July 13, 2020
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio submits partial change application for the use of TREAKISYM®
in combination with polatuzumab vedotin and rituximab
as treatment for relapsed or refractory diffuse large B-cell lymphoma
TOKYO, Japan, July 13, 2020 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo, "SymBio")
today announced that it has submitted an application for partial change to the Marketing Approval ofSymBio’s anti-cancer drug TREAKISYM® (non-proprietary name: bendamustine hydrochloride) for
the use of TREAKISYM® in combination with polatuzumab vedotin and rituximab as treatment for
relapsed or refractory diffuse large B-cell lymphoma (“relapsed or refractory DLBCL”).
For the combination therapy of polatuzumab vedotin with bendamustine and rituximab (“BRtherapy”) in relapsed or refractory DLBCL, Chugai Pharmaceutical Co., Ltd. (Headquarters: Tokyo,“Chugai Pharma”) filed a New Drug Application on June 29, 2020.
In May 2020, SymBio filed a partial change application for the use of BR therapy in relapsed orrefractory DLBCL based on the favorable results from its phase III trial in which the overall response
rate—the primary endpoint of the trial—exceeded expectations. The partial change application isunder review by the Pharmaceuticals and Medical Devices Agency.
TREAKISYM® will be approved for use in combination with polatuzumab vedotin and rituximab astreatment for relapsed or refractory DLBCL upon the National Health Insurance (NHI) Price Listingof polatuzumab vedotin after the applications by Chugai Pharma and SymBio are approved.
SymBio anticipates that the additional indication of TREAKISYM® for relapsed or refractory DLBCL
will be one of the key success factors to achieve profitability in 2021 under its own sales organization.
Statement from Fuminori Yoshida, President and CEO of SymBio: "Given the limited treatment
options for relapsed or refractory DLBCL, multi-drug combination therapy is currently used as arescue therapy in Japan, and there has been strong demand from patients for a more effective option
with reduced side effects. We will continue to strive to provide an additional treatment option of thecombination therapy of polatuzumab vedotin with BR therapy, in addition to the BR therapy
currently under review."

1About diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a disease where large, malignant B-cell lymphocytes
develop in the lymph nodes or in organs or other areas outside the lymph nodes. DLBCL is the mostprevalent form of malignant lymphoma in Japan, accounting for between 30% and 40% of patients. As
the majority of patients are elderly, with most patients in their 60s and 70s at the time of diagnosis,
patient numbers are expected to increase as Japan’s population continues to age. As the efficacy ofcurrent chemotherapy treatments is limited, and patients with DLBCL who are resistant tochemotherapy, or who relapse or are refractory to treatment have an extremely poor prognosis, there
is a high level of need for new safe and effective drugs.
Based on the favorable clinical results of the Phase II study of BR therapy in relapsed or refractory
DLBCL conducted by SymBio*, BR therapy has been recommended in the National Comprehensive
Cancer Network (NCCN) Guidelines in the United States since 2012.
*Results of the Phase II study (59 patients): Overall response rate of 62.7%, and complete response (CR) of 37.3%.
References:
The Japanese Society for Lymphoreticular Tissue Research, Request for unapproved or off-label drugs,
http://www.mhlw.go.jp/file/06-Seisakujouhou-11120000-Iyakushokuhinkyoku/gakkai3-2-5-1.pdf

Friedberg, JW. Relapsed/ refractory diffuse large B-cell lymphoma. ASH Education Book 2011 (1): 498-505

About rescue chemotherapy for relapsed or refractory DLBCL
Therapeutic relief chemotherapy is used for patients with hematopoietic tumors that do not respondto treatment (refractory) or that have relapsed. Currently, six to seven types of combination therapies
are used as secondary treatment (rescue chemotherapy) for advanced diffuse large B-cell lymphoma
in the event of recurrence, and most of them are combinations of multiple drugs (three to six drugs).
For example, CHASE(R) is a combination of cyclophosphamide, cytarabine, dexamethasone, etoposideand rituximab, while ESHAP(R) is a combination of methylprednisolone, etoposide, cytarabine,cisplatin and rituximab. Both combination therapies are known to cause strong myelosuppression andincreased toxicity in patients with relapsed or refractory DLBCL, who tend to be elderly.
About TREAKISYM®
TREAKISYM® (non-proprietary name: bendamustine hydrochloride), a cytocide anti-cancer drug firstused in Germany in the 1970s, is now widely used in more than 50 countries with indications for lowgrade non-Hodgkin’s lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia.
TREAKISYM® Intravenous Infusion 100 mg was approved in October 2010 for manufacturingand marketing for the indication of relapsed/refractory low-grade B-cell non-Hodgkin's lymphoma
and mantle cell lymphoma in Japan.

TREAKISYM® was approved for the additional indication of chronic lymphocytic leukemia inJapan in August 2016.

TREAKISYM® was approved for the additional indications of first-line treatment of low-grade B-2

cell non-Hodgkin’s lymphoma and mantle cell lymphoma in Japan in December 2016.
SymBio completed registration of the first patient in the Phase III clinical trial in Japan in April
2019 and completed the patient enrollment in March 2020. The primary objective of the trial is toconfirm the safety of TREAKISYM® rapid infusion.

SymBio submitted a New Drug Application for marketing authorization of TREAKISYM® readyto-dilute liquid formulation in September 2019.

SymBio aims to achieve annual sales of JPY 10 billion on a NHI drug price basis at the earliest
possible stage.
About SymBio Pharmaceuticals Limited
SymBio Pharmaceuticals Limited was established in March 2005 by Fuminori Yoshida who
previously served concurrently as Corporate VP of Amgen Inc. and founding President of Amgen
Japan. In May 2016, SymBio incorporated its wholly-owned subsidiary in the U.S., SymBio Pharma
USA, Inc. (Headquarters: Menlo Park, California, President: Mr. Fuminori Yoshida). SymBio’s
underlying corporate mission is to “deliver hope to patients in need” as it aspires to be a leading
global specialty biopharmaceutical company dedicated to addressing underserved medical needs.

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