June 11, 2020

Ono and Seikagaku Announce the Results from a Phase III Clinical Study in Japan ofONO-5704/SI-613 in Patients with Knee Osteoarthritis Presented at an Academic Conference
Ono Pharmaceutical Co., Ltd. (Osaka, Japan; “Ono”) and Seikagaku Corporation (Tokyo, Japan;“Seikagaku”) announced today that the results from a Phase III clinical study of ONO-5704/SI-613 inJapan in patients with knee osteoarthritis (“the Study”) were presented at the 93rd Annual Meeting of theJapanese Orthopaedic Association, an on-line annual meeting being held from Thursday June 11 toMonday August 31, 2020. ONO-5704/SI-613 is being jointly developed in Japan by the companies for thetreatment of osteoarthritis.
Abstract Number: 3-12-15
The phase III study of Diclofenac etalhyaluronate (ONO-5704/SI-613) in osteoarthritis of the knee
The Study was a randomized, double-blind, placebo-controlled, parallel-group comparative study, toevaluate the efficacy and safety of ONO-5704/SI-613 in 440 patients with knee osteoarthritis whoreceived either ONO-5704/SI-613 or a placebo (6 injections into the knee joint cavity every 4 weeks).
ONO-5704/SI-613 group demonstrated a statistically significant difference in the primary endpoint ofthe Study, the mean change in WOMAC pain score (a knee pain evaluation index, 100 mm VAS scale)versus placebo group, from baseline to 12 weeks after the initial administration (3 injections every 4weeks) with the difference of -6.1 mm (p<0.001). ONO-5704/SI-613 group also demonstrated astatistically significant difference (-5.6 mm) compared to placebo group in mean change from baseline to24 weeks after the initial administration (p=0.001). Furthermore, ONO-5704/SI-613 group demonstrated astatistically significant difference compared to placebo group in WOMAC stiffness score and physicalfunction score from baseline to 12 weeks after the initial administration, secondary endpoints of the Study.
In the results of safety evaluation, no difference in frequency of adverse events and no clinically evident
problems were found.
Outline of the Phase III Clinical Study in Patients with Knee Osteoarthritis in Japan (the Study):
Examine superiority of efficacy of ONO-5704/SI-613 over a placebo, when
Purposerepeatedly administered every four weeks into the knee joint cavity of patientswith knee osteoarthritis.

Study design
Observation period

Multicenter, randomized, placebo-controlled, double-blind, parallel-groupcomparative study
24 weeks after the initial administration
Males and females aged 40 to 75
Diagnosed with knee osteoarthritis according to the criteria of the American Collegeof Rheumatology

Subjects

Kellgren-Lawrence radiographic scores of Grade 2 or 3
Pain from knee osteoarthritis continuing one year or longer
Pain from knee osteoarthritis that meets the criteria at the time of participation in theStudy
1Number of patients

440 patients (ONO-5704/SI-613 group: 220 patients / placebo group: 220and randomizationpatients）

Number of study sites 50 sites
Study period

April 2017 to January 2019
WOMAC A (pain) score (100 mm VAS)

Primary endpoint

Primary analysis: mean change from baseline to 12 weeks after the initialadministration

Main secondary
endpoints

WOMAC B (stiffness) score, WOMAC C (physical function) score, etc.

Method ofAdministration of ONO-5704/SI-613 (30 mg/ 3 ml) or a placebo (3 ml) into the knee

administration

joint cavity 6 times every 4 weeks

In January 2020, Seikagaku submitted an application for manufacturing and marketing approval ofONO-5704/SI-613 in Japan for the treatment of osteoarthritis (knee joint, hip joint and ankle joint) basedon the results of the Study and the other two Phase III clinical studies.*1
Ono and Seikagaku aim to contribute to improvement of QOL in patients by providing a new treatment
option for osteoarthritis (of the knee joint, hip joint and ankle joint) and will work together to obtain anapproval of ONO-5704/SI-613 as soon as possible.
*1: 1) Phase III confirmatory study in patients with knee osteoarthritis (the Study)2) Phase III study in patients with osteoarthritis (four joint sites: shoulder, elbow, hip and ankle)
3) Phase III long-term study in patients with osteoarthritis, primarily for safety evaluation(five joint sites: knee, shoulder, elbow, hip and ankle)
About ONO-5704/SI-613
ONO-5704/SI-613 is a formulation in which hyaluronic acid and diclofenac (an anti-inflammatory drug)
are chemically bound using Seikagaku’s own proprietary technology. The product combines the pain
relief and anti-inflammatory effect of diclofenac designed for sustained release*2 using a drug delivery
system*3 with the joint function improving effect of hyaluronic acid. It is expected to provide prompt andlong-lasting relief of the pain and inflammation associated with osteoarthritis (of the knee joint, hip joint,and ankle joint). Further, since the product is administered directly into the joint cavity as an injectable
treatment, systemic exposure to diclofenac is low, and the risk of systemic adverse drug reaction isthought to be low.
*2: Sustained release is the gradual release of the active pharmaceutical ingredients of a drug to achievea sustained therapeutic effect.
*3: Drug delivery system (DDS) is a technology for the controlled release, targeting, and absorption
improvement of drugs.
Contact
Ono Pharmaceutical Co., Ltd.

Seikagaku Corporation

Corporate Communications
public_relations@ono.co.jp

Investor Relations and Public Relations
Corporate Staff
ir@seikagaku.co.jp
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