March 22, 2021

Notification of Application for Approval to Manufacture and Market Anti-TNFα multivalent NANOBODY® compound (ozoralizumab) in Japan
Japan's first NANOBODY® Therapeutic

Taisho Pharmaceutical Co., Ltd. (Head Office: Toshima-ku, Tokyo; President: Shigeru Uehara; “Taisho”) announced today that it submitted an application for approval to manufacture and market the anti-TNFα NANOBODY® therapeutic licensed from Ablynx, Ghent, Belgium (now Ablynx, a Sanofi company) in 2015, and developed by Taisho in Japan (generic name: ozoralizumab [development code: TS-152]) to the Ministry of Health, Labour and Welfare for the planned indication of rheumatoid arthritis (RA), which is to-date inadequately managed by the current available treatments.

This application for approval is based on the results of the phase II/III clinical trial in Japan (3000-JA study). The 3000-JA study is a randomized, placebo-controlled, double-blind study in patients with active RA who have had an inadequate response to methotrexate (MTX) treatment. In this study, ozoralizumab was subcutaneously administered to patients with RA in combination with MTX once every 4 weeks. The ozoralizumab group showed a statistically significant improvement over placebo group on ACR20 improvement rate as the primary endpoint. Additionally, the phase III clinical study in Japan (3001-JA study), in which ozoralizumab was subcutaneously administered once every 4 weeks without administering MTX, showed high clinical efficacy, similar to that in the 3000-JA study. Throughout the clinical trials, ozoralizumab was well tolerated.

Taisho intends to market ozoralizumab and provide new treatment options for the estimated 800,000 patients with RA in Japan.

About Ozoralizumab
Ozoralizumab, initially discovered by Ablynx, is a trivalent humanized low molecular weight compound that combines two anti-TNFα NANOBODY® VHHs and one anti-serum albumin NANOBODY® VHH. Ozoralizumab is about a quarter of the size of conventional IgG antibodies. Ozoralizumab binds to two subunits of TNFα and potently neutralizes its action. Ozoralizumab also has prolonged serum half-life by interacting with serum albumin, which is highly retentive in blood, enabling patients to decrease treatment frequency to once a month. Thanks to these positive features, ozoralizumab is expected to show potentially enhanced penetration to inflamed tissues and clinical efficacy even in the early stage of treatment.

NANOBODY® VHHs are molecules derived from a special type of antibody produced naturally by llamas and other camelid species. At a tenth the size of conventional antibodies, NANOBODY® VHHs have the potential to reach disease targets in the human body that are inaccessible to conventional antibodies. The small, simple architecture also allows the creation of “multivalent” NANOBODY® compounds that can engage multiple targets at the same time by linking the individual NANOBODY® VHHs together.
NANOBODY® therapeutics offer the possibility to replace complex treatment regimens with single, multi-action medicines for a wide range of human diseases and can be generated rapidly for large-scale production.
The first ever NANOBODY® to be approved in Europe (in September 2018) and the United States (in February 2019) is caplacizumab, a next-generation antibody drug developed by Ablynx as a treatment for acquired thrombotic thrombocytopenic purpura (aTTP).
Ozoralizumab has been developed as the first potential NANOBODY® therapeutic in Japan.
"NANOBODY®" is a registered trademark of Ablynx.