OSAKA, Japan & AMSTERDAM, Netherlands & FLORHAM PARK, N.J.–(BUSINESS WIRE)–Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President and CEO: Isao
Teshirogi, Ph.D.) and Shionogi B.V. and Shionogi Inc., the European and
the U.S. subsidiaries of Shionogi & Co., Ltd respectively, (hereafter
“Shionogi”) today announced 12 data presentations taking place at the
European Congress of Clinical Microbiology and Infectious Diseases
(ECCMID), being held April 13-16, 2019 in Amsterdam.

Eight posters will be presented on cefiderocol, a late-stage
investigational, novel siderophore cephalosporin. Cefiderocol has broad
Gram-negative antimicrobial activity against all the critical
Gram-negative pathogens the World Health Organization has identified as
being the highest priority for finding new treatment options.*

Data for XOFLUZA^™ (baloxavir marboxil), a first-in-class,
single-dose oral medicine for the treatment of influenza, will be
presented in two oral presentations and two posters.

Presentations will include data on these Shionogi agents from
company-sponsored or investigator-initiated investigational studies.

“We look forward to sharing findings from several large-scale
surveillance studies conducted in Europe and North America, in which
cefiderocol demonstrated potent in vitro activity against
problematic Gram-negative bacteria. We believe these data further
support the clinical profile of cefiderocol in treating serious and
life-threatening infections,” said Dr. Tsutae Den Nagata, Chief Medical
Officer, Shionogi. “In addition, the XOFLUZA data to be presented add to
the growing body of evidence of the drug’s robust efficacy and utility
against influenza, which remains a global public health concern.”

The details for the presentations are as follows:

Cefiderocol
Poster #P1851:
Cefiderocol in vitro activity against Gram-negative clinical
isolates collected in Europe: results from SIDERO-CR-2014/2016 (Abstract
#740)
Presenter: Masakatsu Tsuji
Date and time: April
15, 13:30-14:30
Session title and location: PS106 – Cefiderocol
in vitro; paper poster area

Poster #P1852: Cefiderocol in vitro activity against
Gram-negative clinical isolates collected in Europe: results from three
SIDERO-WT surveillance studies between 2014-2017 (Abstract #739)
Presenter:
Masakatsu Tsuji
Date and time: April 15, 13:30-14:30
Session
title and location: PS106 – Cefiderocol in vitro;
paper poster area

Poster #P1853: Cefiderocol susceptibility and geographical
analysis against globally isolated meropenem non-susceptible
Gram-negative bacteria containing serine- and metallo-carbapenemase gene
(Abstract #737)
Presenter: Masakatsu Tsuji
Date and
time: April 15, 13:30-14:30
Session title and location: PS106
– Cefiderocol in vitro; paper poster area

Poster #P1854: In vitro and in vivo activity of
cefiderocol against Burkholderia cepacia complex clinical
isolates (Abstract #733)
Presenter: Masakatsu Tsuji
Date
and time: April 15, 13:30-14:30
Session title and location: PS106
– Cefiderocol in vitro; paper poster area

Poster #P1855: In vitro antibacterial activity of
cefiderocol against an international collection of
carbapenem-non-susceptible Gram-negative bacteria isolated from
respiratory, blood, skin/soft tissue, and urinary sources of infection:
SIDERO-WT-2014-2016 (Abstract #6281)
Presenter: Sean Nguyen
Date
and time: April 15, 13:30-14:30
Session title and location: PS106
– Cefiderocol in vitro; paper poster area

Poster #P1857: Characterization of isolates showing high MICs to
cefiderocol from global surveillance study SIDERO-CR-2014/2016 (Abstract
#2832)
Presenter: Akinobu Ito
Date and time: April
15, 13:30-14:30
Session title and location: PS106 – Cefiderocol
in vitro; paper poster area

Poster #P0911: Prevalence and treatment of Stenotrophomonas
maltophilia among adult patients in United States hospitals between
2010 and 2015 (Abstract #6069)
Presenter: Bin Cai
Date
and time: April 14, 12:30-13:30
Session title and location: PS057
– Infection due to Pseudomonas aeruginosa and other
non-fermenters – many challenges; paper poster area

Poster #P1803: Distribution of Gram-negative pathogens by
infection site among hospitalised adult patients in United States
hospitals between 2010 and 2015 (Abstract #6234)
Presenter:
Bin Cai
Date and time: April 15, 12:30-13:30
Session
title and location: PS101 – Clinical epidemiology of
infections due to MDR Gram-negatives; paper poster area

XOFLUZA (baloxavir marboxil)
Oral
presentation #O0817: Clinical, virologic, and safety outcomes in
otherwise healthy adolescent patients with acute influenza: sub-group
analyses in adolescent population from the CAPSTONE-1 phase III clinical
trial (Abstract #3691)
Presenter: Simon Portsmouth
Date
and time: April 15, 14:06-14:16
Session title and location: OS166
– New therapeutic strategies in viral infections; Hall M

Oral presentation #O0819: Treatment emergent influenza
virus variants with reduced baloxavir susceptibility: impact on clinical
and virologic outcomes in otherwise healthy outpatients with acute
influenza (Abstract #2849)
Presenter: Takeki Uehara
Date
and time: April 15, 14:30-14:40
Session title and location: OS166
– New therapeutic strategies in viral infections; Hall M

Poster #P0765: Delayed oral dosing of baloxavir marboxil in
combination with a neuraminidase inhibitor ameliorates virus-induced
infiltration of inflammatory cells into lungs and protected lung
function in mice lethally infected with influenza A virus (Abstract
#4353)
Presenter: Keita Fukao
Date and time: April
14, 12:30-13:30
Session title and location: PS050 – New
therapeutic approaches in viral infections; paper poster area

Poster #P1122: Baloxavir demonstrates clinical and virologic
efficacy in high-risk patients with influenza B infection: CAPSTONE-2
Study (Abstract #3801)
Presenter: Simon Portsmouth
Date
and time: April 14, 13:30-14:30
Session title and location: PS066
– Respiratory viral epidemiology; paper poster area

About Cefiderocol

Cefiderocol is a parenteral siderophore cephalosporin with a novel
mechanism for penetrating the outer cell membrane of Gram-negative
pathogens including multidrug-resistant strains. Cefiderocol binds to
ferric iron and is actively transported into bacterial cells through the
outer membrane via the bacterial iron transporters, which function to
incorporate this essential nutrient for bacteria.¹ In
addition, cefiderocol can also enter cells by passive diffusion through
porin channels and is stable against all known classes of
beta-lactamases, including both the metallo- and serine-β-lactamases.²
These mechanism allows cefiderocol to achieve higher concentrations in
the periplasmic space where it can bind to receptors and inhibit cell
wall synthesis in the bacterial cells.³ Data from global
surveillance studies for cefiderocol demonstrated potent in vitro activity
against a wide spectrum of Gram-negative pathogens including
carbapenem-resistant Acinetobacter baumannii, Pseudomonas
aeruginosa, Enterobacteriaceae, and Stenotrophomonas
maltophilia.⁴ Cefiderocol has poor in vitro activity
against Gram-positive or anaerobic bacteria.

Two Phase III studies are ongoing in patients with HAP/VAP/HCAP†
(APEKS-NP‡) and with carbapenem-resistant pathogens at various infection
sites (CREDIBLE-CR). Information is available at www.clinicaltrials.gov under
the identifiers NCT02714595 and NCT03032380, respectively.

About Gram-negative Infections

The availability of effective therapies against Gram-negative bacteria,
including carbapenem-resistant Enterobacteriaceae and non-fermenting
species such as P. aeruginosa, A. baumannii, and S.
maltophilia, is an important unmet medical need.^4-8 There
are an increasing number of Gram-negative pathogens resistant to
multiple antibiotics, making them difficult to treat and resulting in
high mortality rates.⁹ In the U.S., at least two million
people are infected with antibiotic-resistant bacteria, and at least
23,000 people die as a result each year.¹⁰ In the EU, about
25 000 patients die from an infection with the selected
multidrug-resistant bacteria.¹¹ The World Health Organization
has identified carbapenem-resistant strains of Enterobacteriaceae, P.
aeruginosa, and A.baumannii as the top priority in the
research and development of new antibiotics.⁵

About XOFLUZA™ (baloxavir marboxil)

XOFLUZA, discovered by Shionogi, has a novel mechanism of action that
inhibits cap-dependent endonuclease in the polymerase acidic (PA)
protein (in the United States Prescribing Information, this enzyme is
stated as polymerase acidic endonuclease), an enzyme essential for viral
replication. The regimen for XOFLUZA is a single oral dose to treat
uncomplicated influenza, which is different from all currently available
antiviral treatments. In non-clinical studies, XOFLUZA demonstrated an
antiviral effect against a wide range of influenza viruses including
oseltamivir-resistant strains and avian strains (H7N9, H5N1).^12-14
XOFLUZA was approved and is now available in Japan for the treatment of
influenza Types A and B in adults and paediatric patients.¹⁵
Shionogi submitted a New Drug Application (NDA) for XOFLUZA in Taiwan on
June 29, 2018, for the treatment of influenza in patients 12 years of
age and older.¹⁶

Shionogi and the Roche Group, which includes Genentech in the U.S., have
a license and collaboration agreement to further develop and
commercialize XOFLUZA globally. Under the terms of this agreement, Roche
Group holds worldwide rights to XOFLUZA excluding Japan and Taiwan,
which will be retained exclusively by Shionogi & Co., Ltd. XOFLUZA is
currently available across the U.S. for the treatment of acute,
uncomplicated influenza in people 12 years of age or older.¹⁷
The U.S. Food and Drug Administration (FDA) has accepted a supplemental
NDA for XOFLUZA for the treatment of influenza in individuals at
high-risk for influenza-related complications 12 years and older. The
Prescription Drug User Fee Act (PDUFA) date for an FDA decision is
November 4, 2019. For more information, please refer to the XOFLUZA
website.

Roche is now conducting a Phase III development program including
paediatric populations, and hospitalised patients with severe influenza
and will further assess the potential to reduce transmission in
otherwise healthy patients. Shionogi is conducting a post-exposure Phase
III prophylaxis study in Japan in the 2018/2019 north hemisphere flu
season.

About Influenza

Seasonal and pandemic influenza remain a major public health concern,
and novel influenza drugs that will offer significant improvement over
current therapy are urgently needed. Globally, annual epidemics result
in three-to-five million cases of severe disease, millions of
hospitalizations and up to 650,000 deaths worldwide.^18-22

About Shionogi

Shionogi & Co., Ltd. is a Japanese major research-driven pharmaceutical
company dedicated to bringing benefits to patients based on its
corporate philosophy of “supplying the best possible medicine to protect
the health and wellbeing of the patients we serve.” The company
currently markets products in several therapeutic areas including
anti-infectives, pain, cardiovascular diseases and gastroenterology. Our
pipeline is focused on infectious disease, pain, CNS and oncology. For
more information on Shionogi & Co., Ltd., visit www.shionogi.co.jp/en.
Shionogi B.V. is the European subsidiary of Shionogi & Co., Ltd. based
in Amsterdam, Netherlands. For more information on Shionogi B.V. please
visit http://www.shionogi.eu/.
Shionogi Inc. is the U.S. subsidiary of Shionogi & Co., Ltd. based in
N.J. For more information on Shionogi Inc., please visit https://www.shionogi.com/.

Forward-Looking Statements

This announcement contains forward-looking statements. These
statements are based on expectations in light of the information
currently available, assumptions that are subject to risks and
uncertainties which could cause actual results to differ materially from
these statements. Risks and uncertainties include general domestic and
international economic conditions such as general industry and market
conditions, and changes of interest rate and currency exchange rate.
These risks and uncertainties particularly apply with respect to
product-related forward-looking statements. Product risks and
uncertainties include, but are not limited to, completion and
discontinuation of clinical trials; obtaining regulatory approvals;
claims and concerns about product safety and efficacy; technological
advances; adverse outcome of important litigation; domestic and foreign
healthcare reforms and changes of laws and regulations. Also for
existing products, there are manufacturing and marketing risks, which
include, but are not limited to, inability to build production capacity
to meet demand, unavailability of raw materials, and entry of
competitive products. The company disclaims any intention or obligation
to update or revise any forward-looking statements whether as a result
of new information, future events, or otherwise.

*Acinetobacter, Pseudomonas, Escherichia, Klebsiella and Stenotrophomonas.
†
Hospital-Acquired Pneumonia/Ventilator-Acquired
Pneumonia/Healthcare-Associated Pneumonia.
‡ Nosocomial Pneumonia.

References

1. Ito A, Nishikawa T., Matsumoto S, et al. Siderophore Cephalosporin
Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial
Activity against Pseudomonas aeruginosa. Antimicrob Agents
Chemother. 2016;60(12):7396-7401.

2. Ito-Horiyama T, Ishii Y, Ito A, et al. Stability of Novel Siderophore
Cephalosporin S-649266 against Clinically Relevant Carbapenemases. Antimicrob
Agents Chemother. 2016;60(7):4384-4386.

3. Tillotson GS. Trojan Horse Antibiotics—A Novel Way to Circumvent
Gram-Negative Bacterial Resistance? Infectious Diseases:
Research and Treatment. 2016;9:45-52 doi:10.4137/IDRT.S31567

4. M Hackel, M Tsuji, Y Yamano, et al. In Vitro Activity of the
Siderophore Cephalosporin, Cefiderocol, Against a Recent Collection of
Clinically Relevant Gram-Negative Bacilli from North America and Europe,
Including Carbapenem Non-Susceptible Isolates: The SIDERO-WT-2014 Study. Antimicrobial
Agents Chemotherapy. 2017;61(9):e00093-17. https://doi.org/10.1128/AAC.00093-17.

5. World Health Organization. Global priority list of
antibiotic-resistant bacteria to guide research, discovery, and
development of new antibiotics. February 27, 2017. Retrieved from https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/.

6. Diene SM, Rolain JM. Carbapenemase genes and genetic platforms in
gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter
species. Clin Microbiol Infect 2014; 20:831−38.

7. Livermore DM. Current epidemiology and growing resistance of
gram-negative pathogens. Korean J Intern Med 2012; 27:128−42.

8. Brooke JS. Stenotrophomonas maltophilia: an emerging global
opportunistic pathogen. Clin Microbiol Rev 2012; 25:2−41.

9. Tangden T, Giske CG. Global dissemination of extensively
drug-resistant carbapenemase-producing Enterobacteriaceae: clinical
perspectives on detection, treatment and infection control. J Intern
Med 2015; 277:501−12.T.

10. Centers for Disease Control and Prevention (CDC). Antibiotic
Resistance Threats in the United States 2013. Retrieved from https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf

11. European Centre for Disease Prevention and Control (ECDC). Technical
Report: the bacterial challenge: time to react. 2009. Retrieved from https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf

12. Noshi et al. In Vitro Characterization of Baloxavir Acid, a
First-in-Class Cap-Dependent Endonuclease Inhibitor of the Influenza
Virus Polymerase PA Subunit. Antiviral Research 2018;160:109-117.

13. K.Taniguchi et al. Inhibitory Effect of S-033188, a Novel Inhibitor
of Influenza Virus Cap-Dependent Endonuclease, Against Avian Influenza
A/H7N9 Virus in Vitro and in Vivo. Poster presentation at ESWI,
September 2017.

14. K.Taniguchi et al. Inhibitory Effect of S-033188/S-033447, a Novel
Inhibitor of Influenza Virus Cap-Dependent Endonuclease, Against Highly
Pathogenic Avian Influenza Virus A/H5N1. Poster presentation at ECCMID,
April 2017.

15. Shionogi & Co, Ltd. XOFLUZA^TM (Baloxavir Marboxil)
Tablets 10mg/20mg for the Treatment of Influenza Types A and B launched
in Japan. March 14, 2018. Retrieved from http://www.shionogi.co.jp/en/company/news/2018/pmrltj0000003oid-att/e180314.pdf.

16. Shionogi & Co, Ltd. Shionogi Filed for the New Drug Application of
XOFLUZA in Taiwan for the Treatment of Influenza. July 2, 2018.
Retrieved from http://www.shionogi.co.jp/en/company/news/2018/pmrltj0000003vit-att/e_180702.pdf.

17. Shionogi & Co, Ltd. Shionogi Announces FDA Approval of XOFLUZA^TM
(Baloxavir Marboxil) – for the Treatment of Acute, Uncomplicated
Influenza. October 25, 2018. Retrieved from http://www.shionogi.co.jp/en/company/news/2018/pmrltj0000003xss-att/e_181025.pdf.

18. World Health Organization. Up to 650 000 people die of respiratory
diseases linked to seasonal flu each year. December 14, 2017. Retrieved
from http://www.who.int/mediacentre/news/releases/2017/seasonal-flu/en/.

19. World Health Organization. Influenza (Seasonal). November 6, 2018.
Retrieved from http://www.who.int/mediacentre/factsheets/fs211/en/.

20. Baxter D. Evaluating the case for trivalent or quadrivalent
influenza vaccines. Hum Vaccin Immunother. 2016; 12(10):2712-2717.

21. Centers for Disease Control and Prevention (CDC). Estimated
Influenza Illnesses, Medical Visits, Hospitalizations, and Deaths
Averted by Vaccination. February 21, 2019. Retrieved from https://www.cdc.gov/flu/about/burden-averted/index.htm.

22. Nair H, et al. Global burden of respiratory infections due to
seasonal influenza in young children: a systematic review and
meta-analysis. Lancet. 2011 Dec 3;378(9807):1917-30.

Contacts

For further information, contact:
Shionogi & Co., Ltd.
Corporate
Communications
Telephone: +81-6-6209-7885
Fax: +81-6-6229-9596

Shionogi Europe Media Contact
Russell Stapley
European
Marketing Director
+44 (0) 7741 626375
russell.stapley@shionogi.eu

Shionogi Inc. U.S. Media Contact
Barbara Kalavik
Advocacy &
Communications
+1 973-307-3373
Barbara.Kalavik@shionogi.com