Shionogi to Present New Data at 2018 European Congress of Clinical Microbiology and Infectious
Diseases
Shionogi & Co., Ltd. (hereafter “Shionogi”) today announced that the company will give 13 presentations on investigational
agents at the upcoming European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), in Madrid, Spain, April 21-24,
2018.
Shionogi will present at this congress data on three investigational compounds including cefiderocol (S-649266), an
investigational siderophore cephalosporin with a novel mechanism of cell entry in late stage development with activity against a
broad range of Gram-negative pathogens including multidrug resistant (MDR) strains; baloxavir marboxil (S-033188), an oral
cap-dependent endonuclease inhibitor administered as a single dose for the treatment of influenza; and for the first time, COT-143,
an investigational humanized monoclonal antibody demonstrating anti-virulence activity targeting the PcrV protein, an essential
component of the Pseudomonas aeruginosa type III secretion system. Below is an overview of the oral and poster presentations
at ECCMID 2018.
Presentations will include data on these Shionogi agents from company-sponsored or investigator-initiated investigational
studies.
The following cefiderocol presentations will take place during a cefiderocol-focused poster session on Saturday, April 21, 2018
from 15:30-16:30, in the paper poster arena:
- Poster #P0184: Cefiderocol, a novel siderophore cephalosporin: in vitro activity
against Stenotrophomonas maltophillia isolated globally
Presenter: Masakatsu Tsuji
- Poster #P0185: Stability of cefiderocol against clinically-significant broad-spectrum
oxacillinases
Presenter: Patrice Nordmann
- Poster #P0186: Correlations between cefiderocol broth microdilution MICs and disk diffusion
inhibitory zone diameters among target Gram-negative organisms
Presenter: Masakatsu Tsuji
- Poster #P0187: In vitro activity of cefiderocol (S-649266), a siderophore
cephalosporin, against carbapenem-susceptible and resistant non-fermenting Gram-negative bacteria
Presenter: Robert A. Bonomo
- Poster #P0188: Metabolism and excretion of [14C]-cefiderocol, a siderophore cephalosporin, and
drug-drug interaction potential via transporters of cefiderocol in healthy subjects
Presenter: Miyazaki Shiro
- Poster #P0189: In vivo pharmacokinetic/pharmacodynamic (PK/PD) assessment of
cefiderocol against Stenotrophomonas maltophilia in a neutropenic murine lung infection model
Presenter: Miki Takemura
- Poster #P0190: Efficacy of humanized cefiderocol exposure against Stenotrophomonas
maltophilia in a rat respiratory tract infection model
Presenter: Miki Takemura
- Poster #P0191: Stability and low induction potential of cefiderocol against chromosomal AmpC
beta-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae
Presenter: Miki Takemura
The details for the baloxavir marboxil presentations are as follows:
- Oral presentation #O0469: Lack of pharmacokinetic drug-drug interaction between baloxavir
marboxil, a novel inhibitor of influenza virus cap-dependent endonuclease, and oseltamivir
Presenter: Nao Kawaguchi
Date and time: Sunday, April 22, 2018, 15:18-15:28
Session title and location: Influenza - widening our armory for the next pandemic, hall B
- Poster #P0047: Delayed oral dosing of baloxavir marboxil exhibited significant reduction of
viral titer and amelioration of virus-induced lung inflammation in mice lethally infected with influenza A virus
Presenter: Keita Fukao
Date and time: Saturday, April 21, 2018, 15:30-16:30
Session title and location: New aspects of antiviral therapies, paper poster arena
The following COT-143 presentations will take place Tuesday, April 24, 2018 from 12:30-13:30, in the paper poster arena:
- Poster #P2456: Correlation between production of PcrV protein in vitro/in vivo
of clinical isolates of Pseudomonas aeruginosa and their virulence in a murine infection model
Presenter: Hideki Maki
- Poster #P2457: COT-143, a novel monoclonal antibody against the PcrV protein: in vivo
efficacy and pharmacokinetic/pharmacodynamic assessment against Pseudomonas aeruginosa in murine lung infection models
Presenter: Hideki Maki
- Poster #P2458: COT-143, a novel monoclonal antibody against the PcrV protein: binding affinity
against PcrV and in vitro cytotoxicity inhibitory activity against Pseudomonas aeruginosa
Presenter: Hideki Maki
About cefiderocol—an investigational antibiotic agent
Cefiderocol is a siderophore cephalosporin with a novel mechanism for efficiently penetrating the outer cell membrane of
Gram-negative pathogens. 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 This
mechanism allows cefiderocol to achieve higher concentrations in the periplasmic space where it can then bind to receptors and
inhibit cell wall synthesis in the bacterial cells.2 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-carbapenemases.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, P. aeruginosa,
Enterobacteriaceae, and S. maltophilia.4 Cefiderocol has poor in vitro activity against Gram-positive or
anaerobic bacteria.
Cefiderocol is currently in clinical development. Two Phase 3 studies are ongoing and enrolling 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 baloxavir marboxil —an investigational antiviral product
Baloxavir marboxil is an oral cap-dependent endonuclease inhibitor with a new mechanism of action being studied for the
treatment of influenza. Nonclinical studies with baloxavir marboxil demonstrated its anti-viral spectrum against seasonal influenza
A and B strains and neuraminidase inhibitor-resistant flu strains and avian flu strains (e.g. A/H7N9) of which potential outbreak
is one of several global public health concerns. An additional global Phase 3 study (CAPSTONE-2) in individuals at high risk for
influenza-related complications is ongoing.
Shionogi submitted a New Drug Application (NDA) to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in late 2017
and baloxavir marboxil is now commercially available in Japan. Further development and commercialization of baloxavir marboxil is
in collaboration with F. Hoffmann-La Roche Ltd (hereafter “Roche”). Under the terms of this agreement, Roche holds worldwide rights
to baloxavir marboxil excluding Japan and Taiwan, which will be retained exclusively by Shionogi. Discussions with other health
authorities worldwide are currently ongoing and Shionogi and Roche are committed to bringing this important medicine to patients as
quickly as possible.
Epidemic and pandemic influenza remain a major public health concern, and influenza drugs that will offer significant
improvement over the current therapy are urgently needed. Worldwide, annual influenza epidemics are estimated to result in 3 to 5
million cases of severe illness, and about 250,000 to 500,000 deaths.5 In general, those at highest risk of
influenza-associated complications include children under 2 years of age, adults over 65 years of age, pregnant women, and people
of any age with certain medical conditions, including chronic heart, lung, metabolic diseases (such as diabetes) and weakened
immune systems.
About COT-143—an investigational compound
COT-143 is a humanized monoclonal antibody that binds to the PcrV protein of P. aeruginosa. The PcrV protein is an
essential component of the type III secretion system responsible for releasing harmful toxins and is related to the pathogenicity
of P. aeruginosa. By using a variety of nonclinical in vitro and in vivo models, COT-143 has demonstrated a
reduction in tissue and cellular damage by the toxins released by the type III secretion system, which, if supported by clinical
trials, could lead to a new treatment option for infections caused by P. aeruginosa, including MDR strains.
It is estimated that 51,000 healthcare-associated P. aeruginosa infections occur in the US each year and the rates of
antibiotic resistance are increasing worldwide.6,7 As resistance rises there are limited options to treat or prevent
P. aeruginosa infections. COT-143 is in early-stage development.
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.” Shionogi Inc., the U.S. based subsidiary of Shionogi & Co., Ltd., continues this focus on the development and
commercialization of high quality medicines that protect the health and well-being 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 details on Shionogi Inc., visit www.shionogi.com. For more information on Shionogi & Co., Ltd., visit www.shionogi.co.jp/en.
Forward Looking Statement
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.
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References
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1.
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Ito A, Nishikawa T., Masumoto 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.
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2.
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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.
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3.
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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.
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4.
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M Hackel, M Tsuji, Y Yamano, et al. n 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), posted online.
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5.
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Influenza (Seasonal). World Health Organization. http://www.who.int/mediacentre/factsheets/fs211/en/. Published March 13, 2018. Accessed April 16,
2018.
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6.
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Healthcare-associated Infections. Centers for Disease Control and Prevention. https://www.cdc.gov/hai/organisms/pseudomonas.html. Published March 9, 2018. Accessed April 16, 2018.
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7.
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Hirsch EB, Tam VH. Impact of multidrug-resistant Pseudomonas aeruginosa infection on patient
outcomes. Expert review of pharmacoeconomics & outcomes research. 2010;10(4):441-451. doi:10.1586/erp.10.49.
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Shionogi & Co., Ltd.
Corporate Communications
Telephone: +81-6-6209-7885
Fax: +81-6-6229-9596
or
Investor Relations
Naoki Kouyama, +81 6 6209-7885
Associate Director of Corporate Communications, IR group
naoki.kouyama@shionogi.co.jp
or
U.S. Media
Lindsay Bohlander, +1 973-307-3718
Director
lindsay.bohlander@shionogi.com
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