June 5, 2014
Seikagaku Corporation(Securities Code: TSE 4548)

Seikagaku Announces Results of Phase III Clinical Trial in Japan forSI-6603, Indicated for Treatment of Lumbar Disc Herniation

Seikagaku Corporation (Tokyo) today announced the results of a Phase III clinical trial in
Japan for SI-6603 (generic name: condoliase), indicated for the treatment of lumbar discherniation were presented at the 41st Annual Meeting of The International Society for theStudy of the Lumbar Spine, being held in Seoul, Korea, on June 4, 2014.
The trial was a multicenter, double-blind, randomized, placebo-controlled study in 163
patients with lumbar disc herniation. The primary endpoint was the change from baseline
at 13 weeks after administration in the mean visual analog scale (VAS) score of worst leg
pain over the past 24 hours.
The change from baseline in the VAS score of worst leg pain at 13 weeks afteradministration was significantly greater in the SI-6603 group (p=0.001), indicating marked
improvement in the leg pain. The percentage of subjects whose VAS scores of the leg pain
had improved by 50% or more from baseline values (response rate) was 72.0% in theSI-6603 group compared with 50.6% in the placebo group (p=0.008). In addition, theSI-6603 group demonstrated significantly greater change in physical functional disabilityand quality of life (QOL) evaluation scores, thus improvements in functional disability andQOL were also confirmed. As for safety up to 52 weeks after administration, although thefrequency of adverse events, such as back pain and disc height decrease, was higher in
the SI-6603 group, SI-6603 was well tolerated.
Kazuhiro Chiba, M.D., Ph.D.,Chairman, Department of Orthopaedic Surgery, andAssociate Director, Kitasato University Kitasato Institute Hospital, a lead investigator ofthis clinical trial, said, “The effect of condoliase to improve leg pain is comparable to thatof lumbar disectomy. It was well tolerated and did not cause clinically important adverse
events. Because treatment by condoliase was much less invasive than lumbar
disectomy, it would enhance earlier return of patients to work and normal life andcontribute to reduction of medical expenses and economical burden to the society.
Condoliase can be a novel and potent treatment for patients with lumbar disc herniationunresponsive to conservative treatment.”
Since currently there is no fundamental pharmacological therapy for lumbar discherniation, the launch of SI-6603, of which a single injection treatment expected to be as
efffective as lumbar disectomy in improving symptoms, would contribute to the alleviationof physical burden and improvement of QOL of the patients. Seikagaku submitted a new
drug application to the Ministry of Health, Labor and Welfare of Japan in January 2014 andit is now under review. The company is also focusing on the progress of the Phase IIIclinical trials underway in the U.S.

≪Appendix≫【Reference 1: Overview of the Phase III Clinical Trial of SI-6603 in Japan】
Examine the efficacy and safety of SI-6603 for the treatment ofPurpose
lumbar disc herniation compared with the placebo group
Phase III, multicenter, double-blind, randomized,
Study design
placebo-controlled study
For 52 weeks. After evaluation of efficacy and safety at 13 weeks
Observation period
after administration, a follow-up study related to efficacy andsafety was conducted up to 52 after administration
Patients 20 to 70 years of age with L4/L5 or L5/S1
contained-lumbar disc herniation for which no improvement isSubjects
found from conservative treatment for 6 weeks or longer
Patients with sciatica in a single leg, mean VAS* score of 50 mm
or more, and positive in the straight leg raising (SLR) test
Number of patients
163 patients (SI-6603 group: 82 patients /placebo group: 81 patients)
and group allocation
Sex
Male and female
Number of centers
35
Trial period
March 2012 to February 2014
Change in the score of worst leg pain over the past 24 hours at 13Primary endpoint
weeks after administration from baseline
Main secondary
Worst back pain over the past 24 hours, neurological examination,
endpointschange in disc height and hernia volume in image analysis
Method ofSingle dose intradiscal administration of 1.25 U of condoliase or aadministration
placebo (1 mL)* VAS: A psychometric response scale which can be used in questionnaires.
Patients record his/her current pain level between 100 mm at maximum and 0 mm
at minimum.
【Reference 2: SI-6603 for the treatment of lumbar disc herniation】

Lumbar disc herniation is the partial protrusion of the nucleus pulposus at the core ofeach intervertebral disc or the anulus fibrosus, the disc’s outer layer. The resulting
pressure on the spinal nerve root causes pain and numbness. SI-6603 is an injectable
drug using an enzyme named condoliase that specifically degrades glycosaminoglycans(GAG) *, which are the main components of the nucleus pulposus. A direct injection ofSI-6603 into the intervertebral disc would cause reduction of the pressure on the nerves
by shrinking the nucleus pulposus through degrading GAG. Because SI-6603 does notbreak down proteins, it is thought to have no effect on surrounding tissues such as bloodvessels and nerves.
*Glycosaminoglycans (GAG): one of the constituents of complex carbohydrates suchas chondroitin sulfate and hyaluronic acid.
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