May 11, 2020
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative DirectorPresident and Chief Executive Officer(Securities Code: 4582)

SymBio submits Partial Change Application for use of TREAKISYM® in combination withrituximab as treatment for relapsed or refractory diffuse large B-cell lymphoma
TOKYO, Japan, May 11, 2020 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo, "SymBio"),which previously announced the achievement of the primary endpoint (overall response rate) in its
Phase III study of its anticancer agent TREAKISYM® (non-proprietary name: bendamustinehydrochloride) in combination with rituximab (“BR therapy”) as treatment for relapsed or refractory
diffuse large B-cell lymphoma (“relapsed or refractory DLBCL”)1, today announced that it has
submitted a Partial Change Application with respect to its Marketing Approval for TREAKISYM®.
Diffuse large B-cell lymphoma accounts for 30-40% of all non-Hodgkin's lymphomas and is the mostcommon form of the disease. The frequency of the onset of the disease, especially among the elderly,
has increased in recent years as Japan’s population ages, and treatment for elderly patients has
become an important issue. With respect to relapsed or refractory DLBCL specifically, multi-drug
combination therapy is currently used as a rescue therapy in Japan as there is no effective treatment
method. BR therapy is widely used for patients with relapsed or refractory DLBCL in Europe and theUnited States, and in Japan, patient-advocacy and academic groups have submitted a request to theJapan’s Ministry of Health, Labour and Welfare for the early approval of BR therapy for thetreatment of DLBCL.
Fuminori Yoshida, President and CEO of SymBio, said, "In Japan, the only treatment option forpatients with relapsed or refractory DLBCL is combination therapy, which is a painful treatment for
the elderly, and there has been strong demand from patients for early approval of BR therapy. We areconfident that it will be an important treatment option for Japan’s aging society."
SymBio is currently transitioning its business model from research and development to a profitability
model, to achieve profitability and to further growth potential. The approval of TREAKISYM® incombination with rituximab for treatment of relapsed or refractory DLBCL, together with theestablishment of our own sales system, will be the driving factors for SymBio to achieve profitability
in 2021.

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See SymBio’s press release dated November 5, 2019, announcing the achievement of the primary endpoint(overall response rate) in its Phase III clinical trial of TREAKISYM® in patients with relapsed or refractory
DLBCL: https://www.symbiopharma.com/news/20191105.pdf

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/refractory
diffuse large B-cell lymphoma (“r/r DLBCL”) conducted by SymBio2, BR therapy has been
recommended in the National Comprehensive Cancer Network (NCCN) Guidelines in the UnitedStates since 2012.
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.

2Results of the Phase II study (59 patients): Overall response rate of 62.7%, and complete response (CR) of37.3%.

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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 Bcell 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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