August 2, 2021
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

Collaborative research with Kyoto University on mechanism of response ofbendamustine for diffuse large B-cell lymphoma
TOKYO, Japan, August 2, 2021 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo, "SymBio")announced today that it has concluded a joint research agreement with Kyoto University on themechanism of response of bendamustine in diffuse large B-cell lymphoma (DLBCL).
Under the agreement, SymBio will conduct a collaborative study with the Department of Hematology
and Oncology, Graduate School of Medicine, Kyoto University (Professor Akifumi Takaori), Dr.
Momoko Nishikori (Lymphoma Research Group) to analyze the response mechanism of bendamustineto B-cell lymphoma including activated B-cell ABC-DLBCL.
Traditionally, bendamustine is not cross-resistant to other alkylating agents and clinically has uniqueefficacy, suggesting that its therapeutic effects on lymphoma may also involve effects that differ fromthose of other alkylating agents. On the other hand, in the more refractory ABC-DLBCL, theinvolvement of NF-κB and the linear ubiquitin chain-generating enzymatic complex (LUBAC) that
regulates it has been suggested. In this collaborative study, we analyze the mechanisms of response of
bendamustine itself and in combination with other B-cell lymphoma drugs by analyzing the effects
associated with LUBAC.
Dr. Nishikori's research group has established outstanding research work in a variety of lymphoma
and lymphoproliferative disorders. Recently, the studies first elucidated the mechanisms by which
LUBAC activation promotes the development of lymphoma-like ABC-DLBCL and increases theaccumulation of other genetic mutations, and addressed the possibility that LUBAC may provide
clues for the development of new therapeutic agents.
To improve our understanding of bendamustine's response data to DLBCL, SymBio will work withKyoto University to analyze the mechanisms of response of bendamustine itself and in combination
with other B-cell lymphoma drugs.
Statement of Fuminori Yoshida, President and Chief Executive Officer of SymBio: “TREAKISYM®
showed superior response rates to refractory ABC-DLBCL in the Phase 3 trial, suggesting theinvolvement of NF-κB activation which is regulated by LUBAC. The joint research with Kyoto
University, by furthering our understanding of the mechanism of action of bendamustine, will
potentially help us to develop new therapies."1

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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 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 obtained approval of a partial change
application with respect to its marketing approval in March 2021.
 TREAKISYM® ready-to-dilute (“RTD”) liquid formulation was approved in Japan in September
2020.
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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