COMPANY RESEARCH AND ANALYSIS REPORT

SymBio Pharmaceuticals Limited
4582
JASDAQ Growth Market

21-May-2021
FISCO Ltd. Analyst

Yuzuru SatoFISCO Ltd.
https://www.fisco.co.jp

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/■ Index■Summary---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 01
1. Conditions set for profitability in FY12/21. ...................................................................................................

01

2. Trends in the other development pipeline....................................................................................................

02

3. Mid-Range Plan..................................... ......................................................................................................

02■Company profile---------------------------------------------------------------------------------------------------------------------------------------------------------- 03■Trends in the development pipeline--------------------------------------------------------------------------------------------------------- 06
1. TREAKISYM® (generic name: bendamustine hydrochloride). ......................................................................

06

2. Rigosertib (intravenous formulation/oral formulation). ..................................................................................

11

3. Brincidofovir (intravenous formulation/oral formulation). ..............................................................................

12■Results trends--------------------------------------------------------------------------------------------------------------------------------------------------------------- 16
1. Overview of the FY12/20 results............ ......................................................................................................

16

2. Financial condition.......................................................................................................................................

18■Outlook-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 19
1. Outlook for FY12/21. . ...................................................................................................................................

19

2. Mid-Range Plan..................................... ......................................................................................................

20

3. Long-term targets........................................................................................................................................

22

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/█ Summary
2021 is the first year of the “second foundation,” aiming to be a
global specialty pharma
SymBio Pharmaceuticals Limited <4582> (hereafter, also “the Company”) is a bio-venture progressing developmentsfrom the clinical trial stage, targeting indications for oncology, hematology, and rare diseases for which there arefew patients but medical needs are high. The main development pipeline includes TREAKISYM®, for which it isexpanding indications as a treatment for malignant lymphoma; rigosertib, which it in-licensed from Onconova
Therapeutics, Inc. <ONTX> (hereafter, Onconova) (U.S.); and the antiviral drug brincidofovir (BCV) in-licensed fromChimerix Inc. <CMRX> (U.S.). On March 24, the Tokyo Stock Exchange (TSE) announced the Company’s shares hadentered a grace period based on the standards for delisting from JASDAQ. However, in the new market segments
being introduced from April 2022, the standards for results and recording profit* corresponding to the delisting
standards were ended, so it will not be delisted due to this reason.
*	T he standard for results is a negative amount for operating profit and cash flow from operating activities in the mostrecent fiscal year. The standard for recording profit is a negative amount for operating profit in the fiscal year of the listing
application and for operating profit for nine consecutive fiscal years following the listing.

1. Conditions set for profitability in FY12/21
The outlook for FY12/21 is for the Company to become profitable for the first time since its foundation. The threemain conditions to achieving profitability are constructing its own sales system for TREAKISYM®, switching from theFD formulation (lyophilized powder formulation) to the high-value-added RTD formulation (liquid type), and expanding
the indications of TREAKISYM®. Of these, it completed the construction of its own sales system in June 2020,and started its own sales from December 10, 2020 when the marketing agreement with Eisai Co., Ltd. <4523>
ended. For the RTD formulation as well, it acquired marketing approval in September 2020, and began sales on
January 12, 2021. Regarding the remaining condition of expanding indications, on March 23, 2021, it acquired
marketing approval for BR therapy (bendamustine + rituximab) indicated for relapsed and refractory diffuse large
B-cell lymphoma (DLBCL), while Chugai Pharmaceutical Co., Ltd. <4519> acquired marketing approval for P-BR
therapy (polatuzumab vedotin + BR therapy), and it can sell it for the same indication from FY12/21 2Q onwards.
Therefore, all conditions for profitability are in place. Assuming these conditions are achieved, net sales will increase
206.4% year on year (YoY) to ¥9,151mn and operating profit will be ¥1,361mn (a loss of ¥4,506mn compared tothe previous period) for the fiscal year ending December 2021, so the Company is entering a growth stage from its
previous development stage.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
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SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Summary

2. Trends in the other development pipeline
For rigosertib, in order to explore possibilities for combination therapies with existing drugs, including TREAKISYM®,
the Company concluded a joint research agreement with The Institute of Medical Science, The University of Tokyoin January 2021, and it intends to decide on a new development strategy during 2021. For BCV (intravenous
formulation) as well, from FY12/21 3Q, it plans to start the global joint phase II clinical trial indicated for adenovirus
infections (in infants) that develop after hematopoietic stem cell transplantation. If steady progress is made, theoutlook is to proceed to the phase III clinical trial in 2023. Within Japan also, it plans to progress development for anindication for viral hemorrhagic cystitis after hematopoietic stem cell transplantation. This is because no treatment
for this disease has acquired approval in Japan, so there is strong demand for one from doctors. Moreover, it
intends to utilize the features of BCV, which exhibits antiviral activity against a wide range of viruses, and to progressdevelopments in the future for multi-viral infectious diseases after hematopoietic stem cell transplantation and for
infections after organ transplants. In addition, it is investigating licensing-in new pipeline drugs to follow-on from BCV.
3. Mid-Range Plan
The Company’s results targets in the Mid-Range Plan are net sales of ¥12,369mn, operating profit of ¥2,099mn,
and EPS of ¥46.5 in FY12/23. Sales are expected to grow from expanded use of TREAKISYM® for relapsed andrefractory DLBCL and the start of sales of the RI formulation (reduces the administration period for patients from theprevious 60 minutes to 10 minutes) expected in the second half of 2020, use of which is forecast to spread evenfurther due to the implementation of existing multi-drug combination therapies by medical facilities. For profits, R&D
expenses are forecast to increase, mainly of BCV development expenses, but this will be absorbed by the rise ingross profit from the Company’s own sales and improvement to the gross profit margin from switching to the RTD/RI
formulation. The Company has positioned 2021 as the first year of its “second foundation” with the aim of becoming
a global specialty pharma, and in addition to realizing sustainable growth, it aims to increase the ratio of overseas
sales to 50% by 2030 through the market launch of BCV and to evolve into a global pharmaceutical company.
Key Points
TREAKISYM® has the growth potential to approximately double sales through starting sales of the RTD
formulation and expanding its indications to relapsed and refractory DLBCL• Global clinical trials for BCV started in 2021 for adenovirus infections after hematopoietic stem cell transplantation• Operating profit is forecast to grow by more than 20% a year from 2022 onwards due to the increase in salesof TREAKISYM®
•

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
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SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Summary

Results trends（¥mn）

Net sales（left）

Operating profit（right）

12,000

1,361

9,000

（¥mn）
2,000

0

-2,6566,000-2,0009,151-3,947-4,301-4,506

2,837

2,987

FY12/19

FY12/20

3,000
3,444

3,835

FY12/17

FY12/18-4,0000-6,000FY12/21 E

Source: Prepared by FISCO from the Company’s financial results█ Company profile
A bio-venture that conducts developments from the clinical trial
stage, targeting the fields of oncology, hematology, and rarediseases
SymBio Pharmaceuticals is a bio-venture founded by the current Representative Director and President Chief
Executive Officer Fuminori Yoshida in March 2005. For its business strategy, its basic policy is to conduct drug
discovery and development for underserved therapeutic areas in which development has not been progressed
due to the small numbers of patients. One of its features has a business model that aims to achieve highly efficientand rapid drug discovery within the areas targeting oncology, hematology, and rare diseases, which are fields withhigh medical needs, by in-licensing development candidates for which POC* for humans has been obtained, andconducting development from the clinical trial stage.
*	POC (proof of concept): when the usefulness and efficacy of a new drug candidate compound is recognized following its
administration to animals or humans during research and development.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Company profile

The first development candidate to be in-licensed was the anticancer agent bendamustine hydrochloride (hereafter,
bendamustine hydrochloride; product name in Japan: TREAKISYM®) indicated for malignant lymphoma that wasdeveloped by Astellas Pharma GmbH (Germany), for which the Company concluded an exclusive development
and marketing rights agreement for Japan in December 2005. With the development code SyB L-0501 (FD formulation), the Company began the phase I clinical trial in 2006 for indications for relapsed and refractory low-grade
non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL), and in 2010, it acquired manufacturing andmarketing approval. It progressed licensing activities during this time, and in 2007, it expanded the target areas
for the exclusive development and marketing rights in China, South Korea, Taiwan, and Singapore. Then with Eisai
it concluded licensing agreements for Japan in 2008 and for South Korea and Singapore in 2009*. For Taiwan, in
2012, it concluded a development and marketing agreement with InnoPharmax Inc. (Taiwan) for the FD formulationand it is conducting sales. However, its policy is to end sales in Asia as well of the FD formulation by progressing
the switch from the FD formulation to the RTD formulation.
*	Due to changes in Eisai’s business strategy, the domestic licensing agreement was terminated on the deadline of December
9, 2020, and the Company transitioned to its own sales system. It is also progressing discussions to terminate theagreements for South Korea and Singapore.

TREAKISYM® was launched in the Japanese market in December 2010, and since then, the Company has progressed its development to expand its indications. In 2016, it acquired marketing approval for chronic lymphocytic
leukemia (CLL) and untreated (first line of treatment) low-grade NHL/MCL, and then in March 2021, it acquired
approval for relapsed and refractory DLBCL, so sales are expected to increase from the rise in the number of patientsfor which it is indicated. Also, in 2017, it concluded an exclusive development and marketing rights agreement
for Japan with Eagle Pharmaceuticals, Inc. <EGRX> (U.S.) for the TREAKISYM® liquid type RTD/RI formulation(development codes: SyB L-1701/SyB L-1702)*, acquired marketing approval for the RTD formulation in September
2020 and started sales in January 2021, progressing the switch from the FD formulation. It plans to apply formarketing approval for the RI formulation during 2021.
*	The FD formulation, which it had purchased from Astellas Pharma up to the present time, has to be dissolved at a medicalsite at the time of use (which requires about 3 hours, including the adjustment time). But this work is not required with theliquid type, so it has the advantage of greatly reducing the work burden placed on medical practitioners. Also, the difference
between the RTD formulation and the RI formulation is the intravenous injection time. The RTD formulation takes the sametime, 60 minutes, as existing products, but the time for the RI formulation is as short as 10 minutes, so the burden on thepatient is greatly reduced.

Also, as the second in-licensed product, the Company concluded an exclusive development and marketing rights
agreement in 2011 for Japan and South Korea with Onconova for rigosertib (development codes: SyB L-1101(intravenous formulation) / SyB C-1101 (oral formulation)) as a development candidate indicated for myelodysplastic
syndrome (MDS)*. Moreover, in September 2019, it concluded an exclusive global development, manufacturing,marketing, and licensing agreement with Chimerix for brincidofovir (BCV) for all viral diseases excluding smallpox.
The features of BCV are that compared to cidofovir (CDV; unapproved in Japan), it has high antiviral efficacy andsafety and is effective against multiple DNA viruses.
*	M DS is a disease in which the patient cannot produce normal blood cells due to abnormalities in the hematopoietic
stem cells in their bone marrow, causing a decrease in normal blood cells and symptoms such as anemia, infection andhemorrhage. It also has a high likelihood of transitioning into intractable diseases and often occurs in elderly people. There
are approximately 11,000 patients in Japan. The only treatment of the root cause is hematopoietic stem cell transplantation.
In chemical therapy, azacitidine is used as the drug of first choice. In Japan, Vidaza® of Nippon Shinyaku Co., Ltd <4516>
is on the market, and it has annual sales on a scale of ¥15bn to ¥16bn on a drug price basis.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

21-May-2021

4582 JASDAQ Growth Market

https://www.symbiopharma.com/ir_e/

Company profile

Technology in-licensing agreements
Rigosertib sodium

Brincidofovir

Development
codes

Name
SyB L-0501 (Lyophilized
powder formulation) / SyB
C-0501 (Oral formulation)

SyB L-0501 (Lyophilized
powder formulation) / SyB
C-0501 (Oral formulation)

TREAKISYM®
SyB L-1701 (RTD
formulation) / SyB L-1702(RI formulation)

SyB L-1101 (Intravenous
formulation) / C-1101(Oral formulation)

SyB V-1901(Intravenous formulation)

In-licensing
partner

Astellas Pharma (Germany)

Astellas Deutschland(Germany)

Eagle Pharmaceuticals(U.S.)

Onconova (U.S.)

Chimerix (U.S.)

Dateagreement
wasconcluded /agreement
periodDecember 2005 / 10-year
period from the first
product sales or themarket-exclusive period inJapan, whichever is longer

March 2007 / 10-year
period from the first
product sales or themarket-exclusive period,
whichever is longer

September 2017 / Productpatent period or themarket-exclusive period,
whichever is longer

July 2011 / 10-year period
from the first product sales(7 years in South Korea),
the market-exclusive
period, or the patentvalidity period, whichever islongest, in each country

September 2019 / Eachroyalty period is 10 years
from the start of sales,
the patent period, or themarket-exclusive period,
whichever is longest, foreach product’s indicationand for each country.
The agreement deadline
is when the final royalty
period expires

Content of
the mainagreements

Exclusive development andmarketing rights in Japan

Exclusive development
rights and marketing rights
in China (including HongKong), Taiwan, South
Korea, and Singapore

Exclusive development
rights and marketing rights
in JapanExclusive development
rights and marketing rights
in Japan and South Korea

Exclusive global license
agreement concerning
the rights to develop,
manufacture, andcommercialize BCV in
all DNA virus indications
excluding smallpox

Source: Prepared by FISCO from the Company’s securities report and news release

History
Date
March 2005
December 2005

Summary
Established SymBio Pharmaceuticals Limited at Minato-ku, Tokyo
Concluded a license agreement with Astellas Pharma GmbH (Germany) to acquire exclusive development and marketing rights inJapan for anti-cancer agent Bendamustine Hydrochloride

March 2006

Obtained manufacturer’s license (packaging, labeling and storage) from Tokyo Metropolitan Government

March 2007

Concluded a license agreement with Astellas Deutschland GmbH (Germany) to acquire development and marketing rights in
China, Taiwan, South Korea and Singapore for anti-cancer agent SyB L-0501

August 2008

Concluded a license agreement with Eisai Co., Ltd. to grant co-development and marketing rights in Japan for anti-cancer agent
SyB L-0501

March 2009

Concluded sublicense agreement with Cephalon, Inc. (U.S.) to grant development and marketing rights in China for anti-cancer
agent SyB L-0501

May 2009

Concluded a license agreement with Eisai to grant co-development and marketing rights in South Korea and Singapore for anticancer agent SyB L-0501

September 2010

Launched SYMBENDA® (generic name: bendamustine hydrochloride) in Singapore for the treatment of low-grade non-Hodgkin’s
lymphoma and chronic lymphocytic leukemia

October 2010

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan (launched
in December 2010)

July 2011

Concluded a license agreement with Onconova Therapeutics, Inc. for anti-cancer agents SyB L-1101/SyB C-1101

October 2011

Launched SYMBENDA® (generic name: bendamustine hydrochloride) in South Korea for the treatment of chronic lymphocytic
leukemia and multiple myeloma

October 2011

Listed on Osaka Securities Exchange JASDAQ Growth Market

February 2012

Launched INNOMUSTINE® in Taiwan for the treatment of low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia

October 2015

Concluded a licensing agreement with The Medicines Company (U.S.) to acquire exclusive development and marketing rights inJapan for post-operative, self-administered pain-management medication, SyB P-1501 (the agreement ended in November 2017)

May 2016

Established SymBio Pharma USA, Inc. at Menlo Park, California, USA

August 2016

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan for the
additional indication of chronic lymphocytic leukemia

December 2016

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan for the
additional indication of first-line treatment of low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma

September 2017Concluded a license agreement with Eagle Pharmaceuticals, Inc. to acquire development and marketing rights in Japan forbendamustine liquid formulations (RTD formulation and RI formulation)*RTD: Ready-to-dilute, RI: Rapid Infusion

October 2017

Filed for arbitration for damages against The Medicines Company (U.S.) due to the non-fulfillment of the licensing agreement

July 2018

TREAKISYM® was newly listed as the standard treatment for malignant lymphoma in the 2018 edition of the Japan Society of
Hematology’s Guidelines for the Treatment of Hematopoietic Tumors,

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

21-May-2021

4582 JASDAQ Growth Market

https://www.symbiopharma.com/ir_e/

Company profile

Date

Summary

September 2019Concluded an exclusive global license agreement with Chimerix (U.S.) concerning the rights to develop, manufacture, andcommercialize the antiviral drug, brincidofovir (excluding smallpox)

September 2020

In the final arbitration ruling for the claim for damages filed against the Medicines Company (U.S.) due to the non-fulfillment of
a licensing agreement, the Company will receive from the Medicines Company 50% of its expenses relating to the arbitration
proceedings, including attorneys’ fees.

December 2020

Start of own sales of TREAKISYM®

January 2021

Concluded a joint research agreement with The Institute of Medical Science, The University of Tokyo to search for new indications
for bendamustine and rigosertib

March 2021

Submitted an IND application to the FDA in the U.S. for a global joint clinical trial indicated for adenovirus infections (in infants)
after hematopoietic stem cell transplantation

March 2021

Acquired marketing approval for a TREAKISYM® and rituximab combination therapy and TREAKISYM®, rituximab, andpolatuzumab vedotin combination therapy indicated for relapsed and refractory diffuse large B-cell lymphoma

Source: Prepared by FISCO from the Company’s securities report and website█ Trends in the development pipeline
The sales growth potential of TREAKISYM® will approximately
double by expanding its indications to relapsed and refractory
DLBCL
1. TREAKISYM® (generic name: bendamustine hydrochloride)
TREAKISYM® is an anticancer agent for malignant lymphoma. Malignant lymphoma is a disease in which lymphocytes, which are a type of white blood cell, undergo canceration (tumorification) and lumps (masses) cangrow in lymph nodes distributed throughout the body and organs other than lymph nodes (such as the stomach,intestines, thyroid, spinal cord, lung, liver, skin, and eyes). It is said to be the most common of the blood cancers,
with approximately 10 out of every 100,000 people contracting it each year in Japan. Malignant lymphoma is mainly
divided into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), with about 90% of cases in Japan
being NHL. It is classified into low-grade, medium-grade, and high-grade according to the progression rate of thesymptoms, and there are various disease types.
Types of non-Hodgkin’s lymphoma
Type according to grade
Low grade: Indolent lymphoma(progresses yearly)

Non-Hodgkin’s lymphoma type (disease type)
Follicular lymphoma (grade 1, 2), MALT lymphoma, lymphoplasmacytic lymphoma
Mycosis fungoides, Sezary syndrome, chronic lymphocytic leukemia / small lymphocytic lymphoma, etc.

Follicular lymphoma (grade 3), mantle cell lymphoma, diffuse large B-cell lymphoma
Medium grade: Aggressive lymphoma
Peripheral T cell lymphoma, extranodal NK / T cell lymphoma, adult T cell leukemia / lymphoma (chronic(progresses monthly)type), etc.
High grade: Highly aggressive
lymphoma (progresses weekly)

Burkitt’s lymphoma, acute lymphocytic leukemia / lymphoblastic lymphoma
Adult T-cell leukemia / lymphoma (acute type, lymphoma type), etc.

Source: Prepared by FISCO from National Cancer Center Japan materials

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
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SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline(1) Expansion of indications
As its sales strategy for TREAKISYM®, the Company has been working to sequentially expand its indications. It
acquired marketing approval for relapsed and refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell
lymphoma (MCL) in October 2010, chronic lymphocytic leukemia (CLL) in August 2016 and untreated (first line oftreatment) low-grade NHL/MCL in December 2016. Also, in July 2018, TREAKISYM® and rituximab combination
therapy (BR therapy) was newly listed in the Japan Society of Hematology’s Guidelines for the Treatment of
Hematopoietic Tumors, and it has come to be recommended as the standard treatment option for all indications
for which it has been approved. So TREAKISYM® has come to be positioned as the standard treatment for
malignant lymphoma in both name and reality.
Other than the above, for CD20-positive follicular lymphoma (FL), which is a typical type of low-grade NHL, theCompany acquired approval in July 2018 for partial changes relating to combination use with a new anti-CD20
antibody formulation, in addition to rituximab, and combination therapy with obinutuzumab* 1 was added as atherapy option. Furthermore, in March 2019, it acquired approval for partial changes relating to pre-treatment
with tumor-specific T-cell infusion therapy* 2, and for the first time in Japan, TREAKISYM® can be used as a
pre-treatment for the CAR T-cell therapy*3 Kymriah® intravenous drip*4. In such ways, its position as the standard
therapy for malignant lymphoma is being further solidified.
*1	Obinutuzumab (GAZYVA®; sold by Chugai Pharmaceutical Co., Ltd.): similar to rituximab, which is recommended in thetreatment guidelines domestically and overseas as a therapeutic drug for non-Hodgkin’s lymphoma, it is a glycosylated
modified type II anti-CD20 monoclonal antibody that binds to CD20, a protein that expresses on B cells other than stem
cells and plasma cells, and it directly attacks and destroys the B cells it targets together with the body’s immune system.
*2	Tumor-specific T-cell infusion therapy: a therapy administered to patients after artificially applying and multiplying cancer
specificity outside the body to the cancer patient’s own T cells (a type of lymphocyte).
*3	CAR T-cell therapy (chimeric antigen receptor T-cell therapy): among tumor-specific T-cell infusion therapies, this is atherapy to introduce, amplify, and infuse into the gene-coding T cells the chimeric antigen receptors (CAR) that combine
the antigen-binding site of the antibody that recognizes the membrane antigen on the tumor cell and the T-cell receptor’s
intracellular domain.
*4	K ymriah® intravenous drip (generic name: tisagenlecleucel; sold by Novartis Pharma K.K.): as the first CAR T-celltherapy approved in Japan, in March 2019, it acquired manufacturing and marketing approval indicated for relapsed
and refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) and relapsed and refractory CD19-positive
DLBCL. Then on March 23, 2021, it was announced that it had acquired marketing approval for relapsed and refractory
DLBCL, which is of the same scale in terms of the number of targeted patients as its existing indications*5. In addition
to the combination therapy with rituximab (BR therapy) that was developed by the Company, BR therapy combination
therapy with polatuzumab vedotin*6 (P-BR therapy), which was developed by Chugai Pharmaceutical, was also approved.
Through this marketing approval, the number of patients it is indicated for has doubled compared to previously, so themarket value of TREAKISYM® has risen significantly.
*5	The standard treatment for untreated DLBCL is to provide a combination therapy of rituximab and chemotherapy, but
recurrence is seen in approximately 40% of patients. Also, autologous stem cell transplantation (ASCT) is recommended
as one treatment for relapsed and refractory DLBCL, but for approximately half of patients, the relief chemotherapy
provided prior to ASCT is not successful and ASCT cannot be provided. Moreover, there are many patients for whom
ASCT is not suitable as a treatment, such as due to their age or complications, and it has yet to be established as thestandard treatment.
*6	Polatuzumab vedotin: an anti-CD79b antibody drug compound developed by Roche using the antibody drug conjugate
technologies of Seattle Genetics Inc., in which humanized anti-CD79b monoclonal antibodies and tubulin polymerization
inhibitors are combined with a linker. CD79b proteins are expressed specifically on many B cells, and this is a promisingtarget in terms of developing new therapies. It is considered that polatuzumab vedotin binds with CD79b while suppressing the effects on normal cells and destroys B cells through the delivered chemotherapy agent.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

The number of patients indicated has approximately doubled
from the additional indication for r/r DLBCL

Source: From the Company’s results briefing materials

The results of the phase III clinical trials announced by the Company were excellent, noting a complete response
rate of 47.4% and an overall response rate of 76.3%. In particular, it seems that the medical specialists were
surprised by the level of the complete response rate for persons aged 76 years and older, which was 36.4%.
Also, it seems that the follow-up study (on the total survival period) that is currently being conducted is obtaining
excellent data that is better than expected, and the details are scheduled to be announced during the first halfof 2021.
Expects to acquire approval for additional indications
for r/r DLBCL (BR120 therapy) in 1H of the current period

Source: From the Company’s results briefing materials

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Currently, there is no effective treatment for relapsed and refractory DLBCL, and multi-drug combination therapy
that combines multiple anticancer agents (3 to 6 types) is administered as relief chemotherapy. However, it
has strong side effects, so there are hopes for the development of new highly effective therapeutic drugs andtreatments with few side effects. BR therapy and P-BR therapy have been approved, and it is highly likely thatthe use of these therapies will spread as standard therapies. There have also been request documents submitted
by patient groups and related academic societies to be able to use BR therapy at an early stage, so sales of
TREAKISYM® are forecast to increase further with the start of sales in FY12/21 2Q. The choice of whether to use
BR therapy or P-BR therapy depends on the doctor’s decision, based on factors such as the patient’s symptoms
and the gene type*.
*	In BR therapy, TREAKISYM® 120mg/m2 (body surface area) is administered once a day for 2 consecutive days, and thennot administered for 19 days. This constitutes one cycle, and it is administered for a maximum of six cycles while observing
the patient’s condition. In P-BR therapy, the dosage is 90mg/m2.

(2) RTD/RI formulation
The Company acquired manufacturing and marketing approval for the RTD formulation, which is the TREAKISYM®
liquid type, in September 2020 and started sales on January 12, 2021. The RTD formulation reduces the workburden at medical sites as it does not require dissolving, and it is expected that the switch from the FD formulation
to the RTD formulation will be progressed. It is considered that the percentage of sales from the RTD formulation
will rise from 20% in FY12/21 1Q to 91% in FY12/21 4Q, the majority of which will be from switching to the RTD
formulation. In one year from the start of sales of the RTD formulation, its market penetration rate has reached97%* in the U.S., so this increase is considered to be feasible. Currently, sales of the RTD formulation havestarted for existing indications except for relapsed and refractory DLBCL, but the Company applied for approval
for relapsed and refractory DLBCL as well on March 25. As the application and approval procedure is simple,
the outlook is that approval will be acquired within a few months, and it seems sales could start in the second
half of 2021.
*	In the U.S., sales of the RTD formulation BENDEKA® began in January 2016, and its market penetration rate had reached
70% by May of the same year and 90% after one year.

For the RI formulation also, the observation period for the clinical trials, which started in November 2018, wascompleted in September 2020, and the plan is to apply for marketing approval in the first half of 2021. If theinvestigation proceeds steadily, sales are expected to start in the second half of 2022. The RI formulation reduces
the intravenous administration period from 60 minutes to 10 minutes, so it not only helps medical practitioners,
it also contributes to improving patients’ QOL. Therefore, the replacement of the RTD formulation with the RI
formulation will progress from the second half of 2022, and moreover as its advantages are significant, there is ahigh likelihood it will be introduced at medical facilities that are currently providing multi-drug combination therapies
and it is expected to contribute to further sales growth as the market penetration rate rises.
The exclusive market period for the FD formulation in Japan ended in 2020, so generics may be developed.
However, due to major differences in terms of functionality compared to the RTD/RI formulation, it is expectedthat the exclusive marketing period of TREAKISYM® will actually continue until 2031, which is when the RTD/
RI formulation patent expires. Also, the price of the FD formulation is forecast to fall slightly with the drug pricerevisions in April 2021, but the RTD formulation has only just been launched in the market so its drug price is
expected to be maintained for the time being. On the other hand, there are differences in contract conditions forpurchase prices, and it seems that the prices for the RTD/RI formulation have been set low compared to the FD
formulation, so switching from the FD formulation to the RTD/RI formulation will be a factor causing the profit
margin to rise.

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09 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Alongside the switch from the FD formulation to the RTD formulation, the Company ended purchases of the FD
formulation at the end of 2020 (it has already completed purchases for sales of the FD formulation from 2021
onwards), while it has also completed processing all of its debts and credits with Astellas Pharma. Therefore, italso plans to end sales of the FD formulation in Asia, and it is concentrating on sales of TREAKISYM® in Japan.
Sales progress of TREAKISYM®
Drug

Indication

Progress

r/r low-grade NHL/MCL

Approved for sale in October 2010

CLL

Approved for sale in August 2016

First-line low-grade NHL/MCL

Approved for sale in December 2016r/r DLBCL

Approved for sale in March 2021

SyB L-1701(RTD liquid formulation)

Already approved indications(except for r/r DLBCL)

Marketing approval in September 2020 (applied for approval for r/r
DLBCL in March 2021 and scheduled to acquire it during 2021)

SyB L-1702(RI liquid formulation)

Already approved indications

The clinical trial observation period ended in September 2020 andplans to apply for marketing approval in the first half of 2021)

SyB L-0501(FD lyophilized powder
formulation)

Source: Prepared by FISCO from the Company’s results briefing materials and website(3) Future development plans
The development of TREAKISYM® for malignant lymphoma will complete the current round of expansion ofindications, but the Company is progressing joint research with academia to search for new indications, and its
policy is to work to further increase business value. Specifically, in January 2021, it concluded a joint research
agreement with The Institute of Medical Science, The University of Tokyo, and they plan to progress research,
including into possibilities for new treatments through developments not only for blood cancer, but also for solidcancers and other types of cancer, and through combinations with other drugs, while utilizing AI technologies.
Searching for the “undiscovered power” of TREAKISYM®

Source: From the Company’s results briefing materials

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10 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Is exploring the possibilities of developing rigosertib throughcombinations with other drugs, including TREAKISYM®
2. Rigosertib (intravenous formulation/oral formulation)
Rigosertib is an anticancer agent candidate that has unique multi-kinase inhibitory action (which causes cancer cells
to die by inhibiting the multiple kinases involved in cancer cell proliferation, invasion, and metastasis). Its licensor,
Onconova, has progressed the global joint phase III clinical trials (INSPIRE trial) with the overall survival period as
the primary endpoint for high-risk myelodysplastic syndrome (MDS), for which sufficient treatment efficacy cannot
be obtained through the current standard treatment of hypomethylating drugs, which recurs after treatment, andwhich shows resistance to hypomethylating drugs. In August 2020, it was announced that the primary endpoint
had not been achieved in comparison to the doctor-selected therapy.
The Company is responsible for the clinical development in Japan, and its policy is to search for new disease targets,
including from the findings obtained from the INSPIRE trial’s additional analysis. Specifically, in January 2021, it
concluded a joint research agreement with The Institute of Medical Science, The University of Tokyo to search for
new indications for bendamustine and rigosertib. In the future, they will create new treatments through combination
therapies and combined use with existing drugs, and search for new disease targets, including in treatment areas
other than the cancer area.
When using a treatment with multiple anticancer drugs, there is the risk that the impact of the side effects will be
amplified through drugs that have the same side effects. But the side effects of bendamustine and rigosertib aredifferent, so it seems that their combination therapy is possible. Professor Toshio Kitamura of Advanced ClinicalResearch Center, The Institute of Medical Science, The University of Tokyo is one of the lead researchers in thefield of hematopoietic tumors, and he is using hematopoietic tumor models to search for findings to develop newtreatments. Going forward, while performing gene analysis utilizing AI technologies, he will search for the possibilities
for new cancer treatments and therapeutic drug candidates for new diseases in areas other than cancer. Based on
the joint research, the Company intends to formulate a rigosertib development plan during 2021.
Exploring possibilities through joint research with academia for the same purpose,and searching for new mechanisms of action and new disease targets

Source: From the Company’s results briefing materials

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11 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Also, for the development of the rigosertib oral formulation, Onconova is conducting a global joint phase I/II clinical
trial (combined use with azacitidine) for untreated high-risk MDS, and the results are suggesting that it is effective
and safe. Also, as a new indication, in June 2020, it started a doctor-led phase I/IIa clinical trial (combined use withimmune checkpoint inhibitors) for progressive KRAS*-positive NSCLC (non-small cell lung cancer, stage IV), andthis development is attracting attention. The Company completed the phase I clinical trial in Japan in 2019 in order
to confirm the safety of a high dose of a single drug and its tolerability among Japanese people.
*	KRAS is a cancer gene. The KRAS gene usually inhibits the replication of cells, but when a mutation of the KRAS geneoccurs, a signal for cells to replicate is continually sent out, which causes cancerous cells to actively replicate. Patientswith mutated KRAS genes have been identified in a considerable percentage of patients with certain forms of cancer,
including colorectal cancer and lung cancer.

State of progress of rigosertib’s development
Drug

Indication

SyB L-1101(Intravenous formulation)
SyB L-1101(Oral formulation)

Progress

Relapsed and refractory high-risk MDS single drug

Global joint phase III clinical trial Currently conducting
additional analysis

Relapsed and refractory high-risk MDS single drug

Completed the phase I clinical trial in Japan

Untreated high-risk MDS (combined use with azacitidine) Completed the global joint phase I/II clinical trial

Source: Prepared by FISCO from the Company’s results briefing materials and website

In 2021, started a global trial for brincidofovir for adenovirus
infections after hematopoietic stem cell transplantation
3. Brincidofovir (intravenous formulation/oral formulation)a) Overview and licensing agreement
Brincidofovir (BCV) is a lipid conjugate of cidofovir (CDV), which is known as a treatment of cytomegalovirus (CMV)
retinitis. BCV is an antiviral drug candidate whose features are that it has higher antiviral activity, exhibits antiviral
activity against a wider range of viruses, and has a superior safety profile compared to CDV. BCV has a structurethat conjugates a lipid chain into CDV, which allows for more efficient uptake of BCV into cells than CDV alone.
Once inside target cells, the lipid chain is cleaved, releasing CDV, which is then converted to its active form ofcidofovir diphosphate (CDV-PP), which fulfills the role of inhibiting viral DNA replication. Data obtained from invivo tests and other studies shows that BCV has a much higher antiviral replication effect than CDV and otherantiviral drugs through these action mechanisms. In terms of the safety profile, CDV has risks for side effects
such as strong nephrotoxicity, including renal dysfunction caused by the accumulation of CDV in renal tubularepithelial cells. However, because the lipid conjugation of BCV brings no accumulation of CDV in renal tubularepithelial cells, BCV has the outstanding feature of reducing the risk of nephrotoxicity associated with CDV. CDV
has been granted fast-track designation by the FDA (the U.S. Food and Drug Administration) for the preventionof cytomegalovirus and the treatment of adenovirus and smallpox, while in Europe, the EMA has granted orphan
drug designation for the same viruses.

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12 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

How BCV works

Source: Reprinted from the Company’s website

Chimerix had been developing an oral formulation of BCV, but it discontinued development because it did not
obtain statistically significant results in the phase III clinical trials, and as there were some side effects, including
diarrhea. Subsequently, Chimerix was looking for a partner to whom it could out-license BCV to concentrate its
management resources in the anticancer agent field, while the Company was searching for new drug agentsto in-license. The timing was right for both companies, and in September 2019, they concluded a licensing
agreement for the global manufacture, marketing and development (excluding smallpox) of BCV. The key point for
the Company’s decision to in-license BCV was that it has excellent safety and functionality (high antiviral activity
against a wide range of viruses), and it judged that its development was highly likely to be a success. Also its
target diseases are “rare diseases” and “underserved therapeutic areas,” which are not only consistent with theCompany’s development targets, but are also the same blood disease areas targeted by TREAKISYM®, so it
judged that synergies for sales would be great.
12 reasons for in-licensing BCV

Source: From the Company’s results briefing materials

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13 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

In terms of the reason why Chimerix failed to develop an oral formulation, the Company thinks that as the drug
absorption rate from the digestive organs was low, it was necessary to administer a large dosage. The Company
believes that an intravenous formulation could have the same effect as an oral formulation at just 10% of thedosage, so it thinks there is a lower risk of side effects and a higher probability of success. This agreement covers
both the intravenous formulation and the oral formulation, as the Company believes that going forward, there is apossibility that it can resolve these issues through new improvements to the drug. Of the viral infectious diseases,
the reason why smallpox alone is excluded from the agreement is that the U.S. government needs to maintainits ability to manufacture and stockpile a smallpox treatment independently within the country as a measure tocounter bioterrorism. In December 2020, Chimerix submitted a new drug application for BCV to the FDA for
smallpox, and it announced that the investigation is scheduled to be completed by July 7, 2021. If it is approved,
it is anticipated that the market value of BCV and the degree of attention placed on it will increase even more.
What is notable in this agreement is that it is a global license, and it also covers manufacturing rights. This drug
will be used to treat viral infectious diseases that occur following hematopoietic stem cell transplantation or organtransplants. The organ transplant market in particular is large not only in the U.S. and Europe, but also in Asia,and the potential market scale is significant as well. TREAKISYM® has been marketed in South Korea, Taiwan,
and Singapore through sales partners. However, sales volumes were small and there was only a negligible impact
on the Company’s business performance. If the overseas rollout of BCV is successful, it will expand the scope ofoverseas sales and enable it to grow as a global specialty pharmaceutical company.
Also, the quality issue for TREAKISYM® that arose in 2019 impacted the decision to have the agreement include
manufacturing rights. The Company understands that controlling manufacturing on its own and building a system
to suppress business risks to the fullest extent is critical in order to benefit all stakeholders, including patients,
and aim for growth. It has already decided on the manufacturing outsourcer, and preparations to manufacture theinvestigational new drug are being progressed. In conjunction with the conclusion of the BCV licensing agreement,
the Company paid developer Chimerix an upfront payment of US$5mn (approximately ¥540mn) in FY12/19 3Q,
and it will pay future milestones of up to US$180mn (approximately ¥19.4bn), as well as double-digit royalties on
net sales of brincidofovir products.
b) Future development plans
As its development strategy for BCV (intravenous formulation), the Company decided on its future policy during the
Global Advisory Board meeting held in February 2020. Specifically, it decided the following three points: progressdevelopment utilizing the multi-virus activity of BCV, which is its strength; target multiple viral infections, including
adenoviruses for which there are no treatments and medical needs are high; and conduct development as thehighest priority for the infant transplant area, for which medical needs are high.
Including due to the strong wishes of board members who are medical experts, it will start the global joint phase II
clinical trial for adenovirus infections after hematopoietic stem cell transplantation as the first development target.
It will skip safety as it can utilize the data from the clinical trial conducted by Chimerix (cases on more than 1,000
people). Adenoviruses are viruses existing in nature and they cause infections such as pharyngitis, tonsillitis,
conjunctivitis, gastroenteritis, and hemorrhagic cystitis by infecting the respiratory organs, eyes, intestine, andurinary organs. Serious cases are rare among infections in healthy people. But the risk of severe complications
increases in infections in patients whose immune systems have been weakened after hematopoietic stem celltransplantation and as yet there is no treatment, so there are strong hopes for the development of treatments
and prophylactic drugs. While there are few cases, the plan is to first progress development for infants and afterthat to widen the scope to adults and to other viral infectious diseases.

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14 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

On March 10, 2021, the Company submitted an IND application to the FDA, and if it proceeds smoothly, registrations of the first subjects are expected to start in 3Q of 2021. Regarding the CRO (contract research organization)
to which progress of global clinical trials will be outsourced, it concluded an agreement with Syneos Health, Inc.
of the U.S. in December 2020. The trial design is an open label trial that will divide the 24 subjects into 4 groups
according to dosage to observe safety and tolerability. The trial’s primary endpoint is the number of adverse eventsoccurring during the trial period, and the secondary endpoint is the amount of change of the adenovirus in bloodplasma in the five weeks from the start of administration. The clinical trial is scheduled to be completed in thesecond half of 2022, and if it obtains good results, it will progress to the phase III clinical trial in 2023, toward a
possible market launch in 2026 at the earliest. It is expected that the costs of the phase III clinical trial will be ona scale of billions of yen.
Professor Roy Chemaly of the MD Anderson Cancer Center, which is the largest bone marrow transplantation
surgery-related medical facility in the U.S., announced in a paper in March 2020 that “BCV has less nephrotoxicity
and bone marrow suppression, which are problems with other drugs, and it can be an excellent treatment option,”
indicating his support for the Company’s development. In such ways, it seems that there are great expectations
for BCV.
On the other hand, in Japan, the Company plans to start development for viral hemorrhagic cystitis (vHC)*1 after
hematopoietic stem cell transplantation in 2021. This disease is one of the complications after hematopoietic
stem cell transplantation, but as yet no therapeutic drugs have been approved for it in Japan, and while bladderperfusion is carried out as a therapy to treat it, there are cases of it being treated using imported CDV at a doctor’s
discretion. However, as nephrotoxicity is strong, the effects of CDV are limited and there is strong demand fordevelopment of a highly effective therapeutic drug with few side effects. Initially, the plan was to progress inadvance the global trial for adenovirus infections, but due to the strong wishes, including of the Japanese Society
for Transplantation and Cellular Therapy and doctors, it has been decided to progress development for vHC inparallel in Japan. Going forward, discussions will be held with the Pharmaceuticals and Medical Devices Agency
to decide on the trial design. Other than for vHC, it is also conducting developments for various viral infectious
diseases after hematopoietic stem cell transplantation, including HHV-6 encephalitis*2 and the BK virus, and itplans to progress developments while observing conditions.
*1	One complication after hematopoietic stem cell transplantation, in which a viral infection causes inflammation of the
bladder that results in severe pain, urination disorders and hematuria (blood in the urine). There have been cases of severe
complications, including renal failure and viral nephropathy, and research reports state that it occurs in 10% to 30% ofcases. The cause of infant viral hemorrhagic cystitis is most often an adenovirus infection.
*2	Encephalitis that develops due to infection with the human herpes virus after hematopoietic stem cell transplantation andorgan transplants. The rate of occurrence in Japan is low at 2% to 3%, but if infected, disturbances of consciousness
occur and the risk of death increases. In Japan, foscarnet was approved as a therapeutic drug in March 2019, but its
nephrotoxicity is high. Also, the trial data has confirmed that BCV’s antiviral activity is much higher.

In addition, for viral infectious diseases after organ transplants, the Company’s policy is to search for partnercompanies and to progress developments through collaborations. Looking to the future, it has in its sights adevelopment to improve the oral formulation and developments in the dermatology and ophthalmology areas,
and is considered to be aiming to maximize the market value of BCV by expanding indications through LCM (lifecycle management). Globally, the number of hematopoietic stem cell transplantations (allogeneic transplantations)is 35,000 cases a year, while the market for organ transplants is more than 110,000 cases. So BCV’s growthpotential as a viral infection therapeutic drug and prophylactic drug is enormous, and we shall be paying attention
to development trends in the future.

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15 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Future BCV developments

Source: From the Company’s results briefing materials█ Results trends
In FY12/20, expenses increased to build the Company’s own sales
system for TREAKISYM®, so results were basically unchanged YoY
1. Overview of the FY12/20 results
In the FY12/20 results, net sales increased 5.3% YoY to ¥2,987mn, operating loss was ¥4,506mn (compared to aloss of ¥4,301mn in the previous period), ordinary loss was ¥4,615mn (a loss of ¥4,376mn compared to the same
period of the previous fiscal year), and loss was ¥4,090mn (a loss of ¥4,376mn compared to the same period of
the previous fiscal year), leading to results that were on par with the previous fiscal year.
FY12/20 results(¥mn)
FY12/19
Results

FY12/20
YoY (%)

Vs. forecast

2,837

3,404

2,987

+149

5.3%

-416

Product sales

2,811

3,404

2,977

+165

5.9%

-426

Other sales

26

0

10

-16

-62.2%

10

864

1,146

866

+2

0.2%

-279

SG&A expenses

5,166

6,236

5,373

+206

4.0%

-862

R&D expenses

2,441

2,731

2,266

-174

-7.2%

-464

Other SG&A expenses

2,724

3,505

3,106

+381

14.0%

-398

Operating profit (loss)-4,301-5,090-4,506

-204

-

583

Ordinary profit (loss)-4,376-5,134-4,615

-239

-

518

4

-

529

+525

-

529

-4,376-4,803-4,090

+286

-

712

Net sales

Gross profit

Extraordinary profit (loss)
Profit (loss)

Initial forecast

Results

YoY

Source: Prepared by FISCO from the Company’s financial results

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16 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

Results trends

Due to the prolonged impact of the TREAKISYM® (FD formulation) defective quality issue (contamination and poor
external appearance), which had continued since the spring of 2019, net sales were 12% below the initial forecast.
But from 2Q onwards, sales volume recovered due to the strengthening of the quality inspection system within
Japan and a YoY increase in sales was secured for the full fiscal year. For the products that were determined to beunsellable due to the defective quality, cost of sales of ¥69mn was recorded as an inventory assets valuation loss
(recorded ¥187mn in the previous period).
SG&A expenses increased 4.0% YoY to ¥5,373mn. R&D expenses decreased 7.2% to ¥2,266mn due to reductions
in development expenses for rigosertib and TREAKISYM®, but construction of the Company’s own TREAKISYM®
sales system caused other SG&A expenses to increase 14.0% to ¥3,106mn. Expenses related to the constructionof its own sales system (sales promotion expenses) rose from ¥733mn in the previous period to ¥1,301mn, andif excluding sales promotion expenses, other SG&A expenses decreased ¥185mn YoY following the introductionof the teleworking system in response to the novel coronavirus pandemic and efforts to reduce expenses. Also,
compared to the initial forecasts, both R&D expenses and other SG&A expenses were kept low and total SG&A
expenses decreased ¥862mn. R&D expenses included a milestone payment of approximately ¥500mn following
the acquisition of marketing approval for the RTD formulation (recorded in 3Q).
In FY12/20, the Company recorded settlement received of ¥525mn as extraordinary profit. In October 2017, it
filed a petition* with the International Chamber of Commerce (ICC) against The Medicines Company of the U.S. fordamages for the non-fulfillment of a licensing agreement for the post-operative self-administered pain management
medication SyB P-1501. The ICC announced its final arbitration ruling on September 1, 2020, which became thissettlement received. Specifically, it ruled that The Medicines Company would pay to the Company 50% of the various
costs (US$4.95mn) relating to the arbitration proceedings, including attorneys’ fees.
*	In October 2015, the Company concluded an in-licensing agreement with The Medicines Company for a self-administered short-term acute pain management medication. The Company, acting in the best interests of patients, temporarilysuspended new patient enrollment for the drug from April 2017 due to the concern about the continuity of The Medicines
Company’s business regarding the product. In October 2017, the Company filed for arbitration with the ICC seeking apayment of US$82mn as compensation for damages for the non-fulfillment of the licensing agreement. In the arbitration,
the Company claims that The Medicines Company was not able to provide the Company with adequate assurance of its
performance of obligations under the licensing agreement in light of its decision to discontinue commercialization activities
regarding the product and withdraw from markets in the U.S. and Europe, and that such failure by The Medicines Company
was a material breach of the licensing agreement. The Company then terminated the licensing agreement.

On December 10, 2020, the Company started its own sales of TREAKISYM®. It began preparations to construct
its own sales system in 2019 and completed it in June 2020, and subsequently continued to work with Eisai.
Regarding sales personnel, it has respectively allocated a total of 57 people, consisting of 51 MR with high levels of
expertise in the blood disease area and 6 RSM (regional sales managers), to 6 blocks nationwide. Also, regarding
marketing personnel, it has appointed 1 KAM (KOL key account manager) and 4 HE (hematology experts) for a totalof 62 personnel (of whom, approximately 60% are contract employees). It has completed the training of the sales
personnel so they can respond immediately for the RTD formulation and the expansion of indications to relapsed
and refractory DLBCL, and going forward, the 62 personnel will continue to conduct sales activities.
Also, for its distribution system, on September 7, 2020, the Company concluded basic transaction agreements forthe buying and selling of pharmaceuticals with Suzuken Co., Ltd. <9987> and TOHO PHARMACEUTICAL CO., LTD.
(a consolidated subsidiary of TOHO HOLDINGS CO., LTD. <8129>), and it became a general agent for these twocompanies. It is also outsourcing logistics to S.D. Collabo Co., Ltd., which is a subsidiary of Suzuken Co., Ltd. (onelogistics base in each of eastern and western Japan). For the current sales system, the Company has been highly
evaluated for being able to build an organization that is particularly highly specialized even within its industry, and it
is expected to contribute to increasing sales and improving the profit margin from 2021 onwards.

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17 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

21-May-2021

4582 JASDAQ Growth Market

https://www.symbiopharma.com/ir_e/

Results trends

Has entered a phase for achieving profitability in FY12/21, andfundraising is expected to be mainly borrowings from financial
institutions
2. Financial condition
Looking at the financial condition at the end of FY12/20, total assets were up ¥1,000mn on the end of the previous
fiscal period to ¥6,274mn. In current assets, main factors included that accounts receivable-trade decreased ¥142mn
and cash and deposits declined ¥62mn, but merchandise and finished goods increased ¥944mn. Merchandiseand finished goods were not previously recorded in assets because the FD formulation purchased in the previous
period was only handed over to Eisai, but due to the Company’s own inspection work to address the defective
quality problem, they were recorded in assets in FY12/20. Also, if the year-end level of inventory is calculated fromthe sales forecasts for FY12/21, this means that the Company holds approximately 5 months’ worth of inventory.
Although this level appears somewhat high, it is because the Company completed procurement of the amount of
FD formulation it expects to sell in the future by the end of 2020. In non-current assets, main factors included thatthe total of software and software in progress increased ¥61mn, relating to the construction of the Company’s own
sales system.
Total liabilities were up ¥743mn on the end of the previous fiscal year to ¥1,617mn. Main factors included that
accounts payable-trade increased ¥544mn and that unearned revenue of ¥192mn was recorded. Net assets
increased ¥257mn to ¥4,657mn. Retained earnings decreased ¥4,090mn due to the recording of a loss, but the
total of share capital and capital surplus increased ¥4,350mn following the exercise of stock acquisition rights. As
a result, the equity ratio declined by 7.4 percentage points (pp), from 71.7% to 64.3%.
In December 2020, the Company concluded a commitment line agreement with two banks with an upper limitof ¥3bn. It had previously raised funds for business activities, mainly for R&D expenses, through equity financing
by issuing stock acquisition rights. But as it is expected to become profitable from FY12/21, it has become able
to borrow from financial institutions. Therefore, its policy going forward is to pay for business activities throughfiscal-period earnings and borrowings from financial institutions.
Balance sheet and management indicator(¥mn)
Current assets(Cash and deposits)(Merchandise and finished goods)

FY12/17

FY12/18

FY12/19

FY12/20

Change

4,036

6,038

4,887

5,815

927

2,947

4,821

3,910

3,848

-62

362

533

-

944

944

215

200

386

459

72

Total assets

4,252

6,239

5,273

6,274

1,000

Total liabilities

1,012

1,337

873

1,617

743

-

-

-

-

-

3,239

4,901

4,400

4,657

257

63.6%

70.1%

71.7%

64.3%

-7.4ptNon-current assets(Interest-bearing debt)
Net assets
Management indicator
Equity ratio

Source: Prepared by FISCO from the Company’s financial results

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18 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/█ Outlook
The outlook for FY12/21 is that the Company will become profitable
for the first time since its foundation through its own sales of
TREAKISYM®, switching to the RTD formulation, and the expansionof indications
1. Outlook for FY12/21
For the FY12/21 results, the outlook is that the Company will become profitable for the first time since its foundation,with net sales forecast to increase 206.4% YoY to ¥9,151mn, operating profit of ¥1,361mn (a loss of ¥4,506mn in theprevious period), ordinary profit of ¥1,350mn (a loss of ¥4,615mn), and profit of ¥1,149mn (a loss of ¥4,090mn). AtFISCO, we think that it is highly likely to become profitable as it has previously achieved all of the conditions cited to
become profitable; namely, constructing its own sales system, starting sales of the RTD formulation, and acquiring
marketing approval for relapsed and refractory DLBCL.
Outlook for FY12/21(¥mn)
FY12/20
Results

FY12/21

vs. net sales

Company
forecast

vs. net sales

Change% change

Net sales

2,987

-

9,151

-

6,163

206.4%

Gross profit

866

29.0%

6,957

76.0%

6,090

702.6%

SG&A expenses

5,373

179.9%

5,596

61.2%

222

4.1%

R&D expenses

2,266

75.9%

2,019

22.1%

-247

-10.9%

3,106

104.0%

3,577

39.1%

470

15.1%

Operating profit (loss)-4,506

-

1,361

14.9%

5,867

-

Ordinary profit (loss)-4,615

-

1,350

14.8%

5,965

-

Profit (loss)-4,090

-

1,149

12.6%

5,239

-

Other SG&A expenses

Source: Prepared by FISCO from the Company’s financial results

Net sales are forecast to increase significantly because of the start of the Company’s own sales on December 20,
2020, and in addition, the start of sales of the RTD formulation on January 12, 2021, and the start of sales from
2Q for the new indication of relapsed and refractory DLBCL. On a drug-price basis, sales are expected to increase
by approximately 40%, from the previous period’s result of ¥8.1bn to ¥11.3bn. Breaking down this ¥11.3bn, theforecasts are for untreated low-grade NHL to contribute ¥4.1bn, other existing indications ¥4.6bn, and relapsed
and refractory DLBCL ¥2.6bn. The reason for existing indications increasing from ¥8.1bn in the previous period to¥8.7bn is that sales were restricted in the previous period due to the FD formulation defective quality problem, andas it seems that that BR therapy market penetration rate will further rise due to switching to the RTD formulation.
The rise in the percentage of sales from the RTD formulation is expected to accelerate, from approximately 20% in
1Q to around 91% by December 2021. The Company applied for marketing approval for an indication for relapsed
and refractory DLBCL on March 25 and is expected to acquire approval in just a few months as the investigation
is simple, so it seems that sales may start in the second half of 2021. In FY12/21, the Company estimates thatthe percentage of sales from the RTD formulation will reach 65% to 70%. The gross profit margin is forecast to
rise rapidly from 29.0% in the previous period to 76.0% (assuming an exchange rate of ¥110 to US$1) from theCompany’s own sales and the progress made in switching to the highly profitable RTD formulation.

We encourage readers to review our complete legal statement on “Disclaimer” page.

19 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

OutlookWithin SG&A expenses, R&D expenses are forecast to decrease 10.9% YoY to ¥2,019mn. In the previous period,
the Company incurred a milestone payment of approximately ¥500mn following the acquisition of approval for the
RTD formulation, but no milestone payments are scheduled for FY12/21. Although expenses will actually increase
if excluding this factor, the main reason for this increase is the higher expenses due to the start of the BCV clinical
trial. Conversely, other SG&A expenses are forecast to increase 15.1% YoY to ¥3,577mn. Following the start of theCompany’s own sales, operating expenses (including personnel expenses) are expected to increase from ¥1,301mn
in the previous period to ¥1,961mn.
Looking at the results outlook on a fiscal quarterly basis, while it will depend on the state of progress made inswitching to the highly profitable RTD formulation and the pace of the sales increase for relapsed and refractory
DLBCL, at FISCO we think that it is highly likely that the Company will become profitable from 2Q due to the startof sales for relapsed and refractory DLBCL.
In addition, as the business plan, the Company will apply for approval for the RI formulation by 2Q, and in 2H, its
plans include beginning registrations of subjects for the BCV global joint phase II clinical trial, starting the clinical trial
toward acquiring POC in Japan, starting operations at Symbio Pharma USA (it intends to recruit 1 or 2 personnel)
and formulating the rigosertib development plan.

From 2022 onwards, operating profit is expected to grow by morethan 20% a year from the increase in sales of TREAKISYM®
2. Mid-Range Plan
In the three-year Mid-Range Plan that the Company announced in February 2021, the numerical results targets for
the Plan’s final fiscal year of FY12/23 are net sales of ¥12,369mn, operating profit of ¥2,099mn, ordinary profit of¥2,088mn, and profit of ¥1,778mn. It plans to continuously achieve double digit increases in sales and profits from2022 onwards.
Mid-Range Plan(¥mn)
FY12/21
Company forecast

FY12/22
targets

Growth rate

FY12/23
targets

Growth rate

Net sales

9,151

Operating profit (loss)

1,361

10,98520.0%

12,369

12.6%

1,738

27.7%

2,099

Ordinary profit (loss)

20.8%

1,350

1,727

27.9%

2,088

20.9%

Profit (loss)

1,149

1,470

27.9%

1,778

21.0%

Earnings per share (¥)

30.1

38.5

-

46.5

-

Source: Prepared by FISCO from the Company’s results briefing materials

For net sales, sales will continue to increase for relapsed and refractory DLBCL, and in addition, sales of the RI
formulation will start from the second half of 2022, while it seems the use of TREAKISYM® is progressing in medical
facilities using multi-drug combination therapies, which will also lead to higher sales. On a drug-price basis, sales
are forecast to increase from ¥8.1bn in FY12/20 to ¥15.3bn in FY12/23. Also, currently multiple pharmaceuticalcompanies are progressing clinical trials for multi-drug combination therapies that include TREAKISYM®. So in
the future, it is fully possible that treatments for existing indications and new indications using TREAKISYM® will
increase, leading to sales growth from 2024 onwards. Within Japan, the situation in which in actuality the Company
has exclusive marketing rights is likely to continue until 2031, which is when the patent expires for the RTD/RI
formulation, and TREAKISYM® will be the driver of earnings.

We encourage readers to review our complete legal statement on “Disclaimer” page.

20 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

21-May-2021

4582 JASDAQ Growth Market

https://www.symbiopharma.com/ir_e/

Outlook

TREAKISYM® net sales (drug-price basis)（¥bn）

March 2021, acquired
approval for relapsed andrefractory DLBCL andstarted sales of the RTD
formulation in January of
the same year

20.0

15.0

December 2016,acquired marketing
approval for untreatedlow-grade NHL/MCL

Second half of 2022,
expected to startsales of the RI
formulation

10.0
13.6

15.3

11.3

5.0
4.8

4.8

FY12/15

FY12/16

7.6

8.5

8.4

8.1

FY12/17

FY12/18

FY12/19

FY12/200.0
FY12/21 FY12/22 FY12/23(estimates) (estimates) (estimates)

Sources: the results are from interviews with the Company and from the results briefing materials for FY12/21, while thefigures for FY12/22 onwards are estimates prepared by FISCO based on the FY12/21 figures

The gross profit margin is forecast to rise from 76.0% in FY12/21 to 79% in FY12/22, and to 80% in FY12/23. The
profit margin is expected to increase from the progress made in switching from the FD formulation to the RTD/
RI formulation. By the end of 2022, the percentage of sales from the RTD/RI formulation is forecast to be around
95%. This assumes that going forward, some medical facilities will continue to use the FD formulation, but when
considering the superiority of its functions, it is anticipated that close to 100% of medical facilities will switch to the
RTD/RI formulation.
SG&A expenses are forecast to continue to trend upward, increasing from ¥5,596mn in FY12/21 to ¥6,940mn
in FY12/22, and to ¥7,796mn in FY12/23. Within this amount, R&D expenses are expected to increase from
¥2,019mn in FY12/21 to approximately ¥3.1bn in FY12/22 (of which, milestone payments of around ¥500mn), andto approximately ¥3.8bn in FY12/23 (of which, milestone payments of around ¥500mn). After excluding the milestone
payments, they will continue to trend upwards, but this is mainly due to the increase in BCV development expenses.
Conversely, other SG&A expenses are forecast to increase only slightly, from ¥3,577mn in FY12/21 to approximately¥3.7bn in FY12/22, and to around ¥3.9bn in FY12/23. In TREAKISYM® operating expenses, logistics expenses
will increase somewhat, while the Company plans to maintain the current situation for the personnel system. On
the other hand, personnel expenses are forecast to increase toward BCV’s global deployment. An important issue
for the Company is continuing to grow after 2032, which is when the patent for the RTD/RI formulation expires.
So it is searching for new development candidates to follow-on from BCV, but the current results forecasts do notincorporate any one-off payments relating to in-licensing.

We encourage readers to review our complete legal statement on “Disclaimer” page.

21 22

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited
4582 JASDAQ Growth Market

21-May-2021
https://www.symbiopharma.com/ir_e/

OutlookWith 2021 as the first year of the second foundation, is aiming to bea global specialty pharma
3. Long-term targets
Since it was founded in 2005, the Company has continuously worked to develop TREAKISYM® as a bio-venture,arriving at its current situation in 2021 when it can become profitable for the first time. So in 2021, it is transitioning
from a development stage to an earnings-growth stage. Therefore, the Company has positioned 2021 as the firstyear of its second foundation, and it is aiming to grow as a global specialty pharma by working continuously toincrease and to create business value, and at the same time, to progress overseas business development throughBCV.
Specifically, the Company is aiming for sustainable earnings growth by maximizing earnings from TREAKISYM®,
and in addition, by targeting the market launches of rigosertib and BCV. Moreover, it is finding the fundamental
business value in each pipeline while progressing joint research with academia and others, which is leading to the
maximization of business value. This also includes activities such as the in-licensing of new pipeline drugs.
The Company has set “Local & Global” and “50 and 50 in 30” as the management keywords. Their meaning is
to take a dramatic leap forward as a global pharmaceutical company by successfully guiding the development of
BCV with the aim of increasing the percentage of total sales from overseas sales to 50% by 2030. As previously
explained, BCV is expected to be an effective treatment for various viral infectious diseases after hematopoietic
stem cell transplantation, while it also possible that developments will be progressed for viral infectious diseases
after organ transplants and for viral infectious diseases in other areas (dermatology and ophthalmology). So it hasenormous growth potential, and we shall be paying attention to development trends in the future.

We encourage readers to review our complete legal statement on “Disclaimer” page.

22 22

Disclaimer
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This report has been prepared at the request of the company subject hereto based on theprovision of information by such company through telephone interviews and the like. However,
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◾ For inquiry, please contact: ◾

FISCO Ltd.
5-13-3 Minami Aoyama, Minato-ku, Tokyo, Japan 107-0062
Phone: 03-5774-2443 (IR Consulting Business Division)
Email: support@fisco.co.jp