September 29, 2021
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio announces presentation of the final results of its
Phase 3 Clinical Trial of TREAKISYM® in r/r DLBCL at the83rd Annual Meeting of the Japanese Society of Hematology
TOKYO, Japan, September 29, 2021 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo,"SymBio") today announced that the final results of its phase 3 trial of the anticancer drug
TREAKISYM® (bendamustine hydrochloride) in combination with rituximab ("BR therapy"1;
bendamustine hydrochloride 120mg/m2) for the treatment of relapsed or refractory diffuse large B-cell
lymphoma ("r/r DLBCL") were presented at the 83rd Annual Meeting of the Japanese Society ofHematology (held from September 23 to 25, 2021 in Sendai, Japan).
SymBio conducted a phase 3 study and a long-term follow-up study of BR therapy for relapsed orrefractory DLBCL. The results confirmed the efficacy shown in a phase 2 study earlier conducted inJapan and Korea, and the final results were presented at the 83rd Annual Meeting of the JapaneseSociety of Hematology. The Company obtained regulatory approval of DLBCL as an additionalindication for Treakisym in March of this year.
Key results of the phase 3 trial and a long-term follow-up study (38 patients)•Overall response rate (CR+PR): 76.3%•

Complete response (CR): 47.4%•Median overall survival (OS): 29.2 months

Given the limited treatment options for r/r DLBCL, the approval of BR therapy, and the approval ofpolatuzumab vedotin in combination with BR therapy (Pola-BR therapy2 ;bendamustinehydrochloride 90mg/m2) by Chugai Pharmaceutical Co., Ltd. (Headquarters: Tokyo), provide muchneeded treatment options for patients.
For more information, please visit the 83rd Annual Meeting of the Japanese Society of Hematology
website at: http://www.jshem.or.jp/83/en/index.html

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NOTE 1[Dosage and administration]
For concomitant use of rituximab (genetical recombination)
The usual adult dosage for intravenous drip infusion is 120mg/m2 (body surface area) of
bendamustine hydrochloride over an hour period once daily. Administration is performed daily for 2days, and the drug is withdrawn for 19 days. This is followed by a single cycle with a maximum of 6cycles.
NOTE 2[Dosage and administration]
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 surfacearea) of bendamustine hydrochloride over an hour period once daily. Administration is performed
daily for 2 days, and the drug is withdrawn for 19 days. This is followed by a single cycle with amaximum 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 II study of BR therapy in relapsed/refractory
diffuse large B-cell lymphoma (“r/r DLBCL”) conducted by SymBio Note, BR therapy has been
recommended in the National Comprehensive Cancer Network (NCCN) Guidelines in the UnitedStates since 2012.
(Note on results of the Phase II study (59 patients): Overall response rate (ORR) 62.7%; Completeresponse (CR) 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

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, freeze-dried (FD) formulation, was approved in October 2010
for manufacturing and marketing for the indication of relapsed/refractory low-grade B-cell nonHodgkin'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.

TREAKISYM® ready-to-dilute (RTD) liquid formulation was approved in Japan in September2020 for all the above indications.

TREAKISYM® FD and RTD were approved for the additional indication of relapsed or refractory
DLBCL in March 2021 and April 2021, respectively.

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’sunderlying 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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