As part of Rohto Pharmaceutical's comprehensive management vision for 2030, "Connect for Well-being," we are committed to focusing on the field of medical ophthalmic drugs to contribute to the well-being of people. As a testament to this commitment, we entered into a licensing agreement with JT Inc. in March 2018 to develop ROH-201 as a therapeutic agent in the field of ophthalmology

Janus Kinases are a type of tyrosine kinase found in cells and play a crucial role in the transmission of immune activation signals within cells. ROH-201 is expected to improve eye disorders by inhibiting this function, thus suppressing excessive immune responses. Following the completion of Phase II clinical trials, which included dry eye patients, including those with Sjogren's syndrome, we are commencing Phase II clinical trials. We will continue to advance the development of ROH-201, aiming to contribute to the well-being of patients by promoting healthy eyes, ultimately benefiting society at large.

Glossary

• Tyrosine Kinase

  Enzymes that add phosphate groups to the amino acid tyrosine, playing vital roles in cell proliferation, survival, development, and differentiation. They collectively form a group of enzymes that are crucial for transmitting immune activation signals within cells. Janus Kinases are one type of tyrosine kinase..

• Sjogren's Syndrome

  An autoimmune disease characterized by organ-specific symptoms resulting from an imbalance in the immune system. It is designated as a rare disease. In the field of ophthalmology, it is known to exacerbate and complicate dry eye symptoms due to impaired tear and salivary gland function.

About JT Inc.

JT Inc. is a global tobacco company, and its products are sold in over 130 countries and regions. In addition to its tobacco business, the company is involved in pharmaceuticals and processed food operations, engaging in various business activities. JT Inc. primarily focuses on research and development functions in the areas of "cardiovascular, renal, and metabolic diseases," "immunity and inflammation," and "central nervous system." A group company, Torii Pharmaceutical Co., Ltd., is responsible for manufacturing and sales activities in Japan.
JT Inc. has developed Delgocitinib as a topical cream for the treatment of atopic dermatitis and received manufacturing and marketing approval in January 2020. It is marketed under the product name "CORECTIM® ointment."
For more information, please visit　https://www.jti.co.jp/

The compound is being developed as a treatment for specific ophthalmic diseases, using a compound that has already been marketed for other indications.DWTI introduced the rights for Japan from a British company in 2015 and has been conducting studies on formulation, among other considerations.

Based on the results of previous non-clinical trials, the compound's effectiveness and safety in the non-clinical phase have been confirmed. Therefore, in this trial, we will proceed to confirm the safety and pharmacokinetics of the compound in humans.

We are considering entering the medical pharmaceuticals business and continue to advance various research initiatives in the field of ophthalmology. In the future, we will provide products and services that contribute to the eye health of people and aim to be of service in the field of ophthalmology.
The impact of this agreement on the current fiscal year's performance is expected to be minimal.

About DWTI

Background and Objectives of the Research

In recent years, diagnostic devices in the field of ophthalmology have advanced significantly, enabling multifaceted information gathering. Additionally, new reports have highlighted distinctive changes in the eyes associated with systemic diseases. This means that state-of-the-art ophthalmic diagnostic equipment can be used not only for eye care but also for evaluating overall health conditions.
By integrating eye health information with regular health checkup data and lifestyle survey data, it is expected that we can predict and diagnose the onset of diseases at an early stage and assess one's health status before diseases manifest.
Leveraging the knowledge and diagnostic techniques in ophthalmology at Osaka University's Graduate School of Medicine, SAI's expertise in information science, and their unique AI analysis technology, along with ROHTO Pharmaceutical's cohort data and product/business development capabilities, we will collaborate to create new healthcare initiatives such as personalized medicine and preventive medicine.
Through this collaboration among the three parties, we aim to realize early prediction and diagnosis of disease onset, fostering the innovation of preventing these diseases. This will contribute to extending healthy lifespans and realizing a society where everyone can stay healthy and active throughout their centenary lives.

Figure: Role image of the three

Glossary

• Ganciclovir

  Ganciclovir is an antiviral drug that inhibits viral DNA polymerases. In the field of ophthalmology, It is approved as a treatment for Simple Herpes Eye Infection in over 40 countries worldwide.

• Cytomegalovirus Endotheliitis

  Endotheliitis is a condition that causes inflammation of the corneal endothelial cells. When corneal endothelial cells are extensively damaged, it can lead to bullous keratopathy, resulting in severe vision impairment and, in some cases, blindness. Although the existence of Cytomegalovirus Endotheliitis was first reported in Japan in 2006, there are currently no approved treatments for this condition both domestically and internationally.

About Théa

Théa is a European independent pharmaceutical group company leading the field of ophthalmology. As a family-owned company, Théa is a pioneer in preservative-free eye drops and offers a wide range of ophthalmic treatments. Based in Clermont-Ferrand, France, Théa has approximately 30 subsidiaries and overseas locations across Europe, North America, South America, North Africa, and the Middle East. With around 1,500 employees worldwide, its products are sold in various countries.
For more information, please visit https://www.laboratoires-thea.com/en

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ROHTO Pharmaceutical Co., Ltd. (Head Office: Osaka City, President: Masashi Sugimoto) conducted a performance assessment of a rapid test kit for corononavirus (SARS-CoV-2) antigens using domestic clinical samples, specifically nasopharyngeal samples, in collaboration with the Osaka City University Graduate School of Medicine (Professor Kakeya at Department of Infection Control Science, Associate Professor Yasutoshi Kido at Department of Parasitology and Senior Lecturer Yu Nakagama).
The product was launched on June 16, 2021. Distribution, sales, and promotional activities within the country are entrusted to companies with whom we have sales alliance agreements.
We will continue to actively conduct research and development through industry-academia collaboration and will continue to contribute to the health of people by addressing the requirements of medical institutions and patients.

Background: Rapid antigen testing by immunochromatography

Rapid immunochromatographic antigen test is a simple and rapid point-of-care medicine that detects and guides diagnosis of viral antigens in symptomatic individuals and is useful for screening symptomatic individuals in outpatient settings.
In particular, in regions and countries where large-scale testing equipment such as PCR is not available, the use of such equipment is considered to be even higher, even though the convergence of coronavirus (SARS-CoV-2) infections is not visible.
In addition, on May 28, 2021, Coronavirus Response Headquarters revised and announced the basic response policy,”The government encourages the implementation of testing for individuals with mild symptoms using antigen rapid test kits, among other measures, in workplaces as well, with the perspective of preventing the widespread occurrence of clusters and alleviating the strain on the healthcare system. In the event of a positive case being identified, efforts are made to quickly and flexibly conduct administrative testing, including PCR tests, while reducing the administrative burden on public health offices and ensuring a broad scope of contact tracking.”
We anticipate a continued rise in the demand for high-quality rapid antigen tests.

Study conclusion

A performance evaluation of the coronavirus (SARS-Cov-2) antigen rapid test kit using domestic clinical samples (nasophatyngeal swab) was performed. This evaluation verified that the test kit exhibited high sensitivity (positive percent agreement) for samples with more than 105 copies per test and achieved a specificity (negative percent agreement) of 100%. Based on this results, we conclude that the test kit holds clinical utility for reliably confirming positive or negative diagnosis in patients exhibiting specific symptoms, in accordance to the established test guidelines.

Future Outlook for ROHTO Pharmaceutical and Osaka City University

We will continue our joint research with Osaka City University. Based on the aforementioned background, our commitment is to enhance global public health. This will be achieved by addressing the requirements of medical and research institutions, as well as patients worldwide, through the expansion of coronavirus antigen rapid test kits, including those suitable for self-collected specimens and international deployment. In addition, the Osaka City University Graduate School of Medicine and Parasitology, responsible for the performance evaluation, has been conducting research activities on infectious diseases in regions such as Africa, Central and South America for many years. This collaborative research will be further developed at Osaka City University’s overseas research facility in the Democratic Republic of the Congo.※

※）https://www.osaka-cu.ac.jp/ja/news/2020/200420

Background

Reports on COVID-19 have indicated that approximately 20% of cases progress to severe pneumonia. This severity has been associated with a phenomenon called "cytokine storm," in which the immune cells of infected individuals uncontrollably release cytokines while fighting the virus. Therefore, it is believed that treatment for severe COVID-19 should not only focus on eliminating the virus but also on addressing the cytokine storm. Mesenchymal stem cell therapy using allogeneic mesenchymal stem cells has been explored worldwide, with multiple reports suggesting its potential effectiveness in treating severe COVID-19 cases. Mesenchymal stem cells are believed to possess anti-inflammatory properties through various mechanisms, making them a promising treatment option for patients who do not respond to approved COVID-19 therapies. ROHTO Pharmaceutical is committed to advancing research in this area to establish a mesenchymal stem cell-based treatment approach for COVID-19 and future infectious disease management.

About ADR-001

ROHTO Pharmaceutical's investigational product, "ADR-001," is a cell-based therapy composed of allogeneic adipose tissue-derived stem cells. ADR-001 is cultured using a proprietary serum-free medium designed to maximize the potential of adipose tissue-derived stem cells without the inclusion of animal-derived materials, reducing the risk associated with animal-origin viral infections. Adipose tissue is known to contain numerous mesenchymal stem cells, and its collection is relatively non-invasive, with excess tissue often available from surgeries. This makes it easily accessible for transplantation with allogeneic adipose tissue-derived cells, offering a rapid supply for eligible patients.
Following our ongoing clinical trial for patients with liver cirrhosis※, ROHTO Pharmaceutical has proceeded with the Phase I clinical trial of ADR-001 to assess its safety in severe COVID-19 pneumonia patients. As a result of the Phase I trial confirming a certain level of safety, we have planned a Phase II trial with efficacy as the primary endpoint. This trial will include an ADR-001 treatment group and a placebo group, with a comparative study between the two.※A Phase I/II Trial of ADR-001 in Subjects with Cirrhosis.

Clinical Trial Overview

Trial Name: Phase II Clinical Trial of ADR-001 for Severe Pneumonia Caused by SARS-CoV-2 Infection

• Target Disease: Severe pneumonia caused by SARS-CoV-2 infection
• Trial Design: Randomized, placebo-controlled, double-blind, intergroup comparative trial
• Primary Endpoint: Efficacy
• Administration Method: Intravenous infusion
• Planned Enrollment: 20 participants
• Scheduled Trial Duration: June 2021 to September 2022

About the Licensing Agreement for the Candidate Compound (Quinolone-based Compound)

BioMimetics Sympathies identified a potential treatment for COVID-19 with inhibitory effects on the transcription factor FOXO1, which plays a crucial role in the regulation of gene expression for ACE2 and TMPRSS2. This discovery led to the identification of candidate compounds with FOXO1 inhibitory properties, and one of these compounds, a Quinolone-based compound, is the subject of the licensing agreement announced today.
This compound is groundbreaking as it effectively suppresses the gene expression of both ACE2 and TMPRSS2, which are essential for the entry and infection of the novel coronavirus into human cells. While previous drugs targeted either ACE2 or TMPRSS2 individually, this compound has the unique ability to inhibit both. Going forward, ROHTO Pharmaceutical and BioMimetics Sympathies will collaborate on the joint development of this compound and explore its commercialization.

About "RB+" – Translating Regenerative Medicine Research into Novel Drug Targets

To extend the methodology used to identify candidate compounds for the treatment of COVID-19 from regenerative medicine research to the development of treatments for other diseases, ROHTO Pharmaceutical and BioMimetics Sympathies are launching a new research and development organization called "RB+." "RB+" will aim to unravel the treatment mechanisms for many diseases targeted by mesenchymal stem cells in the near future, discover previously unknown drug targets, and involve other companies through open innovation to accelerate efforts towards practical applications of treatments.

About BioMimetics Sympathies Co., Ltd.

Glossary

• Mesenchymal stem cellsCells with the potential to differentiate into osteoblasts, fat cells, cartilage cells, and other cell types. They are sometimes referred to as mesenchymal stromal cells because it is unclear whether they function as stem cells in their tissue of origin.
• Transcription factorsA group of proteins that specifically bind to DNA and control gene expression.
• FOXO1: A transcription factor.
• ACE2: A protein that cleaves the spike protein of the novel coronavirus bound to ACE2, essential for infection.
• TMPRSS2: A protein that activates a spike protein that is critical for infection by cleaving the spike protein of a novel coronavirus bound to ACE2, essential for infection.
• Spike proteinA protein on the surface of the novel coronavirus that binds to human cell surface proteins.

Reason for Stock Acquisition

Olympus RMS was founded in December 2008 and has been primarily engaged in research and development of treatment methods using autologous cultured chondrocyte transplantation. Currently, clinical trials using the CCI (Cultured Chondrocyte Implantation) kit developed by the company have been underway since November 2018, targeting cartilage defects in knee joints. This CCI kit aims to achieve minimally invasive treatment by using a tissue adhesive (fibrin glue).
This stock acquisition is aimed at adding the orthopedic surgery field to our portfolio of regenerative medical products and accelerating the establishment of regenerative medicine as a future pillar of our business. Furthermore, we expect synergies in the R&D field between Olympus RMS and our cell manufacturing technology, leading to reduced cell manufacturing costs and the creation of new, unique pipelines. We are committed to delivering excellent regenerative medical products to patients and healthcare professionals as quickly as possible, contributing to the field of healthcare.

Overview of Olympus RMS Corporation

Overview of the Company after Stock Acquisition

Future Outlook

The impact on our consolidated performance for the fiscal year ending March 2021 is minimal, and we will promptly inform you if there are any matters that need to be disclosed in the future.

Glossary

• Sjogren's syndrome

  Sjögren's Syndrome: An autoimmune disease characterized by organ-specific symptoms resulting from an imbalance in the immune system, affecting organs such as the tear and salivary glands. In the field of ophthalmology, it is known to worsen due to impairment of the tear glands, leading to dry eye symptoms.
  

• Tyrosine Kinase

  A group of enzymes that add phosphate groups to the amino acid tyrosine, which is a component of proteins. They play a vital role in cell proliferation, survival, development, and differentiation and are a collective term for enzymes that play a crucial role in immune signal transduction within cells.
  

About JT Inc

JT Inc. is a global tobacco manufacturer, with its products being sold in over 130 countries and regions. In addition, the company is engaged in pharmaceutical and processed food businesses, conducting various business activities. JT Inc. primarily leads research and development in the areas of "sugar and lipid metabolism," "immunity and inflammation," and "viruses," with its subsidiary Torii Pharmaceutical Co., Ltd. responsible for manufacturing and sales functions in Japan.
For more information, please visit. https://www.jti.co.jp/

"DW-1001" was introduced to Japan by DWTI in 2015 from a UK-based company, and it has been under consideration for formulation and other developments. Please note that the specific disease targeted by this treatment remains undisclosed.

With the signing of this agreement, ROHTO Pharmaceutical will now take over the development of DW-1001 for the treatment of specific ophthalmic diseases in Japan, commencing with non-clinical trials..

We are actively exploring opportunities in the medical pharmaceuticals business and have been conducting various research activities in the field of ophthalmology. Moving forward, we will continue to provide products and services that benefit healthcare professionals in the ophthalmology sector and contribute to the eye health of individuals.

It is worth mentioning that the impact of this agreement on our current fiscal year's performance is expected to be minimal.

About DWTI

Overview of ROHTO Advanced Research Hong Kong Limited