March 23, 2021
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio receives approval for use of TREAKISYM® in combination withrituximab and polatuzumab vedotin as treatment
for relapsed or refractory diffuse large B-cell lymphoma
TOKYO, Japan, March 23, 2021 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo,"SymBio") today announced that it has obtained approval of a partial change to the Marketing
Authorization of its anticancer agent TREAKISYM® (non-proprietary name: bendamustinehydrochloride) for use of TREAKISYM® in combination with rituximab (“BR therapy”) andpolatuzumab vedotin as treatment for relapsed or refractory diffuse large B-cell lymphoma (“r/rDLBCL”). The approval applies to the 25 mg and 100 mg presentations of TREAKISYM® freeze-driedformulation.
Today Chugai Pharmaceutical Co., Ltd. (Headquarters: Tokyo, “Chugai Pharma”) obtained approval
for the use of polatuzumab vedotin in combination with bendamustine and rituximab in r/r DLBCL.
SymBio obtained approval for the use of TREAKISYM® in combination with rituximab in r/r DLBCL
based on the favorable results from SymBio’s Phase 3 clinical trial in which the overall response rate,
the primary endpoint of the trial, exceeded expectations. TREAKISYM® will be available for use incombination with BR Therapy and polatuzumab vedotin* following NHI price listing and launch ofpolatuzumab vedotin.
Given the limited treatment options for r/r DLBCL, multi-drug combination therapy is currently used
as a rescue therapy in Japan, and there has been strong demand from patients for a more effectiveoption with reduced side effects. Achieving profitability in fiscal year 2021 is the first milestone in theCompany’s second inauguration, and obtaining this approval for r/r DLBCL is a major step towardachieving this goal.
The Company plans to submit an application for partial change to the Marketing Authorization ofTREAKISYM® for the use of TREAKISYM® ready-to-dilute (RTD) liquid formulation in combination
with rituximab and polatuzumab vedotin as treatment for r/r DLBCL within the week of March 22,2021.
The Company will evaluate any financial impact of the information presented herein for the fiscal
year ending December 2021 and make any necessary corresponding timely disclosures.
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Investor Relations
Tel: +81 (0)3 5472 1125*(NOTE)[Dosage and administration]
Relapsed or refractory diffuse large B-cell lymphoma
When rituximab (genetical recombination) and polatuzumab vedotin (genetical recombination) areused in combination.
The usual adult dosage for intravenous drip infusion is 90 mg/m2 (body surface area) of bendamustinehydrochloride over an hour period once daily. Administration is performed daily for 2 days, and thedrug is withdrawn for 19 days. This is followed by a single cycle with a maximum of 6 cycles. The dose
may be adjusted according to the patient’s condition.

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 2 study of BR therapy in relapsed/refractory
diffuse large B-cell lymphoma (“r/r DLBCL”) conducted by SymBio , 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

2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 manufacturing andmarketing for the indication of relapsed/refractory low-grade B-cell non-Hodgkin's lymphoma andmantle cell lymphoma in Japan.
 TREAKISYM® was approved for the additional indication of chronic lymphocytic leukemia in Japanin 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 achieved the primary endpoint (overall response rate) in Phase 3 study of TREAKISYM® incombination with rituximab as treatment for r/r DLBCL and submitted a partial change application
with respect to its marketing approval in May 2020.
 TREAKISYM® ready-to-dilute (“RTD”) liquid formulation was approved in Japan in September
2020.
 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 AmgenJapan. 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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