In the News 2016 - 2017 TABLE OF CONTENTS

Protein Sciences press release 8 June 22, 2017 Superior Protection by Flublok® Influenza in Seniors Documented in New England Journal of Medicine

Protein Sciences press release 10 April 19, 2017 Peer-reviewed Publication Confirms the Absence of Rhabdovirus in Cell Line Used for Manufacturing of Flublok

Protein Sciences press release 12 April 4, 2017 Flublok Quadrivalent Adds a 9-Month Shelf Life to Its List of Benefits

Protein Sciences press release 14 March 21, 2017 Protein Sciences Gears Up to Combat Pandemic Influenza Due to Recent Outbreaks in China

Protein Sciences press release 16 February 22, 2017 Protein Sciences and Partnership for Influenza Vaccine Introduction (PIVI) Team Up to Combat the Flu in Mongolia

Protein Sciences press release 18 January 12, 2017 U.S. Protein Sciences’ Zika Vaccine Shows Good Results in Preclinical Testing: Bio-Manguinhos/ Fiocruz Joins International Consortium

Fierce Pharma 20 December 1, 2016 Small flu vax players poised to win ‘sizable’ share of market, firm predicts TABLE OF CONTENTS

Protein Sciences press release 6 November 11, 2016 Flublok® Influenza Vaccine Now Available in Mexico

Fierce Pharma 8 October 17, 2016 Protein Sciences CEO Eyes GSK, Sanofi goliaths in fight to ‘take over’ quadrivalent flu vax market

Protein Sciences press release 10 October 11, 2016 FDA Approves Flublok® Quadrivalent Flu Vaccine

Protein Sciences press release 12 September 22, 2016 Protein Sciences and Avanzcare Announce Licensing of Influenza for the MENA Region

The Hartford Courant 14 September 8, 2016 Protein Sciences Secures A Potentially Huge Federal Contract For Flu Vaccines

Protein Sciences press release 16 September 7, 2016 BARDA Awards Protein Sciences Multi-Million Dollar Contract for Pandemic Preparedness

Protein Sciences press release 18 August 10, 2016 First Doses of Flublok® Influenza Vaccine of 2016/17 Have Shipped

Protein Sciences press release 19 July 12, 2016 2016/17 Formulation of Flublok® Influenza Vaccine Receives FDA Approval Protein Sciences press release 22 November 11, 2016 Flublok® Influenza Vaccine Now Available in Mexico

Fierce Pharma 24 October 17, 2016 Protein Sciences CEO Eyes GSK, Sanofi goliaths in fight to ‘take over’ quadrivalent flu vax market

Protein Sciences press release 26 October 11, 2016 FDA Approves Flublok® Quadrivalent Flu Vaccine

Protein Sciences press release 28 September 22, 2016 Protein Sciences and Avanzcare Announce Licensing of Influenza Vaccines for the MENA Region

The Hartford Courant 30 September 8, 2016 Protein Sciences Secures A Potentially Huge Federal Contract For Flu Vaccines

Protein Sciences press release 32 September 7, 2016 BARDA Awards Protein Sciences Multi-Million Dollar Contract for Pandemic Preparedness

Protein Sciences press release 34 August 10, 2016 First Doses of Flublok® Influenza Vaccine of 2016/17 Have Shipped

Protein Sciences press release 35 July 12, 2016 2016/17 Formulation of Flublok® Influenza Vaccine Receives FDA Approval

Protein Sciences press release 36 June 29, 2016 UMN Pharma Joins Protein Sciences’ International Zika Vaccine Consortium

Protein Sciences press release 38 June 28, 2016 Protein Sciences Announces Exclusive License to uniQure of Cell Line and Technology for Production of Human Gene Therapies

Protein Sciences press release 39 June 28, 2016 Flublok® Influenza Vaccine a Great Alternative to FluMist for adults 18 and older

Protein Sciences press release 40 June 23, 2016 FDA Approved Longer Shelf Life for Game Changer, Flublok® Influenza Vaccine

Protein Sciences press release 42 April 19, 2016 Protein Sciences Corporation, Sinergium Biotech and Mundo Sano Announce Zika Vaccine Partnership

Protein Sciences press release 44 April 12, 2016 Protein Sciences and Orygen Biotecnologia Announce Agreement to License Flublok® Influenza Vaccine for Brazil

Protein Sciences press release 46 February 12, 2016 Protein Sciences, UNIGEN Reach Agreement to Source Flublok® Influenza Vaccine from Japan

WTNH news story 47 February 4, 2016 Meriden Company Working on Vaccine Superior Protection by Flublok® Influenza Vaccine in Seniors Documented in New England Journal of Medicine

For Immediate Release: Contact: June 22, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT—Protein Sciences Corporation strated statistically significantly better protection announced the publication of results by Flublok based on considerably fewer people comparing Flublok® Quadrivalent – the quadrivalent contracting the flu after with Flublok version of Flublok® influenza vaccine – to a tradition- Quadrivalent. Today, we announce that these peer- al egg-based quadrivalent . The reviewed results have been published in the highly data published in the June 22nd issue of the New respected New England Journal of Medicine. England Journal of Medicine showed that Flublok Furthermore, physicians are eligible for up to 1 Quadrivalent provided significantly improved pro- hour AMA PRA category 1 CME credit for reading tection against laboratory confirmed influenza ill- the article. Clearly, Flublok represents a major step ness in older adults. forward in combating influenza on a global scale.” The publication notes that approximately 9,000 Flublok is the only flu vaccine made without the use people aged 50 and older were enrolled and ran- of eggs and therefore is not subject to the mutations domized in an efficacy study designed to compare that are sometimes introduced into the vaccine dur- Flublok Quadrivalent to a traditional quadrivalent ing the process of egg adaptation that can cause the vaccine. People who were given Flublok Quadriva- traditional vaccines to be ineffective. lent were over 40% less likely to develop culture- Flublok contains three times more active ingredi- confirmed influenza. This data satisfies both pre- ents than traditional vaccines and produced signifi- specified criteria for noninferiority and superiority cantly higher immune responses to the A strains of of Flublok over the traditional egg-based quadriva- influenza (especially H3N2) in the Flublok Quadriva- lent inactivated vaccine. Flublok Quadrivalent was lent study. approved by the FDA in October 2016 and will be Furthermore, Flublok Quadrivalent is the first and available nationwide in prefilled syringes for the up- only high antigen-content quadrivalent flu vac- coming flu season. cine that with its high efficacy makes it ideal for “This study shows that Flublok® Quadrivalent, pro- older adults and those with a compromised im- duced with modern recombinant technology can mune system. Flublok is highly purified and does provide better protection against confirmed influ- not contain influenza virus, antibiotics, formalde- enza-like illness among older adults than standard- hyde, preservatives, egg protein, latex, gluten or dose quadrivalent influenza vaccine produced with gelatin unlike other flu vaccines. Flublok Quad- traditional technology,” said Lisa Dunkle MD, Chief rivalent is FDA approved for adults 18 and older. Medical Officer of Protein Sciences. “We demon- www.flublok.com.

8 PROTEIN SCIENCES About Protein Sciences Healthcare professionals wishing to order Flublok Protein Sciences is a world leader in vaccine should contact one of the following distributors: development and protein production. Our mission  Protein Sciences Corporation: is our inspiration: to save lives and improve health 203-686-0800 through the creation of innovative vaccines and www.flublok.com biopharmaceuticals.  FFF Enterprises: 800-843-7477 About Flublok www.myfluvaccine.com Flublok, the world’s first recombinant protein-  Cardinal Health: based vaccine for the prevention of seasonal influ- 866-677-4844 enza disease, was initially approved by the U.S. FDA www.cardinalhealth.com/flu in January 2013.  McKesson: FDA expanded its approval in October 2014 to in- 877-MCK-4FLU clude everyone over 18 years and approved a nine- mms.mckesson.com month shelf life in June 2016.  Moore Medical: Flublok is also licensed for sale in Mexico and 800-234-1464 licensure in additional countries, including Japan, is www.mooremedical.com/flu expected in the near future.  Henry Schein: Flublok is the only flu vaccine made in a 100% egg- 800-772-4346 free system using modern cell culture technology, www.henryschein.com making it unnecessary to use an infectious influenza virus, antibiotics or harsh chemicals in manufactur- Flublok Safety Information ing. Flublok is approved for people 18 and older to Flublok is highly purified and does not contain any prevent influenza disease. The most common side preservatives (e.g., thimerosal, which contains mer- effect from Flublok is pain at the site of injection. cury), egg proteins, gelatin or latex. Headache, fatigue or muscle ache may occur. In addition, Flublok contains three times more Tell the doctor if you have ever experienced antigen than traditional flu vaccines (3x45mcg Guillain-Barré syndrome (severe muscle weakness) or hemagglutinin protein versus 3x15mcg hemagglu- have had a severe allergic reaction to any component tinin protein) and was shown to have better efficacy of Flublok vaccine. in a 2014/15 post-marketing study.* Vaccination with Flublok may not pro- Flublok is an accurate copy of the virus coat and is tect all individuals. Please see the complete not subject to the egg-adapted mutations that can Package Insert available at www.flublok.com or call be associated with low vaccine effectiveness [see 203-686-0800 for more information. Skowronski et al. (2014) PLOS ONE 9(3), e92153]. *Flublok demonstrated a higher antibody re- sponse to the A strains in two field trials in adults ≥50 years old. The B strain antibody responses were comparable to traditional trivalent and quadrivalent vaccines. Learn more at www.proteinsciences.com and www.flublok.com.

IN THE NEWS 9 Peer-reviewed Publication Confirms the Absence of Rhabdovirus in Cell Line Used for Manufacturing of Flublok®

For Immediate Release: Contact: April 19, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden — Protein Sciences Corporation is pleased “The data in this paper further substantiate that to announce the publication of its manuscript SF+ cells are ideal for manufacturing – they can not entitled “Complete Study Demonstrating the only be scaled to very large volumes, allowing for Absence of Rhabdovirus in a Distinct Spodoptera the production of millions of doses of vaccine, but frugiperda (Sf9) Cell Line” in the peer-reviewed are also free of elements that have been reported for journal PLOS ONE, Volume 12 issue 4. other Sf cell lines, such as rhabdovirus.” The publication follows extensive testing of the SF+ cells are used for the manufacture of parent cells from which Protein Sciences’ proprietary multiple commercial products made by Protein expresSF+® (SF+) cell line is derived. Sciences and others, including FDA-approved The study confirms that a contaminating Flublok® Influenza Vaccine, EMA-approved Glybera®, rhabdovirus previously reported in a related and USDA-approved Ingelvac CircoFLEX®. cell line is not present in SF+ cells. These results To learn more about how Protein Sciences demonstrate that not all cell lines are equal, manufactures vaccines using SF+ cells, please view even if they are derived from the same parent our educational video or visit www.proteinsciences. cell line and highlight the high quality of the SF+ cell com. lineage. About Protein Sciences “The quality of our cells is of the utmost impor- Protein Sciences is a world leader in vaccine tance as they are the vehicle with which we make all development and protein production. Our mission of our vaccines,” said Dr. Manon Cox, President and is our inspiration: to save lives and improve health CEO of Protein Sciences and senior author on the through the creation of innovative vaccines and paper. biopharmaceuticals.

10 PROTEIN SCIENCES RESEARCH ARTICLE Complete study demonstrating the absence of rhabdovirus in a distinct Sf9 cell line

Yoshifumi Hashimoto*, Daniel Macri, Indresh Srivastava, Clifton McPherson, Rachael Felberbaum, Penny Post, Manon Cox

Protein Sciences Corporation, Meriden, Connecticut, Unites States of America

* [email protected] a1111111111 a1111111111 Abstract a1111111111 a1111111111 A putative novel rhabdovirus (SfRV) was previously identified in a Spodoptera frugiperda a1111111111 cell line (Sf9 cells [ATCC CRL-1711 lot 58078522]) by next generation sequencing and extensive bioinformatic analysis. We performed an extensive analysis of our Sf9 cell bank (ATCC CRL-1711 lot 5814 [Sf9L5814]) to determine whether this virus was already present in cells obtained from ATCC in 1987. Inverse PCR of DNA isolated from Sf9 L5814 cellular DNA OPEN ACCESS revealed integration of SfRV sequences in the cellular genome. RT-PCR of total RNA Citation: Hashimoto Y, Macri D, Srivastava I, showed a deletion of 320 nucleotides in the SfRV RNA that includes the transcriptional McPherson C, Felberbaum R, Post P, et al. (2017) motifs for genes X and L. Concentrated cell culture supernatant was analyzed by sucrose Complete study demonstrating the absence of density gradient centrifugation and revealed a single band at a density of 1.14 g/ml. This rhabdovirus in a distinct Sf9 cell line. PLoS ONE 12 fraction was further analysed by electron microscopy and showed amorphous and particu- (4): e0175633. https://doi.org/10.1371/journal. pone.0175633 late debris that did not resemble a rhabdovirus in morphology or size. SDS-PAGE analysis confirmed that the protein composition did not contain the typical five rhabdovirus structural Editor: Miguel Lopez-Ferber, Ecole des Mines d’Ales, FRANCE proteins and LC-MS/MS analysis revealed primarily of exosomal marker proteins, the SfRV N protein, and truncated forms of SfRV N, P, and G proteins. The SfRV L gene fragment Received: June 10, 2016 RNA sequence was recovered from the supernatant after ultracentrifugation of the 1.14 g/ Accepted: March 29, 2017 ml fraction treated with diethyl ether suggesting that the SfRV L gene fragment sequence is Published: April 19, 2017 not associated with a diethyl ether resistant nucleocapsid. Interestingly, the 1.14 g/ml frac- L5814 Copyright: © 2017 Hashimoto et al. This is an open tion was able to transfer baculovirus DNA into Sf9 cells, consistent with the presence of access article distributed under the terms of the functional exosomes. Our results demonstrate the absence of viral particles in ATCC CRL- Creative Commons Attribution License, which 1711 lot 5814 Sf9 cells in contrast to a previous study that suggested the presence of infec- permits unrestricted use, distribution, and reproduction in any medium, provided the original tious rhabdoviral particles in Sf9 cells from a different lot. This study highlights how cell lines author and source are credited. with different lineages may present different virosomes and therefore no general conclu-

Data Availability Statement: All relevant data are sions can be drawn across Sf9 cells from different laboratories. within the paper and its Supporting Information files.

Funding: All authors are (or were at the time the research was conducted) employees of Protein Sciences Corporation (PSC). PSC is the manufacturer of Flublok – an FDA recombinant Introduction influenza vaccine manufactured in insect cells. The 1 safety of Flublok is extremely important to not only Spodoptera frugiperda (Sf) cell lines, such as Sf21, Sf9, and expresSF+ (SF+), BTI-TN5B1 PSC, but also healthcare authorities. PSC has (High Five) cells from the Trichoplusia ni cabbage looper, and BmN cells from the Bombyx conducted and continuous to perform extensive mori silkworm are widely being used in baculovirus research and for recombinant protein

PLOS ONE | https://doi.org/10.1371/journal.pone.0175633 April 19, 2017 1 / 17

IN THE NEWS 11 Flublok Quadrivalent Influenza Vaccine Adds a 9-Month Shelf Life to Its List of Benefits

For Immediate Release: Contact: April 4, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden — Protein Sciences Corporation, mak- differentiate Flublok Quadrivalent from the com- er of Flublok® Influenza Vaccine, announced that petition. FDA’s approval of a 9-month shelf life po- FDA approved an extended shelf life for Flublok sitions Flublok Quadrivalent as one of the leading Quadrivalent from 6 months to 9 months, ensuring vaccines on the market.” that Flublok can be used throughout the flu season. She added, “We expect to receive approval for a Trivalent Flublok was introduced to the market one year shelf life for both formulations of Flublok in 4 years ago. Flublok Quadrivalent will be available the near future.” in prefilled syringes during the upcoming flu sea- Pre-booking for Flublok Quadrivalent is underway. son. Any licensed physician can order the product Shipping is expected to begin in August. directly from Protein Sciences or from one of the distributors listed below. Locations carrying the vaccine will be added to the company’s Flublok Finder on a daily basis starting in August to help people find a location near them. Flublok Quadrivalent protects against four strains of the influenza virus and has 3x more ac- tive ingredients than other quadrivalent flu vac- cines, making it the only high-antigen quadrivalent vaccine on the market and a great option for seniors. Flublok Quadrivalent demonstrated better efficacy compared to a standard quadrivalent flu vaccine in adults 50 and older in a large clinical study, with recipients of Flublok being 43% less likely to get culture-confirmed influenza than those that received the standard vaccine. “Flublok Quadrivalent is a remarkable vaccine,” said Manon Cox, President and CEO of Protein Sciences Corporation. “Protection against more strains, better efficacy, extreme purity, and high antigen content are only a few benefits that

12 PROTEIN SCIENCES About Protein Sciences www.flublok.com Protein Sciences is a world leader in vaccine  FFF Enterprises: development and protein production. Our mission 800-843-7477 is our inspiration: to save lives and improve health www.myfluvaccine.com through the creation of innovative vaccines and  Cardinal Health: biopharmaceuticals. 866-677-4844 www.cardinalhealth.com/flu About Flublok  McKesson: Flublok, the world’s first recombinant protein- 877-MCK-4FLU based vaccine for the prevention of seasonal influ- mms.mckesson.com enza disease, was initially approved by the U.S. FDA  Moore Medical: in January 2013. FDA expanded its approval in Oc- 800-234-1464 tober 2014 to include everyone over 18 years and www.mooremedical.com/flu approved a nine-month shelf life in June 2016.  Henry Schein: Flublok is also licensed for sale in Mexico and 800-772-4346 licensure in additional countries, including Japan, is www.henryschein.com expected in the near future. Flublok is the only flu vaccine made in a 100% egg-free system using mod- Flublok Safety Information ern cell culture technology, making it unnecessary Flublok is approved for people 18 and older to to use an infectious influenza virus, antibiotics or prevent influenza disease. The most common side harsh chemicals in manufacturing. Flublok is high- effect from Flublok is pain at the site of injection. ly purified and does not contain any preservatives Headache, fatigue or muscle ache may occur. (e.g., thimerosal, which contains mercury), egg pro- Tell the doctor if you have ever experienced teins, gelatin or latex. Guillain-Barré syndrome (severe muscle weakness) or In addition, Flublok contains three times more have had a severe allergic reaction to any component antigen than traditional flu vaccines (3x45mcg of Flublok vaccine. hemagglutinin protein versus 3x15mcg hemagglu- Vaccination with Flublok may not pro- tinin protein) and was shown to have better efficacy tect all individuals. Please see the complete in a 2014/15 post-marketing study.* Package Insert available at www.flublok.com or call Flublok is an accurate copy of the virus coat and is 203-686-0800 for more information. not subject to the egg-adapted mutations that can *Flublok demonstrated a higher antibody re- be associated with low vaccine effectiveness (see sponse to the A strains in two field trials in adults Skowronski et al. (2014) PLOS ONE 9(3), e92153). ≥50 years old. The B strain antibody responses were Healthcare professionals wishing to order Flublok comparable to traditional trivalent and quadrivalent should contact one of the following distributors: vaccines.  Protein Sciences Corporation: Learn more at www.proteinsciences.com and 203-686-0800 www.flublok.com.

IN THE NEWS 13 Protein Sciences Gears Up to Combat Pandemic Influenza Due to Recent Outbreaks in China

For Immediate Release: Contact: March 21, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden — In light of the growing concern over Organization (WHO). recent Avian Influenza outbreaks in China, Protein The emergence of a highly pathogenic version Sciences Corporation, maker of the highly effec- among newly identified H7N9 viruses in poul- tive Flublok® Influenza Vaccine, announced today try is raising particular concern. WHO has recom- that the Biomedical Advanced Research and mended two new vaccine strains (one against low Development Authority (BARDA) has requested pathogenic and one against high pathogenic H7N9) the development of two new pandemic vaccine for pandemic preparedness purposes. candidates to combat new H7N9 strains, one “Our technology puts us in the unique position to representing a pathogenic H7N9 virus. deliver vaccine early,” said Manon Cox, President and BARDA is a division of the Office of the Assistant CEO of Protein Sciences. Secretary for Preparedness and Response within the “Since our vaccines can be made from a genetic U.S. Department of Health and Human Services. code and do not require handling of the pathogenic The request for a vaccine candidate is made virus, production can be started 3-6 months earlier under the BARDA contract awarded to the than manufacturers who have to wait for acceptable Company in September as part of the Authority’s starting materials and safety clearance,” she said. medical countermeasures against pandemic influ- “Furthermore, we expect to have a very large enza and influenza strains with pandemic poten- increase in FDA approved production capacity for tial (contract number HHSO100201600005I), with a the manufacturing of pandemic vaccine available value up to $610 million. later this year. The ultimate goal is to have vaccine Protein Sciences’ recombinant technology is ready before the demand for healthcare service is at the only FDA approved platform that can produce its peak during a pandemic. Egg-based manufactur- influenza vaccines fast enough and without use of ing does not allow for that fast turnaround time.” influenza virus in manufacturing to meet the needs Traditionally, egg-based vaccines are available of an emerging pandemic. 16-20 weeks after the declaration of a pandemic. A fifth wave of H7N9 with increasing numbers of Protein Sciences’ technology allows for a highly is occurring in China. effective recombinant vaccine to be available in As of February 14, 2017, 1,223 cases of H7N9 with approximately 12-16 weeks. 380 fatalities have been reported to the World Health

14 PROTEIN SCIENCES IN THE NEWS 15 Protein Sciences and Partnership for Influenza Vaccine Introduction (PIVI) Team Up to Combat the Flu in Mongolia

For Immediate Release: Contact: February 22, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT — Protein Sciences Corporation, a and CEO of Protein Sciences. “When PIVI approached leading vaccine development company and maker us, we immediately thought it was a perfect oppor- of Flublok® Influenza Vaccine, announced today tunity to provide access to Flublok outside the U.S. that they donated 45,000 doses of Flublok to The It is our hope that this donation will not only help Partnership for Influenza Vaccine Introduction protect the people of Mongolia from the flu, but will (PIVI) and the Mongolian Ministry of Health to help also assist them in creating a lasting flu vaccination protect communities from the devastating impacts program.” of the flu. “Given the value of a functional seasonal influenza The doses of Flublok have been distributed and program for pandemic preparedness, PIVI is pleased used in all regions of Mongolia for health care to partner with Protein Sciences and utilize Flublok workers, pregnant women, and those from the in the current vaccination campaign in Mongolia,” general public that come to participating clinics shared Dr. Mark McKinlay, Director of the Center for during the influenza vaccine campaign. Vaccine Equity at the Task Force for Global Health. The government of Mongolia is committed to “Sustainable seasonal influenza vaccine programs developing an expanded, sustainable seasonal are an important building block in the creation of influenza program. PIVI and Protein Sciences health systems that can not only protect people Corporation, through the Flublok donation, are from influenza now, but also help the country re- providing key support to Mongolia to achieve this spond to a future pandemic. vision. Flublok is an important new partner to PIVI be- Flublok is a breakthrough in how flu vaccines are cause this vaccine is not made using eggs, and can manufactured: it is the only flu vaccine that is an ex- be manufactured more quickly than others because act match to circulating flu strains, and it has been it is not dependent on an egg supply.” shown to protect broadly against the flu. In addition, As part of the vaccination campaign, health care it is the only flu vaccine made without ingredients workers will be trained in administering the vaccine that have been found objectionable in traditional flu and will be provided all of the proper vaccines. information in their local language. PIVI agreed that Flublok was a good choice for this Once the campaign is complete, the partners will program because of the urgent need for flu vaccines work together to develop and conduct post-cam- in Mongolia and the quality of the Flublok product. paign evaluation protocols that will provide data to “Flublok can save lives,” said Manon Cox, President improve vaccination services in future years.

16 PROTEIN SCIENCES About The Partnership for Influenza Vaccine through the creation of innovative vaccines and Introduction biopharmaceuticals. PIVI is an innovative public/private program in which The Task Force for Global Health works in partnership About Flublok with the Centers for Disease Control and Preven- Flublok, the world’s first recombinant protein- tion (CDC), Ministries of Health, corporate partners based vaccine for the prevention of seasonal influ- and others to create sustainable, national, seasonal enza disease, was initially approved by the U.S. FDA influenza vaccination programs in low and middle in January 2013. FDA expanded its approval in Oc- income countries. tober 2014 to include everyone over 18 years and This important work protects communities from approved a nine-month shelf life in June 2016. the impacts of flu, while also building the immuni- Flublok is also licensed for sale in Mexico and zation infrastructure required for future pandemic licensure in additional countries, including Japan, is responses, as well as strengthening capacity to expected in the near future. Flublok is the only flu ultimately respond to other emerging disease vaccine made in a 100% egg-free system using mod- threats. ern cell culture technology, making it unnecessary to use an infectious influenza virus, antibiotics or About Protein Sciences harsh chemicals in manufacturing. Flublok is high- Protein Sciences is a world leader in vaccine ly purified and does not contain any preservatives development and protein production. Our mission (e.g., thimerosal, which contains mercury), egg pro- is our inspiration: to save lives and improve health teins, gelatin or latex.

IN THE NEWS 17 U.S. Protein Sciences’ Zika Vaccine Shows Good Results in Preclinical Testing Bio-Manguinhos/Fiocruz Joins International Consortium

For Immediate Release: Contact: January 12, 2017 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden — Protein Sciences Corporation, a lead- “Zika remains a substantial threat in several parts ing vaccine development company and maker of of the world,” said Manon Cox, President & CEO of Flublok Influenza Vaccine®, announced today that Protein Sciences Corporation. “Our new data and its lead protein based Zika vaccine candidate had Fiocruz, through Bio-Manguinhos´ participation in good safety results and induced strong neutraliz- our consortium bring us another step closer to real- ing antibodies against the Zika virus in preclinical izing a vaccine that will protect against this deadly studies. virus.” The product is expected to advance into human Protein Sciences Corporation’s Zika Consortium clinical trials in the next few months. In addition, the consists of five international partners: Mundo Sano Institute of Technology in Immunobiologicals of the and Sinergium Biotech in Argentina, Liomont in Oswaldo Cruz Foundation (Bio-Manguinhos/Fio- Mexico, UMN Pharma in Japan and now Fiocruz cruz), has joined the multinational consortium that in Brazil. Four of these partners are based in Latin is sponsoring development of the vaccine. America where Zika remains a considerable concern. The vaccine candidate is composed of purified pro- tein that matches a protein found on the outer sur- About Bio-Manguinhos/Fiocruz face of the Zika virus (the E protein) and was created Bio-Manguinhos is the Institute of Technology in using Protein Sciences’ proprietary BEVS technology Immunobiologicals of the Oswaldo Cruz Foundation because of its speed, safety and ability to accurately (Bio-Manguinhos/Fiocruz). match the field virus. Fiocruz is a centennial institution belonging to the In preclinical testing, the purified protein formu- Brazilian Ministry of Health with several institutes lated with alum induced strong levels of neutralizing working on different health related areas (R&D, sci- antibodies in outbred mice, which is a positive indi- entific information, history, education, manufactur- cator that the vaccine will protect against Zika virus ing and health care). infection. In addition, the vaccine candidate demon- Currently, Bio-Manguinhos produces 10 vaccines, strated good safety data in a toxicology study spon- 14 in vitro diagnostics (IVDs) and 5 biopharmaceuti- sored by National Institute of Allergy and Infectious cals. See more at www.bio.fiocruz.br Disease, National Institutes of Health through its pre-clinical support program. Based on these data, preparations are being made to start a Phase I clini- cal study in the United States in April 2017.

18 PROTEIN SCIENCES About Protein Sciences  FFF Enterprises: Protein Sciences is a world leader in vaccine 800-843-7477 development and protein production. Our mission www.myfluvaccine.com is our inspiration: to save lives and improve health  Cardinal Health: through the creation of innovative vaccines and 866-677-4844 biopharmaceuticals. www.cardinalhealth.com/flu  McKesson: About Flublok 877-MCK-4FLU Flublok, the world’s first recombinant protein- mms.mckesson.com based vaccine for the prevention of seasonal influ-  Moore Medical: enza disease, was initially approved by the U.S. FDA 800-234-1464 in January 2013. FDA expanded its approval in Oc- www.mooremedical.com/flu tober 2014 to include everyone over 18 years and  Henry Schein: approved a nine-month shelf life in June 2016. 800-772-4346 Flublok is also licensed for sale in Mexico and www.henryschein.com licensure in additional countries, including Japan, is expected in the near future. Flublok is the only flu Learn more at www.proteinsciences.com and vaccine made in a 100% egg-free system using mod- www.flublok.com. ern cell culture technology, making it unnecessary to use an infectious influenza virus, antibiotics or Flublok Safety Information harsh chemicals in manufacturing. Flublok is high- Flublok is approved for people 18 and older to ly purified and does not contain any preservatives prevent influenza disease. The most common side (e.g., thimerosal, which contains mercury), egg pro- effect from Flublok is pain at the site of injection. teins, gelatin or latex. Headache, fatigue or muscle ache may occur. In addition, Flublok contains three times more Tell the doctor if you have ever experienced antigen than traditional flu vaccines (3x45mcg Guillain-Barré syndrome (severe muscle weakness) or hemagglutinin protein versus 3x15mcg hemagglu- have had a severe allergic reaction to any component tinin protein) and was shown to have better efficacy of Flublok vaccine. in a 2014/15 post-marketing study.* Vaccination with Flublok may not pro- Flublok is an accurate copy of the virus coat and is tect all individuals. Please see the complete not subject to the egg-adapted mutations that can Package Insert available at www.flublok.com or call be associated with low vaccine effectiveness (see 203-686-0800 for more information. Skowronski et al. (2014) PLOS ONE 9(3), e92153). *Flublok demonstrated a higher antibody re- Healthcare professionals wishing to order Flublok sponse to the A strains in two field trials in adults should contact one of the following distributors: ≥50 years old. The B strain antibody responses were  Protein Sciences Corporation: comparable to traditional trivalent and quadrivalent 203-686-0800 vaccines. www.flublok.com

IN THE NEWS 19 20 PROTEIN SCIENCES Small flu vax players poised to win ‘sizable’ share of market, firm predicts by Eric Sagonowsky | Dec 1, 2016 12:37 pm

As new flu vaccine technology emerges in the com- But while GlobalData gives Protein Sciences a chance ing years, smaller players will have a shot at stealing and other companies a chance to “carve out a sizable market share from the world leaders who have for niche,” CEO Manon Cox previously told FiercePhar- years had a hold on the market. ma she’s after much more than just a portion of the That’s the word from GlobalData, which predicts market. smaller companies such as Protein Sciences, Mit- Protein Sciences believes its Flublok Quadrivalent subishi Tanabe and Novavax will be able to extract a “is really going to be the product of choice in time,” quarter of total flu vaccine sales or more with new cell Cox said, adding that she believes it’ll eventually “take manufacturing technology. To do that, they’ll need to over.” Protein Sciences is seeking marketing partners wrestle share from Sanofi, GlaxoSmithKline and other for its cell culture vaccine. top vaccine companies that have for years controlled One development that could hold an impact on the the seasonal flu market with egg-based vaccines. market is the CDC’s decision this year to recommend Flu vaccines have seen significant change with No- against any use of AstraZeneca’s quadrivalent FluMist vartis’ exit from the industry, according to GlobalDa- for the current flu season. The company is working to ta’s director of infectious diseases Christopher Pace. bring the nasal vaccine back to the market for future Now, Seqirus is the only top player to market a cell seasons. culture-based vaccine, Flucelvax Quadrivalent, and an Mitsubishi Tanabe is working on a tobacco-based adjuvanted seasonal influenza vaccine, Fluad. flu vaccine that could hit the market by 2018 or 2019; Though bigger players aren’t likely to lose total con- GlobalData infectious diseases analyst Achilleas trol, companies making cell-based seasonal flu vac- Livieratos has previously said such a shot could have cines “are likely to capture at least 25% of market share” a “significant” impact on the seasonal market if ap- in leading countries by 2025, Pace said in a statement. proved. The firm predicts sales for seasonal flu shots will hit Novavax’s nanoparticle influenza vaccine program is $4.3 billion by that year, up from $3.1 billion in 2015. in early development stages.

IN THE NEWS 21 Flublok® Influenza Vaccine Now Available in Mexico

For Immediate Release: Contact: November 11, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT — Mexico welcomed the availability of confirmed influenza than people who received a Flublok last Thursday with the official launch of traditional flu vaccine. Flublok influenza vaccine in Mexico City. Earlier in October, members of the Mexican press Mexican regulatory authority COFEPRIS released toured Protein Sciences’ Flublok manufacturing the first batch of Flublok for the Mexican market on facility in Pearl River, NY to learn about the mod- October 14th. ern manufacturing process and see firsthand how On Thursday, officials from Protein Sciences Cor- Flublok is made. Video coverage of the tour is poration, manufacturer of Flublok, and Laboratorios available at https://youtu.be/CymUoE2palI. Liomont, S.A. de C.V. (Liomont), a leading Mexican Flublok is approved in Mexico for adults 18 years pharmaceutical company and licensee of Flublok for and older. the Mexican market, gathered in Mexico City to ad- “Mexico is the first country outside the United dress the sales team and kick off distribution of the States to launch Flublok and make this modern revolutionary influenza vaccine. vaccine available to its people,” remarked Manon Liomont is partnered with Pfizer to help promote Cox, President and CEO of Protein Sciences. Flublok in Mexico. Several large companies in Mexi- She added, “We are pleased with Liomont’s choice co have already decided to vaccinate their employ- of promotional partner and we anticipate the fall ees with Flublok instead of the traditional egg-based vaccination campaign will be successful.” influenza vaccine. In addition to Mexico, Flublok is available at Unlike other flu vaccines, Flublok is made without hundreds of pharmacies across the United States. using infectious influenza virus, eggs, antibiotics or To find the closest location to you, visit Protein harsh chemicals in its manufacturing process; the re- Sciences’ Flublok Finder. sult is a highly pure, effective flu vaccine that can be If you still have difficulty finding a location made much faster than traditional flu vaccines. close to you, please contact Protein Sciences directly In addition, in a recent clinical study of 9,000 by calling the phone number listed below. adults 50 years and older, people who received For more information about Flublok, please visit Flublok were over 40% less likely to get cell culture www.flublok.com.

22 PROTEIN SCIENCES About Protein Sciences 800-234-1464 Protein Sciences specializes in vaccine develop- www.mooremedical.com/flu ment and protein production. Our mission is our  Henry Schein: inspiration: to save lives and improve health through 800-772-4346 the creation of innovative vaccines and biopharma- www.henryschein.com ceuticals. Learn more at www.proteinsciences.com and About Flublok www.flublok.com. Flublok, the world’s first recombinant protein- based vaccine for the prevention of seasonal influ- About Liomont enza disease, was initially approved by the U.S. FDA Liomont is a 100% Mexican pharmaceutical in January 2013. FDA expanded its approval in Octo- company established in 1938, ranked number 8 in ber 2014 to include everyone over 18 years and ap- the national pharmaceutical market in units and 16 proved a nine-month shelf life in June 2016. in value in 2014, with high quality prescription and Flublok is also licensed for sale in Mexico and OTC products. It has one of the most dynamic growth licensure in additional countries, including Japan, rates in the market. is expected in the near future. Flublok is the only Liomont has a capacity of more than 120 million flu vaccine made in a 100% egg-free system using units per year in a high tech facility considered to modern cell culture technology, making it unnec- be one of the most modern in Latin America. It has essary to use an infectious influenza virus, antibi- approximately 1500 employees, of which more than otics or harsh chemicals in manufacturing. Flublok half are medical sales reps with the aim of creating a is highly purified and does not contain any pre- solid and collaborative team. servatives (e.g., thimerosal, which contains mer- In addition to marketing activities, Liomont has the cury), egg proteins, gelatin or latex. In addition, social mission to be a source of employment, train- Flublok contains three times more antigen than ing and development of its people to ensure a better traditional flu vaccines (3x45mcg hemagglutinin quality of life. The Company has received the Socially protein versus 3x15mcg hemagglutinin protein) and Responsible Company Award for 10 continuous years was shown to have better efficacy in a 2014/15 post- due to its outstanding commitment to society. Other marketing study.* public and private institutions have also recognized Flublok is an accurate copy of the virus coat and is several initiatives in business and ecology among not subject to the egg-adapted mutations that can others. be associated with low vaccine effectiveness (see Skowronski et al. (2014) PLOS ONE 9(3), e92153). Flublok Safety Information Healthcare professionals wishing to order Flublok Flublok is approved for people 18 and older to should contact one of the following distributors: prevent influenza disease. The most common side  Protein Sciences Corporation: effect from Flublok is pain at the site of injection. 203-686-0800 Headache, fatigue or muscle ache may occur. www.flublok.com Tell the doctor if you have ever experienced  FFF Enterprises: Guillain-Barré syndrome (severe muscle weakness) 800-843-7477 or have had a severe allergic reaction to any compo- www.myfluvaccine.com nent of Flublok vaccine. Vaccination with Flublok may  Cardinal Health: not protect all individuals. Please see the complete 866-677-4844 Package Insert available at www.flublok.com or call www.cardinalhealth.com/flu 203-686-0800 for more information.  McKesson: *Flublok demonstrated a higher antibody response 877-MCK-4FLU to the A strains in two field trials in adults ≥50 years mms.mckesson.com old. The B strain antibody responses were compara-  Moore Medical: ble to traditional trivalent and quadrivalent vaccines.

IN THE NEWS 23 Protein Sciences CEO eyes GSK, Sanofi goliaths in fight to ‘take over’ quadrivalent flu vax market by Eric Sagonowsky | Oct 17, 2016 1:55 pm

Just a month after winning a big government con- fable.” tract for pandemic flu preparedness, Protein Sciences “We believe that Flublok Quadrivalent is really going has notched an FDA approval for its next flu vaccine to be the product of choice in time,” she said. “Even offering. influenza vaccine manufacturers are recognizing that, Starting next year, the Meriden, CT-based biotech over time, the egg-based production process will be- will distribute its Flublok Quadrivalent shot, which come obsolete and will be replaced with a more mod- targets four strains of the virus, hoping to gain some ern production process.” steam after facing challenges in the trivalent market. The company is seeking marketing partners for its In its quest for big quadrivalent sales, the private bio- vaccine. Cox said she believes it’ll eventually “take over tech aims to quash the idea that its vaccines are only the market.” for people who are allergic to eggs. Protein Sciences is hoping to sell 900,000 trivalent Protein Sciences’ new vaccine contains three times as vaccine doses this flu season, with a recent report by much active ingredient as other quadrivalent options, the Hartford Courant placing the tally sold so far just the company says, making it a “great choice” for se- north of 300,000. According to wholesale price list- niors and people with compromised immune systems. ings, the trivalent Flublok runs at about $39 per dose. The company hasn’t decided on a price. It’s $32.75 if purchased directly through the company. Protein Sciences has some head-to-head data to Last year, Protein Sciences sold about 250,000 doses of tout in its bid for sales in the quadrivalent arena. In a Flublok trivalent. study of nearly 9,000 adults aged 50 or older, Flublok The FDA approval comes quickly after Protein recipients were more than 40% less likely to get lab- Sciences sealed a pandemic flu vaccine pact last month confirmed flu compared with those receiving GlaxoS- with the U.S. government’s BARDA potentially worth mithKline’s Fluarix. $610 million. But the company will have formidable competition Although it’s unlikely the full value would be real- in the quadrivalent market, not only with GSK, but ized, the contract tasks Protein Sciences with getting Sanofi and Seqirus as well. Each of those companies “starting materials” ready so that the company could ships millions of vaccine doses to the U.S. each season respond in the event of a flu pandemic or strain mis- across their respective portfolios. match by major vaccine providers. The Protein Sciences product is different from tra- Protein Sciences’ cell culture flu vaccines can be ditional vaccines in that it’s made using an egg-free produced more quickly than traditional flu vaccines, process, making it suitable for people with egg aller- making them the only government-recognized prod- gies. Protein Sciences develops, harvests and purifies ucts capable of responding to a pandemic, according hemagglutinin proteins from insect cells, according to to the company. Cox told the Courant last month that Medscape. the arrangement would provide “stability … while we But the biotech is working hard to distance its vac- are building the flu business.” cine from the “pigeonhole effect that Flublok is Apart from its influenza vaccines, Protein Sciences is only for egg-allergic people,” CEO Manon Cox told working in preclinical stages on vaccines against Zika FiercePharma, adding that the notion is an “absolute and SARS. 24 PROTEIN SCIENCES IN THE NEWS 25 Protein Sciences Secures A Potentially Huge Federal Contract For Flu Vaccines

By Dan Haar develop, gain approval and ramp up Protein September 8, 2016 Sciences’ main product, known as Flublok; and most of it has been spent, Cox said. rotein Sciences Corp. has won a federal contract to make sure the government is The large contracts are not single deals. Rather, prepared for flu outbreaks, a deal that could they are spread out in numerous, smaller tasks, or Pbe worth as much as $610 million over the next assignments, typically a few million dollars each. five years. The first of which, under the latest contract, has already been awarded, at just over $2 million. That would be an astounding sum for a company that now employs 125 people, about 100 of them Much larger amounts could come in the event of at its Meriden home base. The likelihood is that an actual pandemic, or if there is a mismatch be- the actual amount it receives will be significantly tween the type of vaccine made by conventional less. drug manufacturers and the strains of flu that appear in a winter season – a situation that has Still, for Protein Sciences, which has developed happened in recent years. and is marketing a flu vaccine made from cell cultures, rather than eggs, the contract is a finan- Protein Sciences’ technology allows the company cial lifeline at a time when commercial sales have to move faster in turning out specific vaccines, fallen short of expectations. and its vaccine works without side effects, and protects against a broader range of flu viruses, “This really brings stability to the company while according to independent research. we are building the flu business,” CEO Manon Cox said. Cox could not say whether the latest federal deal would lead to hiring, and if so, when and where The company would use the money from the U.S. – in part because sales of the company’s vaccines Department of Health and Human Services in have not done as well as the company had hoped, several ways. It could directly supply the govern- despite the scientific triumphs. ment with vaccines in an emergency, and it could also prepare for a possible influenza pandemic, or In preparation for last winter’s flu season, the develop vaccines for new strains of the virus. third one for Flublok, Protein Sciences sold 250,000 doses. Protein Sciences previously received a contract for $149 million from the same agency within “This year we really need to sell 900,000,” Cox HHS, the Biomedical Advanced Research and said. “We lost quite a bit of money last year but it Development Authority, or BARDA – which is did put us on the map.” also the agency funding efforts to fight the Zika virus. Most of that 2009 contract was used to The Centers for Disease Control and Prevention

26 PROTEIN SCIENCES agreed to buy 300,000 doses this year for distri- “We can’t predict the likelihood of a pandemic bution to states, but as the season gets underway, occurring during the term of the contract, but states have ordered only 2,500 doses, Cox said, such contracts are an important part of our pan- adding, “so we are not too happy with that.” demic preparedness strategy, and Protein Scienc- Earlier this year, Protein Sciences said it was es is one of only three companies with influenza developing a Zika virus based on its cell-culture vaccine manufacturing facilities in the United technology. In April, it announced a deal with a States,” the agency said. pharmaceutical company and a health foundation in Argentina to license and produce the medica- Protein Sciences insists Flublok is the safest, nim- tion. The latest BARDA contract covers flu vac- blest and most broadly effective flu protection, cines and preparation, not Zika. though it costs somewhat more than convention- al vaccines. “Most important, the government wanted to have a mechanism to be able to purchase products Late Wednesday, Cox was visiting officials in New from us, and this is that mechanism,” Cox said. York state, where the company two years ago set up a potentially large manufacturing operation HHS confirmed the $610 million “ceiling” value in Pearl River, a small part of the sprawling, 2.9 of the long-term agreement, which is known as million-square-foot former Wyeth manufac- an “indefinite delivery-indefinite quantity con- turing labs, which were dismantled after Pfizer tract.” bought Wyeth.

“The value of this contract is not unusual for a Cox’s hope is that Flublok takes off on its own, contract of its type,” the agency said, because it apart from any federal purchases. “We’re doing would provide for “substantial quantities of pan- an all-out effort to get people to buy the product,” demic influenza vaccine” if necessary. she said.

IN THE NEWS 27 FDA Approves Flublok® Quadrivalent Influenza Vaccine

For Immediate Release: Contact: October 11, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT — Protein Sciences Corporation beginning in 2017. Flublok Quadrivalent has announced today that the FDA has approved its the same purity advantages as trivalent Flublok, quadrivalent formulation of Flublok® influenza containing pure protein made without infectious vaccine. influenza virus, antibiotics, eggs, thimerosal, Flublok Quadrivalent protects against 4 strains of preservatives, gelatin or latex. influenza, 3 of the same strains found in trivalent Trivalent Flublok is available at hundreds of Flublok plus an additional B strain. pharmacies across the United States, as listed Significantly, Flublok Quadrivalent is the first and on the Flublok Finder here: only high antigen content quadrivalent flu vac- https://www.flublok.com/get-flublok/flublok-find- cine approved by FDA. It contains 3x more active er/. ingredient than all other quadrivalent vaccines, “The U.S. has been trending toward the use of making it a great choice for seniors and those with quadrivalent flu vaccines in recent years,” said compromised immune systems, among others. Manon Cox, President and CEO of Protein Sciences In a clinical study of 9,000 adults 50 years of age and Corporation. older, people who received Flublok Quadrivalent “We are pleased to bring Flublok Quadrivalent were over 40% less likely to get cell-culture to market to give consumers additional options, confirmed influenza than those that received a especially seniors who have no other high antigen leading egg-produced quadrivalent flu vaccine. content quadrivalent vaccine available to them. We These results are relevant for trivalent Flublok, are looking forward to launching the vaccine next as the H3N2 component of the vaccine that is year and, in the meantime, continuing to make shared between trivalent and Flublok Quadrivalent trivalent Flublok available this year.” predominately contributed to the improved efficacy. To find the closest location to you offering This data can be found in the updated Package Insert Flublok, visit our Flublok Finder today. If you still have for trivalent Flublok that can be downloaded here: difficulty finding a location close to you, please https://www.flublok.com/media/1062/flublok-triva- contact Protein Sciences directly by calling us at the lent-pi.pdf. phone number listed below. Flublok Quadrivalent is approved for adults 18 For more information about Flublok, please visit and older and will be available in pre-filled syringes www.flublok.com.

28 PROTEIN SCIENCES About Protein Sciences marketing study.* Protein Sciences specializes in vaccine Flublok is an accurate copy of the virus coat and is development and protein production. Our mission not subject to the egg-adapted mutations that can is our inspiration: to save lives and improve health be associated with low vaccine effectiveness (see through the creation of innovative vaccines and Skowronski et al. (2014) PLOS ONE 9(3), e92153). biopharmaceuticals. Healthcare professionals wishing to order Flublok should contact one of the following distributors: About Flublok  Protein Sciences Corporation: Flublok, the world’s first recombinant protein- 203-686-0800 based vaccine for the prevention of seasonal influ- www.flublok.com enza disease, was initially approved by the U.S. FDA  FFF Enterprises: in January 2013. FDA expanded its approval in Octo- 800-843-7477 ber 2014 to include everyone over 18 years and ap- www.myfluvaccine.com proved a nine-month shelf life in June 2016.  Cardinal Health: Flublok is also licensed for sale in Mexico and 866-677-4844 licensure in additional countries, including Japan, www.cardinalhealth.com/flu is expected in the near future. Flublok is the only  McKesson: flu vaccine made in a 100% egg-free system using 877-MCK-4FLU modern cell culture technology, making it unnec- mms.mckesson.com essary to use an infectious influenza virus, antibi-  Moore Medical: otics or harsh chemicals in manufacturing. Flublok 800-234-1464 is highly purified and does not contain any pre- www.mooremedical.com/flu servatives (e.g., thimerosal, which contains mer-  Henry Schein: cury), egg proteins, gelatin or latex. In addition, 800-772-4346 Flublok contains three times more antigen than www.henryschein.com traditional flu vaccines (3x45mcg hemagglutinin protein versus 3x15mcg hemagglutinin protein) and Learn more at www.proteinsciences.com and was shown to have better efficacy in a 2014/15 post- www.flublok.com.

IN THE NEWS 29 Protein Sciences and Avanzcare Announce Licensing of Influenza Vaccines for the MENA Region

For Immediate Release: Contact: September 22, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Connecticut, USA and Doha, Qatar — Protein of pharmaceutical products make it a strong part- Sciences Corporation (headquarters: Meriden, CT, ner that will allow us to reach many countries while USA) and Avanzcare, the medical arm of Al Sawari streamlining operations.” He noted, “We acknowl- Holding (headquarters: Doha, Qatar) announced edge and are very grateful for the role the U.S. Com- that they have signed an agreement designating mercial Service of the U.S Embassy in Qatar played in Avanzcare as the exclusive distributor of Protein initiating and assisting in the successful completion Sciences’ proprietary Flublok® (seasonal) and of this important partnership.” Panblok® (pandemic) influenza vaccines and poten- Sheikh Turki Bin Faisal al Thani, Chairman for Al tially other vaccines to be developed in the future Sawari Holding, said, ”Avanzcare is determined to for certain Middle East and North Africa (MENA) make a difference on patient’s daily life by ensur- markets. ing access to innovative products and services that Under the terms of the agreement, Avanzcare will contribute to a healthier life. Protein Science’s will pursue registration of Flublok in all licensed innovative vaccines will generate significant value countries and will initially purchase Flublok from to our region’s healthcare and above all protect our Protein Sciences for distribution in the region. people.” The MENA region represents about 6% of the to- Dana Shell Smith, U.S. Ambassador to the State tal world population. This agreement dramatically of Qatar said, “We are so pleased to see another U.S. expands the global footprint of Flublok and other company successfully enter the Qatari market. There Protein Sciences’ vaccines. are so many promising opportunities here in a va- Dan Adams, Executive Chairman and Global Head riety of sectors such as biotech and healthcare and of Business Development for Protein Sciences said, American companies like Protein Sciences are help- “Representatives from the MENA region have long ing to pave the way towards innovative solutions.” been interested in Flublok and other Protein Sciences’ John Youssef, General Manager of Avanzcare said, vaccines because of Flublok’s attractive product “We are pleased to associate with Protein Sciences profile as a high efficacy, high purity flu vaccine. Our as this partnership represents an important step for platform technology that allows safe and rapid de- our company that is committed to constantly devel- velopment of vaccines against viral threats in the re- op the healthcare sector and improve the quality of gion has also driven the interest.” life in our region. Together we will be able to deliver He added, “Avanzcare’s extensive network in the re- a highly effective, pure, and safe flu vaccine, a latent gion and experience in securing regulatory approval need in the MENA region.”

30 PROTEIN SCIENCES About Protein Sciences About Flublok Protein Sciences is a vaccine development and pro- Flublok, the world’s first recombinant protein‐ tein production company that is dedicated to saving based vaccine for the prevention of seasonal influ- lives and improving health through the creation of enza disease, was initially approved by the U.S. FDA innovative vaccines and biopharmaceuticals. The in January 2013. FDA expanded its approval in Oc- Biomedical Advanced Research and Development tober 2014 to include everyone over 18 years and Authority (BARDA), a division of the U.S. Department approved a nine month shelf life in June 2016. of Health and Human Services, recently awarded the Flublok is also licensed for sale in Mexico and li- Company a contract that is part of the Authority’s censure in additional countries, including Japan, is medical countermeasures against pandemic influ- expected in the near future. Flublok is the only flu enza and influenza strains with pandemic potential vaccine made in a 100% egg‐free system using mod- (contract number HHSO100201600005I). Protein Sci- ern cell culture technology, making it unnecessary ences stands to receive up to $610 million through to use an infectious influenza virus, antibiotics or 2021 if BARDA exercises all options. harsh chemicals in manufacturing. Flublok is highly purified and does not contain any About Avanzcare preservatives (e.g., thimerosal, which contains mer- Avanzcare is a Qatari company serving the healthcare cury), egg proteins, gelatin or latex. sector through pharmaceutical distribution, manu- In addition, Flublok contains three times more an- facturing, healthcare centers, retailing, and Co‐Mar- tigen than traditional flu vaccines (3x45mcg hem- keting. Through selective partnerships, Avanzcare agglutinin protein versus 3x15mcg hemagglutinin strives to identify latent needs and offer the most protein) and was shown to have superior efficacy in innovative and efficient products and services to a 2014/15 post‐marketing study.* address them. Its well‐defined strategy unites their Flublok is an accurate copy of the virus coat and regional expertise with their strong global network is not subject to the egg‐adapted mutations associ- to work towards the final goal: constantly improve ated with low vaccine effectiveness (see Skowronski people´s well‐being. Avanzcare is invariably seeking et al. (2014) PLOS ONE 9(3), e92153). to contribute to the development of the healthcare sector in the region by providing advanced health Learn more at www.proteinsciences.com and solutions. www.flublok.com.

IN THE NEWS 31 U.S. Biomedical Advanced Research and Development Authority (BARDA) Awards Protein Sciences Multi- Million Dollar Contract for Pandemic Preparedness

For Immediate Release: Contact: September 7, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden — Protein Sciences Corporation announced She added, “Prior support from BARDA was critical today that the Biomedical Advanced Research and in the development and scale-up of our technology, Development Authority (BARDA), a division of the which is now the only platform that is used to manu- U.S. Department of Health and Human Services, has facture an FDA-approved vaccine (i.e., Flublok) and awarded the company a contract that is part of the can address a pandemic in time.” Authority’s medical countermeasures against pan- To learn more about Protein Sciences technol- demic influenza and influenza strains with pandemic ogy and Flublok, visit www.proteinsciences.com and potential (contract number HHSO100201600005I). www.flublok.com. Protein Sciences will perform the contract using its proprietary platform technology for producing vac- About Protein Sciences cines that according to the Food and Drug Adminis- Protein Sciences specializes in vaccine develop- tration has revolutionized influenza vaccine manu- ment and protein production. Our mission is our in- facturing and stands to receive up to $610 million spiration: to save lives and improve health through through 2021 if BARDA exercises all options. the creation of innovative vaccines and biopharma- The company’s Flublok® (seasonal) and Panblok® ceuticals. (pandemic) influenza vaccines can be made with unprecedented speed, safety and precision. The About Flublok new contract with BARDA taps into this technology Flublok, the world’s first recombinant protein- and ensures the country will be prepared with suf- based vaccine for the prevention of seasonal influ- ficient supplies of vaccine in a timely manner should enza disease, was initially approved by the U.S. FDA an influenza pandemic strike. in January 2013. FDA expanded its approval in Oc- The contract will finance preparation of starting tober 2014 to include everyone over 18 years and materials for multiple potential pandemics that that approved a nine month shelf life in June 2016. could shave a month or more off the time when the Flublok is also licensed for sale in Mexico and li- company have a vaccine available. censure in additional countries, including Japan, is Protein Sciences President and CEO Dr. Manon Cox expected in the near future. Flublok is the only flu said, “We are very pleased to extend our relationship vaccine made in a 100% egg-free system using mod- with BARDA and support them in their mission to ern cell culture technology, making it unnecessary provide ‘More, Faster, Better’ vaccines in the face of to use an infectious influenza virus, antibiotics or a pandemic.” harsh chemicals in manufacturing.

32 PROTEIN SCIENCES Flublok is highly purified and does not contain any www.henryschein.com preservatives (e.g., thimerosal, a mercury derivative), egg proteins, gelatin or latex. In addition, Flublok Flublok Safety Information contains three times more antigen than traditional Flublok is approved for people 18 and older to flu vaccines (3x45mcg hemagglutinin protein versus prevent influenza disease. The most common side 3x15mcg hemagglutinin protein)*. effect from Flublok is pain at the site of injection. Flublok is a perfect copy of the virus coat and is not Headache, fatigue or muscle ache may occur. subject to the egg-adapted mutations associated Tell the doctor if you have ever experienced with low vaccine effectiveness (see Skowronski et al. Guillain-Barré syndrome (severe muscle weakness) (2014) PLOS ONE 9(3), e92153). or have had a severe allergic reaction to any compo- nent of Flublok vaccine. Healthcare professionals wishing to order Flublok Vaccination with Flublok may not protect all indi- should contact one of the following distributors: viduals. Clinical effectiveness in adults 50 and older  Protein Sciences Corporation: 203-686-0800 is based on the immune response elicited by Flublok www.flublok.com and not on demonstration of decreased influenza  FFF Enterprises: 800-843-7477 disease. www.myfluvaccine.com Please see the complete Package Insert available  Cardinal Health: 866-677-4844 at www.flublok.com or call 203-686-0800 for more www.cardinal.com/us/en/SPD/Ordering information.  McKesson: 877-MCK-4FLU *Flublok demonstrated a higher antibody response www.mckesson.com to the A strains in two field trials in adults ≥50 years  Moore Medical: 800-234-1464 old. The B strain antibody responses were com- www.mooremedical.com/flu parable to traditional trivalent and quadrivalent  Henry Schein: 800-772-4346 vaccines.

IN THE NEWS 33 First Doses of Flublok® Influenza Vaccine of 2016/17 Have Shipped New Flublok Finder Launched at www.flublok.com

For Immediate Release: Contact: August 10, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT — Protein Sciences announced that the About Protein Sciences FDA has approved and released the first lots of Flu- Protein Sciences specializes in vaccine develop- blok® influenza vaccine for distribution this season. ment and protein production. Our mission is to save Doses have been shipped and healthcare profession- lives and improve health through the creation of in- als and pharmacies that have pre-ordered Flublok novative vaccines and biopharmaceuticals. should receive the vaccine this week. The Company also announced the launch of its brand new Flublok About Flublok Finder that is incorporated into the Flublok website, Flublok, the world’s first recombinant protein-based enabling consumers to find the nearest Flublok loca- vaccine for the prevention of seasonal influenza dis- tion with ease. To find your nearest Flublok vaccina- ease, was initially approved by the U.S. FDA in Janu- tion center, input your zip code at https://www.flu- ary 2013. FDA expanded its approval in October 2014 blok.com/get-flublok/flublok-finder/. to include everyone over 18 years and approved a 9- Flublok is approved for all people 18 and older and month shelf life in June 2016. Flublok is also licensed was recently shown in a clinical study of adults 50 and for sale in Mexico and licensure in additional coun- older to provide over 40% better protection against tries, including Japan, is expected in the near future. cell culture confirmed influenza compared to a flu Flublok is the only flu vaccine made in a 100% egg-free vaccine made using embryonated hens’ eggs – the system using modern cell culture technology, making 60-year-old vaccine production technology. it unnecessary to use an infectious influenza virus, an- Flublok also offers a pure choice for vaccination as tibiotics or harsh chemicals in manufacturing. Flublok it is comprised of purified protein and lacks the un- is highly purified and does not contain any preserva- necessary ingredients contained in other flu vaccines, tives (e.g., thimerosal, which contains mercury), egg such as influenza virus, antibiotics, preservatives, egg proteins, gelatin or latex. Flublok contains three times protein, gelatin or latex. “With early release of Flu- more antigen than traditional flu vaccines (3x45mcg blok, we will be one of the first vaccines available to hemagglutinin protein versus 3x15mcg hemaggluti- protect adults,” said Manon Cox, President and CEO of nin protein) and was shown to have superior efficacy Protein Sciences Corporation. “You have a choice in in a 2014/15 post-marketing study.* Flublok is an ac- flu vaccines and why not demand the vaccine made curate copy of the virus coat and is not subject to the with today’s technology – Flublok?” egg-adapted mutations associated with low vaccine For more information about Flublok, please visit effectiveness (see Skowronski et al. (2014) PLOS ONE www.flublok.com. 9(3), e92153).

34 PROTEIN SCIENCES 2016/17 Formulation of Flublok® Influenza Vaccine Receives FDA Approval

For Immediate Release: Contact: July 12, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Meriden, CT — Protein Sciences Corporation “In a surprise turn of events, CDC recently announced that FDA has approved the 2016/17 for- recommended against the use of FluMist® (LAIV) mulation of Flublok® influenza vaccine. vaccine that will result in a significant shortage of flu Unlike other vaccines, all flu vaccines are adjusted vaccines this season. Flublok is an excellent alterna- annually to protect against the new strains of influen- tive for adults 18 and older. Flublok’s game-changing za that are predicted to be the dominant circulating technology produces a highly pure and effective strains during the upcoming fall and winter. vaccine that has broad consumer appeal.” This year, FDA mandated two new components be  made for trivalent flu vaccines, including a new H3N2 About Flublok component that is also required for quadrivalent Trivalent Flublok is approved for people 18 and vaccines. older to prevent influenza disease. The most com- H3N2 vaccine components are historically the most mon side effect from Flublok is pain at the site of in- challenging for egg-based flu vaccine manufactur- jection. Headache, fatigue or muscle ache may occur. ers to make and are the components that have been Tell the doctor if you have ever experienced linked to poor vaccine efficacy in the past. Guillain-Barré syndrome (severe muscle weakness) or In contrast, Protein Sciences’ technology platform have had a severe allergic reaction to any component for making Flublok allows for a perfect match to of Flublok vaccine. H3N2 strains. In a post-marketing clinical study of Vaccination with Flublok may not protect all indi- 9,000 adults 50 years and older during the 2014/15 flu viduals. Clinical effectiveness of trivalent Flublok in season where H3N2 influenza was dominant, people adults 50 and older is based on the immune response who received Flublok were over 40% less likely to get elicited by trivalent Flublok and not on demonstra- cell culture confirmed influenza than people who re- tion of decreased influenza disease. ceived an egg-based flu vaccine. Please see the complete Package Insert available FDA approval of the 2016/17 formulation of Flublok at www.flublok.com or call 203-686-0800 for more means that Flublok is on track to ship to healthcare information. providers in early August. *Trivalent Flublok demonstrated a higher antibody “The timing of this approval could not be better. We response to the A strains during 2 clinical trials in will be able distribute Flublok earlier this season than adults ≥50 years old. before,” said Manon Cox, President and CEO of Protein The B strain antibody response was comparable to Sciences Corporation. traditional trivalent vaccines.

IN THE NEWS 35 UMN Pharma Joins Protein Sciences’ International Zika Vaccine Consortium

For Immediate Release: Contact: June 29, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

USA and Japan — Protein Sciences Corporation He added, “We are making a Zika vaccine using (Meriden, CT and Pearl River, NY), manufacturer of the same platform technology that we use to make Flublok® influenza vaccine, and UMN Pharma Inc. Flublok, which has been proven to be safe and (Akita, Akita prefecture, Japan) announced today effective in tens of thousands of healthy adults.” that UMN has signed on as the latest partner of the UMN is no stranger to Protein Sciences’ international Zika vaccine consortium initiated by technology. The Company holds a license for Protein Sciences. Flublok in Japan, China, Korea, Hong Kong, Taiwan The consortium, which also includes partners and Singapore. UNIGEN, a joint venture of UMN Sinergium Biotech (Buenos Aires, Argentina) and and IHI Corporation, will manufacture Flublok and Mundo Sano, a private foundation with activities in Astellas will market it in Japan. Argentina, Spain and Africa, is developing a vaccine Tatsuyoshi Hirano, Chairman and CEO at UMN to combat the Zika virus based on Protein Sciences’ Pharma said, “We are pleased to join the Zika proprietary technology. The partners are pooling vaccine consortium. As a world class biopharmaceu- resources to drive advancement of their vaccine tical and vaccine supplier, we would like to contrib- candidate into the clinic as quickly as possible, which ute the use of our 21,000L bioreactors to provide is anticipated for later this year. Zika vaccine to emerging countries in addition to Under the terms of the agreement, UMN will providing influenza vaccine to the Japan and U.S. pay an upfront fee to fund the development and markets.” manufacture of the vaccine being produced at Protein Sciences. About Protein Sciences and Flublok In return, UMN will receive manufacturing and Protein Sciences specializes in vaccine develop- commercial rights to the vaccine in Japan and other ment and protein production. Our mission is our counties to be determined. inspiration: to save lives and improve health through Dan Adams, Protein Sciences Executive Chairman the creation of innovative vaccines and biopharma- and Global Head of Business Development, said, ceuticals. “Our consortium is gaining traction because people Flublok, the world’s first recombinant protein- realize that only by using a proven platform based vaccine for the prevention of seasonal technology such as ours will it be possible to influenza disease, was approved by FDA in January get a Zika vaccine approved by authorities and 2013. distributed to where it is needed quickly.” Flublok is the only flu vaccine made in a 100%

36 PROTEIN SCIENCES egg-free system using modern cell culture tech- Astellas Pharma in September 2010. nology, making it unnecessary to use an infectious The companies have submitted an application influenza virus or antibiotics in manufacturing. for approval of manufacture and sale of the recom- Flublok is highly purified and does not contain any binant seasonal influenza HA vaccine UMN-0502 preservatives (e.g., thimerosal, a mercury derivative), (Astellas Pharma development code: ASP7374) egg proteins, gelatin or latex. to the Ministry of Health, Labor and Welfare, based In addition, Flublok contains three times more on its results and efficacy on May 30, 2014. antigen than traditional flu vaccines (3x45mcg hemagglutinin protein versus 3x15mcg hemagglu- Flublok Safety Information tinin protein)*. Flublok is a perfect copy of the virus Flublok is approved for people 18 and older to coat and is not subject to the egg-adapted muta- prevent influenza disease. The most common side tions associated with low vaccine effectiveness (see effect from Flublok is pain at the site of injection. Skowronski et al. (2014) PLOS ONE 9(3), e92153). Headache, fatigue or muscle ache may occur. Tell Learn more at www.proteinsciences.com and the doctor if you have ever experienced Guillain- www.flublok.com. Barré syndrome (severe muscle weakness) or have had a severe allergic reaction to any component of About UMN Pharma Flublok vaccine. UMN Pharma is a bio-venture established in 2004 Vaccination with Flublok may not protect all and is headquartered at Akita, Akita prefecture in individuals. Clinical effectiveness in adults 50 and Japan. The company received a license from Protein older is based on the immune response elicited by Sciences for dealership and exclusive development Flublok and not on demonstration of decreased and manufacture of the recombinant influenza influenza disease. Please see the complete Package HA vaccine in Japan in August 2006 and for other Insert available at www.flublok.com or call 203-686- regions in Asia (China, Korea, Taiwan, Hong Kong 0800 for more information. and Singapore) in October 2010. *Flublok demonstrated a higher antibody In Japan, the company concluded a cooperation response to the A strains during 2 clinical trials in agreement for joint development and exclusive adults ≥50 years old. The B strain antibody response sales of the recombinant influenza HA vaccine with was comparable to traditional trivalent vaccines.

IN THE NEWS 37 PSC Exclusively Licenses to uniQure its Cell Line and Technology for Production of Human Gene Therapies

For Immediate Release: Contact: June 28, 2016 Courtney A. Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800 ext. 301

Connecticut, USA — Protein Sciences Corporation, disease, was approved by the U.S. FDA in January makers of Flublok® influenza vaccine, announced 2013. Flublok is the only flu vaccine made in a 100% today that it has entered into an agreement with egg-free system using modern cell culture technol- uniQure NV, a leader in gene therapy, under ogy, making it unnecessary to use an infectious influ- which Protein Sciences has exclusively licensed its enza virus or antibiotics in manufacturing. Flublok is proprietary expresSF+® cell line (SF+) and associated highly purified and does not contain any preservatives technology to uniQure for production of its human (e.g., thimerosal, a mercury derivative), egg proteins, gene therapy products based on rAAV vectors. gelatin or latex. The companies, which have had a relationship that Flublok contains three times more antigen than tra- spans nearly a decade, will expand their agreement ditional flu vaccines (3x45mcg hemagglutinin protein to include uniQure’s broad pipeline of investigational versus 3x15mcg hemagglutinin protein)*. Flublok is a gene therapies in development. perfect copy of the virus coat and is not subject to the Under the terms of the agreement, Protein Sciences egg-adapted mutations associated with low vaccine will receive an undisclosed upfront payment and is effectiveness (see Skowronski et al. (2014) PLOS ONE eligible for a one-time milestone payment. 9(3), e92153). Learn more at www.proteinsciences. Manon Cox, President and CEO of Protein Sciences, com and www.flublok.com. said, “We are very pleased to expand our license agreement with uniQure. The company was one Flublok Safety Information of the first to use our SF+ cell line and technology Flublok is approved for people 18 and older to pre- platform, and we look forward to helping uniQure vent influenza disease. The most common side effect bring new transformative gene therapy products to from Flublok is pain at the site of injection. Headache, patients.” fatigue or muscle ache may occur. Tell the doctor if you have ever experienced Guillain-Barré syndrome About Protein Sciences and Flublok (severe muscle weakness) or have had a severe Protein Sciences is a vaccine development and allergic reaction to any component of Flublok protein production company that is dedicated to vaccine. Vaccination with Flublok may not protect saving lives and improving health through the cre- all individuals. Clinical effectiveness in adults 50 and ation of innovative vaccines and biopharmaceuticals. older is based on the immune response elicited by Flublok, the world’s first recombinant protein-based Flublok and not on demonstration of decreased vaccine for the prevention of seasonal influenza influenza disease.

38 PROTEIN SCIENCES Flublok® Influenza Vaccine is a great alternative to FluMist for adults 18 and older

For Immediate Release: Contact: June 28, 2016 Courtney A. Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800 ext. 301

Meriden, CT — On Wednesday, the CDC’s Advisory • 3X more active ingredients than traditional flu Committee on Immunization Practices (ACIP) recom- vaccines* mended against the use of live attenuated influenza • Approved for adults 18 years and older vaccine (LAIV), also known as the “nasal spray” flu vac- • Fully covered by most insurance companies, in- cine and marketed as FluMist®, for the 2016/17 flu cluding Medicare/Medicaid season. The decision was based on data that showed • Now with a 9-month shelf life poor effectiveness of LAIV from 2013 through 2016. Without FluMist, 14 million less doses of flu vaccine To pre-order Flublok for 2016/17, contact Protein will be available this fall. Sciences at 203-686-0800 or one of these distributors: FluMist is approved for ages 2-49 and its absence FFF Enterprises: 800-843-7477 www.myfluvaccine.com will impact both pediatric and adult flu vaccine sup- Cardinal Health: 866-677-4844 www.cardinal.com/us/ ply. Providers should anticipate that remaining sup- en/SPD/Ordering plies of recommended flu vaccines will be depleted McKesson: 877-MCK-4FLU https://mms.mckesson.com quickly. It is advisable to plan ahead and pre-book Henry Schein: 800-772-4346 www.henryschein.com replacement vaccines now. Flublok influenza vaccine,  a pure protein flu vaccine with high efficacy, low side About Protein Sciences and Flublok effects and no harmful additives, is CDC recommend- Protein Sciences specializes in vaccine development and protein production. Our mission is our inspiration: ed and a great alternative for the adult population. to save lives and improve health through the creation of innovative vaccines and biopharmaceuticals. Why Flublok? Flublok, the world’s first recombinant protein- • Flublok is a safe and effective flu vaccine for the based vaccine for the prevention of seasonal influenza entire adult population. It is a pure protein vaccine disease, was approved by FDA in January 2013. Flublok is – the only flu vaccine made without influenza virus, the only flu vaccine made in a 100% egg-free system using antibiotics, formaldehyde, eggs, thimerosal (that modern cell culture technology, making it unnecessary to contains mercury), latex or gelatin use an infectious influenza virus or antibiotics in manu- • Sought after by millennials, pregnant women, facturing. Flublok is highly purified and does not contain immune-compromised patients, holistics, and many any preservatives (e.g., thimerosal, a mercury derivative), others egg proteins, gelatin or latex. In addition, Flublok contains three times more antigen than traditional flu vaccines • Superior efficacy in 2014/15 post-marketing (3x45mcg hemagglutinin protein versus 3x15mcg hem- study* agglutinin protein)*.

IN THE NEWS 39 FDA Approved Longer Shelf Life for the Game Changer, Flublok® Influenza Vaccine

For Immediate Release: Contact: June 23, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Merden, CT — Protein Sciences Corporation an- About Protein Sciences nounced today that FDA has extended the shelf life Protein Sciences is a vaccine development and for Flublok, its game changing seasonal influenza protein production company that is dedicated to vaccine, to 9 months from the date of manufacture- saving lives and improving health through the increasing the previous shelf life by 3 months. creation of innovative vaccines and biopharmaceu- The longer shelf life will make it easier for health- ticals. care providers and pharmacies to stock Flublok and vaccinate people throughout the influenza season, About Flublok which in some years can last as long as April or May. Flublok, the world’s first recombinant protein- “We are pleased to add an extended shelf life to based vaccine for the prevention of seasonal the list of product improvements we have been influenza disease, was initially approved by the able to achieve for Flublok,” said Dr. Penny Post, U.S. FDA in January 2013 and the age range was Protein Sciences Vice President, Regulatory Affairs. expanded to make Flublok available to everyone “We were first able to expand the approved age over 18 years of age in October 2014. range for Flublok to everyone 18 years and older in The FDA has accepted for filing and is reviewing October 2014. In addition to the 9 month shelf life Flublok Quadrivalent. Flublok is the only flu vaccine we just achieved, Flublok Quadrivalent is under re- made in a 100% egg-free system using modern cell view and FDA approval is anticipated this fall. We culture technology, making it unnecessary to use an are working towards securing a one-year shelf life as infectious influenza virus or antibiotics in manufac- well.” turing. In addition to Flublok’s undeniable purity due to Flublok is highly purified and does not contain any the absence of many ingredients that make tradi- preservatives (e.g., thimerosal, a mercury derivative), tional flu vaccines objectionable to some like mer- egg proteins, gelatin or latex. In addition, Flublok cury, antibiotics, or formalin, Flublok is highly ef- contains three times more antigen than traditional fective. In a clinical study of approximately 9,000 flu vaccines (3x45mcg hemagglutinin protein versus adults 50 years and older, Flublok proved to be 3x15mcg hemagglutinin protein)*. 43% more effective than a traditional egg-based Flublok is a perfect copy of the virus coat and is not flu vaccine in protecting people against cell culture subject to the egg-adapted mutations associated confirmed influenza. Therefore, Flublok is a high with low vaccine effectiveness (see Skowronski et al. efficacy vaccine for the entire adult population. (2014) PLOS ONE 9(3), e92153).

40 PROTEIN SCIENCES Flublok Safety Information and not on demonstration of decreased influenza Flublok is approved for people 18 and older to disease. prevent influenza disease. The most common side Please see the complete Package Insert available effect from Flublok is pain at the site of injection. at www.flublok.com or call 203-686-0800 for more Headache, fatigue or muscle ache may occur. information. Tell the doctor if you have ever experienced *Flublok demonstrated a higher antibody re- Guillain-Barré syndrome (severe muscle weakness) sponse to the A strains during 2 clinical trials in or have had a severe allergic reaction to any compo- adults ≥50 years old. The B strain antibody response nent of Flublok vaccine. was comparable to traditional trivalent vaccines. Vaccination with Flublok may not protect all indi- viduals. Clinical effectiveness in adults 50 and older Learn more at www.proteinsciences.com and is based on the immune response elicited by Flublok www.flublok.com.

IN THE NEWS 41 Protein Sciences Corporation, Sinergium Biotech and Mundo Sano Announce Zika Vaccine Partnership

For Immediate Release: Contact: April 19, 2016 Courtney Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800, ext 301

Connecticut, USA and Buenos Aires, Argentina Protein Sciences’ technology is well known for its — Protein Sciences Corporation (headquarters: speed and safety, as it is used to manufacture the Meriden, CT, USA), manufacturer of Flublok® FDA-approved Flublok influenza vaccine and has influenza vaccine, Sinergium Biotech (headquar- been recognized by the U.S. government as the ters: Buenos Aires, Argentina) and Mundo Sano, a only approved technology that can respond to a private foundation with activities in Argentina, pandemic influenza outbreak in time. The technology Spain and Africa, announced today that they have is plug-and-play, removing potential regulatory and entered into an agreement to become members of safety hurdles that can dramatically delay novel a consortium that will jointly develop a Zika virus vaccine development time lines. vaccine to combat the recent outbreak of Zika that Manon Cox, President and CEO of Protein Sciences is wreaking havoc in Latin America and spreading to said, “We are very pleased to partner with Sinergium other continents. Biotech and Mundo Sano on our Zika vaccine. Their Under the terms of the agreement, Sinergium focus on vaccine development and manufacturing will pay an upfront fee to fund the development make them a natural fit for the adoption of our and manufacture of the vaccine being produced at technology.” Protein Sciences using Protein Sciences’ proprietary She added, “We initiated Zika vaccine develop- technology. In return, Sinergium will receive ment in February and are rapidly advancing vaccine manufacturing and commercial rights to the vaccine candidates to the clinic. Sinergium’s proximity to the in Argentina and other counties to be determined. heart of the outbreak opens up channels of support The companies also said they are in active discussions that would otherwise be inaccessible.” with additional strategic partners worldwide Alejandro Gil, President and CEO of Sinergium that could strengthen and rapidly advance the Biotech added, “This is an important step for our development program. country to prevent Zika and an important step for The vaccine being developed is based on produc- our company that is committed to developing safely tion of recombinant variations of the E protein from and rapidly different vaccines for the public health. the Zika virus. Similar vaccine candidates produced We are also very enthusiastic to cooperate with at Protein Sciences against and Japa- Protein Sciences. Their great scientific technology nese Encephalitis Virus, which are close relatives of and quality standards led to previous approvals of the Zika virus, have previously been shown to neu- their influenza products in markets including FDA.” tralize their respective viruses in preclinical studies. Silvia Gold, President of Mundo Sano Foundation,

42 PROTEIN SCIENCES said, “After more than 20 years working in the international partners, the know-how of new tech- prevention of neglected diseases, and specifically the nologies was transferredintoArgentina, assuring a vector-transmitted ones, we are also very happy to local supply of strategic products. be part of this consortium opening the opportunity SinergiumBiotech owns a 20,000 sqm production of having a vaccine after WHO declared an impera- facility located in Garin, Buenos Aires, Argentina, tive need of it.” with state-of-the-art technology aligned with the highest quality standards. Sinergium Biotech is About Protein Sciences currently manufacturing more than 13 million doses Protein Sciences is a vaccine development and of different vaccines, including for seasonal influenza, protein production company that is dedicated to pneumococcal and HPV. saving lives and improving health through the creation of innovative vaccines and biopharmaceu- About Mundo Sano ticals. Mundo Sano Foundation was created in 1993, aiming to promote and create better conditions to About Flublok improve the health of those exposed to neglected Flublok, the world’s first recombinant protein- diseases. It works in increasing awareness, preven- based vaccine for the prevention of seasonal tion, diagnosis and long-term treatment of commu- influenza disease, was initially approved by the nities affected in strategic locations of Argentina, U.S. FDA in January 2013 and the age range was Spain and Africa. expanded to make Flublok available to everyone It has created partnerships with authorities, over 18 years of age in October 2014. universities, renowned scientists, civil societies, The FDA has accepted for filing and is reviewing private partners and international organizations. Its Flublok Quadrivalent. Flublok is the only flu vaccine community actions and investigations contribute made in a 100% egg-free system using modern cell to scientific knowledge. Learn more at culture technology, making it unnecessary to use an www.mundosano.org. infectious influenza virus or antibiotics in manufac- turing. Flublok Safety Information Flublok is highly purified and does not contain any Flublok is approved for people 18 and older to preservatives (e.g., thimerosal, a mercury derivative), prevent influenza disease. The most common side egg proteins, gelatin or latex. In addition, Flublok effect from Flublok is pain at the site of injection. contains three times more antigen than traditional Headache, fatigue or muscle ache may occur. flu vaccines (3x45mcg hemagglutinin protein versus Tell the doctor if you have ever experienced 3x15mcg hemagglutinin protein)*. Guillain-Barré syndrome (severe muscle weakness) Flublok is a perfect copy of the virus coat and is not or have had a severe allergic reaction to any compo- subject to the egg-adapted mutations associated nent of Flublok vaccine. with low vaccine effectiveness (see Skowronski et al. Vaccination with Flublok may not protect all indi- (2014) PLOS ONE 9(3), e92153). viduals. Clinical effectiveness in adults 50 and older is based on the immune response elicited by Flublok Learn more at www.proteinsciences.com and and not on demonstration of decreased influenza www.flublok.com. disease. Please see the complete Package Insert available at www.flublok.com or call 203-686-0800 About Sinergium for more information. Sinergium Biotech is an Argentinean biotech com- *Flublok demonstrated a higher antibody re- pany focused on the development, manufacturing sponse to the A strains during 2 clinical trials in and marketing of different vaccines. Through a adults ≥50 years old. The B strain antibody response model of different strategic alliances with local and was comparable to traditional trivalent vaccines.

IN THE NEWS 43 Protein Sciences and Orygen Biotecnologia Announce Agreement to License Flublok® Influenza Vaccine for Brazil

For Immediate Release: Contact: April 12, 2016 Courtney A. Reis, Communications Associate Protein Sciences Corporation Phone: (203) 686-0800 ext. 301

Connecticut, USA and São Paulo, Brazil — Protein es said, “Our partnership with Orygen gives way for Sciences Corporation and Orygen Biotecnologia SA, Flublok to enter the Southern Hemisphere, which a joint venture between the Brazilian pharmaceuti- has an opposite flu season from the Northern Hemi- cal companies Eurofarma Laboratórios SA and Biolab sphere, and thereby opens up a second sales cycle for Sanus Farmaceutica Ltda, announced today that they the vaccine.” She added, “Orygen is a young but highly have agreed on the terms of a licensing partnership professional company with founders that have deep that grants Orygen an exclusive license to Flublok® roots in pharmaceuticals. We expect our relationship influenza vaccine for the Brazilian market. will have long-lasting benefits.” Brazil is experiencing a severe outbreak of H1N1 swine flu that has killed almost twice as many peo- About Protein Sciences ple over the past three months as it did in all of 2015, Protein Sciences is a vaccine development and pro- according to Brazil’s Health Ministry, evidencing the tein production company that is dedicated to saving need for effective influenza prevention. lives and improving health through the creation of in- Flublok is the world’s first recombinant influ- novative vaccines and biopharmaceuticals. enza vaccine that has been shown in a recent large field trial to provide significantly better protection About Orygen against the flu than a traditional, egg-based influenza Orygen is a Brazilian biopharmaceutical company vaccine. focused the development, manufacture and market- Under the terms of the agreement, Orygen will ing of therapeutic monoclonal antibodies and vac- seek regulatory approval for and will market Flublok cines for disorders that affect Brazil and other emerg- in Brazil. Protein Sciences will manufacture Flublok ing economies. and will receive significant license and commercial milestone payments. About Flublok Andrew Simpson, Scientific Director of Orygen said, Flublok, the world’s first recombinant protein-based “Flublok represents an advance in the performance vaccine for the prevention of seasonal influenza dis- and quality of an influenza vaccine that will be a wel- ease, was approved by the U.S. FDA in January 2013. come addition in Brazil. We admire this achievement Flublok is the only flu vaccine made in a 100% egg- of Protein Sciences and are very pleased to be their free system using modern cell culture technology, partner in bringing Flublok to the Brazilian people.” making it unnecessary to use an infectious influenza Manon Cox, President and CEO of Protein Scienc- virus or antibiotics in manufacturing.

44 PROTEIN SCIENCES antigen than traditional flu vaccines (3x45mcg seasonal influenza HA vaccine UMN-0502 (Astellas hemagglutinin protein versus 3x15mcg hemag- Pharma development code: ASP7374) to the Ministry glutinin protein)*. Flublok is a perfect copy of the of Health, Labor and Welfare, based on its results and virus coat and is not subject to the egg-adapted efficacy on May 30, 2014. mutations associated with low vaccine effectiveness (see Skowronski et al. (2014) PLOS ONE 9(3), e92153). Flublok Safety Information Healthcare professionals wishing to pre-order Flublok Flublok is approved for people 18 and older to should contact one of the following distributors: prevent influenza disease. The most common side effect from Flublok is pain at the site of injection. FFF Enterprises: 800-843-7477 www.myfluvaccine.com Headache, fatigue or muscle ache may occur. Cardinal Health: 866-677-4844 www.cardinal.com/us/ Tell the doctor if you have ever experienced en/SPD/Ordering Guillain-Barré syndrome (severe muscle weakness) or McKesson: 877-MCK-4FLU https://mms.mckesson.com have had a severe allergic reaction to any component Henry Schein: 800-772-4346 www.henryschein.com of Flublok vaccine. Vaccination with Flublok may not protect all About UMN Pharma individuals. Clinical effectiveness in adults 50 and UMN Pharma is a bio-venture established in 2004 older is based on the immune response elicited by and is headquartered at Akita, Akita prefecture in Flublok and not on demonstration of decreased Japan. The company received a license from Protein influenza disease. Please see the complete Sciences for dealership and exclusive development Package Insert available at www.flublok.com or call and manufacture of the recombinant influenza HA 203-686-0800 for more information. vaccine in Japan in August 2006 and for other regions *Flublok demonstrated a higher antibody response in Asia (China, Korea, Taiwan, Hong Kong and Singa- to the A strains during 2 clinical trials in adults ≥50 pore) in October 2010. years old. In Japan, the company concluded a cooperation The B strain antibody response was comparable to agreement for joint development and exclusive sales traditional trivalent vaccines. of the recombinant influenza HA vaccine with Astel- las Pharma in September 2010. Learn more at www.proteinsciences.com and The companies have submitted an application for www.flublok.com. approval of manufacture and sale of the recombinant

IN THE NEWS 45 Protein Sciences and UNIGEN Reach Agreement to Source Flublok® Influenza Vaccine from Japan Expanded capacity could supply up to 25 million doses to U.S. market

For Immediate Release: Contact: February 12, 2016 Dan Adams, Executive Chairman Protein Sciences Corporation Phone: (203) 599-6064 ext. 162

USA and Japan — Protein Sciences Corporation Gifu plant will allow us to provide enough vaccine to (Meriden, CT and Pearl River, NY) and UMN Pharma meet this growing need.” Inc. (Akita, Akita prefecture, Japan) announced today Tatsuyoshi Hirano, Chairman and CEO at UMN that Protein Sciences and UNIGEN Inc., a joint venture Pharma said, “We are pleased to partner with Protein of UMN and IHI Corporation (Koto-ku, Tokyo, Japan), Sciences to enter into the U.S. flu vaccine market that entered into an agreement to source bulk Flublok is the biggest and two and a half times larger than influenza vaccine from Japan for the U.S. market. Japanese market. We will expand the capacity of Gifu The drug substances will be manufactured at the plant up to four 21,000 L biological reactors from two Gifu (Japan) Plant of UNIGEN. UNIGEN manufactures in order to meet the expected demands from Protein Flublok for the Japan market in two 21,000 L Sciences.” bioreactors – ten times the scale the vaccine is This agreement represents an expansion of the manufactured in the United States. With this added relationship between Protein Sciences and UMN capacity, Protein Sciences could provide as many as Pharma. UMN Pharma holds a license from Protein 25 million additional doses of Flublok each year to the Sciences for Flublok for the territories of Japan, China, U.S. flu vaccine supply. Korea, Hong Kong, Taiwan and Singapore. Astellas The companies have been working together for has the right to market Flublok in Japan. months on the preparation of a submission to secure  FDA licensure of the Gifu plant and have requested a About Protein Sciences and Flublok Type C meeting to initiate the process. Two Flublok Protein Sciences specializes in vaccine development manufacturing facilities in the U.S. operated by and protein production. Our mission is our inspiration: Protein Sciences are already licensed by the FDA. to save lives and improve health through the creation Flublok vaccine is FDA approved for all adults 18 of innovative vaccines and biopharmaceuticals. years and older and studies are underway to secure Flublok, the world’s first recombinant protein-based licensure for younger age groups. vaccine for the prevention of seasonal influenza Dan Adams, Executive Chairman and Global Head disease, was approved by FDA in January 2013. of Business Development at Protein Sciences said, Flublok is the only flu vaccine made in a 100% egg-free “The demand for Flublok is continuously increasing system using modern cell culture technology, making especially since we reported the results of our it unnecessary to use an infectious influenza virus or large field study that showed that Flublok provides antibiotics in manufacturing. Flublok is highly purified significantly better protection in older adults than and does not contain any preservatives, egg proteins, a traditional flu vaccine. Sourcing Flublok from the gelatin or latex. Flublok contains 3ximes more

46 PROTEIN SCIENCES Meriden company working on Zika virus vaccine By Brian Spyros, Reporter

February 4, 2016, 6:20 am

MERIDEN, CT (WTNH) — The Zika virus continues to spread in Central and South America, where much of it is concentrated. There are currently 48 cases in the United States. Health officials say those people got the virus after traveling to the affected areas. Protein Sciences, based in Meriden, is currently working on a Zika virus vaccine. “The way we make vaccines is perfectly suited for this kind of emergency,” said Rachel Felberbaum, senior director of business development at Protein Sciences. Work began on the vaccine weeks ago, before the mosquito-borne virus started making headlines. There’s a great deal of science that goes into making a vaccine. Protein Sciences is no stranger to this task. They’re world-renowned for their influenza vaccine, Flublok. As well as other vaccines for SARS and most recently Ebola. Scientists look at the genetic sequence of a virus, which is called the outer surface protein. That gives them an idea of what’s needed in the vaccine to neutralize the virus if someone gets infected. Work on the Zika virus vaccine could not come at a more critical time, especially after the World Health Organization recently declared it a public health emergency. “We’ve already started designing the vaccine, we’ve started the early phase,” said Felberbaum. “We are now in discussion with people from other governments and our government about how quickly to develop this vaccine. We believe we can have the first product for testing in six to eight weeks.” The vaccine would be used as a preventative measure in areas greatly affected, such as Brazil, Colombia and the Caribbean. The risk is greatest to pregnant women since Zika has been linked to serious birth defects. A Zika vaccine could also be given to Americans traveling out of the country. There is currently no approved Zika virus vaccine.

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