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December 20, 2021

Data from Japan's First Phase II/III Clinical Trial of NANOBODY® Ozoralizumab for Rheumatoid Arthritis Presented at the 36th Annual Meeting of the Japanese Society for Clinical Rheumatology and Related Research

Taisho Pharmaceutical Co., Ltd. (Head Office: Toshima-ku, Tokyo; President: Shigeru Uehara; “Taisho”) announced today that it presented clinical data of generic name: ozoralizumab (development code:TS-152), the anti-TNFα NANOBODY® therapeutic licensed from Ablynx [Ghent (Belgium)] (currently a Sanofi company) in 2015 and developed by Taisho in Japan at the 36th Annual Meeting of the Japanese Society for Clinical Rheumatology and Related Research held in Toyama Prefecture, Japan on December 18 and 19, 2021. The presentation included the interim results from a 24-week administration in the phase II/III clinical trial (OHZORA study) in adult patients with rheumatoid arthritis (RA).

This is the first presentation of results from the phase II/III clinical trial (OHZORA study) of ozoralizumab in RA. The data presented here suggest that ozoralizumab may be useful for patients with RA who have had an inadequate response to methotrexate (MTX) treatment.

The study results demonstrate Taisho's commitment to helping improve the lives of patients with RA.

Results of the Interim Analysis of the Phase II/III Clinical Trial of Ozoralizumab in Patients with Active Rheumatoid Arthritis Concomitantly Treated with MTX (OHZORA study)

The OHZORA study was a randomized, placebo-controlled, double-blind study in 381 patients with active RA who have had an inadequate response to methotrexate (MTX) treatment, consisting of a 24-week placebo-controlled, double-blind period and a 28-week open-label period. The results of the interim analysis at Week 24 week were reported at this meeting.

Ozoralizumab 30 mg or 80 mg was subcutaneously administered once every 4 weeks in combination with MTX. The results revealed that the percentage of the patients who achieved the primary endpoint (improvement in ACR20 at Week 16) was 79.6% in the ozoralizumab 30 mg group and 75.3% in the ozoralizumab 80 mg group, while it was 37.3% in the placebo group. Both of the ozoralizumab groups showed significant improvement over placebo, demonstrating their superiority over placebo. The rate of improvement in ACR20 in the both ozoralizumab groups showed a significant improvement over the placebo group at Week 1 and after.

At the meeting, Taisho reported that ozoralizumab showed positive results also in other secondary endpoints from the early stage of the treatment and its high clinical efficacy was demonstrated.

The incidence of adverse events up to Week 24 was 62.7% in the placebo group, 76.3% in the ozoralizumab 30 mg group, and 72.1% in the ozoralizumab 80 mg group, with the most frequent adverse event being nasopharyngitis. Serious adverse events occurred in 2 patients in the placebo group, 4 patients in the ozoralizumab 30 mg group, and 5 patients in the ozoralizumab 80 mg group, indicating that ozoralizumab was well-tolerated.

The following subject was also presented at the meeting:

Results of the Long-Term Efficacy of Ozoralizumab and the Efficacy Study against Secondary Failure to the Existing Anti-TNFα Antibody using Human TNF Gene Induction (Tg197) Mice

 Secondary failure due to the production of anti-drug antibodies (ADA) may occur in some patients with RA being treated with TNF inhibitors. At this meeting, Taisho reported the study results in Tg197 mice on the long-term efficacy of ozoralizumab and its efficacy against secondary failure to the existing anti-TNFα antibody (adalimumab).

 Ozoralizumab markedly suppressed arthritis in Tg197 mice without inducing the production of ADA. In mouse models of secondary failure in which ADA against adalimumab was produced, switching to ozoralizumab prevented exacerbation of arthritis. Further, unlike adalimumab, ozoralizumab did not result in the formation of large immune complexes, which can cause immunogenicity.

 These results suggest that ozoralizumab, which is structurally different from conventional IgG, is less immunogenic and may be useful not only as a first-line TNF inhibitor but also as a second-line TNF inhibitor in patients with secondary failure to the existing anti-TNFα antibody.

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. The drug has a molecular weight of approximately 25% 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.

About NANOBODY® VHHs

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.