At SHIONOGI, we seek to continue creating new drugs that balance innovation with healthcare affordability, by investing appropriate sums in R&D and maintaining small molecule drug discovery as a key strength while also diversifying into nonstandard peptide drug discovery and deepening collaboration with all manner of partners including the IT industry, in order to expand into new modalities and acquire entirely new technologies.
Protect people from the threat of infectious diseases
Acute infectious diseases, incl. pandemic response
COVID-19 spread around the world immediately after its outbreak, having a major impact not only on human health, but on political, economy and lifestyles. Even now, three years after the outbreak, the aftermath continues, and its scars remain in society.
While pharmaceutical companies around the world are striving to overcome the unprecedented battle against this virus that has destroyed society, SHIONOGI will make maximum use of its in-house antiviral drug research know-how, resources, and external network, has broken “Usual” of its own research process, leading to the creation of a unique new protease inhibitor, Ensitrelvir. We are working every day to deliver Ensitrelvir as quickly as possible, first from Japan, and then to patients around the world.
However, the COVID-19 epidemic has not yet been controlled, and many patients are suffering from the aftereffects. As the company SHIONOGI for infectious diseases, we will continue our creative research and development with the high aspiration of “we will end the pandemic” and will continue to fight to liberate patients suffering from COVID-19.
Respiratory syncytial virus (RS virus) is a pathogen that causes severe symptoms, especially in infancy, and infection during the first few weeks to months of life can lead to severe disease. In addition, caution should be exercised if low birth weight infants, the elderly, those with underlying cardiopulmonary diseases, or immunosuppressed persons are infected. In this way, although RSV poses a threat to many patients, it can be said that it is a disease with high unmet medical needs because there are no therapeutic drugs.
SHIONOGI is engaged in drug discovery research every day with the aim of liberating patients from infectious diseases. For RS virus with high unmet medical needs, we target an enzyme called RNA-dependent RNA polymerase in the L protein, and combine our know-how in antiviral drug research with UBE's ability to synthesize small molecules, led to the discovery of a new compound, S-337395. We are currently preparing for clinical trials.
There are still many infectious diseases with no cures. SHIONOGI continues to deliver therapeutic drugs through original research and development as soon as possible, in order to relieve people who are suffering from infectious diseases.
Antimicrobial resistance (AMR) infections
Infectious diseases caused by AMR bacteria is called a "silent pandemic" that creeps up without people being aware of it, and is a threat to humankind. In particular, the emergence and spread of carbapenem-resistant Gram-negative bacteria, such as carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp., has become a global problem, and the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) have issued warnings that new antibacterial drugs are urgently needed for drug-resistant bacteria.
Cefiderocol is an injectable siderophore cephalosporin with antimicrobial activity against Gram-negative bacteria, including carbapenem-resistant strains, approved in the US and Europe in 2019-2020. It has the advantage of being able to efficiently enter the bacterial cells via the iron uptake pathway, which is essential for bacterial growth. Such a unique mechanism is called a "Trojan horse".
In addition, cefiderocol is highly stable against all four Ambler classes of β-lactamases that hydrolyze β-lactam antimicrobials. As a result, it exhibits strong antibacterial activity against Gram-negative bacteria that produce various carbapenemases, making it possible to overcome carbapenem resistance.
Shionogi will continue to work on new drug discovery to solve the problems of patients and society, aiming to be free from the threat of AMR infectious diseases, which is expanding on a global level.
Three major infectious diseases
Cabenuva is approved for once-monthly and bimonthly dosing in Europe and the US, and is also approved for once-monthly dosing in Canada.
With the once-every-two-months treatment method, HIV treatment is possible with administration six days a year.
In addition, for cabotegravir monotherapy, Apretude, the world's first long-acting injectable drug for the prevention of HIV infection, has been approved for the prevention of HIV infection.
At SHIONOGI's research institute, we are working on new drug discovery so that HIV patients can choose new treatment methods that match their lifestyles and receive appropriate treatment and prevention.
SHIONOGI will start a full-scale vaccine business to realize total care for infectious diseases. So far, with UMN Pharma as a wholly owned subsidiary, we have promoted the creation of vaccines using the BEVS1) production technology for recombinant protein vaccines using viral antigen proteins with established rhabdo-free2) insect cell culture technology. SHIONOGI's COVID-19 vaccine is a recombinant protein vaccine that combines an adjuvant3) with an antigen produced by BEVS technology. Starting with the launch of the COVID-19 vaccine, we will provide the products that meet unmet needs to our society, while accumulating a track record as a vaccine manufacturer.
In addition to the COVID-19 vaccine, we are also working on the creation of vaccines for respiratory infections such as influenza. The challenge in creating vaccines against novel coronaviruses and influenza viruses is that mutations in the causative viruses evade immunity, weakening the effectiveness of existing vaccines. SHIONOGI is working on research and development of a universal vaccine4) to cut off this negative chain and to combat the next pandemic that may occur. For the new coronavirus vaccine, with the support of SCARDA5), we will collaborate with KOTAI Biotechnologies, Inc. which has strengths in antigen design and analysis of immune status, and the National Institute of Infectious Diseases, a leading Japanese institution in infectious disease research. We are working on the creation of a universal vaccine that covers all sarvecoviruses, including the new coronavirus6).
In the prevention of respiratory infections caused by SARS-CoV-2 and influenza viruses, it is considered very important to induce mucosal immunity in the mucosa of the nose and throat to prevent viral infection itself. Aiming to create nasal vaccines that can effectively induce mucosal immunity, we are conducting research in collaboration with the Department of Human Mucosal Vaccinology7) established at Chiba University Hospital.
Adjuvants are substances given with vaccines that are used to make the vaccine more effective. To date, SHIONOGI has created a squalene-based oil-in-water emulsion adjuvant A-910823, and a novel Toll-like receptor 9 agonist adjuvant S-540956, which is an improved B-type CpG ODN2006. We will further develop the technology platform that we have cultivated through these activities, and promote our research aimed at selecting the optimal vaccine adjuvant for enhancing immune response.
1) BEVS: Baculovirus Expression Vector System
2) rhabdo-free: not contaminated with rhabdovirus3) adjuvant: a substance that enhances immunogenicity
3) adjuvant: a substance that enhances immunogenicity
4) Universal vaccine: Vaccine with broad-spectrum that crosses all viruses
5) SCARDA: Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response
6) Adoption of Universal Antigen Vaccine Research and Development for Vaccine and New Modality Research and Development Project by AMED (Press release, June 30, 2022) | Acceptance | Shionogi Pharmaceutical (Shionogi) (shionogi.com)
7) Shionogi Announces the Conclusion of a Contract for the Establishment of a Research Department for Mucosal Vaccines with Chiba University Hospital. (Press Release, February 10, 2022) ｜Shionogi Pharmaceutical (Shionogi) (shionogi.com)
Contribute to a healthy and prosperous life
The number of people with dementia currently exceeds approximately 55 million people worldwide, and it is estimated that 20% of people aged 65 and over are suffering from dementia. A recent approval of an amyloid antibody, a disease modifying agent, for Alzheimer’s dementia gives patients and their families a long-awaited hope. Indeed, the drug slowed the progression but failed to stop it. In addition, it cannot be applied to the other types of dementia. The social cost of dementia in Japan is estimated to be 14.5 trillion yen, where Approximately 90% are related to be nursing care. One reason for the increase in the cost of care is symptoms related to dementia. They include not only cognitive impairment but also behavioral and psychological symptoms of dementia (BPSD), such as hallucination, delusion, and agitation. Patients and their families with dementia are suffering from the symptoms not biomarker abnormalities such as amyloid. Through removing the symptoms, SHIONOGI will contribute to “People with dementia spend the rest of their lives happily without anxiety of becoming a burden to loved ones"
SHIONOGI is conducting research and development to eliminate the symptoms and has various pipelines from the early research to the late stage clinical development. BPN14770, now in the clinic, is a unique candidate that can activate the mechanism involved in memory formation and has the potential to improve learning and memory in dementia as well as psychiatric disorders. In addition, we are promoting research using the prior art drug discovery technologies such as AI to identify the brain mechanisms and drug targets related to BPSD.