January 22, 2021

Whom It May Concern
Company:
Representative:Contact:
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KYORIN Holdings, Inc.
Yutaka Ogihara
Representative Director, President(Security Code: 4569, TSE 1st Sec.)
Yoshinori Tanifuji
Director, Corporate Planning03-3525-4707

Kyorin Pharmaceutical Receives Marketing Approval for theInterstitial cystitis “Zymso® Intravesical Solution 50%”
TOKYO, Japan (January 22, 2021) ―Kyorin Pharmaceutical Co., Ltd. (Head office: Chiyoda-ku, Tokyo,
President: Shigeru Ogihara, hereinafter "KYORIN "), a wholly owned subsidiary of KYORIN Holdings, Inc.,
received approval from the Ministry of Health, Labour and Welfare (hereinafter “MHLW”) as of January 22,2021 to market the Interstitial cystitis “Zymso® Intravesical Solution 50%” (hereinafter “Zymso ”) in Japan.

Zymso is an intravesical infusion containing 50% (w / w) of dimethyl sulfoxide, and its phase III
clinical trial (multicenter, randomized, double-blind, placebo-controlled, parallel-group study) in 96
Japanese patients with interstitial cystitis was conducted, and its efficacy and safety were evaluatedand approved.
As a result of the review by The Evaluation Committee on Unapproved or Off-labeled Drugs withHigh Medical Needs set by MHLW, Intravesical instillation therapy of dimethyl sulfoxide was judged
to meet the "standards for medical need". After that, MHLW widely recruited the development
company and KYORIN expressed its development intentions and developed the drug in Japan. In
September 2017, Zymso was designated as an orphan drug by MHLW.
KYORIN adds Zymso to its product lineup in the urology field which is a priority therapeutic areafor KYORIN. KYORIN further contributes to the treatment and QOL improvement for patients withinterstitial cystitis as a therapeutic drug that meets unmet medical needs.
Further details, including the timing of release and projected sales, will be announced in a timely
manner after Zymso is listed on the National Health Insurance drug price list.
(Product Information)
Brand name

: Zymso® Intravesical Solution 50%

Generic name

: Dimethyl Sulfoxide

Indications: Improvement of symptoms of interstitial cystitis (Hunner type) (chronic pelvic pain,pressure and discomfort associated with the bladder, lower urinary tract symptoms such asincreased urgency or pollakiuria)

Dosage and Administration:
The usual dosage for adults is 50 mL of 50% (w / w) dimethyl sulfoxide solution per vial
(27g as dimethyl sulfoxide) instilled into the bladder 6 times at 2-week intervals. After
intravesical injection, hold it in the bladder for at least 15 minutes before draining it.

[Reference for interstitial cystitis]■About interstitial cystitis disease, pathophysiology and epidemiology
Interstitial cystitis is a disease that presents with frequent, increased, urgent urination andbladder pain. Among them, bladder pain that occurs when the bladder is full is acharacteristic symptom, but in some cases, remarkable frequent urination without bladderpain is main complaint. Persistent symptoms greatly interfere with the patient's daily life andlead to a significant decrease in QOL. It mainly affects middle-aged and older women, but it
is not uncommon for younger people and male to develop it. Although the exact number ofpatients in Japan is unknown, a survey in 2013 reported that the number of patients undertreatment in Japan was about 4,500, making it one of the orphan diseases.
In the Clinical Guideline for Interstitial Cystitis/Bladder Pain Syndrome issued in 2019
(hereinafter “Clinical Guideline for IC / BPS”), only the Hunner type was defined asinterstitial cystitis. The pathological findings of the Hunner type are defect of the urothelium,
infiltration of inflammatory cells in the submucosa of the bladder, and small vascular growth,which are different from those of the non-Hunner type. In addition, increase of inflammationrelated molecules on the inner wall of the bladder was observed only in the Hunner type,
and whole genome analysis showed that only the Hunner type had obvious inflammatory
findings in the inner wall of the bladder.
■ About treatment method of interstitial cystitis
Clinical Guideline for IC / BPS includes conservative treatment, drug treatment,
intravesical instillation therapy, and endoscopic treatment etc. for interstitial cystitis, butthere is no established treatment as recommended grade A (highly recommended). In
addition, at present, the only treatment method covered by health insurance in Japan isbladder hydrodistension, therefore treatment option under health insurance is limited.

(Background materials)
Yamada Y, Nomiya A, Niimi A, Igawa Y, Ito T, Tomoe H, et al. A survey on clinical practice ofinterstitial cystitis in Japan. Transl Androl Urol. 2015; 4(5): 486-90.
Clinical Guideline for Interstitial Cystitis/Bladder Pain Syndrome 2019 edited by Society of Interstitial
Cystitis of Japan / The Japanese Urological Association