December 2016.
Alidornase alfa (PRX-110) – proprietary plant cell-expressed recombinant form of human deoxyribonuclease I (DNase I), that Protalix has designed, through chemical modification, to be resistant to inhibition by actin. DNase I is part of current Cystic Fibrosis therapy, intended to reduce sputum viscosity that accumulates in the lungs of Cystic Fibrosis patients, which exposes patients to recurrent infections and compromises lung function.{{Cite news|url=http://protalix.com/products/prx-110-alidornase-alfa/|title=alidornase alfa (PRX-110) for Cyctic Fibrosis - Protalix|work=Protalix|access-date=2017-05-05|language=en-US}} AIR DNase (alidornase alfa), developed to make mucus in the lungs of cystic fibrosis patients less sticky, showed remarkably good results in 2017.{{Cite web|url=https://cysticfibrosisnewstoday.com/2017/01/06/protalix-air-dnase-shows-improved-cf-patient-lung-function-in-small-study/|title=CF Patients in Small Study Seen to Have Better Lung Function with AIR DNase|date=2017-01-06|website=Cystic Fibrosis News Today|access-date=2017-05-05}}
Pegunigalsidase alfa (PRX-102) – plant cell culture expressed and a chemically modified version of the recombinant alpha-Galactosidase-A protein. Protein sub-units are covalently bound via chemical cross-linking using PEG chains, resulting in a more active and stable molecule than the current available versions. Protalix is currently conducting [https://clinicaltrials.gov/ct2/results?term=protalix&recr=Open Phase 3 clinical trial for PRX-102] for the treatment of Fabry Disease following a successful meeting with U.S. Food and Drug Administration. Protalix announced positive results from its clinical trial for PRX-102.{{Cite news|url=https://globenewswire.com/news-release/2016/08/10/863147/0/en/Protalix-BioTherapeutics-Announces-Additional-Positive-Data-from-its-Phase-I-II-Clinical-Trial-for-PRX-102-for-the-Treatment-of-Fabry-Disease.html|title=Protalix BioTherapeutics Announces Additional Positive Data from its Phase I/II Clinical Trial for PRX-102 for the Treatment of Fabry Disease|work=GlobeNewswire News Room|access-date=2017-05-05|language=en-US}} Pegunigalsidase alfa is being developed to replace Fabrazyme and interim data shows potential superiority in efficacy.{{Cite news|url=https://globenewswire.com/news-release/2017/04/18/961601/0/en/Protalix-BioTherapeutics-Announces-New-Preclinical-Results-Demonstrating-a-Positive-Effect-of-pegunigalsidase-alfa-PRX-102-on-Small-fiber-Neuropathy-in-Fabry-Disease-Models-Compare.html|title=Protalix BioTherapeutics Announces New Preclinical Results Demonstrating a Positive Effect of pegunigalsidase alfa (PRX-102) on Small-fiber Neuropathy in Fabry Disease Models Compared to Commercially Available Enzyme Replacement Therapies|work=GlobeNewswire News Room|access-date=2017-05-05|language=en-US}}
OPRX-106 – plant cell-expressed recombinant human tumor necrosis factor receptor II fused to an IgG1 Fc domain (TNFRII-Fc), in development for oral administration. If successful, OPRX-106 will be the first ever oral enzyme treatment as currently there are no other oral enzyme treatments available.
PRX-105 – a recombinant human Acetylcholinesterase, produced from genetically modified cell line of tobacco cells (Nicotiana tabacum),{{cite journal| doi=10.1016/j.taap.2015.06.004 | pmid=26051873 | volume=287 | issue=3 | title=Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R | journal=Toxicology and Applied Pharmacology | pages=202–209| year=2015 | last1=Atsmon | first1=Jacob | last2=Brill-Almon | first2=Einat | last3=Nadri-Shay | first3=Carmit | last4=Chertkoff | first4=Raul | last5=Alon | first5=Sari | last6=Shaikevich | first6=Dimitri | last7=Volokhov | first7=Inna | last8=Haim | first8=Kirsten Y. | last9=Bartfeld | first9=Daniel | last10=Shulman | first10=Avidor | last11=Ruderfer | first11=Ilya | last12=Ben-Moshe | first12=Tehila | last13=Shilovitzky | first13=Orit | last14=Soreq | first14=Hermona | last15=Shaaltiel | first15=Yoseph }} which can be used as a counter-measure against nerve agents attack. PRX-105 completed exploratory Phase I clinical trials.{{cite web|url=https://clinicaltrials.gov/show/NCT01093859|title=An Exploratory Phase 1 Microdose Study of PRX-105|website=clinicaltrials.gov|access-date=March 31, 2019}}