November 27, 2019

Completion of Investigator-initiated Clinical Trial for the Treatment of Male Stress Urinary Incontinencewith Uncultured Autologous Adipose Derived Regenerative Cells in JapanADRESU※1, an investigator-initiated clinical trial led by Nagoya University Hospital for the treatment ofmale stress urinary incontinence using uncultured autologous adipose derived regenerative cells(ADRCs)※2 began enrollment in September 2015. The trial commenced following consultation with thePharmaceuticals and Medical Devices Agency (PMDA) and successful submission of the Clinical Trial
Notification to the Ministry of Health, Labour and Welfare (MHLW) in Japan, in collaboration with Cytori
Therapeutics, K.K.
ADRESU is the world’s first clinical trial for regenerative medicine-based treatment of male stress urinary
incontinence with ADRCs.

Nagoya University Hospital conducted the prospective, multicenter, single-arm study (with Dr. Momokazu Gotoh, Professor of the Department of Urology as Coordinating
Investigator), in cooperation with Kanazawa University Hospital, Shinshu University Hospital and Dokkyo
Medical School Hospital, and supported by the Department of Advanced Medicine at Nagoya University
Hospital. ADRCs, prepared with Cytori’s Celution® System※3 (consisting of the Celution® Centrifuge andCelution® Cell Therapy Kit) were administered to male patients with stress urinary incontinence andevaluated for 52 weeks to investigate the treatment’s efficacy and safety.
ADRESU was completed in March 2019, and a clinical study report has been issued.

Male patients withmild to moderate stress urinary incontinence persisting for more than one year and resistant topharmacological and behavioral therapies were administered a single transurethral endoscopic injection ofADRCs into the periurethral region. Results confirm safety and the primary efficacy endpoint for the trial
was achieved.
Based on the successful results of ADRESU, Cytori Therapeutics, K.K., in cooperation with Nagoya
University Hospital, is in preparations to apply for medical device marketing approval for the Celution®
System, and intends to seek reimbursement coverage under Japan’s National Health Insurance System nextyear (2020).

With the support of The Japanese Urological Association and The Japanese Continence Society, we strive
towards improving the quality of life of male patients with stress urinary incontinence as well as developinga regenerative medicine-based treatment using ADRCs.
※1 ADRESU
The subjects of the clinical trial were men with stress urinary incontinence that persisted for more than one
year after prostatectomy for prostate cancer or benign prostatic hyperplasia, and resistant topharmacological and behavioral therapies. Safety and efficacy were evaluated over a 52-week follow-up
period after periurethral injection of autologous ADRCs prepared using the Celution® System.
ADRESU was supported by grants-in-aid - the Health and Labour Sciences Research Grant from theMinistry of Health, Labour and Welfare, grants from the Japan Agency for Medical Research andDevelopment, as well as a support grant for advanced research from Nagoya University Hospital.
For more details, please refer to: BMC Urol. 17(1): 89, 2017 （ UMIN.ID ： UMIN000017901,ClinicalTrials.gov Identifier：NCT02529865）※2 Regenerative medicine-based treatment of male stress urinary incontinence using ADRCs
About 250 mL of subcutaneous fat was harvested from the abdomen by liposuction under anesthesia, andprocessed using the Celution® System (provided by Cytori Therapeutics, K.K.) to produce autologous
uncultured ADRCs. The ADRCs were transurethrally injected under endoscopic vision into the urethral
sphincter, and a mixture of ADRCs and fat tissue was injected into the submucosal space of the sphincter.
This novel regenerative medicine-based treatment for stress urinary incontinence caused by urethral
sphincter deficiency is safe and minimally invasive, and may be performed within 3 hours in a single
procedure without the need for ex vivo cell culture.
For more details, please visit:https://www.med.nagoya-u.ac.jp/uro08/advanced/regenerative-therapy/index.html.
※3 The Celution® SystemThe Celution® System is a proprietary medical technology platform developed by Cytori Therapeutics toprepare autologous ADRCs for same-day treatment without the need for ex vivo cell culture. Physicians
and scientists have demonstrated the frequency of stem cells in fat tissue to be 2,500 times greater than thefrequency of similar cells in bone marrow1-3. Further, fat tissue can be more easily collected than bonemarrow, with less co-morbidities4. As Cytori technology is based on autologous tissue sources, treatment
with ADRCs avoid common transplantation issues such as cell rejection or disease transmission, and does
not require anti-rejection or immunosuppressant drugs.

The Celution® System is a fully-automated,functionally closed system designed to extract and concentrate regenerative and stem cells found in fattissue.

Freshly isolated (uncultured) ADRCs may be administered in real-time without further

manipulation, retaining pre-existing cell properties and therapeutic benefits.
1. Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009 Jan;217(2):318-24.
2. Fraser J, Wulur I, Alfonso Z, Zhu M, Wheeler E. Differences in stem and progenitor cell yield indifferent subcutaneous adipose tissue depots. Cytotherapy. 2007;9(5):459-67.
3. Jurgens WJ, Oedayrajsingh-Varma MJ, Helder MN, Zandiehdoulabi B, Schouten TE, Kuik DJ, Ritt MJ,
van Milligen FJ. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue:
implications for cell-based therapies. Cell Tissue Res. 2008 Jun;332(3):415-26.
4. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells forbiotechnology. Trends Biotechnol. 2006 Apr;24(4):150-4.