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SymBio Pharmaceuticals / 4582
COVERAGE INITIATED ON:

2014.10.31

LAST UPDATE:

2019.07.01

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2019.07.01

Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp

INDEX
How to read a Shared Research report: This report begins with the trends and outlook section, which discusses the company’s most recent
earnings. First-time readers should start at the business section later in the report.

Executive summary ----------------------------------------------------------------------------------------------------------------------------------- 3
Key financial data ------------------------------------------------------------------------------------------------------------------------------------- 5
Recent updates ---------------------------------------------------------------------------------------------------------------------------------------- 6
Highlights ------------------------------------------------------------------------------------------------------------------------------------------------------------6
Trends and outlook -----------------------------------------------------------------------------------------------------------------------------------------------8
Business ------------------------------------------------------------------------------------------------------------------------------------------------ 17
Business description -------------------------------------------------------------------------------------------------------------------------------------------- 17
Business strategy ------------------------------------------------------------------------------------------------------------------------------------------------ 20
Pipeline ------------------------------------------------------------------------------------------------------------------------------------------------------------- 23
Earnings structure ----------------------------------------------------------------------------------------------------------------------------------------------- 33
Strengths and weaknesses------------------------------------------------------------------------------------------------------------------------------------ 35
Market and value chain---------------------------------------------------------------------------------------------------------------------------- 36
Market strategy -------------------------------------------------------------------------------------------------------------------------------------------------- 36
Historical performance ---------------------------------------------------------------------------------------------------------------------------- 39
Income statement ----------------------------------------------------------------------------------------------------------------------------------------------- 51
Balance sheet ----------------------------------------------------------------------------------------------------------------------------------------------------- 52
Cash flow statement -------------------------------------------------------------------------------------------------------------------------------------------- 53
Other information ---------------------------------------------------------------------------------------------------------------------------------- 54
Claim for damages ---------------------------------------------------------------------------------------------------------------------------------------------- 54
History -------------------------------------------------------------------------------------------------------------------------------------------------------------- 54
News and topics ------------------------------------------------------------------------------------------------------------------------------------------------- 56
Major shareholders --------------------------------------------------------------------------------------------------------------------------------------------- 61
Top management ----------------------------------------------------------------------------------------------------------------------------------------------- 61
Employees --------------------------------------------------------------------------------------------------------------------------------------------------------- 61
Other ---------------------------------------------------------------------------------------------------------------------------------------------------------------- 62
Company profile ------------------------------------------------------------------------------------------------------------------------------------------------- 66

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SymBio Pharmaceuticals / 4582
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Executive summary
SymBio in-licenses drugs for development and sale
◤ SymBio Pharmaceuticals Ltd. is a specialty pharmaceutical company that buys the right to develop and commercialize drugcandidates in order to address the underserved medical needs of patients in Japan and the rest of Asia. With its main focus on
the areas of oncology, hematology, and pain management, the company typically seeks in-licensing opportunities for nichemarkets from pharmaceutical and biotech companies based in the US or EU.

◤ Notably, the company does not conduct basic research and outsources preclinical/clinical development, employing a fablessin-licensing approach. Using its proprietary in-house “search engine,” the company identifies, assesses and in-licenses only

quality drug candidates having proof-of-concept established in human subjects. The company first screens third-party drugcandidates being tested in clinical trials, then presents the in-licensing opportunities to its Scientific Advisory Board for further
assessment of the science behind each molecule, preclinical/clinical data, target market, and the feasibility of receiving
marketing approval from Japanese regulatory authorities.
◤ According to the company, the typical development timeline of an oncology drug in Japan from preclinical studies tomarketing approval is about 10 to 17 years. However, the company secured marketing approval for its first oncology drug
under development in Japan, Treakisym®, in only four years after the first clinical trial was initiated, with product launch only
two years after US marketing approval and around the same time that approval was granted in Europe. Within three years of
its launch, Treakisym® captured more than 50% of the non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL)
market in Japan.

◤ As of February 2019, the company had obtained approval for and launched Treakisym® (anticancer agent for hematologic

malignancies) for the indications of relapsed or refractory low-grade NHL and MCL, first-line treatment of relapsed or
refractory low-grade NHL and MCL, and chronic lymphocytic leukemia (CLL). Treakisym® is included in the Practical

Guidelines for Hematological Malignancies 2018 edited and published by Japanese Society of Hematology as the standard
treatment for relapsed or refractory low-grade B-cell NHL, MCL, and CLL, and as a treatment option for untreated low-gradeNHL.
◤ Drugs in the development pipeline include Treakisym® for the indication of relapsed or refractory diffuse large B-cell

lymphoma (DLBCL), liquid formulations (RTD and RI products) of Treakisym®, and rigosertib (anticancer agent for
myelodysplastic syndromes) IV and oral formulations.

Earnings◤ FY12/18 sales were JPY3.8bn (+11.4% YoY). Product sales totaled JPY3.8bn (+10.6% YoY) and royalty revenue totaled

JPY26mn (JPY0mn in FY12/17). The operating loss totaled JPY2.7bn (loss of JPY3.9bn). The company also reported a recurring

loss of JPY2.7bn (loss of JPY4.0bn). Net loss was JPY2.7bn (loss of JPY4.0bn).
◤ As a result of sales growth of Treakisym®, SymBio forecasts FY12/19 sales of JPY4.5bn (+16.4% YoY), an operating loss of

JPY3.6bn (operating loss of JPY2.7bn in FY12/18), a recurring loss of JPY3.6bn (recurring loss of JPY2.7bn), and a net loss of
JPY3.6bn (net loss of JPY3.1bn).

◤ In its medium-term plan, with the aims of achieving sales growth and higher profit margins, SymBio projects sales of JPY11.3–

11.8bn and a net income of JPY1.7–2.1bn in FY12/22. The company expects higher sales from increased market penetration ofTreakisym® for approved indications and anticipated approval of additional indication of Treakisym® for relapsed or refractory
diffuse large B-cell lymphoma (DLBCL). The company projects a significant increase in profit on higher sales as well as on
higher GPM attributed to profit generated from the sale of Treakisym® following the shift to in-house sales of the product. The
company has factored the cost of establishing and operating its own sales structure into its forecast, but Shared Researchthinks the increase in GPM driven by the shift to in-house sales structure will easily offset the increase in costs. The company’s
own sales structure is specialized to the area of hematologic disorders, and will also handle the sale of rigosertib in addition to
Treakisym®.

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SymBio Pharmaceuticals / 4582
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Strengths and weaknesses
Shared Research thinks SymBio’s strengths include its unique candidate selection process, strong product development team,and business strategy focusing on niche markets. Weaknesses include the lack of its own sales force and funding needs (seeStrengths and weaknesses).

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SymBio Pharmaceuticals / 4582
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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp

Key financial data
Income statement(JPYmn)Sales
YoY

Gross profit

FY12/09Par.
1,191

FY12/10Par.
1,450

FY12/11Par.
1,883

FY12/12Par.
1,955

FY12/13Par.
1,532

FY12/14Par.
1,955

FY12/15Par.
1,933

FY12/16Par.
2,368

FY12/17Par.
3,444

FY12/18
Par.
3,836

1,191

1,212

658

593

318

527

583

904

1,031

1,173

-208

-613

-2,067-1,700-1,681-1,303-2,552-2,127-3,947-2,656-3,587-214-638-2,095-1,729-1,601-1,110-2,630-2,317-3,977-2,749-3,612

-

-

-

-

-

-

-

-

-

-

-

-218

-642

-2,105-1,733-1,605-1,116-2,632-2,313-3,978-2,753-3,616

-

-

-

-

-

-

-

-

-

-

-

101
-32.5
402.8

112
-59.3
365.4

19,131-143.6345.3

19,131-90.6
254.7

30,634-69.3
239.5

30,634-36.3
208.8

32,391-81.3
127.6

46,531-58.8
108.6

54,049-79.8
50.0

82,399
-41.4
53.1

4,121
4,218
13
27
2
4,261
205
2
207
4,054

4,016
4,213
22
27
1
4,263
1
178
2
180
4,083

6,511
7,178
17
48
13
7,256
309
646
5
651
6,606

4,840
5,421
14
57
11
5,502
330
599
4
602
4,900

7,264
7,634
9
37
8
7,687
251
3
254
7,433

6,591
7,290
49
49
66
7,454
306
488
2
490
6,964

4,261
4,827
53
53
52
4,984
320
551
2
552
4,432

5,719
6,685
75
77
42
6,878
322
942
451
1,394
5,485

2,947
4,037
47
100
69
4,252
604
1,011
1
1,013
3,239

4,821
6,038
57
73
71
6,239
726
1,336
1
1,338
4,902

-

-

-

-

-

-

-

-

-

-

-211
-4
2,963

-754
-116
663

-2,074-117
4,611-1,659-411-1-1,677-1,332
4,057-1,266314
544-2,272
1,489-3-1,960-44
3,658-3,817-78
1,164-2,325
-26
4,272

-7.6%
-8.1%
95.1%

-15.1%-15.8%
95.8%-36.5%-39.4%
91.0%-27.2%-30.2%
89.1%-24.3%-26.3%
96.7%-14.7%-15.8%
93.4%-42.3%-48.3%
88.9%-39.0%-50.4%
79.7%-71.5%-102.6%76.2%-52.5%-77.8%
78.6%-26.9%

YoY
GPM-26.9%
100.0%YoY
OPM-

Operating profit
Recurring profit
YoY
RPM

Net income
YoY
Net margin

Per share data (JPY)
Shares issued (year-end; '000)
EPS
EPS (fully diluted)
Dividend per share
Book value per share
Balance sheet (JPYmn)
Cash and cash equivalents
Total current assets
Tangible fixed assets
Investments and other assets
Intangible fixed assets
Total assets
Accounts payable
Short-term debt
Total current liabilities
Long-term debt
Total fixed liabilities
Total liabilities
Net assets
Total interest-bearing debt
Statement of cash flows (JPYmn)
Cash flows from operating activities
Cash flows from investing activities
Cash flows from financing activities
Financial ratios
ROA (RP-based)
ROE
Equity ratio

21.7%

1.7%
83.6%
-

29.8%

-45.7%
35.0%
-

3.9%

-9.9%
30.3%
-

-21.6%-46.4%
20.8%
-

27.6%

65.6%
26.9%
-

-1.1%

10.7%
30.2%
-

22.5%

55.1%
38.2%
-

45.4%

14.1%
29.9%
-

11.4%

13.7%
30.6%
-

FY12/19
Est.
4,465
16.4%

-

-43.9

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2019.07.01

Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp

Recent updates
Highlights
On July 1, 2019, Shared Research updated the report following interviews with SymBio Pharmaceuticals Ltd.

On June 12, 2019, the company announced a change of its representative director (resignation).

Details of change (resigning representative director)
Name
Kazuo Asakawa

Current position
Representative Director and Corporate Officer
Executive Vice President
Chief Commercial Officer

Reason for change (resignation)
Mr. Kazuo Asakawa requested to resign from the positions of representative director and corporate officer due to health reasons.
His resignation will be effective as of June 30, 2019.

On May 22, 2019, the company announced the launch of a regenerative medicine product that uses its anticancer drug
Treakisym® as a pretreatment agent.
On the same day, Novartis Pharma K.K. announced that its chimeric antigen receptor T-cell (CAR-T) therapy Kymriah® IV Infusion(hereinafter Kymriah®) targeting CD19 positive relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and CD19
positive relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was listed on the National Health Insurance drug price list.
In March 2019, SymBio obtained approval to make a partial revision to the marketing approval of anticancer drug Treakisym®
(non-proprietary name: bendamustine hydrochloride) as a pretreatment agent for antigen-specific T-cell infusion therapy*. With
the launch of Kymriah®, Treakisym® can be used as a pretreatment agent for the CAR-T therapy.

*Antigen-specific T cell infusion therapy for cancer involves the administration of T cells that recognize specific tumor antigens to patients. In mostcases, patients have few such T cells in their bodies. Thus a treatment was developed in which T cells taken from patients are engineered ex vivo andadministered to patients after expanding them (T cell infusion therapy). The two main T cell infusion therapies for cancer are TCR-T therapy, which
entails introducing a gene coded with a T cell receptor specific to a tumor cell-derived peptide antigen into T cells, which are administered to patientsby infusion after expansion; and CAR-T therapy, in which genes coding for chimeric antigen receptors (CAR) that combine intracellular signaling
domains of T cell receptors and an antigen-binding site that recognizes tumor cell membrane antigens are introduced to T cells, and administered topatients by infusion after expansion. Clinical trials using CD19 expressed in B cells as the target for CAR, in which T cells engineered with
CD19-targeting CAR were administered to patients with B-cell malignancies, demonstrated a high level of clinical efficacy.

On May 14, 2019, the company announced earnings results for Q1 FY12/19; see the results section for details.

On April 10, 2019, the company announced the enrollment of the first patient for the clinical trial of its rapid infusion (RI) liquid
formulation of Treakisym®.
SymBio enrolled its first patient for a clinical trial mainly intended to confirm the safety of Treakisym®’s RI formulation, which
reduces infusion duration to 10 minutes. The clinical trial will have a total of 36 patients, and the trial results will be submitted forregulatory approval to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in addition to all other previously
approved indications.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2019.07.01

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In September 2017, the company entered into an exclusive license agreement with Eagle Pharmaceuticals, Inc. (based in the US)
for rights to develop and market ready-to-dilute (RTD) and rapid infusion (RI) liquid formulation products of Treakisym® in Japan.
Obtaining the exclusive rights for these patent-protected products enables the company to extend the product lifecycle ofTreakisym® until 2031. Like the RTD formulation (currently in preparation for application), the RI formulation eliminates the needto dissolve the formulation. Moreover, the RI formulation reduces the infusion duration from 60 minutes under the current
freeze-dried (FD) formulation to 10 minutes, providing added-value by reducing the burden on both healthcare providers andpatients.
The company aims to apply for regulatory approval of the RTD formulation in Q3 FY12/19 and release the product in 1Q FY12/21.
It plans to apply for approval of the RI formulation after completing the clinical trial and release it in 1H FY12/22.

On April 8, 2019, the company announced the completion of patient enrollment for a phase III clinical trial of Treakisym®
targeting relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The company completed patient enrollment for the ongoing phase III clinical trial of Treakisym® for relapsed or refractory diffuse
large B-cell lymphoma (DLBCL). Once the follow-up period of the enrolled cases is over, it will conduct a statistical analysis toconfirm the drug’s efficacy and safety. It aims to apply for the additional indication of relapsed or refractory DLBCL in Q2 FY12/20.

For previous releases and developments, please refer to the News and topics section.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2019.07.01

Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp

Trends and outlook
Quarterly trends and results
FY12/18

Cumulative

FY12/19(JPYmn)

Q1

Q2

Q3

Q4

Q1

Sales

888

1,928

3,032

3,836

1,611

YoY

2.1%

8.0%

25.5%

11.4%

81.4%

Gross profit

250

573

924

1,173

609

YoY

4.4%

12.4%

37.0%

13.7%

144.0%

GPM

28.1%

29.7%

30.5%

30.6%

37.8%

964

1,898

2,832

3,829

1,205

YoY

26.1%

8.7%

-32.3%-23.1%

25.0%

SG&A ratio

108.5%

98.4%

93.4%

99.8%

74.8%

-715

-1,325-1,908-2,656

-596

YoY

-

-

-

-

-

OPM

-

-

-

-

-

-749

-1,378-1,938-2,749

-616

YoY

-

-

-

-

-

RPM

-

-

-

-

-

-760

-1,389-1,941-2,753

-617

YoY

-

-

-

-

-

Net margin

-

-

-

-

-

SG&A expenses

Operating profit

Recurring profit

Net income

FY12/18

Quarterly
Q1

Q2

Q3

Q4

Q1

1,040
13.5%
324

1,104
75.1%
351

803
-21.8%
249

1,611
81.4%
609

YoY

4.4%

19.5%

113.0%-30.3%

144.0%

GPM

28.1%

31.1%

31.8%

31.0%

37.8%

964

934

934

997

1,205

YoY

26.1%

-4.9%

-61.7%

25.4%

25.0%

SG&A ratio

108.5%

89.8%

84.6%

124.2%

74.8%

-715
-

-610
-

-583
-

-749
-

-596
-

-749
-

-629
-

-560
-

-811
-

-616
-

-760
-

-629
-

-552
-

-812
-

-617
-

Sales
YoY

Gross profit

SG&A expenses

Operating profit
YoY
OPM

Recurring profit
YoY
RPM

Net income
YoY

Net margin

FY12/19
Q3

Q4% of FYFY Est.

38.4%

4,201
9.5%

-

-2,981---3,044---3,056-

FY12/19

888
2.1%
250

(JPYmn)

Q2

Q2

Q3

Q4

Q3

Q4

Q3

Q4

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

Breakdown of SG&A expenses
FY12/18

Cumulative

FY12/19(JPYmn)

Q1

Q2

Q3

Q4

Q1

SG&A expenses

964

1,898

2,832

3,829

1,205

YoY

25.0%

26.1%

8.7%

-32.3%-23.1%

R&D expenses

416

839

1,293

1,833

472

YoY

5.3%

-0.1%

-52.3%-39.3%

13.4%

548

1,059

1,539

1,996

733

48.5%

16.9%

4.6%

1.8%

33.8%

SG&A expenses excl. R&D
YoY

FY12/18

Quarterly

FY12/19(JPYmn)

Q1

Q2

Q3

Q4

Q1

SG&A expenses

964

934

934

997

1,205

YoY

25.0%

26.1%

-4.9%

-61.7%

25.4%

R&D expenses

416

423

454

540

472

YoY

5.3%

-4.9%

-75.7%

76.0%

13.4%

SG&A expenses excl. R&D
YoY

Q2

548

511

479

458

733

48.5%

-4.8%

-15.2%

-6.4%

33.8%

Q2

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2019.07.01

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Q1 FY12/19 results▷

Sales:▷

Recurring loss:

JPY616mn (loss of JPY749mn in Q1 FY12/18)

Net loss:

JPY617mn (loss of JPY760mn in Q1 FY12/18)▷▷

JPY1.6bn (+81.4% YoY)

Operating loss: JPY596mn (loss of JPY715mn in Q1 FY12/18)

Sales rose on domestic sales of Treakisym®, whose sales based on the NHI drug price were up 11.0% YoY.
Thanks to higher sales, gross profit grew 144.0% YoY to JPY609mn and GPM was up 9.7pp YoY to 37.8%.
SG&A expenses rose 25.0% YoY to JPY1.2bn; of which, R&D expenses increased 13.4% YoY to JPY472mn, including expenses for
conducting clinical trials of intravenous and oral formulations of Treakisym® and rigosertib. Excluding the climb in R&D expenses,
SG&A expenses increased by 33.8% YoY to JPY733mn owing to hiring of additional Treakisym® managers in preparation forbuilding an in-house sales structure.
As a result, operating loss, recurring loss, and net loss shrank YoY.
Major progress in Q1 FY12/19 was as follows:▷ In April 2019, the first patient was enrolled in the clinical trial of the liquid formulation of Treakisym® (rapid infusion [RI]
formulation), whose primary goal was to confirm safety of the drug.

▷ In April 2019, patient enrollment was completed for the phase III clinical trial of anticancer drug Treakisym® as a treatment for
relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Once the follow-up period is over, the company plans tostatistically analyze the efficacy and safety of the drug with an aim of filing for approval for the additional indication of relapsed or
refractory DLBCL in Q2 FY12/20.

▷ In March 2019, the company obtained approval to partially revise the marketing approval of anticancer drug Treakisym® as apretreatment agent in antigen-specific T cell infusion therapy. This enabled the use of Treakisym® as a pretreatment agent for the
chimeric antigen receptor T-cell (CAR-T) therapy Kymriah® intravenous infusion.

Domestic
Preparations for in-house sales organization begin
The business alliance agreement between SymBio and Eisai Co., Ltd. under which Eisai acts as a sales agent expires in December
2020. SymBio started to build an in-house sales organization for Treakisym® in the domestic market in October 2018. Key
management priority is to move into the black in FY12/21 and ongoing profit growth thereafter. The company is therefore laying
the groundwork for a shift to an internal sales organization to drive future business development.
Twenty Treakisym® managers are to form the core of the marketing team in the internal sales organization. The company
conducted the necessary recruitment activities as planned by the end of Q1. It also started readying the infrastructure such as
logistics, distribution, and information systems.

Treakisym® (SyB L-0501[lyophilized injection]/SyB L-1701 [RTD]/SyB L-1702 [RI]/SyB C-0501 [oral]; anticancer agent; generic name:bendamustine hydrochloride)The company markets the anticancer agent Treakisym® in Japan through its business partner, Eisai Co., Ltd. (TSE1: 4523) for theindications of untreated low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma (marketing approval obtained in
December 2016), refractory or relapsed low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma (October 2010), andchronic lymphocytic leukemia (August 2016).

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As a result of additional indications, Treakisym® is steadily increasing its market share in the area of first-line treatment in medical
settings by replacing R-CHOP, the conventional standard treatment. The combination therapy of Treakisym® and rituximab (BRtherapy) was newly included in the Practical Guidelines for Hematological Malignancies 2018 edited and published by JapaneseSociety of Hematology as a standard treatment option, which applies to all of the approved indications. This has seen Treakisym®
establish its position as a standard treatment for lymphatic cancer. Sales of Treakisym® based on the National Health Insurance(NHI) drug price grew steadily by 11.0% YoY.
In addition to the above three approved indications, the company is conducting Phase III clinical trials for the fourth indication of
relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) and these are progressing well with an aim to obtain approval. In
response to strong medical needs, the company began phase III clinical trials in August 2017, and with the enrollment of the first
patient in January 2018, is working on enrolling patients. The company has made steady progress in enrollments following thefirst patient in January 2018, completing enrollments in April 2019. Going forward, after completing the follow-up period forenrolled cases, it will prepare to file an application for regulatory approval.
In addition to efforts for new indications, in September 2017, the company concluded an exclusive licensing agreement with
Eagle Pharmaceuticals (based in New Jersey, US) to develop, market, and sell liquid formulations of Treakisym® (RTD and RI
formulations) in Japan for Treakisym®’s product life cycle management. The RTD and RI products offer significant value added(reduced burden) to patients and healthcare professionals, and liquid formulation patent protection extends Treakisym®’s
product life until 2031. The company has already consulted with PMDA and is preparing to file for approval of the RTD
formulation. SymBio launched clinical trials for the RI formulation in November 2018 primarily to confirm safety, and finishedenrolling the first patient in April 2019.
In July 2018, SymBio obtained approval for the partial revision to the marketing authorization of Treakisym®. As a result,
Treakisym® can now be used in combination with not only rituximab but new anti-CD20 antibodies as well. One of these isobinutuzumab (launched in August 2018) for the treatment of CD 20-positive follicular lymphoma (FL), the most common
histological type of low-grade NHL, enabling the company to provide patients with a new treatment therapy. In March 2019, thecompany obtained approval for the partial revision to the marketing authorization allowing the use of Treakisym® as apretreatment agent in tumor-specific T cell infusion therapy. The first chimeric antigen receptor T-cell (CAR-T) therapy CTL019(Kymriah® intravenous infusion) was approved for use in Japan in the same month. Once this goes on sale Treakisym® will be able
to be used as a pretreatment agent.
To reinforce the position of Treakisym® at the core of its business to strengthen its business foundation, SymBio is developing anoral formulation of the drug in addition to the injection currently under development or on sale. The company commenced aphase I clinical trial for progressive solid tumors in January 2018, with the aim of examining the recommended dosage andschedule as well as tolerability and safety of the oral formulation of Treakisym®, and narrowing down the types of potential target
tumors. With the enrollment of the first patient in May 2018, the company is currently working on enrolling more patients for thetrial. To evaluate the effect of oral administration of Treakisym® on the immune system, the company concluded a joint research
agreement with Keio University in May 2018 and began a preclinical study to verify the efficacy of the oral form of Treakisym® intreating systemic lupus erythematosus (SLE), a form of autoimmune disease.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, is currently conducting a global Phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015 (43 patients enrolled as of May 2019). The global Phase III trial addresses higher-risk
myelodysplastic syndromes (higher-risk MDS), which do not respond to the current standard treatment with hypomethylating
agents, which relapse after treatment under the current standard of care, or which are intolerant to hypomethylating agents, andis under way at clinical trial sites in more than 20 countries worldwide. As of March 2019, the company had reached 75% of its
target of enrolling 360 patients worldwide. Based on these trial results, the company plans to apply for approval in Japan at thesame time as in the US and Europe.

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Regarding the oral formulation of rigosertib, Onconova has completed Phase I/II clinical trials for the drug used in combination
with azacytidine as first-line treatment for higher-risk MDS and Phase II clinical trials for transfusion-dependent lower-risk MDS in
the US. To verify the tolerability and safety of the oral formulation of rigosertib among Japanese patients, SymBio began Phase I
clinical trials in Japan in June 2017 and is making steady progress with the clinical trial after enrolling the first patients in October
2017. After completing the Phase I trials, the company plans to start Phase I clinical trials for rigosertib used in combination withazacytidine, participate in global Phase III clinical trials of the drug used in combination with azacytidine as first-line treatment forhigher-risk MDS currently planned by Onconova, and apply for approval of the oral formulation of the drug in Japan at the sametime as in the US and Europe. In December 2018, Onconova submitted a Special Protocol Assessment (SPA) request to the US
Food and Drug Administration (FDA) to speed up the approval review for the global trials, and expects an outcome of the
discussions in 1H 2019. In regards to development of rigosertib for transfusion-dependent lower-risk MDS, the company isconsidering participating from Japan while monitoring Onconova’s development progress.

SyB P-1501, a post-operative patient-controlled analgesia
Regarding SyB P-1501 licensed by the Medicines Company (through its wholly owned subsidiary Incline Therapeutics, Inc.) in
October 2015, SymBio found a fact that raised concerns about the continuity of its business, and in the interests of patient
welfare, it suspended further patient enrollment in April 2017. The license agreement was terminated in November 2017, andthe development of the drug was terminated in February 2018.
The Company initiated an arbitration against The Medicines Company in October 2017, under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s
repudiation of the license agreement. Arbitration proceedings against The Medicines Company are still ongoing.

New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. The company is considering licensing rights for several drug candidates. Further, in May 2016, the company
established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base for overseas business development.
The company looks to leverage this subsidiary to actively acquire rights over new drug development candidates globally, andengage in development and commercialization in major markets including the US, Japan, and Europe to transition to a global
specialty pharmaceutical company.

Overseas
The company marketed SyB L-0501 in South Korea, Taiwan, and Singapore, and product sales were in line with the company'splans.

For details on previous quarterly and annual results, see the Historical performance section.

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Full-year company forecasts
FY12/18(JPYmn)Sales
Gross profit

FY12/19

1H Act.
1,928
573

2H Act.
1,907
600

FY Act.
3,836
1,173

FY Est.
4,465
1,466
32.8%

GPM

29.7%

31.4%

30.6%

SG&A expenses

1,898

1,931

3,829

5,053

SG&A ratio

98.4%

101.3%

99.8%

113.2%

R&D expenses
Excluding R&D expenses
Operating profit

1,059
839
-1,325774
1,157-1,331

1,833
1,996-2,656

2,508
2,545-3,587

Recurring profit-1,378-1,371-2,749-3,612

Net income-1,389-1,364-2,753-3,616

-

-

-

-

OPM
RPM

-

Net margin

-

-

-

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

Earnings outlook▷ Sales:

JPY4.5bn (+16.4% YoY)

▷ Operating loss:

JPY3.6bn (loss of JPY2.7bn in FY12/18)▷ Net loss:

JPY3.6bn (loss of JPY2.8bn in FY12/18)▷ Recurring loss:

JPY3.6bn (loss of JPY2.7bn in FY12/18)

SymBio expects sales growth primarily on rising domestic product sales for Treakisym®. The company targets Treakisym® sales on
an NHI drug reimbursement price basis of JPY10.1bn (+18.8% YoY). In FY12/18, too, SymBio had anticipated full-year sales of
JPY10.1bn, but sales on a drug price basis only came to JPY8.5bn, largely because Treakisym® distributor Eisai adopted a greater
focus on sales of its own products. Against this backdrop, SymBio finished FY12/18 with ten highly specialized product managers
for Treakisym®, up from five as of December 2017. In FY12/19 it plans to take the number of Treakisym® managers up to 20.
SymBio aims to further promote uptake of Treakisym® as first-line treatment of low-grade non-Hodgkin’s lymphoma (NHL), with aview to raising market share to 70% as of end-FY12/20 and 75% as of end-FY12/21. Shared Research expects the following factors
to contribute to market share expansion, alongside growth in Treakisym® manager numbers.

▷ According to the company, R-CHOP therapy—a combination of rituximab with CHOP chemotherapy drugs (cyclophosphamide,
doxorubicin, vincristine, and prednisolone)—was standard first-line treatment for low-grade NHL and mantle cell lymphoma(MCL) in Japan prior to December 2016. In July 2018, Treakisym® was newly included as a standard treatment option for
low-grade NHL and MCL in the Guidelines for Tumors of Hematopoietic and Lymphoid Tissues 2018 issued by the Japan Societyof Hematology.

▷ Phase III clinical trials conducted overseas have demonstrated that rituximab in combination with bendamustine (BR therapy) was
safer and more efficacious than standard R-CHOP therapy for previously untreated low-grade NHL. These findings were

presented at the American Society of Hematology Annual Meeting in December 2012 (see the Business section).

SymBio forecasts SG&A expenses of JPY5.1bn (+32.0% YoY).

▷ The company expects R&D expenses of JPY2.5bn (+36.8% YoY). It plans to continue developing Treakisym® for relapsed or

refractory diffuse large B-cell lymphoma (r/r DLBCL) and liquid formulations of Treakisym® (RTD and RI formulations), Treakisym®
(oral), and oral and intravenous rigosertib products.

▷ The company forecasts SG&A expenses excluding R&D at JPY2.5bn (+27.5% YoY). With the increase in product managers it

expects a rise in personnel expenses and higher expenses due to more activities. As indicated earlier, SymBio plans to increase

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the number of product managers from 10 to 20, with a view to gaining market share for Treakisym® and building an in-housesales structure in FY12/20.

The main pipeline development plans are as follows.

Treakisym®
▷ For r/r DLBCL, in FY12/19 the company plans to continue enrolling patients for phase III clinical trials already underway, with theaim of filing for approval in Q2 FY12/20▷ For Treakisym® in-licensed from Eagle Pharmaceuticals, SymBio is preparing to file for approval of the RTD formulation (in Q3

FY12/19) and progressing with clinical trials of the RI formulation mainly to confirm safety (under way since November 2018,with 36 patients enrolled)▷ The company has already launched phase I clinical trials for Treakisym® (oral)
Oral and intravenous rigosertib products▷ SymBio is continuing to develop intravenous rigosertib formulation, and is enrolling patients in Japan as part of global phase III
clinical trials▷ For oral rigosertib, following confirmation of safety in domestic phase I clinical trials for single drug applications which is currently

enrolling patients, SymBio is preparing for early participation in global phase III trials of rigosertib azacitidine combination therapy

that Onconova Therapeutics is planning

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Long-term outlook
Medium-term plan (FY12/19–FY12/22)
When it released its FY12/18 results, SymBio also announced a four-year medium-term plan for FY12/19 through FY12/22. The
main goals of the medium-term plan are to build an in-house sales structure, grow sales of Treakisym® from already approved
indications, expand indications for Treakisym®, and extend the product lifecycle for Treakisym®.

▷ Build in-house sales structure: The business alliance agreement with Eisai expires in December 2020, and the company has been
making preparations to sell Treakisym® in-house from the start of 2021, after the agreement expires. To prepare for the start of

in-house sales and the later launch of rigosertib IV formulation, SymBio plans to increase the number of medical representatives
as necessary, build a sales and marketing organization specializing in the area of blood cancers, and set up a sophisticated anddedicated training system by 1H FY12/20.

▷ Grow sales of Treakisym® from already approved indications: The company seeks to increase market share to 70% by the end of
FY12/20 by further promoting penetration in first-line treatment of low-grade non- Hodgkin’s lymphoma.

▷ Expand indications for Treakisym®: SymBio aims to complete the phase III clinical trial for the indication of relapsed or refractory
diffuse large B-cell lymphoma, with the aim of filing a new drug application in Q2 FY12/20 and launching in Q3 FY12/21.

▷ Extend the product lifecycle for Treakisym®: The company looks to launch the RTD formulation in Q1 FY12/21 and the RI

formulation in 1H FY12/22, proceeding 90% of the way toward a switch from the current lyophilized powder formulation to aliquid formulation by the end of 2021 and 100% by the end of 2022. It aims to achieve an annual average switch rate of 60% in
2021.

Earnings objectives laid out in medium-term plan
Under the action plan outlined above, SymBio seeks to achieve profitability in FY12/21 and realize sustainable profit growth
thereafter, with the following as earnings objectives. The company expects higher sales from increased market penetration ofTreakisym® for approved indications and anticipated approval of additional indication of Treakisym® for relapsed or refractory
diffuse large B-cell lymphoma (DLBCL). The company projects a significant increase in profit on higher sales as well as on higher
GPM attributed to profit generated from the sale of Treakisym® following the shift to in-house sales of the product. The company
has factored the cost of establishing and operating its own sales structure into its forecast, but Shared Research thinks theincrease in GPM driven by the shift to in-house sales structure will easily offset the increase in costs. The company’s own sales
structure is specialized to the area of hematologic disorders, and will also handle the sale of rigosertib in addition to Treakisym®.
Medium-term plan

FY12/18

FY12/19

FY12/20

FY12/21

FY12/21(JPYmn)

Act.

Est.

MTP

MTP

MTP

Sales

3,810

4,465

3,282

9,132

11,282–11,809

Operating profit (losses)-2,656-3,587-5,1801,225

2,084–2,464

Recurring profit (losses)-2,749-3,612-5,2241,181

2,040–2,420

Net income (losses)-2,753-3,616-5,2281,005

1,736–2,060

Source: Shared Research based on company data.

Sales targets in medium-term plan (FY12/19–FY12/22)
SymBio expects product sales of Treakisym® to account for the bulk of sales. The company looks to grow Treakisym® sales byachieving greater market penetration in first-line treatment of low-grade non-Hodgkin’s lymphoma, transitioning to an in-housesales structure, and expanding indications to include relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Greater market penetration in first-line treatment of low-grade non- Hodgkin’s lymphoma
In December 2016, Treakisym® was approved in Japan for the additional indication of first-line treatment of low-grade
non-Hodgkin’s lymphoma (NHL), and in Q3 FY12/18 Treakisym® accounted for 56% of drugs used for the first-line treatment of
low-grade NHL. On an NHI drug reimbursement price basis, Treakisym® sales have increased from JPY4.8bn in FY12/16 to

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JPY8.5bn in FY12/18. According to SymBio, the indication of first-line treatment of low-grade NHL has accounted for most of that
JPY3.7bn increase.
SymBio aims to further promote uptake of Treakisym® as first-line treatment of low-grade non-Hodgkin’s lymphoma, with a viewto raising market share to 70% as of end-FY12/20. The following factors are seen contributing to market share expansion.

▷ R-CHOP therapy—a combination of rituximab with CHOP chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, andprednisolone)—was standard first-line treatment for low-grade NHL and mantle cell lymphoma (MCL) in Japan prior to December

2016. In July 2018, Treakisym® was newly included as a standard treatment option for low-grade NHL and MCL in the Guidelines
for Tumors of Hematopoietic and Lymphoid Tissues 2018 issued by the Japan Society of Hematology.

▷ Phase III clinical trials conducted overseas have demonstrated that rituximab in combination with bendamustine (BR therapy) was

safer and more efficacious than standard R-CHOP therapy for previously untreated low-grade NHL. These findings were
presented at the American Society of Hematology Annual Meeting in December 2012 (see the Business section).

▷ SymBio plans to increase the number of Treakisym® product managers from 10 in FY12/18 to 20 in FY12/19, and 60 in FY12/20, in
doing so contributing to further market penetration for Treakisym®.

Transition to in-house sales structure
SymBio has entrusted Treakisym® sales to Eisai until end-FY12/20. During this period product shipments to Eisai are being booked
as sales. However, Eisai’s exclusive sales period expires in FY12/20, and from FY12/21 SymBio will switch to selling Treakisym®
in-house. Up to and including FY12/20, Shared Research assumes that the price of shipments to Eisai will be around 50% of the
NHI drug price. With the transition to an in-house sales structure in FY12/21, though, Shared Research thinks the price that
SymBio charges to wholesalers will rise to roughly 90% of the NHI drug price. Thus even if volume remains largely unchanged,
the company expects higher selling prices to drive sharp YoY sales growth in FY12/21.
As noted, the company plans to shift to its own sales organization and switch product shipments from Eisai to pharmaceuticalwholesalers in FY12/21. In the run-up to this it will be necessary to reduce Eisai’s inventories toward the end of FY12/20. Sales ofTreakisym® based on an NHI drug price should remain solid, reflecting actual market demand, but SymBio plans to stop shipping
to Eisai with a target date of end-1H FY12/20. It expects FY12/20 sales to decline by a commensurate amount.

Additional indication of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL)The company plans to seek approval of Treakisym® for the additional indication of r/r DLBCL in Q2 FY12/21. It aims to commence
sales of Treakisym® for this indication in Q3 FY12/21, with a view to growing Treakisym® product sales in FY12/21 onward. The
company says that its sales target range for FY12/22 is based on an estimated market penetration rate due to the additional
indication.
As reference for the anticipated impact of adding the indication of r/r DLBCL, the company estimates that the number of patients
being treated for relapsed or refractory low-grade NHL and MCL in Japan is 9,336 and the number of patients with untreatedlow-grade NHL and MCL is 6,967, for a total of 16,303. For these indications, SymBio targets FY12/19 sales of JPY10.1bn on an
NHI drug price basis. By comparison, the company estimates that the number of Japanese patients with r/r DLBCL is 18,672.

Gross profit under medium-term plan
Based on historical performance, Shared Research estimates a gross profit margin of about 30% for Treakisym® shipments to Eisai.
As outlined earlier, from FY12/21 SymBio will conduct sales of Treakisym® in-house rather than entrusting them to Eisai. With this,the company will be shipping Treakisym® to pharmaceutical wholesalers instead of to Eisai. The gross profit earned thus far willremain, but will be augmented by the gross profit that hitherto had gone Eisai’s way (difference between the procurement pricepaid by Eisai and the price on shipments from Eisai to wholesalers). Shared Research believes that the transition to in-house sales
will lift SymBio’s gross profit margin to 60–70%.

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Shared Research also sees potential for SymBio to further alter the gross profit margin by procuring Treakisym® from a different
source. The company procures Treakisym® in lyophilized powder form from Astellas Deutschland GmbH, but procures the RTD
and RI formulations from Eagle Pharmaceuticals. SymBio looks to launch the RTD formulation in Q1 FY12/21 and the RI
formulation in 1H FY12/22, proceeding 90% of the way toward a switch from the current lyophilized powder formulation to aliquid formulation by the end of 2021 and 100% by the end of 2022.

SG&A expenses under medium-term plan
The company has broken down SG&A expenses into primarily R&D spending and other SG&A expenses.

R&D expenses
In its medium-term plan, the company has calculated R&D expenses based on the latest development plans for its existing
pipeline comprising Treakisym® and rigosertib IV and oral formulations. While paying due regard to the impact on FY12/21
earnings, SymBio also will continue to search for, evaluate, and consider in-licensing rights to other promising drug candidates, inorder to ensure long-term growth opportunities.

▷ The company forecasts R&D expenses of JPY2.5bn (+36.9% YoY) in FY12/19. It plans to continue developing Treakisym® forrelapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), as well as liquid formulations of Treakisym® (RTD and RI

formulations), Treakisym® (oral), and oral and intravenous rigosertib products.

▷ In FY12/20 the company looks for R&D expenses to increase YoY, as it expects to book clinical trial expenses for the RI formulationof Treakisym® as well as oral rigosertib. Also, SymBio aims to win approval for the RTD formulation of Treakisym® in Q4 FY12/20,
at which point it expects to make a milestone payment.

▷ From FY12/21, the company expects R&D expenditure to decrease in comparison with FY12/20. Clinical trial expenses for the RI

formulation of Treakisym® as well as oral rigosertib should decrease. For FY12/22, SymBio is targeting an operating profit range of
JPY2.1–2.5bn; this is because its sales target also is a range, and there is a possibility that in-licensing drug candidates will give rise
to one-time payments and higher R&D expenses.

Other SG&A expenses
Other SG&A expenses comprise primarily Treakisym® marketing, production and distribution, business development, andmanagement related expenses. SymBio is factoring in expenses associated with building and operating its own sales organizationfrom FY12/19 onward ahead of the expiration of Eisai’s exclusive sales period at end-FY12/20 and move to sell Treakisym®
in-house from FY12/21. It forecasts an increase primarily in personnel expenses due to a higher medical representative headcountand higher expenses due to more activities.

▷ For FY12/19, the company forecasts SG&A expenses excluding R&D of JPY2.6bn (+27.5% YoY). It forecasts an increaseprimarily in personnel expenses due to a higher medical representative headcount and higher expenses due to more activities. In

FY12/18 the company increased the number of medical representatives to 10, and it plans a further rise to 20 in FY12/19.

▷ In FY12/20, Shared Research expects SG&A expenses excluding R&D to increase in comparison with FY12/19, largely because

the company plans to increase the number of medical representatives to 60, from 20 in FY12/19. However, for the 40 medical

representatives that it plans to add in FY12/20, SymBio may make use of copromotion partners (collaborating withpharmaceutical company sales staff), and contract-based medical representatives specializing in oncology. The company also
intends to allocate the bare minimum of necessary personnel in other parts of the organization.

Funding plans
In April 2018, the company decided to issue its 45th through 47th stock acquisition rights to secure funds needed to operate
until it moves into the black in FY12/21. The proceeds were basically sufficient for its already in-licensed drug development
pipeline, creation of an in-house sales structure, and new in-licensing or M&A activity necessary to take advantage of long-term
growth opportunities.

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Business
Business description
SymBio licenses drugs for development and sale in Japan and Asia Pacific
President and CEO, Fuminori Yoshida, established SymBio in March 2005 to address underserved medical needs in Japan and theAsia Pacific region, with main focus on oncologic, hematologic and autoimmune diseases. The company aspires to be a leading
specialty pharmaceutical company in the Asia Pacific region. Its strategic approach to drug development negates the need forcostly and time-consuming investment in earlier-stage R&D activities with an in-house search and evaluation team to identify andassess only quality drug candidates having proof-of-concept established in human subjects.

Strategy Overview (details to follow)◤ Proof-of-concept: The company reduces product development risk by focusing on drug candidates undergoing clinicaldevelopment with preclinical/clinical data establishing safety and efficacy in human subjects.

◤ Screening: The company uses an in-house search and evaluation team to screen and evaluate drug candidates having a highunmet medical in Japan and other Asia Pacific markets with the potential to secure marketing approval in a shorter clinicaldevelopment period. A select number of drug candidates will then undergo rigorous review by the company’s Scientific
Advisory Board (SAB).

◤ Fabless: The company outsources preclinical/clinical studies and manufacturing to reduce fixed costs.

◤ New areas: The company targets drugs with the potential to receive orphan drug designation and thus, secure a longer

marketing exclusivity period due to high unmet medical needs—including oncology, hematology, and pain

management—and smaller patient populations. Larger pharmaceutical companies may be reluctant to develop drugs in nichemarkets due to limited sales potential—SymBio sees an opportunity to avoid intense competition in the marketplace byfocusing on the development of orphan or ‘orphan-like’ drugs.
◤ Global expansion strategy: The company identifies and capitalizes on opportunities to grow sales by acquiring the right todevelop drug candidates in Japan and other international markets.

Proof-of-concept: Per company materials, “confirming the efficacy and safety of a new drug candidate in human subjects through clinical trials…”

The company have in-licensed new drug candidates after rigorously evaluating them.
According to the company, the development of a drug—from preclinical studies to approval—usually takes 10 to 17 years. A
newly developed chemical compound has a 1/100,000 chance of securing regulatory approval. By contrast, the company’s first
product, Treakisym®, received approval for domestic production only five years after signature of the License Agreement. The
company achieved sales of JPY4.2bn in Japan in the third year after launch (FY12/13), equivalent to a market share of over 50%.
An example of the company’s ability to identify and pursue quality in-licensing opportunities with proof-of-concept established isthe license agreement signed for the development and commercialization right to rigosertib—currently in phase I clinical trials inJapan. In July 2011, once phase II clinical trials in the US established the drug’s proof-of-concept, SymBio secured an exclusive
right to all indications for rigosertib in Japan and South Korea from Onconova within seven months from the initial meeting
between the two companies. The following year, Baxter International Inc. entered into an agreement with Onconova for thecommercialization rights to rigosertib in Europe with a USD50mn upfront payment and USD337.5mn in pre-commercial
milestones tied to MDS and pancreatic cancer indications (in addition to an existing equity investment with Onconova of
USD55mn), a market that is approximately twice the size of Japan.

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Products under development: Treakisym® (FD), Treakisym® (RTD and RI), and rigosertib (IV and oral)
Treakisym® (FD)For patients that have developed resistance to other drugs, Treakisym® is safer and more efficacious than existing treatments. As
outlined below, the company has gained approval in Japan for the indications of refractory or relapsed low-grade non-Hodgkin’s
lymphoma and mantle cell lymphoma, chronic lymphocytic leukemia, and first-line treatment of low-grade non-Hodgkin’s
lymphoma and mantle cell lymphoma.

▷ Refractory or relapsed low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma: After designation as an orphan drug
(drug for the treatment of rare diseases), Treakisym® won marketing approval for this indication in October 2010.

▷ Chronic lymphocytic leukemia: SymBio received approval for this to be added as indication for Treakisym® in August 2016.

▷ First-line treatment of low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma: The company gained approval for this tobe added as indication for Treakisym® in December 2016.

As of February 2019, phase III clinical trials for an additional indication of relapsed or refractory diffuse large B-cell lymphoma(DLBCL) were under way.

Treakisym® (RTD and RI)
In September 2017, Eagle Pharmaceuticals and SymBio concluded a license agreement that licenses to SymBio rights to develop,
market, and sell Eagle’s bendamustine hydrochloride ready-to-dilute (RTD) and rapid infusion (RI) products in Japan. Securing
products to replace existing freeze-dried (FD) product (whose exclusive sales rights in Japan expire in 2H 2020) had been apriority for the company. SymBio looks to gain approval for the RTD formulation in Q4 FY12/20 and win approval for and launch
the RI formulation in FY12/22. With this, it aims to promote a switch in clinical settings from the current lyophilized powder
formulation to RTD and RI formulations that lighten the workload for medical professionals, at the same time curtailing uptake ofTreakisym® generics (filing for approval of generics will be possible from 2H 2020, although Shared Research believes that even if
generics launch it will not be until around 2022). Because it has the exclusive rights to sell the RTD and RI formulations in Japan,
SymBio will be able to extend the Treakisym®’s product lifecycle until 2031.

Rigosertib
Rigosertib is a treatment for myelodysplastic syndromes (MDS). According to the company, rigosertib may be used alone or—due
to its safety—in combination with other anticancer drugs. The drug is being developed in both intravenous (IV) and oral forms.
In February 2014, Onconova completed phase III clinical trials for the IV form of rigosertib in patients with relapsed or refractory
MDS in Europe, and its efficacy was proven in subgroup analysis. SymBio also completed patient registration for phase I domestic
clinical trials in January 2015. From August 2015, Onconova has been conducting global phase III clinical trials for patients withhigher-risk MDS who had failed or relapsed after prior therapy with hypomethylating agents (HMAs) in more than 20 countries.
Within Japan, the company has been conducting joint global phase III clinical trials in cooperation with Onconova. On the basis ofresults of an interim analysis performed in January 2018, Onconova decided to continue with the trial with a larger patient
population based on pre-planned statistical criteria. Based on these results, the company plans to apply for approval in Japan at
the same time as in the US and Europe.
For the oral form of the drug, SymBio is conducting a phase I clinical trial for higher-risk MDS in Japan to evaluate safety. The
company plans to begin a clinical trial in combination with azacitidine after confirming safety in the phase I clinical trials, and thenit may participate in global phase III trials of rigosertib azacitidine combination therapy targeting first-line treatment of higher-risk
MDS that Onconova plans to launch.

Revenue: milestone payments and Treakisym®
Revenue comes from milestone payments and product sales. Operating losses have persisted since the company’s foundation
with the exception of FY12/08 when the company booked an operating profit due to a one-time contract payment from Eisai foran exclusive domestic right to sell Treakisym® (see Historical performance).

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For FY12/19, the company expects a JPY3.6bn operating loss, JPY3.6bn recurring loss, and net loss of JPY3.6bn. Over the course of
the medium-term plan (FY12/19–FY12/22), the company expects to post an operating loss of JPY5.2bn in FY12/20. In FY12/21,
the company forecasts an operating profit of JPY1.2bn. It is targeting an operating profit of JPY2.1–2.5bn in FY12/22, and plans toremain in the black thereafter.

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Business strategy
Unlike conventional pharmaceutical companies, SymBio does not conduct basic research or develop its own drug candidates inlabs or clinics. Rather, it in-licenses drug candidates from pharmaceutical and biotech companies based in the US or EU.
The company focuses on developing drugs that have strong safety and efficacy data in clinical trials, providing an opportunity todevelop new drugs more likely to succeed and secure regulatory approval with the use of bridging data whenever possible toshorten development timelines. Because the company does not conduct basic research, the company can file an NDA and start
selling a drug within five to six years of securing the development and commercialization right. The company increases the
chance that drug candidates it in-licenses will be approved in the future through an effective in-house screening process andrigorous evaluation by the company’s Scientific Advisory Board.
The overall aim is to reduce development risk, streamline expenses, and expand revenue opportunities. This hinges on the five
strategies, namely post proof-of-concept, screening, fabless, niche market, and global expansion.

SymBio targets compounds with an established proof-of-concept
The pharmaceutical business requires substantial financial commitment in terms of upfront investment, not to mention thenumber of years of development required in order to realize a return on the investment and the high risk of failure in clinicalstudies from phase I through III. According to the company, the probability of a chemical compound having a signal withpharmacological activity in a particular disease being approved as a drug is 1/20,000 to 1/25,000, and only 15–20% of drugs thatmanage to enter the marketplace achieve profitability for the sponsor.
Given the high rate of attrition of drug candidates in clinical development, SymBio reduces development risk by only targeting
quality drug candidates undergoing clinical development with proof-of-concept (confirming the efficacy and safety of a new
drug candidate through clinical trials) established in human subjects and/or market sales. NDA filings that use clinical data
generated overseas can expedite product development in Japan and other parts of Asia, slashing development costs andimproving the overall success rate.
Post-proof-of-concept strategy

Source: Shared Research based on company data.

Screening: independent search network plus evaluation experience
The company identifies quality chemical compounds owned by pharmaceutical and biotech companies in the US or EU using aproprietary “search engine” and rigorous evaluation process. These candidates are first screened in-house by the search andevaluation team, whose members have extensive product development experience working at various pharmaceutical andbiotech companies.

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Onsite due diligence
After a select team visits the potential licensor to conduct due diligence, a decision is made regarding whether to pursue thein-licensing opportunity based on the results of onsite due diligence and input from the company’s SAB members.

Only a few new drug candidates have met the company’s stringent criteria since its foundation
The company had screened several hundred new drug candidates since its foundation, of which it has in-licensed only a few thathave met its stringent criteria. The first was Treakisym®, which Eisai Co., Ltd. (TSE1: 4523) currently sells in Japan (as of February2019). Clinical trials for additional Treakisym® indications are underway, as are preparations to file for approval of, and begin
clinical trials of RTD and RI Treakisym® products. In addition, the company is also developing intravenous and oral versions ofrigosertib, an anticancer drug for myelodysplastic syndromes.
Drug candidate selection process

Source: Shared Research based on company data.
CDA = confidential disclosure agreement

Scientific Advisory Board
The Scientific Advisory Board is comprised of former directors of pharmaceutical companies, researchers, and doctors, and meets
three times a year. Typically, the SAB panel evaluates two to three drug candidates that have been selected via the company’s
in-house screening process. This in-house screening of only those drug candidates having proof-of-concept established in humansubjects with supportive efficacy and safety data followed by SAB assessment enables the company to reduce development risk
and to pursue only those opportunities having the best chance of reaching the marketplace.
Scientific Advisory Board members
NameProfileGeorge Morstyn, M.D., Ph.D.

Presently Chairman GBS Venture Capital firm, Deputy Chairman Victorian Comprehensive Cancer Centre,
Director of Co-operative Research Centre for Cancer Therapeutics and Proacta.
Former Senior Vice-President of Development and CMO at Amgen Inc.
Former Senior Vice-President of US R&D, Aventis Pharmaceuticals;
Chief Scientific Officer, Cell Therapeutics; Head of Discovery Research,

Robert Lewis, M.D., Ph.D.

Syntex Pharmaceuticals; Associate Professor, Harvard Medical School
Currently serves as consultant in Immunology/Inflammation, Roche Palo Alto;
Adjunct Faculty Member, Rockefeller University, New YorkTomomitsu Hotta, M.D.
Makoto Ogawa, M.D., Ph.D.
Tatsutoshi Nakahata, M.D.,
Ph.D.

Toshio Suda, M.D., Ph.D.

Honorary President, National Cancer Center
Honorary Director, Nagoya Medical Center
Honorary President, Aichi Cancer Center
Advisor and Program-Specific Research Center Professor at Center for iPS Cell Research and Application(CiRA), and Head of Drug Discovery Technology Development Office, Kyoto University
Honorary member, The Japanese Society of Hematology
Distinguished Professor, International Research Center for Medical Sciences, Kumamoto University
Professor, Cancer Science Institute of Singapore, National University of Singapore
Vice President, The Japanese Society of Hematology in 2012

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Tsutomu Takeuchi, M.D., Ph.D.

Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp

Professor of Medicine, Keio University, School of Medicine (Division of Rheumatology, Department ofInternal Medicine)
Professor, Kanazawa University College of Medical, Pharmaceutical and Health Sciences, Division of Cancer

Shinji Nakao, M.D., Ph.D.

Koichi Takahashi, M.D.

Medicine Cellular Transplantation Biology (Hematology/Respirology)
Executive Director, The Japanese Society of Hematology in 2012
Assistant Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center,
The University of Texas

Source: Shared Research based on company data.

A fabless strategy with a lean management team
SymBio seeks to reduce costs and raise profits by finding the right partner(s) to develop and commercialize drugs nimbly andefficiently through flawless execution.
Specifically, the company designs clinical trial protocols and whenever possible, will participate in global phase III studies being
conducted by its partner(s) overseas with the aim of shortening development timelines in Japan. It may be possible to file NDAs
in Japan using foreign data to support or "bridge” data generated in Japanese clinical trials, thereby avoiding the need tocomplete domestic phase II and/or phase III studies for marketing approval. The company uses its well-established network forbendamustine to coordinate with medical professionals, outsourcing routine development duties. Production is also outsourced
either to the company that originally granted the product license, or to other domestic or foreign manufacturer(s). The company
is preparing to establish its own sales organization to start in-house sales from FY12/21, but as of February 2019, marketing rights
are granted to outside partners.

Focusing on niche markets: oncology, hematology, and pain management
SymBio focuses on drugs for underserved medical needs—even when the market may be as small as JPY10bn—rather thanfocusing on blockbuster drugs with sales in the hundreds of billions of yen. It aims to take advantage of therapeutic areas that
tend to be overlooked in the pharmaceutical industry and thus, lack effective drugs. Specifically, the company specializes intherapeutic areas with high barriers to entry, such as oncology, hematology, and pain management.
According to the company, globally Japan has the third largest oncology market after the US and EU, and the market is expected
to continue to expand due to Japan’s aging population. However, regarding the type of tumors that anticancer drugs caneffectively treat, there is a considerable range of indications with a limited number of patients who will benefit from approved
cancer treatments, particularly in the elderly population where the occurrence of serious adverse events can be prohibitive. As aresult, barriers to entry are high—developing cancer drugs for niche markets is especially difficult and requires a high level ofexpertise. Concerns about having sufficient profit margins from marketed drugs to fund large operations means that major
pharmaceutical companies may be reluctant to target indications with limited patient numbers for development, presenting an
opportunity with fewer competitors in the marketplace for smaller and more specialized pharmaceutical companies such as
SymBio. The company can also increase value added of niche disease areas by additional indications and putting new productson the market. For example, its first in-house proprietary drug Treakisym® has gained over 50% market share three years after
going on sale.

Strategy for global expansion
The company is seeking to develop new drugs that are complementary to Treakisym® and rigosertib to sell in China/Hong Kong,
Taiwan, South Korea, and Singapore, as well as in Japan.

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Pipeline
Name/CodeTreakisym®

LicensedcountryJapan

SyB L-0501(FD)

Indications

Development stage

Sales partner

Relapsed or refractory

Approval obtained (Oct.

Eisai Co., Ltd.

low-grade NHL and MCL

2010)

Relapsed or refractory

Phase III clinical trials(co-developed: exclusive sales rights
granted to Eisai)

DLBCL (aggressive NHL)

underway

Untreated low-grade NHL and Approval granted
MCL(Dec. 2016)

CLL

Approval granted(Aug. 2016)

SingaporeLow-grade B-cell NHL

Approval granted

Eisai Co., Ltd.

(Jan. 2010)(Exclusive development and sales
rights granted to Eisai)

CLLMMApproval granted(May 2011)

Eisai Co., Ltd.
(Exclusive development and sales

Relapsed or refractory
low-grade NHL

Approval granted(Jun. 2014)

rights granted to Eisai)

China

Low-grade NHL

Clinical trials underway

Hong Kong

Low-grade NHL

Approval granted

Cephalon, Inc. (US)(Exclusive development and sales

CLL(Dec. 2009)

rights granted to Eisai)

Low-grade NHL
CLL

Approval granted(Oct. 2011)

InnoPharmax, Inc. (Taiwan)(Exclusive development and sales

Japan

All indications

Preparing for approval filing

—

Japan

All indications

Clinical trials underway

—

Japan

Systemic lupus erythematosus Phase I clinical trials underway —CLLSouth Korea

TaiwanTreakisym®
SyB L-1701

rights granted to Eisai)(RTD)
Treakisym®
SyB L-1702(RI)
Treakisym®
SyB C-0501(SLE)(oral)
Rigosertib

Japan

(IV)
SyB L-1101
Rigosertib(oral)SyB C-1101

Japan

Relapsed or refractory

Global phase III clinical trials

higher-risk MDS

underway—

Relapsed or refractory
higher-risk MDS

Phase I clinical trials underway —(single drug)
Untreated higher-risk MDS

Preparing for phase I clinical(with azacitidine)

trials
Preparing for global phase III—

clinical trials
Source: Shared Research based on the company website

As of February 2019, the main drugs for which SymBio was preparing filing for approval or in the development pipeline were as
follows:▷ Treakisym®, targeting indication for relapsed or refractory DLBCL (aggressive NHL): Enrolling participants for phase III clinical trial(initiated August 2017)▷ Treakisym®, preparing to file for approval of RTD formulation and clinical trials on RI formulation: In preparations for approvalfiling for RTD formulation, clinical trials on RI formulation initiated in November 2018

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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp▷ Rigosertib (intravenous form), targeting indication for relapsed or refractory higher-risk myelodysplastic syndrome (MDS):
Enrolling participants for global phase III clinical trial▷ Rigosertib (oral form), targeting indication for higher-risk MDS: Enrolling participants for phase I clinical trial (initiated June 2017),
in preparations for phase I clinical trial in combination with azacitidine, in preparations for global phase III clinical trial in

combination with azacitidine

SyB L-0501 (generic: bendamustine HCI; product name: Treakisym®)
SyB L-0501 (Treakisym®) or bendamustine hydrochloride is an anticancer agent. It is used as a treatment for low-grade NHL, MCL,
MM and CLL.

*Bendamustine was developed in 1971 by Jenapharm in former East Germany, where it was approved as a first-line treatment for low-grade NHL, MM,
and CLL. After the unification of Germany in 1990, bendamustine was again evaluated for its effectiveness against these indications. In 2005, Germany
approved the use of the drug for untreated low-grade NHL, MM and CLL. The drug was also approved in several other European countries in 2007. In
the US, Treanda (bendamustine) was approved in March 2008 for relapsed or refractory NHL and CLL, with sales in October the same year. A separate
application was filed in the US (2008) for the additional indication of previously untreated CLL.

According to the company, no cross-resistance (resistance to drugs with a similar structure or action as the study drug) has beenshown for this drug, which means it is safer and more efficacious than existing treatments for target indications. In October 2010,
SymBio received regulatory approval in Japan to market the drug for relapsed or refractory low-grade NHL and MCL. Eisai has
been selling the drug since its launch in December 2010. The company received permission to add CLL as an indication for
Treakisym® in August 2016, and first-line treatment of low-grade NHL and MCL in December 2016.
In August 2017, the company initiated phase III clinical studies of Treakisym® for an additional indication of relapsed or refractory
DLBCL (aggressive NHL).

Lymphatic cancer
Lymphatic cancer a malignant growth of lymphatic corpuscles in white blood cells
Lymphatic cancer is a malignant growth of lymphatic corpuscles in white blood cells. It causes inflammation of the lymphatic
nodes. The most common symptom is a painless lump or swelling in one or more lymph nodes, usually in the neck, armpit or
groin. In lymphatic cancer, the lump or swelling grows persistently without decreasing in size, also spreading to other parts ofthe body and eventually presenting as generalized symptoms, including fever, weight loss, and night sweats. Other symptoms
can include widespread itching and skin rash, as well as airway obstruction, interrupted blood flow, and numbness arising frompressure of swollen lymph nodes on the respiratory tract, blood vessels, and spinal cord.
Lymphatic cancer is divided into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Among the Japanese
population, only 4% of lymphatic malignancies are HL. About 70–80% of NHL cases affect B-cells; the remaining 20–30% affect
T/NK cells. According to the Japanese Association of Clinical Cancer Centers (JACCC), the five-year relative survival rates for
lymphatic malignancies (among patients diagnosed between 2001 and 2005) are as outlined in the table below. In Hodgkin’s
lymphoma (all cases) the five-year relative survival rate was 76.0%, as compared with 68.3% for non-Hodgkin’s lymphoma (allcases).
Lymphatic malignancy: frequency by type
Category

Frequency

Non-Hodgkin's lymphoma

94%

B lymphocytes

69%

T/NK lymphocytes

25%

Hodgkin's lymphoma

4%

Other

2%

Source: Japanese Society for Lymphoreticular Tissue Research (JSLTR)

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Five-year relative survival rate for lymphatic malignancies (in patients diagnosed between 2001 and 2005)
Stage

Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma

Number of cases

Number of cases

5-year relative
survival rate (%)

5-year relative
survival rate (%)

Ⅰ

19

91.4

462

86.7

Ⅲ

46

84.6

385

74.3

22

65.3

319

64.0

19

44.7

535

54.6

122

76.0

1,844

68.3

Ⅱ
Ⅳ

All cases

Source: Survival Statistics of Japanese Association of Clinical Cancer Centers (November 2015)
Note: Covers not just patients undergoing chemotherapy, but also those undergoing radiation therapy or some other form of cancer treatment.
Note: Cancer progression is categorized into stages; in lymphatic malignancies, these are Stage I, Stage II, Stage III, and Stage IV.

Method of treatment determined by grade; separate clinical trials required for each disease subtype
Physicians examine tissue and determine the method of treatment depending on the type of cancerous cells observed: they lookat the grade (high, intermediate, or low, depending on the aggressiveness of the disease) and clinical staging, which shows towhat extent the cancer has spread. To gain approval to manufacture and sell pharmaceuticals, companies must conduct separate
clinical trials for each disease subtype. Clinical trial subjects are categorized as either treatment-naïve, or relapsed/refractory(patients who have received treatment in the past, which has proven ineffective).

Treakisym® in-licensed from Astellas; Eisai handles sales
In December 2005, SymBio signed a license agreement for the exclusive right to bendamustine in Japan with Astellas
Deutschland GmbH (“Astellas”), a subsidiary of Astellas Pharma Inc. The company entered into a second license agreement with
Astellas in March 2007 to extend its exclusive development and commercialization right for bendamustine to China/Hong Kong,
Taiwan, South Korea, and Singapore.
In August 2008, SymBio granted Eisai Co., Ltd. the co-development and exclusive marketing right for Treakisym® in Japan. Under
the agreement, SymBio receives one-time payments from Eisai as well as milestone payments based on the clinical trial stage for aparticular indication, plus revenues after supplying Treakisym® to Eisai. Eisai shoulders half of the development costs for
Treakisym®, including labor costs for researchers and outsourcing costs for clinical trials (see the Earnings structure section).
SymBio has granted exclusive marketing rights for Treakisym® to InnoPharmax, Inc. in Taiwan, Cephalon, Inc. in China, and Eisai in
South Korea and Singapore. In return, SymBio receives one-time milestone payments, and books revenue from the sale of the
drug to these companies.

Approval for relapsed or refractory low-grade NHL, MCL in October 2010
In October 2010, five years after acquiring the right to Treakisym®, SymBio received marketing approval in Japan for relapsed or
refractory low-grade NHL and MCL. In FY12/16—six years after the domestic launch of the drug in December 2010—Treakisym®
sales to end users reached JPY4.7bn on an NHI drug price basis.
According to the company, Japan has about 4,700 patients who suffer from relapsed or refractory NHL and MCL. SymBio thinks
annual Treakisym® sales could reach JPY4.5–5.0bn.

Treakisym®: additional indications, RTD, RI, and oral forms
Approval for first-line treatment of low-grade NHL, MCL in December 2016 and additional indication for CLL in
August 2016
In December 2016, Treakisym® was approved in Japan for first-line treatment of low-grade NHL/MCL and for CLL in August 2016.
In August 2017, the company started phase III clinical studies for relapsed or refractory DLBCL (aggressive NHL) as part of its
plans to add indications.

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Market for Treakisym® and number of patients
Non-Hodgkin's Lymphoma
Low-grade B-cell
First-line

Relapsed andrefractory

Chronic Lymphatic Leukemia
Moderate- to high-grade

Number of patients

6,967

656

Approval

Obtained

Obtained

Development status

Dec. 2016 approval obtained

Aug. 2016 approval obtained

Number of patients

9,336

18,672

Approval

Obtained

Completed phase II clinical trials in Japan

Development status

Approval obtained in Japan in Oct. 2010

Phase III clinical trials underway in Japan

Source: Shared Research based on company data.

First-line treatment of low-grade NHL and MCL
According to the company, R-CHOP therapy—a combination of rituximab with CHOP chemotherapy drugs (cyclophosphamide,
doxorubicin, vincristine, and prednisolone)—was standard first-line treatment for low-grade NHL and MCL in Japan prior to
December 2016. In December 2016, Treakisym® won approval for the additional indication of first-line treatment of low-grade
NHL and MCL, and subsequently in July 2018, Treakisym® was newly included as a standard option for first-line treatment of
low-grade NHL and MCL in the Guidelines for Tumors of Hematopoietic and Lymphoid Tissues 2018 issued by the Japan Societyof Hematology.
Phase III clinical trials conducted overseas have demonstrated that rituximab in combination with bendamustine (BR therapy) was
safer and more efficacious than standard R-CHOP therapy for previously untreated low-grade B-cell NHL. These findings were
presented at the American Society of Hematology Annual Meeting in December 2012. Based on these results, the National
Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines recommend the use of
BR therapy as first-line therapy for patients with untreated low-grade NHL.
The subject phase III clinical trials were conducted at 81 facilities in Germany, treating patients who were newly diagnosed
between September 2003 and August 2008 with stage III or IV low-grade NHL or MCL. The trials involved a comparison between
R-CHOP and the bendamustine-rituximab (BR) regimen (bendamustine is marketed as Levact®, Ribomustin®, or Ribovact® inEurope). A total of 275 patients underwent R-CHOP therapy, while 274 were administered the BR combination. The medianfollow-up period was 45 months. Clinical results showed that the median progression-free survival period was 69.5 months forthe bendamustine hydrochloride-rituximab group while that for the R-CHOP group was 31.2 months (p<0.0001), demonstrating
the superiority of the BR therapy. Comparison of overall survival and safety between the two groups also showed superior results
for the BR group.
p-value: In statistics, the p-value indicates the randomness of an observed result, or how trustworthy the sample is. A p-value of 0.01 indicates that an
observed result will occur randomly one out of 100 times. Generally, if the value is below 5%, the result is statistically significant.

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Results of trial comparing B-R and R-CHOP therapies as first-line treatment for patients with low-grade NHL/MCL

Source: Company data

Treakisym® approved in December 2016 for first-line treatment of low-grade NHL and MCL
In December 2016, SymBio received approval to manufacture and sell in Japan Treakisym® targeting first-line treatment of
low-grade NHL and MCL. The company expects the shift from R-CHOP to BR therapy to progress domestically in the medium
term. Shared Research believes this shift will gain support from the aforementioned data demonstrating that BR therapy is more
efficacious than R-CHOP therapy, and inclusion of BR therapy as a standard treatment option in the Guidelines for Tumors of
Hematopoietic and Lymphoid Tissues 2018.

Untreated low-grade NHL and MCL: Patient population
SymBio estimates that there are 6,967 first-line low-grade NHL and MCL patients in Japan. Although fewer than the number ofpatients with relapsed or refractory low-grade NHL and MCL, the company expects higher market penetration amid the trend of
switching from R-CHOP to BR therapy. Treakisym® sales could reach JPY5.0–7.0bn as the Japanese population continues to age.

Treakisym® targeting chronic lymphocytic leukemia (CLL)
Astellas’ European subsidiary has obtained approval in the US and the EU to market Treakisym® for the indication of CLL. In Japan,
Treakisym® was designated as an orphan drug (drug for the treatment of rare diseases) in June 2012 by the Review Committee on
Unapproved or Off-Label Drugs with High Medical Needs after it was determined that this drug met critical demand for new
therapies to treat CLL.

Additional indication for CLL granted in August 2016
In Japan, SymBio completed a pivotal phase II trial for Treakisym® in CLL as a joint project with Eisai in October 2015. In August
2016, the company received permission to add CLL as an indication for Treakisym®.

Potential patient population, expected sales
SymBio estimates that there are about 656 CLL patients in Japan. Shared Research estimates that sales could reach JPY300mn–
JPY350mn. This estimate is based on Treakisym® sales per patient with relapsed or refractory low-grade NHL or MCL.

Treakisym® indicated for relapsed or refractory DLBCL (aggressive NHL)
Diffuse large B-cell lymphoma (DLBCL), or aggressive NHL, progresses rapidly but recovery may be expected in patients forwhom anticancer drugs are effective. R-CHOP is the standard initial therapy for relapsed or refractory DLBCL, the most common
type of NHL.
But according to the company, 40% of untreated patients treated with R-CHOP relapse or become refractory, and only patients
who are 65 or younger can undergo chemotherapy at higher doses together with autologous stem cell transplants. Because the

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majority of relapsed or refractory DLBCL patients are elderly, physicians must consider potential side effects when selecting asuitable treatment. Weaker patients—due to age or other illnesses—have limited choices for treatment, and there is a need for asafer, more efficacious method of treatment such as Treakisym®.

R&D status: Began phase III clinical trials of Treakisym® to treat relapsed or refractory DLBCL in August 2017
Phase II clinical trial data demonstrates potential for improved prognosis in patients with relapsed or refractory DLBCL (aggressive NHL)In March 2012, the company completed final analysis and evaluation of data from its phase II clinical trials using Treakisym® incombination with rituximab for relapsed or refractory DLBCL (aggressive NHL). The trial, with clinical trial sites in both Japan andSouth Korea, demonstrated an improved prognosis as well as clinically manageable side effects in elderly patients.

Planning to file for approval in FY12/20 for indication of relapsed or refractory DLBCL
Following consultations with the Pharmaceuticals and Medical Devices Agency (PMDA), the company commenced phase III
clinical trials using Treakisym® in combination with rituximab for relapsed or refractory DLBCL. The purpose of the study is to test
the efficacy and safety of BR therapy, with the overall response rate (ORR; antitumor effect) as the primary endpoint and anenrollment target of 60 patients. SymBio aims to file for approval in Q2 FY12/20 with a view to launching in Q3 FY12/21.

Potential for use of Treakisym® as pretreatment agent for CAR-T therapy
In April 2018, Novartis Pharma K.K. applied in Japan for approval of the chimeric antigen receptor T-cell (CAR-T) therapy CTL019(US product name: Kymriah®), for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in patients
aged 25 years or younger and relapsed or refractory DLBCL. In May 2018, Novartis obtained approval in the US for use of CTL019
to treat adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy. Since the use of CTL019 islimited to adult patients for whom two or more lines of therapy have proved ineffective, Shared Research understands that
CTL019 is different from Treakisym® and that the two companies do not compete in this area. In September 2018, the company
applied for approval of a partial revision to manufacture and marketing approval of Treakisym® to enable its use as a pretreatment
agent for CTL019 targeting relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) and relapsed or refractory diffuse
large B-cell lymphoma (DLBCL) in adults.

Potential patient population
According to SymBio, the number of relapsed or refractory diffuse large B-cell lymphoma (DLBCL; aggressive NHL) patients inJapan is approximately 18,672. We estimate annual peak sales for the indication (NHI drug reimbursement price basis) at JPY8.0–
10.0bn.

Concluded license agreement for RTD and RI formulations of bendamustine hydrochloride (marketed as
Treakisym® in Japan) in September 2017
In September 2017, Eagle Pharmaceuticals and SymBio concluded a license agreement that licenses to SymBio rights to develop,
market, and sell Eagle’s bendamustine hydrochloride ready-to-dilute (RTD) and rapid infusion (RI) products (marketed in the US
by Teva Pharmaceutical Industries as BENDEKA®) in Japan. SymBio will pay Eagle a USD12.5mn upfront payment and a milestone
payment upon approval. The company will also pay additional milestone payments on the achievement of cumulative sales
thresholds and royalties on future sales of licensed bendamustine products.

RTD and RI products do not require reconstitution; RI product can be administered in one sixth of the time as FD product
The FD powder injection product currently available must be reconstituted manually before administration by intravenous
infusion. Since RTD and RI products are already liquidized, they do not require the time-consuming process of reconstitution andsubstantially reduce the workload of healthcare professionals. RI products also do not require reconstitution and can beadministered by intravenous infusion in 10 minutes instead of 60 minutes for FD powder injection and RTD products, which
reduces stress on patients.

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Comparison of RTD/RI products and currently available (freeze-dried) product

RTD products
Generic name

RI products

Currently available products

bendamustine hydrochloride

Dosage form

LiquidFreeze-dried powder injection

Reconstitution

Not required

Required (manual reconstitution)

Dilution

Dilute with 250ml physiologicalsalineDilute with 50ml physiologicalsalineAdministration time

60 minutes

10 minutes

Dosage form

100mg/4mL

100mg/vial
25mg/vial

Storage

Refrigerated storage (2–8°C)

Room temperature

Dilute with 250ml physiologicalsaline60 minutes

Can extend life cycle of Treakisym® until 2031
The re-examination term for the FD product of Treakisym® ends in 2020, after which generics can be manufactured and sold.
SymBio believes that by selling the RTD and RI products that offer the advantages of reducing healthcare professionals’ workload
and stress on patients after 2020, it can extend the exclusive sales period until 2031. This increases the possibility of prolonging
the life cycle of Treakisym® and limiting the spread of generics.
Bendamustine hydrochloride RTD and RI injection products are marketed in the US by Teva Pharmaceutical Industries as
BENDEKA®, which has 97% share of the US bendamustine market within two years after its sales.

R&D status: Aiming to obtain approval in FY12/20 for bendamustine hydrochloride RTD productAs of February 2019, the company is respectively preparing to file for approval and conducting clinical trials for the bendamustinehydrochloride RTD and RI products.
SymBio will be allowed to file for approval of the RTD product without conducting clinical trials, because its ingredients, efficacy,
and administration time are identical to those of the Treakisym® freeze-dried (FD) product; the only difference being that it does
not need reconstitution. As of February 2019, the company has completed consultation with PMDA and is preparing to file forapproval. Based on the time needed to prepare the documents required for this application, and subsequent period between
filing and approval, SymBio aims to submit an application in FY12/19, obtain approval in FY12/20, and launch in Q1 FY12/21.
However, clinical trials will be required for the RI product, because the administration time is different from the FD product. In
November 2018, the company began a clinical trial of the Treakisym® RI product in 36 patients. It apparently plans to launch the
RI product in 1H FY12/22.

Treakisym® (oral) SyB C-0501
SymBio is exploring the possibility of expanding the business by progressing development of the oral form of Treakisym®
targeting new indications such as solid tumors and autoimmune diseases. As part of this project, the company has started a phase
I clinical trial to evaluate dosage and dosing schedule, tolerability, and safety of the oral form on select types of cancer.

Treakisym® as a pretreatment agent for a regenerative medicine product (CAR-T cell therapy)
In September 2018, the company applied for approval of a partial revision to manufacture and marketing approval of anticancer
drug Treakisym® to enable its use as a pretreatment agent for regenerative medical products.
In April 2018, Novartis Pharma K.K. filed for manufacture and marketing approval for the first chimeric antigen receptor T-cell(CAR-T) therapy (CTL019) in Japan for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) inpatients aged 25 years or younger and relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients. If thetherapy is approved, Treakisym® can be used as a pretreatment agent for CAR-T therapy for the treatment of ALL and DLBCL.
Further, the approval would mark the addition of regenerative medicine as a new area of indication for Treakisym®.

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CAR-T cell therapy genetically modifies T-cells collected from patients’ blood samples to express chimeric antigen receptors (CARs) on their surface at acell processing center. Then, the genetically modified T-cells (CAR-T cells) are infused back into the patients where they assume the role of immune
system and specifically attack cells that express target proteins including cancer cells. CTL019 is an immune cell therapy that collects T-cells frompatients’ blood samples and genetically modifies them so that they specifically recognize CD19 proteins expressed on cancer cells among others andattack them. CTL019 therapy requires only a single administration.

SyB L-1101 (intravenous)/SyB C-1101 (oral) (generic name: rigosertib)
Rigosertib is a tumor-specific dual-specificity inhibitor, which inhibits both the PI3K (phosphoinositide 3-kinase) and the PLK(polo-like kinase 1) pathway. It is being developed in the US and EU by Onconova as a treatment for myelodysplastic syndromes(MDS) as well as in other indications such as first-line MDS and AML (in combination with Vidaza), and head and neck cancer(solid tumor).
According to SymBio, rigosertib’s high safety profile enables the drug to be used as both a monotherapy and in combination withother anticancer drugs. It is being developed in both intravenous and oral forms.
Onconova: A US biopharmaceutical company. Established in 1998, Onconova focuses on discovering and developing small molecule drug candidates
to treat cancer.

Myelodysplastic Syndromes (MDS)
MDS is a refractory disease with a poor prognosis and progression to acute myeloid leukemia (AML) in approximately 30% ofcases. It leads to abnormalities in hematopoietic stem cells that produce blood cells, resulting in a lack of blood. Blood cells
produced this way are abnormally shaped. This change in the cells is called dysplasia. The disease typically leads to frequentanemia with some patients dying from infection or bleeding due to the reduction in blood cells. The average survival period isabout three to five years, with some patients surviving 10 years or longer. It is still not clear what environmental or genetic factors
are responsible for the occurrence of MDS, although those who have received radiation treatment or taken anticancer drugs may
have a higher risk of developing the disease (source: Japan Adult Leukemia Study Group: JALSG).
The seriousness of MDS is determined with the use of the International Prognostic Scoring System (IPSS). The IPSS score is
calculated based on the ratio of myeloblasts (immature blood cells) in the bone marrow, chromosome analysis, and the results ofa general laboratory blood test. The risk level is assessed based on the number of years that the patient is expected to live,
disease progression, and the probability that the disease may lead to acute myeloid leukemia. Risk categories: low,intermediate-1, intermediate-2, and high. Lower-risk MDS refers to low and intermediate-1 patients, while higher-risk MDS refers
to intermediate-1 and high in the IPSS risk categories.

Acquired rights from Onconova to develop and sell rigosertib in Japan, South Korea
In July 2011 SymBio bought the exclusive right to develop and sell the intravenous (IV) and oral forms of rigosertib following
completion of Onconova’s phase II US clinical trial for the IV form. In September 2012, Baxter International Inc. acquired theexclusive right to develop and sell rigosertib in Europe.

Development status of rigosertib
As of February 2019, SymBio is developing the IV form of rigosertib for the indication of relapsed or refractory higher-risk MDS,
and the oral form for higher-risk MDS.
Onconova has been conducting joint global phase III clinical trials in over 20 countries since August 2015 for the intravenous
form of rigosertib in higher-risk MDS patients who had failed or relapsed after prior therapy with hypomethylating agents (HMAs).
In the Japanese market, the company has been conducting the joint global phase III clinical trials in cooperation with Onconova
since December 2015.
The company had started phase I clinical trials for the oral form of rigosertib for the indications of higher-risk MDS (incombination with azacitidine) in December 2015. The supply of the study drug from Onconova had been delayed, but with

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resumption of study drug supply SymBio restarted phase I clinical trials in Japan in June 2017, to verify the tolerability and safetyof the oral formulation of rigosertib among Japanese patients. After establishing safety in phase I clinical trials, the company plansto resume the trial of rigosertib in combination with azacitidine and participate in global phase III clinical trials planned by
Onconova in higher-risk MDS patients, and in combination with azacitidine.
Market for Rigosertib (oral form) and number of patients

Intravenous

Oral

Low-risk MDSHigh risk MDSFirst-line

First-line

Relapsed and refractory

Number of patients

3,200

Approval

Obtain approval in FY12/19 (expected)

Development status

Global phase III trials

Number of patients

7,800

3,200

Approval

TBC

TBC

Development status

Phase II trials underway in the US

Phase II clinical trials underway in the US
Phase I clinical trials underway in Japan

Source: Shared Research based on company data.

IV form of Rigosertib for post-HMA higher-risk MDSHigher-risk MDS (patients in the Intermediate-2 risk and High-risk groups based on International Prognostic Scoring System) is
likely to cause a decline in blood cells or lead to leukemia. Treatment may involve stem cell transplants, depending on thepatient’s age, condition, and the compatibility of the donor. In the US and Europe, Vidaza (azacitidine) and Dacogen(decitabine) are standard drug therapies for this treatment. In Japan, Vidaza (being marketed by Nippon Shinyaku) is also
administered in cases where stem cell transplants are not used. (for Vidaza, see Market and value chain)
However, some cases of higher-risk MDS show resistance to standard treatment with hypomethylating agents (HMAs) such as
Vidaza and Dacogen, including relapse following treatment. The most advanced research being conducted for rigosertib was forthe treatment of patients with higher-risk MDS who had progressed on, failed or relapsed after prior therapy with HMAs.
According to the company, no drugs have been approved for the treatment of post-HMA higher-risk MDS patients as of February
2019.

R&D status: ongoing joint global phase III clinical trials in patients with relapsed higher-risk MDS following HMA therapy
In February 2014, Onconova completed its phase III ONTIME clinical trial for the intravenous form of the drug in MDS patients in
the US who showed resistance to standard treatment with HMAs, or who experienced recurrence of the disease after treatment
with HMAs.
Of the 299 patients enrolled in the phase III clinical trial, 199 were administered rigosertib and 100 were placed in the control
group. The overall survival (OS) period for those who received rigosertib was 8.2 months, while OS for the control group (BSC)
was 5.8 months. However, with a p-value of 0.27, there was no statistically significant difference between the two groups.
Among patients whose condition had deteriorated or not responded to previous treatment using hypomethylating agents (184of 299 people, or 62%), the overall survival period for higher-risk MDS patients who received rigosertib was 8.5 months, while forthose in the control group (BSC) it was 4.7 months. The p-value was 0.022, showing a statistically significant difference. The
hematological toxicity of the conventional anticancer agent was approximately 60%. With rigosertib, toxicity of Grade 3 or above
did not exceed 7%, and non-hematological toxicity did not exceed 3%, confirming safety of the drug.

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In August 2015, Onconova submitted plans to US Food and Drug Administration (FDA) and regulatory agencies in England,
Germany, and Australia for global phase III comparative trials of rigosertib for patients who did not see results from low
methylation, or experienced higher-risk refractory or relapsed MDS following HMA treatment. These global trials are currently
ongoing.

SymBio responsible for operation of global phase III clinical trials within Japan
Based on the outcome of discussions with the FDA and European regulatory agencies and Onconova’s future development, thecompany has been operating the global phase III clinical trials within Japan since December 2015. The first patient was registeredin July 2016 and 40 patients had been registered as of end-December 2018 versus the target 25–30. Onconova decided toproceed with the clinical trial on the basis of results of an interim analysis performed in January 2018 by increasing the number ofpatients registered from 225 to 360 based on preplanned statistical criteria. SymBio plans to increase the number of patientsregistered to 50 to continue the trial.

Oral form of rigosertib for first-line higher-risk MDS
R&D status: phase I and II clinical trials underway
Onconova, the anticancer drug rigosertib’s licensor, presented phase II clinical trial data on oral rigosertib for patients withhigher-risk myelodysplastic syndromes (MDS) at the 58th American Society of Hematology (ASH) Annual Meeting held in
December 2016.
The data on the efficacy and safety of oral rigosertib and azacitidine combination for 33 MDS patients (20 HMA naïve; 13 HMA
resistant) was presented at the poster presentation, “Combination of Oral Rigosertib and Injectable Azacitidine in Patients with
Myelodysplastic Syndromes (MDS): Results from a Phase II Study.” The complete remission (CR) rate amongst HMA-naïve
patients was higher (35%) and responses occurred more rapidly and durably with the oral rigosertib combination compared tothe single-agent azacitidine. The median duration of CR was eight months, comparing very favorably to the historic duration of
CR of 3.2 months with single-agent azacitidine.
As of February 2019, Onconova is making efforts toward finalizing the design for a pivotal phase III oral rigosertib/azacitidine
combination trial for the first-line treatment of higher-risk MDS.

Domestic phase I clinical trials
In FY12/16, the company launched phase I clinical trials to confirm the safety of the drug in combination with azacitidine fortreatment of higher-risk MDS. However, patient enrollment had not started because of delayed supply of the study drug from
Onconova Therapeutics. After the supply of the study drug resumed in June 2017, the company restarted the domestic phase I
clinical trial to confirm the safety of the drug at high doses (an additional requirement for phase III clinical trials conducted by
Onconova in the US for the indication of untreated and relapsed or refractory higher-risk MDS). After establishing safety in thephase I clinical trial, the company plans to resume the trial of the drug in combination with azacitidine and participate in global
phase III clinical trials conducted by Onconova

Patient population, estimated sales
According to SymBio estimates, patients with lower-risk MDS in Japan number about 7,800, with 3,200 MDS patients classified as
higher-risk.
Nippon Shinyaku Co., Ltd. (TSE1: 4516) has been selling azacitidine in Japan as first-line therapy for MDS under the productname Vidaza since March 2011. According to Nippon Shinyaku, sales of Vidaza were JPY15.6bn for FY03/18 (+11.1% YoY) andforecast to reach JPY13.6bn in FY03/19. Shared Research thinks that sales of the intravenous and oral forms of rigosertib could
match or exceed sales of Vidaza, used for patients who have not received treatment with Vidaza or in combination therapy withVidaza.

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Earnings structure
FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

Sales

1,191

1,450

1,883

1,955

1,532

1,955

1,933

2,368

3,444

3,836

YoY

-26.9%

21.7%

29.8%

3.9%

-21.6%

27.6%

-1.1%

22.5%

45.4%

11.4%

-

326

1,632

1,955

1,432

1,940

1,933

2,137

3,444

3,810

-

-

401.3%

19.8%-26.8%

35.5%

-0.3%

10.6%

61.1%

10.6%

(JPYmn)Product sales
YoY

FY12/18

Treakisym sales to end users (reference)

-

644

3,390

3,940

4,230

4,320

4,760

4,720

7,600

8,500

Product sales / Sales to end users

-

50.6%

48.2%

49.6%

33.9%

44.9%

40.6%

45.3%

45.3%

44.8%

Royalty revenue

1,191

1,124

250

-

100

15

-

231

-

26

Sales to Eisai

1,085

1,446

1,872

1,930

1,486

1,908

1,852

2,265

3,382

3,648

YoY

-32.2%

33.2%

29.5%

3.1%

-23.0%

28.4%

-2.9%

22.3%

49.4%

7.9%

106

4

10

26

46

47

81

104

62

187

-

238

1,224

1,362

1,214

1,428

1,350

1,464

2,413

2,663

Non-Eisai sales
CoGS
CoGS / Product sales

-

73.1%

75.0%

69.7%

84.8%

73.6%

69.8%

68.5%

70.1%

69.9%

CoGS / Sales to end users

-

37.0%

36.1%

34.6%

28.7%

33.1%

28.4%

31.0%

31.7%

31.3%

-

238

1,434

1,322

1,175

1,550

1,242

1,606

2,589

2,969

1,191

1,212

658

593

318

527

583

904

1,031

1,173

Product procurement
Gross profit
Product gross profit

0

87

408

593

218

512

583

673

1,031

1,147

-

27%

25%

30%

15%

26%

30%

32%

30%

30%

1,191

1,124

250

-

100

15

-

231

-

26

1,399

1,825

2,725

2,293

1,999

1,830

3,135

3,031

4,978

3,829

GPM

Royalty revenue
SG&A expenses
Personnel expenses

323

343

365

413

441

479

488

541

554

504

R&D expenses

817

1,118

1,945

1,438

1,053

774

2,035

1,667

3,018

1,833

Other
Operating profit

259

364

415

442

505

577

612

823

1,406

1,492

-208

-613

-2,067-1,700-1,681-1,303-2,552-2,127-3,947-2,656

Source: Shared Research based on company data.

Sales
The company’s sales are made up of product sales and royalty revenue. Per the above table, most of the sales have originatedfrom Eisai.

Product sales
Product sales are revenue from selling Treakisym®. The company began booking product sales in FY12/10, when it obtained
approval for Treakisym® and started selling the anticancer agent in December 2010. ThroughFY12/16, the company booked salesof Treakisym® indicated for relapsed or refractory low-grade NHL and MCL.
In FY12/17, the company booked sales of additional indications of untreated low-grade NHL and MCL, resulting in a strong sales
YoY.

Royalty revenue
Royalty revenue includes one-time contract payments and milestone payments. Since granting the exclusive marketing right for
Treakisym® to Eisai in August 2008, SymBio books one-time payments and milestone payments in accordance with clinical trial
stage.

CoGS
Cost of goods sold refers to procurement costs for drugs. SymBio purchases Treakisym® from Astellas Deutschland GmbH. Astellas
supplies Treakisym® to the company for about 70% of SymBio’s wholesale price to Eisai.
SymBio pays Astellas in euros, with these transactions usually taking place several months apart. Thus, the company faces the riskthat euro-yen forex rates will change during this period. The company hedges this risk with forward foreign-exchange contracts,
and by reporting gains and losses on forex as a non-operating profit (or loss).

SG&A expenses
Personnel and R&D are the main SG&A expenses.

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Personnel expenses
Personnel expenses consist of directors’ remuneration as well as expenses for personnel involved in such tasks as marketing,searching for in-licensing candidates and general administration. Personnel expenses have been trending upward in line withadditions to the pipeline and business expansion.

R&D expenses
R&D expenses include personnel expenses for R&D staff as well as clinical trial outsourcing expenses and upfront payments
accompanying product in-licensing. R&D expenses fluctuate depending on the progress of clinical trials and new license
agreements from in-licensing activities. According to the company, in-licensing expenses are between JPY500mn and JPY1bn perdrug, and domestic clinical trials cost between JPY1bn and JPY2bn.
Eisai pays half of the development costs for the Treakisym® freeze-dried (FD) product in Japan. In its income statement, SymBio
accordingly books total R&D expense less the portion of R&D expenditure borne by Eisai.

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Strengths and weaknesses
Strengths◤ Unique candidate selection process: SymBio makes decisions on in-licensing new drug candidates based on an initialassessment and screening process by its in-house search and evaluation team. The final decision is made by the company after

evaluation by a team of medical experts—the Scientific Advisory Board (SAB). President Yoshida’s extensive range of contacts
in the pharmaceutical industry built during his tenure at Amgen Japan and Amgen Inc. is a significant hurdle for competitors
attempting to emulate the quality of the company’s search and evaluation team, SAB panel and selection process.
◤ Strong product development: Treakisym® (bendamustine hydrochloride)—the first drug the company developed—received

marketing approval in Japan just five years after the license agreement was signed with Astellas. Treakisym®, launched by thecompany in December 2010, is being used by a number of Japanese physicians and is considered to be an essential drug forthe treatment of relapsed or refractory low-grade NHL and MCL. The company’s success with Treakisym® demonstrates its
strong product development capabilities and nimbleness.
◤ Strong share in niche markets: SymBio focuses on niche markets for rare oncologic and hematologic diseases and pain

management. The company takes advantage of a less competitive environment by developing drugs for indications that servea limited number of patients and require a high degree of in-house expertise. Thus, the company has succeeded in securing
more than 50% of the target market for Treakisym® in relapsed or refractory low-grade NHL and MCL in the third year after

launch.

Weaknesses◤ Lack of sales force: The company does not currently have its own sales force, thus Treakisym® is being sold through Eisai, analliance partner. Eisai will be responsible for sales of Treakisym® in Japan through FY12/20. At end-FY12/20, though, the sales
agreement with Eisai expires. At this point the company will switch to in-house sales, likely triggering improvement in profit
margins.

◤ Funding needs: It takes time and significant investment for pharmaceutical and biotech companies to develop andcommercialize drugs, and they must secure funding on a regular basis to cope with the uncertainty of their earnings. For
SymBio, cash and equivalents plus short-term investments totaled about JPY4.8bn at end-FY12/18. But the company expects a
total net loss of JPY8.8bn over the first two years of its medium-term plan (FY12/19–FY12/22). SymBio aims to secure the funds
required through its April 2018 issue of the 45th through 47th stock acquisition rights with exercise price revision clauses(Commit Issue Program) and conclusion of an unsecured loan facility agreement. The company’s operations could be affected,
though, if it fails to secure additional funding as planned.

◤ Dependence on a single individual: Founding President and CEO, Fuminori Yoshida, has played a central role in all aspectsof SymBio’s management since its foundation. If for any reason Mr. Yoshida is unable to perform his duties, this could have an
impact on company operations.

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Market and value chain
Market strategy
Lymphatic cancer: patient population, market size, drugs
Newly diagnosed patients with lymphatic cancer
In 2014, the number of people diagnosed with lymphatic cancer in Japan was 28,486 (+10.6% YoY; average annual increase inpast 10 years is 5.0%), according to the Center for Cancer Control and Information Services. Of these, 22,557 (+11.0% YoY), or
79.2% (78.9% in 2013), were 60 years or older. Of the 876,713 (+1.7% YoY) people diagnosed with cancer, those diagnosed
with lymphatic cancer accounted for only 3.2% (3.0% in 2013), but their number increased 62.8% between 2004 and 2014
versus a 40.7% increase in the number of people newly diagnosed with cancer.
Patients newly diagnosed with lymphatic malignancy
30,00025,00020,00015,00010,000

5,000

0

1975

1980

Number of patients
Incidence rate (per 100,000)

1985

1990

1995

2000

2005

2010

1975

1980

1985

1990

1995

2000

2005

2010

4,013

4,741

6,635

9,297

11,195

13,307

16,991

23,919

3.6

4.1

5.5

7.5

8.9

10.5

13.3

18.7

Source: Shared Research based on data from Center for Cancer Control and Information Services, National Cancer Center.

Market for anticancer drugs to expand
According to the Fuji Keizai Group, the domestic market potential l for anticancer agents was JPY1.6tn (+12.2% YoY) in 2016. The
market is growing amid new products going on sale and additional indications, and is expected to hit JPY1.4tn by 2025.

Treakisym® market potential and patient population
The company estimates that the number of patients being treated for relapsed or refractory low-grade NHL and MCL in Japan is9,336 and the number of patients with untreated low-grade NHL and MCL is 6,967. On an NHI drug reimbursement price basis,
Treakisym® sales reached JPY8.5bn in FY12/18 (JPY7.6bn in FY12/17).
The company estimates that the number of Japanese patients with relapsed or refractory DLBCL for which the company isconsidering application for approval of an additional indication is 18,672.

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Treakisym® indications and number of patients
Patients

Indications

Progress

Relapsed or refractory low-grade NHL and relapsed or
refractory MCL

9,336 Approval granted

Untreated low-grade NHL, and untreated MCL

6,967 Approval granted

Notes
Sales: JPY8.5bn (FY12/18)

656 Approval granted

CLL

18,672 Clinical trials underway

Relapsed or refractory NHL
Source: Shared Research based on company data.
*Sales based on NHI prices.

Drugs competing with Treakisym®
As of February 2015, these include rituximab and ibritumomab tiuxetan.

Rituximab (product name: Rituxan)
The drug, co-developed by the US companies IDEC Pharmaceuticals and Genentech, Inc. received US approval in November
1997 as the world’s first monoclonal antibody.
Rituxan consists of a portion of both mouse antibody and IgG, a human antibody. It attaches itself to the CD20 antigen thatappears on B cells in the body and fights tumors through complement-dependent cytotoxicity and antibody‐dependent cell‐
mediated cytotoxicity effects (source: Chugai, Zenyaku Kogyo).
In Japan, Zenyaku Kogyo and Chugai have been jointly selling the drug since September 2001. Chugai’s Rituxan sales were
JPY21.3bn (-36.2% YoY) in FY12/18.

Ibritumomab tiuxetan (product name: Zevalin)
Like Rituxan, the antibody drug Zevalin targets CD20 antigen on B cells. It combines the antibody with a radioactive substanceand attacks B cells with radiation. The treatment is only available at medical institutions authorized to handle radioactive
elements.
Zevalin was approved in January 2008 as a treatment for refractory lymphatic cancer (low-grade B-cell NHL). It is sold by Fujifilm
RI Pharma Co., Ltd., a subsidiary of Fujifilm Holdings Corporation.

MDS patients, drugs: market potential and number of patients
MDS patient population estimated at 11,000
A high proportion of people aged 60 or older suffer from MDS. The number of patients totaled 9,000 in 2008, with 2,781 deaths
from the disease according to Japan’s Ministry of Health, Labour and Welfare (MHLW). SymBio estimates that there are currently
about 11,000 MDS patients in Japan amid a larger elderly population. Even though the number of patients continues to rise,
there is a high unmet medical need in Japan with no efficacious treatment available.
Rigosertib indications and number of patients
Condition

Patients

Low-risk MDS

7,800

High-risk MDS

3,200

Source: Shared Research based on company data.

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Drugs competing with rigosertib
According to the company, as of February 2018, Nippon Shinyaku Co., Ltd.’s Vidaza is the only IV drug approved in Japan for themain indication of MDS.

Azacitidine (product name: Vidaza)
Vidaza, developed by Pharmion Corporation (now Celgene Corporation) in the US, is a treatment for first-line intermediate andhigher-risk MDS. Nippon Shinyaku Co., Ltd. signed a license agreement with Pharmion in 2006 to sell this drug in Japan,
obtaining marketing approval in January 2011 following the completion of domestic clinical trials.
In addition to killing cancerous cells, azacitidine inhibits DNA methylation. It becomes efficacious after use for three to six months,
with bone marrow suppression as the main side effect (a decline in white blood cells and platelets). However, while the use of
hypomethylating agents such as azacitidine and decitabine (Dacogen) in the treatment of MDS has improved the outcome ofpatients who tend to have very poor survival, about half of MDS patients do not respond, progress, or relapse at different times
after their response on these HMAs, followed by an extremely poor prognosis.
According to Nippon Shinyaku, Vidaza is the only approved drug in Japan for the first-line treatment of higher-risk MDS, with noefficacious treatment available once patients treated with Vidaza relapse. Nippon Shinyaku booked Vidaza sales of JPY15.6bn in
FY03/18 (+11.1% YoY) and expects sales of JPY13.6bn in FY03/19.

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Historical performance
Full-year FY12/18 results▷ Sales:

JPY3.8bn (+11.4% YoY)

▷ Recurring loss:

JPY2.7bn (loss of JPY4.0bn in FY12/17)▷ Operating loss:▷ Net loss:

JPY2.7bn (loss of JPY3.9bn in FY12/17)

JPY2.8bn (loss of JPY4.0bn in FY12/17)

Sales rose as product sales totaled JPY3.8bn (+10.6% YoY) mainly owing to domestic sales of Treakisym®.
Due to sales growth, gross profit rose 13.7% YoY to JPY1.2bn, with the gross profit margin increasing 0.7pp YoY to 30.6%.
SG&A expenses fell 23.1% YoY to JPY3.8bn, with R&D expenses dropping 39.3% YoY to JPY1.8bn. Although the company
incurred expenses for conducting clinical trials of intravenous and oral formulations of Treakisym® and rigosertib, R&D expenses
fell nonetheless in the absence of JPY1.4bn in-licensing expenses for liquid formulation products of Treakisym® (RTD and RI
formulations) in FY12/17. Excluding the drop in R&D expenses, SG&A expenses would have risen by 1.8% YoY to JPY2.0bn.
As a result, operating loss, recurring loss, and net loss shrank YoY.
Sales fell short of full-year forecast of JPY4.2bn. On an NHI drug reimbursement price basis, SymBio had anticipated full-year salesof JPY10.1bn (+32.9% YoY), but for the two reasons outlined below, sales on a drug price basis only came to JPY8.5bn.

▷ Treakisym® distributor Eisai adopted a greater focus on sales of its own products, against which backdrop SymBio finished
FY12/18 with ten highly specialized product managers for Treakisym®, up from five as of December 2017.

▷ In December 2018, a batch of Treakisym® 25mg imported from Astellas Deutschland GmbH was determined to be unsalable due
to its poor external appearance, prompting a temporary halt to imports and domestic shipments of the 25mg dosage.

Progress made in the company’s main businesses in FY12/18 was as follows:▷ Regarding anticancer agent Treakisym®, the company began a phase III clinical trial for the additional indication of relapsed or

refractory diffuse large B-cell lymphoma (DLBCL), and completed enrollment of the first patient in January 2018. As of February 6,

2019, the company had enrolled 35 patients, versus its target of 60.

▷ In July 2018, the company obtained approval for a partial change to its manufacture and marketing authorization for Treakisym®,
allowing its combined use with not only rituximab but also obinutuzumab (once it is launched), for the treatment of low-grade
non-Hodgkin’s lymphoma (low-grade NHL).

▷ Also in July 2018, Treakisym® was newly included as a standard treatment option in the revised Clinical Practice Guidelines 2018
for healthcare professionals as a standard therapy.

▷ In April 2018, the company raised JPY10,413mn (net of expenses) through the issuance of 45th through 47th stock acquisitionrights with exercise price revision clauses (Commit Issue Program) in order to secure the fund it needed during the three years
from 2018 through 2020. The proceeds, which are slated for use between April 2018 and December 2020, will go to thedevelopment of in-licensed drugs (JPY4.7bn) and creation of an independent sales structure (JPY3.3bn). All of the 45th stockacquisition rights were exercised as of October 2018 (20mn units, 20mn shares), raising JPY2.6bn in net proceeds.

▷ In September 2018, the company applied for approval of a partial revision to manufacture and marketing approval of Treakisym®
to enable its use as a pretreatment agent for regenerative medicine products.

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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp▷ In October 2018, the company announced that it had begun preparing for the sale of Treakisym® through its own sales structure.
The business alliance agreement the company had concluded with Eisai Co., Ltd. in 2008 regarding the sale of Treakisym® will

expire in December 2020. The company began making preparations to build its own sales structure to sell Treakisym® in Japanafter the agreement expires. With an eye toward FY12/21, the company plans to establish a sales structure highly specialized forhematologic disorders, and use the structure to sell rigosertib (IV and oral formulation) targeting myelodysplastic syndrome(MDS) currently under development in addition to Treakisym®.

▷ In November 2018, the company commenced a clinical trial of Treakisym® liquid formulation (rapid infusion [RI] formulation,

intravenous administration for 10 minutes), primarily to verify the drug’s safety. A total of 36 patients are enrolled in the clinical
trial, and the company plans to apply for approval of the RI formulation upon completion of the trial, with plans to launch in
2022.

Domestic
Preparations for in-house sales organization begin
In October 2018, SymBio announced that it had started preparing to build an in-house sales organization for Treakisym® in thedomestic market. The business alliance agreement the company reached with Eisai in 2008 regarding the sale of Treakisym® will
expire in December 2020. The company considered all of its business development options including business alliances withother companies, but concluded that it was best to move to its own sales organization to better look after its patients’ interestsand maximize the business value. SymBio is considering the organizational structure and personnel requirements ahead of theshift to its own sales organization from early FY12/21, and planning appropriate investments in building systems and creating thenecessary logistics infrastructure. These initiatives will help it engage in sophisticated marketing and enable a quality productsupply structure. The company aims to move into the black in FY12/21 and post ongoing profit growth thereafter.

Treakisym® (SyB L-0501[lyophilized injection]/SyB L-1701 [RTD]/SyB L-1702 [RI]/SyB C-0501 [oral]; anticancer agent; generic name:bendamustine hydrochloride)The company markets the anticancer agent Treakisym® in Japan through its business partner, Eisai Co., Ltd. (TSE1: 4523) for theindications of untreated low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma (marketing approval obtained in
December 2016), refractory or relapsed low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma (October 2010), andchronic lymphocytic leukemia (August 2016).
As a result of additional indications, Treakisym® is steadily increasing its market share in the area of first-line treatment in medical
settings by replacing R-CHOP, the conventional standard treatment. The combination therapy of Treakisym® and rituximab (BRtherapy) was newly included in the Practical Guidelines for Hematological Malignancies 2018 edited and published by JapaneseSociety of Hematology as a standard treatment option. This has seen Treakisym® establish its position as a standard treatment for
lymphatic cancer. Sales of Treakisym® based on the National Health Insurance (NHI) drug price grew steadily by 11.6% YoY.
In addition to the above three approved indications, the company has started Phase III clinical trials for the fourth indication of
relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) and is currently enrolling patients for the trial with an aim to
obtain approval. In response to strong medical needs, the company began phase III clinical trials in August 2017, and with theenrollment of the first patient in January 2018, is working on enrolling patients.
In addition to efforts for new indications, in September 2017, the company concluded an exclusive licensing agreement with
Eagle Pharmaceuticals (based in New Jersey, US) to develop, market, and sell liquid formulations of Treakisym® (RTD and RI
formulations) in Japan for Treakisym®’s product life cycle management. The RTD and RI products offer significant value added(reduced burden) to patients and healthcare professionals, and extend Treakisym®’s product life cycle until 2031. The company
has already consulted with PMDA and is preparing to file for approval of the RTD formulation. SymBio launched clinical trials for
the RI formulation in November 2018 primarily to confirm safety.

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In July 2018, SymBio obtained approval for the partial revision to the marketing authorization of Treakisym®. As a result,
Treakisym® can now be used in combination with not only rituximab but also obinutuzumab (launched in August 2018) for thetreatment of CD 20-positive follicular lymphoma (FL), the most common histological type of low-grade NHL, enabling thecompany to provide patients with a new treatment therapy. According to the company, as of July 2018 there were nearly 100
drugs for lymphatic malignancies being developed in the US and Europe combining BR (bendamustine and rituximab) or justbendamustine with anti-CD20 antibodies (20 in phase III clinical trial, 67 in phase II, and six in phase I). The development of atreatment therapy combining immune checkpoint inhibitors with BR or just bendamustine is also under way. SymBio thinks theapproval of these therapies will lead to increased market penetration and recognition of Treakisym®, without development costs.
In September 2018, the company applied for approval of a partial revision to the marketing authorization of Treakisym® to enable
its use as a pretreatment agent for regenerative medical products.
To reinforce the position of Treakisym® at the core of its business to strengthen its business foundation, SymBio is developing anoral formulation of the drug in addition to the injection currently under development or on sale. The company commenced aphase I clinical trial for progressive solid tumors in January 2018, with the aim of examining the recommended dosage andschedule as well as tolerability and safety of the oral formulation of Treakisym®, and narrowing down the types of potential target
tumors. With the enrollment of the first patient in May 2018, the company is currently working on enrolling more patients for thetrial. To evaluate the effect of oral administration of Treakisym® on the immune system, the company concluded a joint research
agreement with Keio University in May 2018 and began a preclinical study to verify the efficacy of the oral form of Treakisym® intreating systemic lupus erythematosus (SLE), a form of autoimmune disease.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, is currently conducting a global Phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015 (40 patients enrolled as of end-December 2018). The global Phase III trial addresses higher-risk
myelodysplastic syndromes (higher-risk MDS), which do not respond to the current standard treatment with hypomethylating
agents, which relapse after treatment under the current standard of care, or which are intolerant to hypomethylating agents, andis under way at clinical trial sites in more than 20 countries worldwide. Patient enrollments are smoothly accumulating. Based on
the results of an interim analysis performed in January 2018, SymBio decided to continue the trial in an adoptive design agreed
upon in advance with the US Food and Drug Administration (FDA), increasing the number of patient enrollment in accordancewith pre-determined statistical criteria. Based on these results, the company plans to apply for approval in Japan at the same time
as in the US and Europe.
Regarding the oral formulation of rigosertib, Onconova is conducting Phase I/II clinical trials for the drug used in combination
with azacytidine as first-line treatment for higher-risk MDS and Phase II clinical trials for transfusion-dependent lower-risk MDS in
the US. To verify the tolerability and safety of the oral formulation of rigosertib among Japanese patients, SymBio began Phase I
clinical trials in Japan in June 2017 and is steadily enrolling patients. After completing the Phase I trials, the company plans topromptly start clinical trials for rigosertib used in combination with azacytidine, participate in international Phase III clinical trialsof the drug used in combination with azacytidine as first-line treatment for higher-risk MDS Onconova is planning, and apply for
approval of the oral formulation of the drug in Japan at the same time as in the US and Europe. In regards to development ofrigosertib for transfusion-dependent lower-risk MDS, the company is considering participating from Japan while monitoring
Onconova’s development progress.

SyB P-1501, a post-operative patient-controlled analgesia
Regarding SyB P-1501 licensed by the Medicines Company (through its wholly owned subsidiary Incline Therapeutics, Inc.) in
October 2015, SymBio found a fact that raised concerns about the continuity of its business, and in the interests of patient
welfare, it suspended further patient enrollment in April 2017. The license agreement was terminated in November 2017, andthe development of the drug was terminated in February 2018.
The Company initiated an arbitration against The Medicines Company in October 2017, under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s
repudiation of the license agreement. Arbitration proceedings against The Medicines Company are still ongoing.

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New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. The company is considering licensing rights for several drug candidates. Further, in May 2016, the company
established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base for overseas business development.
The company looks to leverage this subsidiary to actively acquire rights over new drug development candidates globally, andengage in development and commercialization in major markets including the US, Japan, and Europe to transition to a global
specialty pharmaceutical company.

Overseas
The company marketed SyB L-0501 in South Korea, Taiwan, and Singapore, and product sales exceeded the company's plans.

Q3 FY12/18 results
Cumulative Q3 FY12/18 sales totaled JPY3.0bn (+25.5% YoY) mainly owing to domestic sales of Treakisym®.
Due to sales growth, gross profit rose 37.0% YoY to JPY924mn with the gross profit margin increasing 2.6pp YoY to 30.5%.
SG&A expenses fell 32.3% YoY to JPY2.8bn due to a 52.3% YoY drop in R&D expenses to JPY1.3bn, which included expenses for
conducting clinical trials of intravenous and oral formulations of Treakisym® and rigosertib. Excluding the drop in R&D expenses,
SG&A expenses would have risen by 4.6% YoY to JPY1.5bn.
As a result, operating loss narrowed to JPY1.9bn (versus a loss of JPY3.5bn in Q3 FY12/17). Recurring loss was JPY1.9bn (versus aloss of JPY3.5bn in Q3 FY12/17) due in part to the booking of non-operating expenses of JPY34mn (mainly on share issuancecosts). Net loss was JPY1.9bn (versus a loss of JPY3.5bn in Q3 FY12/17). Losses were in line with the company's forecast.
Progress made in Q3 FY12/18 was as follows:▷ Regarding anticancer agent Treakisym®, the company began a phase III clinical trial for the additional indication of relapsed or
refractory diffuse large B-cell lymphoma (DLBCL), and completed enrollment of the first patient in January 2018.

▷ In January 2018, the company began a phase I clinical trial of oral Treakisym® for progressive solid tumors, aiming to examine therecommended dosage and dosage regimen, along with tolerability and safety of the formulation, and to identify potential target
tumor types.

▷ In May 2018, with a view to evaluate the effect of oral administration of Treakisym® on the immune system, the company

concluded a joint research agreement with Keio University to conduct a pre-clinical study to verify the therapeutic value of theformulation in the treatment of systemic lupus erythematosus (SLE), a form of autoimmune disease.

▷ In July 2018, the company obtained approval for a partial change to its manufacture and marketing authorization for Treakisym®,
allowing its combined use with not only rituximab but also obinutuzumab (once it is launched), for the treatment of low-grade
non-Hodgkin’s lymphoma (low-grade NHL).

▷ Also in July 2018, Treakisym® was newly included as a standard treatment option in the revised Clinical Practice Guidelines 2018
for healthcare professionals as a standard therapy.

▷ Regarding Rigosertib (IV form), based on the results of an interim analysis performed in January 2018, the company decided tocontinue the trial after increasing the number of patient enrollment in accordance with pre-determined statistical criteria.

▷ In February 2018, the company terminated development of patient-controlled pain management drug SyB P-1501.

▷ In April 2018, the company raised JPY10,413mn (net of expenses) through the issuance of 45th through 47th stock acquisitionrights with exercise price revision clauses (Commit Issue Program) in order to secure the fund it needed during the three years
from 2018 through 2020. The proceeds, which are slated for use between April 2018 and December 2020, will go to the

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development of in-licensed drugs (JPY4.7bn) and creation of an independent sales structure (JPY3.3bn). All of the 45th stockacquisition rights were exercised as of October 2018, raising JPY2.6bn in net proceeds.

▷ In September 2018, the company applied for approval of a partial revision to manufacture and marketing approval of Treakisym®
to enable its use as a pretreatment agent for regenerative medicine products.

▷ In October 2018, the company announced that it had begun preparing for the sale of Treakisym® through its own sales structure.
The business alliance agreement the company had concluded with Eisai Co., Ltd. in 2008 regarding the sale of Treakisym® will

expire in December 2020. The company began making preparations to build its own sales structure to sell Treakisym® in Japanafter the agreement expires. With an eye toward FY12/21, the company plans to establish a sales structure highly specialized forhematologic disorders, and use the structure to sell rigosertib (IV and oral formulation) targeting myelodysplastic syndrome(MDS) currently under development in addition to Treakisym®.

Domestic
Treakisym® (SyB L-0501[lyophilized injection]/SyB L-1701 [RTD]/SyB L-1702 [RI]/SyB C-0501 [oral]; anticancer agent; generic name:bendamustine hydrochloride)The company markets the anticancer agent Treakisym® in Japan through its business partner, Eisai Co., Ltd. (TSE1: 4523) for theindications of relapsed or refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL), untreatedlow-grade NHL and MCL, and chronic lymphocytic leukemia (CLL). (The company obtained marketing approval for relapsed or
refractory low-grade NHL and MCL in October 2010, for untreated low-grade NHL and MCL in December 2016, and for CLL in
August 2016.)
As a result of additional indications, Treakisym® is steadily increasing its market share in the area of first-line treatment byreplacing R-CHOP, the conventional standard treatment. The combination therapy of Treakisym® and rituximab (BR therapy) was
newly included in the Practical Guidelines for Hematological Malignancies 2018 edited and published by Japanese Society of
Hematology as a standard treatment option. Sales of Treakisym® based on the National Health Insurance (NHI) drug price grewsteadily by 15.2% YoY, and product sales to Eisai also progressed in line with plan.
In addition to the above three approved indications, the company has started phase III clinical trials for the fourth indication of
relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and is currently enrolling patients for the trial with an aim to obtainapproval. In response to strong medical needs, the company began phase III clinical trials in August 2017, and with theenrollment of the first patient in January 2018, is working on enrolling patients.
In addition to efforts for new indications, in September 2017, the company concluded an exclusive licensing agreement with
Eagle Pharmaceuticals (based in New Jersey, US) to develop, market, and sell liquid formulations of Treakisym® (RTD and RI
formulations) in Japan for Treakisym®’s product life cycle management. The RTD and RI products offer significant value added topatients and healthcare professionals, and extend Treakisym®’s product life cycle until 2031. The company has already consulted
with PMDA on the details of the application for approval of the RTD formulation and clinical trial design for the RI formulation,and is preparing for obtaining approval and launching Treakisym® liquid formulation in 2021 or later.
In July 2018, SymBio obtained approval for the partial revision to the marketing authorization of Treakisym®. As a result,
Treakisym® can now be used in combination with not only rituximab but also obinutuzumab (launched in August 2018) for thetreatment of CD 20-positive follicular lymphoma (FL), the most common histological type of low-grade NHL, enabling thecompany to provide patients with a new treatment therapy. According to the company, as of July 2018 there were over 160
drugs for lymphatic malignancies being developed in the US and Europe combining BR (bendamustine and rituximab) or justbendamustine with anti-CD20 antibodies (19 in phase III clinical trial, 104 in phase II, and 42 in phase I). The development of atreatment therapy combining immune checkpoint inhibitors with BR or just bendamustine is also under way. SymBio thinks theapproval of these therapies will lead to increased market penetration and recognition of Treakisym®, without development costs.
Further, in September 2018 the company applied for approval of a partial revision to the marketing authorization of Treakisym® toenable its use as a pretreatment agent for regenerative medical products.

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To reinforce the position of Treakisym® at the core of its business to strengthen its business foundation, SymBio is developing anoral formulation of the drug in addition to the injection currently under development or on sale. The company commenced aphase I clinical trial for progressive solid tumors in January 2018, with the aim of examining the recommended dosage andschedule as well as tolerability and safety of the oral formulation of Treakisym®, and narrowing down the types of potential target
tumors. With the enrollment of the first patient in May 2018, the company is currently working on enrolling more patients for thetrial. To evaluate the effect of oral administration of Treakisym® on the immune system, the company concluded a joint research
agreement with Keio University in May 2018 and began a preclinical study to verify the efficacy of the oral form of Treakisym® intreating systemic lupus erythematosus (SLE), a form of autoimmune disease.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, is currently conducting a global phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015 (37 patients enrolled so far). The global phase III trial addresses higher-risk myelodysplastic
syndromes (higher-risk MDS), which do not respond to the current standard treatment with hypomethylating agents, which
relapse after treatment under the current standard of care, or which are intolerant to hypomethylating agents, and is under way
at clinical trial sites in more than 20 countries worldwide. Patient enrollments are smoothly accumulating. Based on the results ofan interim analysis performed in January 2018, SymBio decided to continue the trial in an adoptive design agreed upon inadvance with the US Food and Drug Administration (FDA), increasing the number of patient enrollment in accordance withpre-determined statistical criteria. Based on these results, the company plans to apply for approval in Japan at the same time as in
the US and Europe.
Regarding the oral formulation of rigosertib, Onconova is conducting phase I/II clinical trials for the drug used in combination
with azacitidine as first-line treatment for higher-risk MDS and phase II clinical trials for transfusion-dependent lower-risk MDS in
the US. To verify the tolerability and safety of the oral formulation of rigosertib among Japanese patients, SymBio began phase I
clinical trials in Japan in June 2017 and is steadily enrolling patients. After completing the phase I trials, the company plans topromptly start clinical trials for rigosertib used in combination with azacitidine, participate in global phase III clinical trials of the
drug used in combination with azacitidine as first-line treatment for higher-risk MDS Onconova is planning, and apply for
approval of the oral formulation of the drug in Japan at the same time as in the US and Europe. In regards to development ofrigosertib for transfusion-dependent lower-risk MDS, the company is considering participating from Japan while monitoring
Onconova’s development progress.

SyB P-1501, a post-operative patient-controlled analgesia
Regarding SyB P-1501 licensed by the Medicines Company (through its wholly owned subsidiary Incline Therapeutics, Inc.) in
October 2015, SymBio found a fact that raised concerns about the continuity of its business, and in the interests of patient
welfare, it suspended further patient enrollment in April 2017. The license agreement was terminated in November 2017, andthe development of the drug was terminated in February 2018.
The Company initiated an arbitration against The Medicines Company in October 2017, under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s
repudiation of the license agreement. Arbitration proceedings against The Medicines Company are still ongoing.

New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. The company is considering licensing rights for several drug candidates. Further, in May 2016, the company
established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base for overseas business development.
The company looks to leverage this subsidiary to actively acquire rights over new drug development candidates globally, andengage in development and commercialization in major markets including the US, Japan, and Europe to transition to a global
specialty pharmaceutical company.

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Overseas
The company marketed SyB L-0501 in South Korea, Taiwan, and Singapore, and sales were largely in line with plans.

1H FY12/18 results
1H FY12/18 sales totaled JPY1.9bn (+8.0% YoY) mainly owing to domestic sales of Treakisym®, which increased 22.3% YoY basedon the National Health Insurance (NHI) drug price. Overseas sales of Treakisym® also increased by over 20% YoY. Productshipment to Eisai Co., Ltd. at end-Q2 was pushed back to Q3. Excluding this factor, overall sales increased 21% YoY.
Due to the sales increase, gross profit came to JPY573mn (+12.4% YoY). Gross profit margin was 29.7% (+1.2pp).
SG&A expenses rose 8.7% YoY to JPY1.9bn. R&D expenses came in at JPY839mn (-0.1% YoY). There were expenses for clinical
trials for intravenous and oral formulations of Treakisym® and rigosertib. SG&A expenses excluding R&D expenses were up 16.9%
at JPY1.1bn. In an effort to bolster marketing of Treakisym®, the company hired additional product managers who are highly
specialized and capable of providing product information, but these additions led to higher personnel costs.
As a result, operating loss totaled JPY1.3bn (loss of JPY1.2bn in 1H FY12/17). The company also reported a recurring loss of
JPY1.4bn (loss of JPY1.3bn in 1H FY12/17) partly due to non-operating expenses of JPY54mn (mainly on forex losses). Net loss was
JPY1.4bn (loss of JPY1.3bn in 1H FY12/17).
Progress made in 1H FY12/18 was as follows.

▷ Regarding anticancer agent Treakisym®, the company began a phase III clinical trial for the additional indication of relapsed or
refractory diffuse large B-cell lymphoma (DLBCL), and completed enrollment of the first patient in January 2018.

▷ In January 2018, the company began a phase I clinical trial of oral Treakisym® for progressive solid tumors, aiming to examine therecommended dosage and dosage regimen, along with tolerability and safety of the formulation, and to identify potential target

tumor types.

▷ In May 2018, with a view to evaluate the effect of oral administration of Treakisym® on the immune system, the company

concluded a joint research agreement with Keio University to conduct a pre-clinical study to verify the therapeutic value of theformulation in the treatment of systemic lupus erythematosus (SLE), a form of autoimmune disease.

▷ In July 2018, the company obtained approval for a partial change to its manufacture and marketing authorization for Treakisym®,
allowing its combined use with not only rituximab but also obinutuzumab (once it is launched), for the treatment of low-grade
non-Hodgkin’s lymphoma (low-grade NHL).

▷ Also in July 2018, Treakisym® was newly included as a standard treatment option in the revised Clinical Practice Guidelines 2018
for healthcare professionals as a standard therapy.

▷ Regarding Rigosertib (IV form), based on the results of an interim analysis performed in January 2018, the company decided tocontinue the trial after increasing the number of patient enrollment in accordance with pre-determined statistical criteria.

▷ In February 2018, the company terminated development of patient-controlled pain management drug SyB P-1501.

▷ In April 2018, the company raised JPY10,413mn (net of expenses) through the issuance of 45th through 47th stock acquisitionrights with exercise price revision clauses (Commit Issue Program) in order to secure the funds it needed during the three years
from 2018 through 2020. The proceeds, which are slated for use between April 2018 and December 2020, will go to thedevelopment of in-licensed drugs (JPY4.7bn) and creation of an independent sales structure (JPY3.3bn).

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Domestic
Treakisym® (SyB L-0501/SyB L-1701 (RTD) /SyB L-1702 (RI) /SyB C-0501 (oral); anticancer agent; generic name: bendamustinehydrochloride)The company markets the anticancer agent Treakisym® in Japan through its business partner, Eisai Co., Ltd. (TSE1: 4523) for theindications of relapsed or refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL), untreatedlow-grade NHL and MCL, and chronic lymphocytic leukemia (CLL). (The company obtained marketing approval for relapsed or
refractory low-grade NHL and MCL in October 2010, for untreated low-grade NHL and MCL in December 2016, and for CLL in
August 2016.)
As a result of additional indications, Treakisym® is steadily increasing its market share in the area of first-line treatment byreplacing R-CHOP, the conventional standard treatment, and sales of Treakisym® based on the National Health Insurance (NHI)
drug price grew significantly by22.3% YoY. Product sales to Eisai is also progressing in line with plan.
According to the company, the market share of Treakisym® targeting relapsed or refractory low-grade non-Hodgkin’s lymphoma(NHL) and mantle cell lymphoma (MCL) was around 60%. Further, the market share of BR therapy (use of rituximab in
combination with Treakisym®) targeting untreated low-grade NHL reached around 55% as of July 2018, exceeding that of the
R-CHOP (combination of rituximab with chemotherapy drugs cyclophosphamide, doxorubicin, vincristine, and prednisolone)therapy.
In July 2018, Treakisym® was newly included as a standard treatment option in the Guidelines for Tumors of Hematopoietic andLymphoid Tissues 2018 issued by the Japan Society of Hematology. The guidelines were revised to include as indications ofTreakisym® mantle cell lymphoma and chronic lymphocytic leukemia in addition to relapsed or refractory low-grade B-cell
non-Hodgkin’s lymphoma. Further, Treakisym® was newly included as a treatment option for untreated low-grade NHL.
According to the company, inclusion of all approved indications of Treakisym® in the guidelines positioned the drug as standard
treatment for malignant lymphoma. The company believes these developments will lead to further market penetration ofTreakisym®.
In addition to the aforementioned three approved indications, the company has started phase III clinical trials for the fourth
indication of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and is currently enrolling patients for the trial with an
aim to obtain approval. In response to strong medical needs, the company finished consultation with the Pharmaceuticals andMedical Devices Agency (PMDA) and began phase III clinical trials toward the addition of an indication in August 2017, enrollingthe first patient in January 2018. As of end-July 2018, patient enrollment has reached 20.
In September 2017, the company concluded an exclusive licensing agreement with Eagle Pharmaceuticals (based in New Jersey,US) to develop, market, and sell liquid formulations of Treakisym® (RTD and RI formulations) in Japan for Treakisym®’s product life
cycle management. The RTD and RI products offer significant value added to patients and healthcare professionals, and extend
Treakisym®’s product life cycle until 2031. The company has already consulted with PMDA on the details of the application for
approval of the RTD formulation and clinical trial design for the RI formulation. It looks to launch Treakisym® liquid formulation in
Japan in 2021 or later, and is preparing application documents for the RTD formulation and creating a clinical trial plan for the RI
formulation.
In July 2018, SymBio obtained approval for the partial revision to the marketing authorization. As a result, Treakisym® can now be
used in combination with not only rituximab but also anti-CD20 antibodies for the treatment of low-grade NHL, enabling thecompany to provide patients with a new treatment therapy. According to the company, as of July 2018, there were over 160
drugs for lymphatic malignancies being developed in the US and Europe combining BR (bendamustine and rituximab) or justbendamustine with anti-CD20 antibodies (19 in phase III clinical trial, 104 in phase II, and 42 in phase I). The development of atreatment therapy combining immune checkpoint inhibitors with BR or just bendamustine is also under way. SymBio thinks theapproval of these therapies will lead to increased market penetration and recognition of Treakisym®, without development costs.

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SymBio will explore further expansion of the Treakisym® business by developing an oral formulation in addition to the injection
currently under development or on sale to treat solid tumors and autoimmune diseases. In this context, the company
commenced a phase I clinical trial for progressive solid tumors in January 2018, with the aim of examining the recommended
dosage and schedule as well as tolerability and safety of the oral formulation of Treakisym®, and narrowing down the types ofpotential target tumors. The enrollment of the first patient was completed in May 2018, and four patients have been enrolled asof end-July 2018. To evaluate the effect of oral administration of Treakisym® on the immune system, the company concluded a
joint research agreement with Keio University in May 2018 and began a preclinical study to verify the efficacy of the oral form ofTreakisym® in treating systemic lupus erythematosus (SLE), a form of autoimmune disease.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, is currently conducting a global phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015 (36 patients enrolled so far). The global phase III trial addresses higher-risk myelodysplastic
syndromes (MDS), which do not respond to the current standard treatment with hypomethylating agents, which relapse after
treatment under the current standard of care, or which are intolerant to hypomethylating agents, and is under way at clinical trialsites in more than 20 countries worldwide. Patient enrollments are smoothly accumulating. Based on the results of an interim
analysis performed in January 2018, SymBio decided to continue the trial, increasing the number of patient enrollment inaccordance with pre-determined statistical criteria. Based on these results, the company plans to apply for approval in Japan at
the same time as in the US and Europe.
Regarding the oral formulation of rigosertib, Onconova is conducting phase I/II clinical trials for the drug used in combination
with azacitidine as first-line treatment for higher-risk MDS and phase II clinical trials for transfusion-dependent lower-risk MDS in
the US. To verify the tolerability and safety of the oral formulation of rigosertib among Japanese patients, SymBio began phase I
clinical trials in Japan in June 2017 and six patients have been enrolled as of end-July 2018. After completing the phase I trials, thecompany plans to promptly start clinical trials for rigosertib used in combination with azacitidine, participate in global phase III
clinical trials of the drug used in combination with azacitidine as first-line treatment for higher-risk MDS Onconova is planning,
and apply for approval of the oral formulation of the drug in Japan at the same time as in the US and Europe. In regards todevelopment of rigosertib for transfusion-dependent lower-risk MDS, the company is considering participating from Japan while
monitoring Onconova’s development progress.

SyB P-1501, a post-operative patient-controlled analgesia
Regarding SyB P-1501 licensed by the Medicines Company (through its wholly owned subsidiary Incline Therapeutics, Inc.) in
October 2015, SymBio found a fact that raised concerns about the continuity of its business, and in the interests of patient
welfare, it suspended further patient enrollment in April 2017. The license agreement was terminated in November 2017, andthe development of the drug was terminated in February 2018.
The Company initiated an arbitration against The Medicines Company in October 2017, under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s
repudiation of the license agreement. Arbitration proceedings against The Medicines Company are still ongoing.

New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. The company is considering licensing rights for several drug candidates. Further, in May 2016, the company
established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base for overseas business development.
The company looks to leverage this subsidiary to actively acquire rights over new drug development candidates globally, andengage in development and commercialization in major markets including the US, Japan, and Europe to transition to a global
specialty pharmaceutical company.

Overseas
The company marketed SyB L-0501 in South Korea, Taiwan, and Singapore, and sales were largely in line with plans.

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Full-year FY12/17 results
FY12/17 sales totaled JPY3.4bn (+45.4% YoY) thanks to domestic sales of Treakisym®. Sales broke down into product sales of
JPY3.4bn (+61.1% YoY) and zero royalty revenue (JPY231mn in FY12/16).
The company obtained approval for additional indications for Treakisym® of first-line treatment of low-grade malignant NHL and
MCL in December 2016. Sales of Treakisym® indicated for first-line treatment of low-grade malignant NHL and MCL overall
Treakisym® sales (product sales). For royalty revenue, the company booked revenue for reaching a sales milestone of SyB L-0501
in Taiwan in FY12/16, but received no milestone payments in FY12/17.
Due to the sales increase, gross profit came to JPY1.0bn (+14.1% YoY). Gross profit margin was 29.9% (-8.2pp). GPM fell in
FY12/17, because the company received no milestone payments as note above, and GPM on product sales fell 1.6pp.
SG&A expenses rose 64.2% YoY to JPY5.0bn. R&D expenses increased 81.0% to JPY3.0bn. There were expenses for clinical trials
for Treakisym®, the intravenous and oral formulations of Rigosertib Sodium and SyB P-1501, and the USD12.5mn cost of
in-licensing liquid formulation products of Treakisym® (RTD and RI formulations). SG&A expenses excluding R&D expenses wereup 43.7% at JPY2.0bn. Fees and commissions paid totaled JPY567mn (+313.2%) due to an increase in expert consultations.
As a result, operating loss totaled JPY4.0bn (loss of JPY2.1bn in FY12/16). The company also reported a recurring loss of JPY4.0bn(loss of 2.3bn in FY12/16), partly due to non-operating expenses of JPY34mn (mainly on share issuance costs of JPY14mn, forex
losses of JPY10mn, and fees and commissions paid of JPY9mn). Net loss was JPY4.0bn (loss of JPY2.3bn in FY12/16).
Progress made in FY12/17 was as follows.

▷ The company announced in August 2017 that it would begin phase III clinical trials in Japan for anticancer agent Treakisym® forthe additional indication of relapsed or refractory diffuse large B-cell lymphoma (DLBCL; aggressive NHL), and registered the first
patient in January 2018.

▷ In January 2018, the company began phase I clinical trials of oral Treakisym®, targeting indication for progressive solid tumors.

▷ In June 2017, the company restarted domestic phase I clinical trials for oral Rigosertib, because the supply of the study drug had
resumed, and registered the first patient in October 2010.

▷ The Medicines Company (MDCO) had filed a report (Form 8-K) with the US Securities and Exchange Commission in June 2017
stating that it would withdraw the patient-controlled pain management drug IONSYS® (SyB P-1501) from the US market andsuspend commercial activities. In May 2017, SymBio announced temporary suspension of new patient enrollment in thedomestic phase III clinical trial of SyB P-1501. In October 2017, the company initiated an arbitration against MDCO under therules of the International Chamber of Commerce, seeking damages of USD82mn (approximately JPY9bn) arising from MDCO’s
repudiation of the license agreement.

▷ In November 2017, the company announced that the license agreement it had entered with MDCO for the exclusive rights todevelop and commercialize SyB P-1501 (IONSYS in the US) for the short-term management of acute post-operative pain has

terminated. In conjunction with the termination of the license agreement, the development of SyB P-1501 was terminated in
February 2018.

▷ In August 2017, the company announced the subscription for its 42nd stock acquisition rights by third-party allotment(8,800,000 residual shares corresponding to 17.97% of outstanding shares) to raise JPY1.9bn on an estimated net proceeds basis,
and all stock acquisition rights were exercised as of January 2018. The funds are mainly to be used for expenses related todevelopment of Treakisym® indicated for relapsed or refractory DLBCL (aggressive NHL) totaling JPY900mn and expenses for
obtaining rights to the oral formulation of Treakisym® and development after obtaining the rights totaling JPY1.0bn.

▷ In September 2017, the company concluded a license agreement with Eagle Pharmaceuticals, Inc. (Eagle) for bendamustinehydrochloride ready-to-dilute (RTD) and rapid infusion (RI) injection products. The agreement licenses to SymBio rights to

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develop, market, and sell Eagle’s bendamustine hydrochloride RTD and RI injection products (marketed in the US by Teva
Pharmaceutical Industries as BENDEKA®) in Japan.

Domestic
Treakisym® (SyB L-0501/SyB L-1701 (RTD) /SyB L-1702 (RI) /SyB C-0501 (oral); anticancer agent; generic name: bendamustinehydrochloride)The company markets the anticancer agent Treakisym® in Japan through its business partner, Eisai Co., Ltd. (TSE1: 4523) for theindications of relapsed or refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL), untreatedlow-grade NHL and MCL, and chronic lymphocytic leukemia (CLL).
As a result of additional indications, sales of Treakisym® based on the National Health Insurance (NHI) drug price grew 60.9% YoY,
and accordingly product sales to Eisai increased 62.7%.
In addition to the above three approved indications, the company has filed an NDA for a fourth indication to help patients whoneed new treatments and maximize the value of the product. The company has completed phase III clinical trials for relapsed or
refractory diffuse large B-cell lymphoma (DLBCL, or aggressive NHL). In response to strong medical needs, the company finishedconsultation with the Pharmaceuticals and Medical Devices Agency and began phase III clinical trials toward the addition of an
indication in August 2017, enrolling the first patient in January 2018.
In addition to ongoing efforts to add new indications, in September 2017, the company concluded an exclusive licensing
agreement with Eagle Pharmaceuticals (based in New Jersey, US) to develop, market, and sell liquid formulations of Treakisym®
(RTD and RI formulations) in Japan for Treakisym®’s product life cycle management. The RTD and RI products offer significant
value added to patients and healthcare professionals, and extends Treakisym®’s product life cycle until 2031.
SymBio is exploring further expansion of the Treakisym® business by developing an oral formulation in addition to the injection
currently under development or on sale to treat solid tumors and autoimmune diseases. In this context, the company
commenced a phase I clinical trial for progressive solid tumors in January 2018, with the aim of examining the recommended
dosage and schedule as well as tolerability and safety of the oral formulation of Treakisym®, and narrowing down the types ofpotential target tumors.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, is currently conducting a global phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015 (30 patients enrolled so far). The global phase III trial addresses higher risk myelodysplastic
syndrome (MDS) patients who do not respond to treatment or relapsed after treatment with hypomethylating agents (HMAs),
the current standard of care (“Primary HMA Failure”) and is under way at clinical trial sites in more than 20 countries worldwide.
The company completed the first patient enrollment in July 2016 and enrollments are smoothly accumulating. Based on the
results of an interim analysis performed in January 2018, SymBio decided to continue the trial, increasing the number of patient
enrollment in accordance with some pre-determined statistical criteria.
SymBio planned to start domestic phase I clinical trials for the oral form of Rigosertib (used in combination with azacitidine) for
higher-risk myelodysplastic syndrome (MDS), however, due to delays in the supply of drugs by Onconova for the trials, patient
enrollment did not make progress. Since Onconova resumed the supply of clinical trial materials, SymBio initiated a phase I
clinical trial in Japan in June 2017 and enrolled the first patient in October. The purpose of the Japanese phase I study is to confirm
the safety of high-dose oral rigosertib, which was added to the ongoing US phase II study by Onconova in untreated orrelapsed/refractory patients with higher-risk MDS. After demonstrating the safety of high-dose oral rigosertib, SymBio intends to
immediately recommence an oral rigosertib/azacitidine combination trial in Japan, and participate in the global phase III study inuntreated higher-risk MDS patients that Onconova is planning.

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SyB P-1501, a post-operative patient-controlled analgesia
The company started a domestic phase III clinical trial for SyB P-1501—licensed by the Medicines Company (through its wholly
owned subsidiary Incline Therapeutics) in October 2015—for the short-term management of acute post-operative pain duringhospitalization in June 2016. The company enrolled the first patient in November 2016 and was making progress with caseaccumulation. However, SymBio later found a fact that raises concerns about the continuity of The Medicines Company’s SyB
P-1501 business. In the interests of patient welfare, SymBio has suspended further patient enrollment since April 2017 and is intalks with The Medicines Company regarding how the SyB P-1501 clinical trial and commercialization in Japan would be affected.
The license agreement with Incline Therapeutics, Inc. was terminated in November 2017.
The Company initiated an arbitration against The Medicines Company in October 2017, under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s
repudiation of the license agreement.
In conjunction with the termination of the license agreement, the Company terminated the development of SyB P-1501 in
February 2018.

New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. At present, the company is considering licensing rights for several drug candidates. Further, in May 2016, thecompany established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base for overseas businessdevelopment. The company looks to leverage this subsidiary to actively acquire rights over new drug development candidates
globally, and engage in development and commercialization in major markets including the US, Japan, and Europe to transition
to a global specialty pharmaceutical company.

Overseas
The company marketed Treakisym® in Korea, Taiwan, and Singapore, and overseas sales were ahead of target.

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Income statement
FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

FY12/18(JPYmn)Sales

Income statement

Par.
1,191

Par.
1,450

Par.
1,883

Par.
1,955

Par.
1,532

Par.
1,955

Par.
1,933

Par.
2,368

Par.
3,444

Par.
3,836

YoY

-26.9%

1,191

21.7%

238
1,212

29.8%

1,224
658

1,362
593

3.9%

-21.6%

27.6%

1,428
527

1,350
583

-1.1%

22.5%

1,464
904

45.4%

2,413
1,031

11.4%

2,663
1,173

GPM

100.0%

83.6%

35.0%

30.3%

20.8%

26.9%

30.2%

38.2%

29.9%

30.6%

SG&A ratio

117.5%

125.8%-613

144.8%-2,067117.3%-1,700130.4%-1,68193.6%-1,303

162.1%-2,552128.0%-2,127144.5%-3,94799.8%-2,656

-

-

-

-

-

-

-

-

-

-

CoGS
Gross profit
SG&A expenses
Operating profit
YoY
OPM

Non-operating income
Non-operating expenses
Recurring profit

1,399

-208

2,293

1,999

1,830

3,135

3,031

4,978

3,829

13
38
-638

56
85
-2,0957
37-1,729114
35-1,601215
22-1,11017
96-2,6307
196-2,3175
34-3,9772
95-2,749

-

-

-

-

-

-

-

-

-

-

Extraordinary gains
Extraordinary losses
Tax charges
Implied tax rate

2,725

20
26
-214

YoY
RPM

Net income

1,825

1,214
318

4

-

0
4

-

5
4

-

0
4

-

4

-

2
3
4

-

3
1
4

-

9
1
4

-

17
15
4

-

10
10
4

-

-218

-642

-2,105-1,733-1,605-1,116-2,632-2,313-3,978-2,753

-

-

-

-

-

-

-

-

-

-

YoY
Net margin

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

See the Earnings Structure section for more information about specific items (from total sales to recurring profit) on thecompany’s income statement. There are no matters requiring special mention regarding non-operating profit/loss, extraordinary
profit/loss, corporate income tax, etc.

Historical forecast accuracy
Results vs. Initial Est.
(JPYmn)Sales (Initial Est.)
Sales (Results)
Results vs. Initial Est.
Operating profit (Initial Est.)
Operating profit (Results)
Results vs. Initial Est.
Recurring profit (Initial Est.)
Recurring profit (Results)
Results vs. Initial Est.
Net income (Initial Est.)
Net income (Results)
Results vs. Initial Est.

FY12/09Par.
-

FY12/10Par.
-

FY12/11
Par.
1,933
1,883
-2.6%
-2,351-2,067-2,398-2,095-2,407-2,105-

FY12/12
Par.
2,338
1,955
-16.4%-1,625-1,700-1,652-1,729-1,656-1,733-

FY12/13
Par.
1,927
1,532
-20.5%-1,889-1,681-1,922-1,601-1,926-1,605-

FY12/14
Par.
1,785
1,955
9.5%
-1,654-1,303-1,650-1,110-1,654-1,116-

FY12/15
Par.
1,785
1,933
8.3%
-1,654-2,552-1,650-2,630-1,654-2,632-

FY12/16
Par.
2,339
2,368
1.2%
-2,778-2,127-2,811-2,317-2,815-2,313-

FY12/17
Par.
2,903
3,444
18.6%
-3,238-3,947-3,303-3,977-3,306-3,978-

FY12/18
Par.
4,201
3,836
-8.7%
-2,981-2,656-3,044-2,749-3,056-2,753-

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.
Note: The company listed its common shares in October 2011, so the forecasts are from FY12/11 onward.

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Balance sheet
Balance sheet(JPYmn)AssetsCash and deposits
Marketable securities
Accounts receivable
Inventories
Other current assets
Total current assets
Buildings (net)
Tools, furniture, and fixtures (net)Total tangible fixed assets
Total other fixed assets
Software
Other
Total intangible fixed assets
Total fixed assets
Total assets

FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

FY12/18

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

3,902
219
97
4,218
3
11
13
27
2
2
42
4,261

2,314
1,701
6
191
4,213
3
19
22
27
1
1
50
4,263

4,559
1,953
162
207
297
7,178
2
15
17
48
10
3
13
78
7,256

4,540
300
148
165
268
5,421
3
11
14
57
8
3
11
82
5,502

6,163
1,100
125
245
7,634
2
6
9
37
6
2
8
53
7,687

5,692
899
273
245
181
7,290
22
27
49
49
62
4
66
164
7,454

4,261
301
133
131
4,827
22
31
53
53
51
1
52
158
4,984

5,719
487
273
205
6,685
31
43
75
77
42
42
193
6,878

2,947
490
363
237
4,037
28
18
47
100
66
3
69
216
4,252

4,821
412
534
271
6,038
37
20
57
73
51
20
71
201
6,239

182
23
205
-

1
124
52
178
-

309
278
59
646
-

330
196
73
599
-

207
44
251
-

306
143
39
488
-

322
553
68
942
450
1
451
1,394

604
331
76
1,011
1
1
1,013

726
504
107
1,336
1
1
1,338

Liabilities
Accounts payable
Accounts payable–other
Short-term debt
Other
Total current liabilities
Long-term debt
Corporate bonds
Other fixed liabilities
Total fixed liabilities
Total interest-bearing debt
Total liabilities
Net assets
Capital stock
Capital surplus
Retained earnings
Treasury stock
Subscription rights to shares
Total net assets

2
2
207

2
2
180

5
5
651

4
4
602

3
3
254

2
2
490

320
184
47
551
2
2
552

3,378
3,348
-2,666
4,054

3,711
3,681
-3,309
4,083

6,025
5,995
-5,413
-0
6,606

6,025
5,995
-7,146
-0
27
4,900

8,059
8,029
-8,752
-0
97
7,433

8,331
8,301
-9,868
-0
200
6,964

8,331
8,301
-12,500
-0
300
4,432

9,948
9,918
-14,813
-0
431
5,485

10,762
10,732-18,791
-0
537
3,239

12,973
12,943-21,543
-0
530
4,902

Working capital
Total interest-bearing debt
Net debt-3,9025-2,31461-4,559-17-4,540125-6,163212-5,692

114-4,261439-5,719249-2,947220-4,821

Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

Assets
SymBio does not have its own manufacturing facilities, clinical facilities or salesforce: the company outsources manufacturing,clinical development, and sales and marketing. Therefore, most of the company’s assets are cash and deposits.
Within current assets, inventory assets consist of Treakisym® merchandise inventory.

Liabilities
The company does not have interest-bearing liabilities. Booked liabilities are accounts payable and arrears.

Net assets
Capital and capital reserves are increasing as a result of fundraising efforts. However, the deficit in retained earnings is expanding
as the company continues to post losses.

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Cash flow statement
Cash flow statement(JPYmn)Cash flows from operating activities (1)Cash flows from investing activities (2)Free cash flow (1+2)
Cash flows from financing activities

FY12/09
Par.
-211
-4
-215
2,963

FY12/10
Par.
-754
-116
-870
663

FY12/11Par.
-2,074-117-2,1914,611

FY12/12Par.
-1,659-411-2,069-1

FY12/13
Par.
-1,677-1,332-3,0104,057

FY12/14Par.
-1,266
314
-952
544

FY12/15
Par.
-2,272
1,489
-783
-3

FY12/16Par.
-1,960-44-2,004
3,658

FY12/17Par.
-3,817-78-3,8941,164

FY12/18
Par.
-2,325-26-2,351
4,272

Capital expenditures (B)Working capital change (C)Simple FCF (NI + A + B - C)

4
-3
-217

7
-14
5
-655

8
-12
56
-2,1659-3-78-1,6508
142-1,73913-109
86-1,29824-24-98-2,53426-28
325-2,64030-57-190-3,81535-40-29-2,729Cash and cash equivalents (year-end)

4,121

3,916

6,311

4,240

5,294

5,092

4,261

5,719

2,947

4,821

Depreciation and good will amortization (A)Source: Shared Research based on company data.
Note: Figures may differ from company materials due to differences in rounding methods.

Cash flows from operating activities
Cash flows from operating activities almost matches the company’s current net loss before tax.

Cash flows from investing activities
Outlays on the purchase of tangible fixed assets and intangible assets are limited as SymBio outsources manufacturing, clinicaldevelopment, and sales and marketing. But investment in time deposits and securities meant outflow from investing activities
widened in FY12/12 and FY12/13. SymBio booked an inflow of JPY1.5bn in FY12/15 due to payments from time deposits and theredemption of securities.

Cash flows from financing activities
The company has reported a series of inflows from financing activities. As the table below shows, the company has raised capitalon multiple occasions in order to finance its operations in the face of continuous operating losses.
Main sources of funding
Date

Change in sharesissuedTotal sharesissuedChange in capitalstock and capital

Capital stock andcapital surplus

surplus (JPYmn)(JPYmn)Mar. 2009

7,404

66,017888

4,643 Paid-in private placement

Nov. 2009

8,334

90,268500

6,104 Paid-in private placement

Dec. 2009

9,553

100,651573

6,727 Paid-in private placement

Feb. 2011

11,032

122,769772

8,164 Paid-in private placement

Feb. 2011

17,368140,137

1,216

9,380 Paid-in private placement

Oct. 2011

5,100,000

19,130,900

2,628

12,019 Paid-in public offering (price determinedby the book building process)Jan. to Dec.
2013

3,921,257

23,052,157

1,244

13,263 Exercise of stock options attached to

Dec. 2013

6,720,200

convertible corporate bonds and otherstock options
29,772,357

2,504

15,767 Paid-in public offering (price determinedby the book building process)Dec. 2014

1,756,666

32,390,923

544

16,632 Exercise of stock options attached toconvertible corporate bonds and otherstock options

Jan. to Dec.
2016

14,139,901

46,530,824

3,235

19,867 Exercise of stock options attached toconvertible corporate bonds and otherstock options

Jan. to Dec.
2017

7,518,400

Apr. to Dec.
2018

28,349,700

54,049,224

1,627

21,493 Exercise of stock options attached toconvertible corporate bonds and otherstock options

82,398,924

4,422

25,915 Exercise of stock options

Source: Shared Research based on company data.

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Other information
Claim for damages
SymBio initiated arbitration against The Medicines Company, seeking damages of USD82mn
The license agreement the SymBio entered with The Medicines Company (MDCO) on October 5, 2015 for the exclusive rights todevelop and commercialize the patient-controlled pain management drug SyB P-1501 (IONSYS in the US) has terminatedeffective November 30, 2017, pursuant to the terms of the subject agreement.
As disclosed in MDCO’s Form 10-Q filing of November 9, 2017, the company initiated an arbitration against MDCO on October
11, 2017, under the rules of the International Chamber of Commerce, seeking damages of USD82mn (approximately JPY9bn)
arising from MDCO’s repudiation of the license agreement. In the Request for Arbitration, SymBio claims that MDCO failed toprovide SymBio with adequate assurances of performance of MDCO's contractual obligations under the license agreement in thelight of MDCO's decision to (1) discontinue and withdraw the drug (IONSYS®) from the markets in the US and EU and (2) ceaserelated commercialization activities. SymBio claims such failure by MDCO to be a repudiation and material breach of the license
agreement, resulting in its termination.
The International Chamber of Commerce, a Paris-based international organization, has around 130 participating countries including Japan. Its flagshipinstitution, the International Court of Arbitration, aims to solve disputes arising from international commercial agreements not by lawsuits, but by
arbitration. When one party does not obey the court’s judgment, the other party may perform compulsory execution.

History
SymBio was established in March 2005 by Fuminori Yoshida, former Corporate Vice President of Amgen Inc., and founding
President and CEO of the Japanese subsidiary, Amgen Japan. Mr. Yoshida’s desire to address the unmet medical needs of patientsin underserved markets often overlooked by the pharmaceutical industry due to limited patient numbers inspired him to create
SymBio Pharmaceuticals.
In 2013, Amgen Inc. was the largest biopharmaceutical company in the world by revenue. It was established in 1980 in Thousand Oaks, California as
Applied Molecular Genetics. Mr. Yoshida established Amgen Japan in May 1993, serving as President and CEO for 12 years prior to founding SymBio
Pharmaceuticals in March 2005. In February 2008, Takeda Pharmaceutical Co. Ltd. acquired Amgen Japan.

After its establishment, SymBio obtained financing totaling JPY1bn from Daiichi Pharmaceutical Co., Ltd. (now Daiichi Sankyo,
Inc.; TSE1: 4568), Medical & Biological Laboratories Co., Ltd. (JASDAQ: 4557), EPS Corporation (TSE1: 4282), and SBI Holdings,
Inc. (TSE1: 8473). The company used the cash raised to in-license its first drug candidate, bendamustine hydrochloride, from
Astellas Pharma GmbH in December 2005 with the exclusive right to develop and commercialize the drug in Japan.
After the global financial crisis of September 2008, the company experienced a shortage of capital as Treakisym® was advancing in
the clinic. Mr. Yoshida visited at least 50 venture capital firms in Japan and elsewhere in December 2008, eventually raising
JPY1.5bn in capital from Cephalon, Inc. (acquired by Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) in October 2011).
SymBio obtained Japanese marketing and manufacture approval for Treakisym® in October 2010 and began domestic sales in
December of that year.
As of February 2019, Treakisym® for relapsed or refractory low-grade NHL and MCL is the company’s mainstay product. Clinical
trials are also in preparation or under way toward attaining domestic approval for additional Treakisym® indication, RTD and RI
products of Treakisym®, and anticancer drug rigosertib for myelodysplastic syndromes.

March 2005

SymBio Pharmaceuticals Limited established with JPY30mn in capital.

December 2005

License Agreement finalized with Astellas Pharma GmbH for SyB L-0501 (bendamustine) development and

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commercialization rights in Japan.
March 2006
March 2007

Manufacturer's License (packaging, labeling and storage) obtained from Tokyo Metropolitan Government (License#13AZ200010).
Abeille Pharmaceuticals licensed SyB D-0701 (granisetron patch) to SymBio Pharmaceuticals for development &commercialization in Japan, China (HK), Taiwan, South Korea and Singapore.

March 2007

License Agreement finalized with Astellas Deutschland GmbH for SyB L-0501 (bendamustine) development &commercialization rights in China (HK), Taiwan, South Korea and Singapore.

August 2008

License Agreement finalized with Eisai Co., Ltd. for co-development and commercialization rights of SyB L-0501(bendamustine) in Japan.

March 2009

SymBio Pharmaceuticals concluded Sublicense Agreement with Cephalon, Inc. for development and commercializationrights of bendamustine hydrochloride in China (HK).

May 2009

License Agreement finalized with Eisai Co., Ltd. for co-development and commercialization rights of SyB L-0501(bendamustine) in South Korea and Singapore.

September 2010

SymBio Pharmaceuticals and Eisai launch SYMBENDA® (bendamustine) in Singapore for the treatment of Low-grade
Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia.

October 2010

Announced NDA Approval of Treakisym® (bendamustine) in Japan.

December 2010

Launched Treakisym® in Japan.

July 2011

Onconova and SymBio Pharmaceuticals completed License Agreement for SyB L-1101/SyB C-1101 (rigosertib, a phaseⅢ stage multi-kinase inhibitor for Myelodysplastic Syndromes).

October 2011
October 2011
February 2012

Launched Symbenda® (bendamustine hydrochloride) in South Korea for the treatment of Chronic Lymphocytic
Leukemia and multiplemyeloma.
Listed on Osaka Securities Exchange JASDAQ Growth Market.
Launched Innomustine® (bendamustine hydrochloride) in Taiwan for the treatment of Low-grade Non-Hodgkin's
Lymphoma and Chronic Lymphocytic Leukemia.

October 2015

Obtained exclusive development and marketing rights to Ionsys (patient-controlled analgesia system) in Japan from The
Medicines Company (US).

August 2016

Received approval for Chronic Lymphocytic Leukemia to be added as indication for Treakisym®.

December 2016

Announced approval of the anticancer drug Treakisym® for the additional indication of first-line treatment of low-grade
non-Hodgkin's lymphoma and mantle cell lymphoma.

September 2017Concluded license agreement with Eagle Pharmaceuticals, Inc. (US), granting SymBio exclusive rights to develop,
market, and sell Eagle’s bendamustine hydrochloride RTD and RI products in Japan.

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News and topics
March 2019
On March 26, 2019, the company announced that a partial change application had been approved for use of Treakisym® as apretreatment agent to chimeric antigen receptor T-cell (CAR-T) therapy.
The company announced that a partial change application for marketing approval of anticancer drug Treakisym® (generic name:bendamustine hydrochloride) has been approved.
Development of novel pharmaceuticals has been progressing worldwide in the field of antigen-specific T cell infusion therapy forcancers*. The latest approval of Treakisym® gives patients a choice of pretreatments for these novel therapies. Also on March 26,
2019, Novartis Pharma K.K. received marketing approval in Japan for the first CAR-T therapy (product name: Kymriah®
intravenous infusion) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in patients aged 25 oryounger, and relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in older patients. This allows the use of Treakisym® asa pretreatment agent for CAR-T therapy in treating these diseases once Kymriah® goes on sale.

*Antigen-specific T cell infusion therapy for cancer involves the administration of T cells that recognize specific tumor antigens to patients. In mostcases, patients have few such T cells in their bodies. Thus a treatment was developed in which T cells taken from patients are engineered ex vivo andadministered to patients after expanding them (T cell infusion therapy). The two main T cell infusion therapies for cancer are TCR-T therapy, which
entails introducing a gene coded with a T cell receptor specific to a tumor cell-derived peptide antigen into T cells, which are administered to patientsby infusion after expansion; and CAR-T therapy, in which genes coding for chimeric antigen receptors (CAR) that combine intracellular signaling
domains of T cell receptors and an antigen-binding site that recognizes tumor cell membrane antigens are introduced to T cells, and administered topatients by infusion after expansion. Clinical trials using CD19 expressed in B cells as the target for CAR, in which T cells engineered with
CD19-targeting CAR were administered to patients with B-cell malignancies, demonstrated a high level of clinical efficacy.

February 2019
On February 28, 2019, the company announced a reverse stock split and partial amendment to its Articles of Incorporation.
SymBio plans to conduct a reverse stock split, subject to approval by shareholders at the Ordinary General Meeting of
Shareholders scheduled for March 28, 2019. Shares held by the shareholders recorded in the final shareholder register as of June30, 2019 (effectively, as at the end of June 28, 2019), are to be consolidated at a ratio of four to one on July 1, 2019. Before theshare consolidation (as of December 31, 2018), the number of issued shares stands at 82,398,924 shares. The number of shares
to be reduced upon consolidation is 61,799,193 shares, leaving 20,599,731 shares as the number of issued shares after
consolidation. Although the total number of issued shares will decrease to one quarter as a result of the share consolidation, net
assets will not change, and therefore book value per share will quadruple. Accordingly, excluding changes in stock market
conditions and other external factors, the share consolidation will not alter the asset value of the company’s stock.
The shareholder composition based on the register of shareholders as of December 31, 2018 is as follows. On this basis, as aresult of the reverse stock split the 13,466 shareholders holding less than 400 shares (holding 2,234,613 shares in total) will lose
shareholder status.
Reduction in number of shareholders upon reverse stock split
Number of shareholders (%)

Number of shares held (%)

Total shareholders

31,858 persons (100.00％)

82,398,924 shares

Less than 400 shares

13,466 persons(42.27％)2,234,613 shares(2.71％)

400 shares or more

18,392 persons(57.73％)80,164,311 shares(97.29％)(100.00％)

On February 7, 2019, the company announced a medium-term plan covering FY12/19–FY12/22.

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Medium-term plan targets(JPYmn)FY12/18

FY12/19

FY12/20

FY12/21

FY12/21

Act.

Est.

MTP

MTP

MTP

Sales

3,810

4,465

3,282

9,132

11,282–11,809

Operating profit (losses)-2,656-3,587-5,1801,225

2,084–2,464

Recurring profit (losses)-2,749-3,612-5,2241,181

2,040–2,420

Net income (losses)-2,753-3,616-5,2281,005

1,736–2,060

Source: Shared Research based on company data

Targets in medium-term plan (FY12/19–FY12/22)
Sales
SymBio expects product sales of Treakisym® to account for the bulk of sales. Product sales targets reflect the recent pace of market
penetration and sales trends, which feed into the company’s revised sales growth rates calculated over the medium-term plan
period. Currently sales are booked based on product shipment sales to the sales distributor, Eisai. From FY12/21 onward, sales
will be booked on product shipment sales to pharmaceutical wholesalers from the company’s own in-house sales organization.
The company plans to shift to its own sales organization and switch product shipments from Eisai to pharmaceutical wholesalers
in FY12/21. In the run-up to this it will be necessary to reduce Eisai’s inventories toward the end of FY12/20. Sales of Treakisym®
based on the National Health Insurance (NHI) drug price should remain solid, reflecting actual market demand, but SymBio plans
to stop shipping to Eisai with a target date of end-1H FY12/20. It expects FY12/20 sales to decline by a commensurate amount.
SymBio forecasts increased product sales of Treakisym® from FY12/21 onward as it expects to gain approval of the drug as atreatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in Q2 FY12/21. The company said that its sales target
range for FY12/22 is based on an estimated market penetration rate due to the additional indication.

SG&A expenses
The company has broken down SG&A expenses into primarily R&D spending and other SG&A expenses.

▷ The company calculated R&D expenses based on the latest development plans for its existing pipeline comprising Treakisym®
and rigosertib IV and oral formulations▷ The company has not factored in in-licensing or development costs for drug candidates outside its existing pipeline, although it
will continue to evaluate and investigate them

▷ Other SG&A expenses comprise primarily Treakisym® marketing, production and distribution, business development, andmanagement related costs. SymBio is factoring in costs associated with building and operating its own sales organization from
FY12/19 onward ahead of the move to sell Treakisym® in-house from FY12/21. It forecasts an increase primarily in personnel costs
due to a higher medical representative headcount and higher costs due to more activities

Personnel plans
SymBio assumes it will increase the number of medical representatives to as many as 60 to prepare for in-house sales from
FY12/21 and subsequent launch of rigosertib IV. It plans to allocate the bare minimum of necessary personnel in other parts of theorganization and is budgeting for personnel expenses accordingly.

Funding plans
In April 2018, the company decided to issue its 45th through 47th stock acquisition rights to secure funds needed to operate
until it moves into the black in FY12/21. The proceeds were basically sufficient for its already in-licensed drug development
pipeline, creation of an in-house sales structure, and new in-licensing or M&A activity necessary to take advantage of long-term
growth opportunities.

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January 2019
On January 7, 2019, the company announced the submission of a Special Protocol Assessment request to the US Food andDrug Administration regarding phase III clinical trial of oral rigosertib.
In December 2018, Onconova Therapeutics, Inc. (Onconova), from which the company had in-licensed the anticancer agent
rigosertib in July 2011, submitted a Special Protocol Assessment (SPA) request to the US Food and Drug Administration (FDA).
The subject request was regarding the phase III clinical trial of oral rigosertib combination therapy with azacytidine for thetreatment of adult patients with treatment-naïve higher-risk myelodysplastic syndrome (MDS).

Special Protocol Assessment (SPA): A system under which after completion of a phase II trial and prior to the launch of phase III trial, sponsors can reachan agreement with the FDA regarding the phase III trial protocol such as target illness, purpose, trial design, primary and secondary endpoints, andmethod of data analysis. The agreement indicates that the FDA concurs with the adequacy of the overall protocol design and the design can be used(without changing the terms) in the approval filing process when the phase III trial is completed. The SPA is intended to shorten FDA’s review period of
new drug application, as it boosts the possibility of drug approval provided the trial endpoints are achieved.

According to Onconova, the discussion between the FDA and Onconova regarding this SPA submission is expected to conclude
in 1H FY12/19. The phase III trial, for which the overall response rate (the percentage of complete remission and partial remission
against total enrollment) has been designated as its primary endpoint, is scheduled to begin thereafter.

December 2018
On December 4, 2018, the company announced that Onconova gave a presentation on phase II clinical trials of oral rigosertib
at the American Society of Hematology conference.
Onconova Therapeutics, Inc. (Onconova), from whom the company had in-licensed the anticancer agent rigosertib in July 2011,
gave a presentation on the results of phase II clinical trials of oral rigosertib at the 60th Annual Meeting and Conference ofAmerican Society of Hematology held in San Diego, California on December 1, 2018.
Summary of Onconova’s presentation is as follows:
In a clinical trial of oral rigosertib 840mg or 1,120mg administered daily in combination with azacitidine, overall response
efficiency (ORR) in 29 hypomethylating agent (HMA) naïve, myelodysplastic syndrome (MDS) patients was 90%, and of which 10
patients (34%) achieved complete remission (CR). Further, 26 HMA failed, relapsed or refractory MDS patients showed an ORR of
54%, with 8% achieving complete or partial remission. Except those related to the urinary system, adverse events of the
combination therapy were identical to those of azacitidine administered as a single agent, and the incidence of urinary adverse
events were mitigated with various safety measures implemented for high dosage (1,120mg) administration. In conclusion, oral
rigosertib administered in combination with azacitidine demonstrated high tolerability and excellent ORR and CR in HMA naïve
and relapsed or refractory MDS patients. The result of the clinical trial has opened the door to phase III clinical trials of rigosertib
targeting untreated MDS.
Based on the results of clinical trial presented at the American Society of Hematology conference, SymBio plans to makepreparations to participate in Onconova’s global phase III clinical trials of rigosertib administered in combination with azacitidine
targeting untreated, higher-risk MDS in Japan.

November 2018
On November 30, 2018, the company announced that it has begun a clinical trial of Treakisym® liquid formulation (rapid
infusion formulation).
The company has begun a clinical trial of Treakisym® liquid formulation (rapid infusion [RI] formulation, intravenous
administration for 10 minutes) to primarily verify the drug’s safety. A total of 36 patients are enrolled in the clinical trial. In
addition to previously approved indications, the company will apply for approval of the drug as treatment for relapsed or
refractory diffuse large B-cell lymphoma (DLBCL).

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SymBio is preparing to apply for approval of the RTD formulation with the goal of launching the product in the first half of 2021.
Regarding the RI formulation, the company will apply for approval upon completion of the clinical trial, with plans to launch the
product in 2022.

October 2018
On October 16, 2018, the company announced that it has begun preparing for own sales organization of anticancer agent
Treakisym®.
According to the company, the business alliance agreement it has entered with Eisai Co., Ltd. regarding the sale of bendamustine(Treakisym®) will expire in December 2020. The company announced that it has begun preparing to establish its own salesorganization to sell the anticancer agent in Japan after the expiration of the business alliance agreement.
SymBio is currently selling Treakisym® in Japan through Eisai as its sales distributor. However, upon reviewing the terms ofbusiness alliance with Eisai with the aims of moving into the black by FY12/21 and continually expanding earnings afterwards, thecompany has decided to establish its own sales organization for in-house sales of Treakisym®.
With an eye toward FY12/21, the company aims to establish a sales organization specialized for drugs targeting hematologic
diseases. In addition to Treakisym®, it plans to sell Rigosertib (injections and oral agents) targeting myelodysplastic syndrome(MDS) currently under development using the sales organization. In doing so, SymBio aims to achieve high operational
efficiency.
No revisions were made to the earnings forecasts for FY12/18 and four-year medium-term management plan announced in
February 2018 as the impact of in-house sales of Treakisym® from FY12/21 has already been factored in.

September 2018
On September 27, 2018, the company announced it has applied for approval of a partial revision regarding the use of
Treakisym® as a pretreatment for regenerative medical products.
The company applied for approval of a partial revision to manufacture and marketing approval of anticancer drug Treakisym®
(generic name: bendamustine hydrochloride) to enable its use as a pretreatment agent for regenerative medical products.
On April 23, 2018, Novartis Pharma K.K. filed for manufacture and marketing approval for the first chimeric antigen receptor
T-cell (CAR-T) therapy in Japan for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in patients
aged 25 years or younger and relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients. If the therapy isapproved, Treakisym® may be used as a pretreatment agent for CAR-T therapy for the treatment of ALL and DLBCL.

July 2018
On July 30, 2018, the company announced inclusion of anticancer agent Treakisym® as standard therapy in revised Clinical
Practice Guidelines 2018 for healthcare professionals.
The company announced that anticancer agent Treakisym® (generic name: bendamustine hydrochloride) was newly included asa standard treatment option in the Guidelines for Tumors of Hematopoietic and Lymphoid Tissues 2018 issued by Japan Societyof Hematology on July 20, 2018. The guidelines were revised to include as indications of Treakisym® mantle cell lymphoma andchronic lymphocytic leukemia in addition to relapsed or refractory low-grade B-cell non-Hodgkin’s lymphoma (relapsed or
refractory low-grade NHL). Further, Treakisym® was newly included as a treatment option for untreated low-grade NHL.
According to the company, inclusion of all approved indications of Treakisym® in the guidelines positioned the drug as standard
treatment for malignant lymphoma. As a result, Treakisym® can potentially replace conventional standard therapy and penetrate
the market even further.

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On July 2, 2018, the company announced it has obtained approval for combined use of Treakisym® with anti-CD20 antibodies.
The company obtained approval for a partial change to its manufacture and marketing authorization for the anticancer agent
Treakisym® (non-proprietary name: bendamustine hydrochloride).
In Europe and the US, a significant number of new anti-CD20 antibodies* are being developed for treatment of low-grade B-cell
non-Hodgkin's lymphoma (low-grade NHL). The approval permits the use of Treakisym® in combination with rituximab or othernew anti-CD20 antibodies and will expand the treatment options available to patients. On the same day, Chugai PharmaceuticalCo., Ltd. obtained manufacture and marketing approval for Gazyva® (non-proprietary name: obinutuzumab) for CD20-positive
follicular lymphoma, a typical histologic type of low-grade NHL. After the launch of Gazyva®, the approval will allow the
combined use of Treakisym® and Gazyva® for the treatment of CD20-positive follicular lymphoma.
CD20 is a transmembrane phosphoprotein that is a surface-membrane molecule specifically expressed on lymphocyte B cells. Anti-CD20 antibodies
recognize and bind to CD20 in vivo, and target the binding to kill B cells by natural killer cells.

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Major shareholders
Fuminori Yoshida
Cephalon, Inc. (Standing proxy: Teva Pharmaceutical K.K.)
Matsui Securities Co Ltd
Japan Securities Finance Co., Ltd.
Eisai Co., Ltd.
J.P. Morgan Securities plc (Standing proxy: J.P.Morgan Securities Japan Co., Ltd.)
Waseda No. 1 Investment Limited Partnership
Aizawa Securities Co., Ltd.
BNY GCM CLIENT ACCOUNT JPRD AC ISG (FE-AC) (Standing
proxy: MUFG Bank, Ltd.)BNP Paribas London Branch for Prime Brokerage Clearance for Third Party(Standing proxy: The Hongkong and Shanghai Banking Corporation, Limited,Tokyo branch, Custody Department)

3,451,000
2,589,000
1,238,100
1,224,700
833,400
695,158
684,000
606,200

Shareholding
ratio
4.19%
3.14%
1.50%
1.49%
1.01%
0.84%
0.83%
0.74%

599,8760.73%

583,000

0.71%

SUM

12,504,434

15.18%

Top shareholders

Shares held

Source: Shared Research based on company data.
As of December 31, 2018
Note: Shareholding ratio calculated excluding treasury shares from shares issued.

Top management
Representative Director, President and CEO, Fuminori Yoshida established SymBio Pharmaceuticals Limited, his third company, in
March of 2005. As founding president of two other major healthcare companies, Nippon BioRad Laboratories (1980) and Amgen
Japan (1993), he has earned high visibility and credibility within Japan's healthcare and academic communities. Following his
graduation from Gakushuin University in 1971 with a B.S. in Organic Chemistry, he went on to receive an M.S. in Molecular
Biology from MIT (1973) and M.S. in Health Policy and Management from Harvard University Graduate School (1975). He
possesses dual experience and expertise in the management of major Japanese and American corporations due to his prior work
experience at various companies, including Mitsubishi Corporation and AHS Japan, Syntex Japan (1993) as President and CEO,and Amgen Inc. where he served concurrently as Corporate Vice-President, President and CEO of Amgen Japan, for 12 years.

Employees
SymBio had a total of 90 employees as of December 31, 2018.
Employees
No. of employees
YoY change

FY12/09
Par.
52

FY12/10Par.
56

FY12/11Par.
71

FY12/12Par.
76

FY12/13Par.
72

FY12/14
Par.
69

FY12/15Par.
74

FY12/16
Par.
77

FY12/17Par.
78

FY12/18
Par.
90

10

4

15

5

-4

-3

5

3

1

12

Source: Shared Research based on company data.

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Other
Overview of clinical trials
Development of a new drug takes between 10 and 17 years
The development process of a new drug follows the four stages described below. It usually takes 10 to 17 years for a new drug to
win regulatory approval, according to the company.
Ordinary process and periods of developing new drugs
Process

PeriodWhat is done

Basic research

2-3 years

Creation of new substances and decision on candidates for drugs

Preclinical test

3-5 years

Confirmation of efficacy and safety through experiments on animals

Clinical trials

3-7 years

Phase I: Confirmation of safety and pharmacokinetics with a small number of healthy people
Phase II: Confirmation of efficacy and safety with a small number of patients
Phase III: Confirmation of efficacy and safety with many patients in comparison to existing drugs

Application and approval

1-2 years

Examination by the Ministry of Health, Labour and Welfare

Source: Shared Research based on company data.

Probability of a compound receiving drug approval is 1/100,000
The probability of a chemical compound receiving regulatory approval is said to be 1/100,000, according to the company.
According to the 2013 edition of the Thomson Reuters Pharmaceutical R&D Factbook, the success rate of pharmaceuticalcompanies around the globe from 2006 to 2009 at various stages in the development process was:▷ Preclinical: 67%▷ Phase I clinical trials: 46%▷ Phase II clinical trials: 19%▷ Phase III clinical trials: 77%▷ Regulatory approval: 90%.
The success rate of cancer drugs tends to be lower than that of other drugs. The success rate of cancer drugs that went throughclinical trials in the US between 2004 and 2011 was only 6.7%, compared with 12.1% for other drugs, according to BIOtechNow.
The success rate of cancer drugs that went through phase III clinical trials was 45%, while other drugs had a 64% success rate.

Ethnic factors in the acceptability of foreign clinical data
Japan’s Ministry of Health, Labour, and Welfare (MHLW) in 1998 released a report entitled Ethnic Factors in the Acceptability ofForeign Clinical Data (ICH-E5 Guideline) to spell out the government’s stance on the use of data on clinical trials conducted
outside Japan. The report discusses whether the use of such extrapolated data is acceptable.
Applications for drug approval in Japan normally require pharmacokinetic data, dose-responsive data, and clinical trial data on
efficacy for Japanese people. However, data from overseas clinical trials are acceptable if a bridging study demonstrates that suchdata can be used for Japanese people.

Pharmacokinetic data: Data concerning the fate of substances administered externally to a living organism: absorption, distribution, metabolization,and excretion (ADME).

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Glossary
AntigenNormally, a protein or other substance carrying bacteria and viruses that the body rejects as foreign, causing an antigen-antibody
reaction (AAR). When antigens enter the body, they either stimulate the production of antibodies or combine with them.

Bridging Data
Data generated from overseas clinical trials that can be applied to Japanese patients and used in Japan regulatory filings formarketing approval. The goal is to shorten the number of preclinical/clinical studies required for marketing approval in Japan by
avoiding the need to repeat the same studies that have already been carried out overseas (e.g., dispense with the need to do aphase II and/or III clinical trial in Japan).

Chronic Lymphocytic Leukemia (CLL)
A disease in which white blood cells, called lymphatic corpuscles, become cancerous.

Contract Research Organization (CRO)
Pharmaceutical companies often outsource some of their work to contract research organizations so they can focus on core
operations. Outsourced work may include monitoring of clinical trials to ensure that they are proceeding according to plan, andthe management of clinical trial data.

Dose-Responsiveness
Does-responsiveness shows the relationship between the dosage and efficacy of a drug. It is used to determine the method anddosage. Under normal circumstances, the effectiveness of a drug corresponds to its dosage.

First-line Drug
The first drug given to a patient for a disease that is typically part of a standard set of treatments such as surgery followed bychemotherapy and radiation. When used by itself, first-line therapy is the one accepted as the best treatment. If it doesn’t curethe disease (the patient has a relapse) or causes severe side effects, other treatments (second-line, third-line etc.) may be addedor used instead.

Immunoglobulin G (IgG)
The main antibody isotype found in blood and extracellular fluid which protects the body from infection by binding to manykinds of pathogens such as viruses, bacteria, and fungi —it does this via several immune mechanisms: IgG-mediated binding ofpathogens causes their immobilization and binding together.

Iontophoresis
A method for transdermal administration of ionized drugs using a tiny electric current.

Key Opinion Leader (KOL)
Key opinion leaders are physicians whose opinions concerning the treatment of certain illnesses have a strong influence on otherdoctors.

Mantle-Cell Lymphoma (MCL)
A type of fast-growing B-cell non-Hodgkin’s lymphoma that normally affects people over a certain age. It is characterized by small
and medium-sized cancer cells that appear in lymphatic nodes, the spleen, bone marrow, blood, and the digestive system.

Monoclonal Antibody
A single antibody molecule taken from a single cell. It is possible to produce large amounts of these special antibodies and use
them in the development of antibody drugs.

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Multikinase Inhibitor
Multikinase inhibitor blocks tyrosine kinases, which play an important role in transmitting signals involving the multiplication anddivision of cells. Tyrosine kinases can be energized due to genetic mutations. If this happens, the number of cells rapidly increases,
causing cancer or other illnesses.

Myelodysplastic Syndromes
Myelodysplastic Syndrome leads to abnormalities in hematopoietic stem cells that produce blood cells, resulting in a lack ofblood. Blood cells produced this way are abnormally shaped. This change in the cells is called dysplasia. The disease typicallyleads to frequent anemia with some patients dying from infection or bleeding due to the reduction in blood cells. The disease ismost common among the elderly. 10 to 20% of MDS patients progress to acute leukemia.

Non-Hodgkin’s Lymphoma (NHL)A group of ailments associated with all types of malignant tumors other than Hodgkin’s lymphoma.
In Japan, many of these diseases are diffuse large cell lymphomas.

Overall Survival (OS)Overall survival refers to the duration between the initiation of treatment and a patient’s death.

Progression-Free Survival (PFS)
Progression-free survival refers to the duration between the initiation of treatment, and either death or disease progression.

Proof-of-Concept (POC)
A proof-of-concept, when applied to drug development, is the concept that the efficacy and safety of a new drug candidate must
be validated through data generated in clinical trials.

Rare Disorders
Rare disorders are illnesses that affect few people, although they may be serious and/or life-threatening. Drugs designed to treat
rare medical conditions are called ‘orphan drugs’, and pharmaceutical companies often receive government incentives for thedevelopment of these drugs.
In Japan, the Ministry of Health, Labour and Welfare seeks to promote the development of orphan drugs by offering subsidies.
When a drug is designated as an orphan, it is placed on a fast track for approval (the time between the application and approval isreduced). The period of market exclusivity can also be extended to 10 years, and a system is in place to keep the NHI price oforphan drugs above a certain level.

R-CHOP therapy
A combination of rituximab with chemotherapy drugs cyclophosphamide, doxorubicin (hydroxydaunomycin), vincristine(Oncovin®), and prednisolone. R-CHOP is an acronym derived from the names of the drugs used. It is the standard initial
treatment for low-grade non-Hodgkin’s lymphoma (NHL) and mantle-cell lymphoma (MCL).

Special Protocol Assessment (SPA)
A system under which the US Food and Drug Administration (FDA) approves the protocol or design of a planned phase III clinical
trial, such as target illness, purpose, primary and secondary endpoints, and method of data analysis – the protocol may be revised
following FDA consultation prior to the start of the study. The SPA is intended to shorten the review period of new drug
applications (NDAs) by the FDA.

Standard Therapy
Standard therapy refers to treatment that is considered to be the best therapy currently available. It is a treatment widely
recommended to patients by physicians.

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Company name
SymBio is derived from the words “symbiosis” and “biotechnology.” The company’s corporate philosophy emphasizes the
symbiotic or mutually supportive relationship that exists among major players in the healthcare industry, and is reflected in thecompany’s logo which symbolizes physicians, scientists, regulators, and investors, with patients at its center. The color of thelogo represents the evergreen tree—the company’s endeavor to create and sustain a life-giving force.

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Company profile
Company nameHead office
Toranomon 30 Mori Building, 3-2-2 Toranomon

SymBio Pharmaceuticals Limited

Minato-ku, Tokyo, JAPAN
105-0001

Phone

Listed on+81-3-5472-1125

TSE JASDAQ GrowthEstablishedExchange listing

March 25, 2005

October 20, 2011

WebsiteFiscal year-end

http://www.symbiopharma.com/index_e.html

December

IR contact

IR web

Tsutomu Abe

http://www.symbiopharma.com/ir_e/01.html

IR mail

IR phonetabe.ta02@symbiopharma.com+81-3-5472-1125

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