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SymBio Pharmaceuticals / 4582
COVERAGE INITIATED ON:

2014.10.31

LAST UPDATE:

2020.06.16

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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 -----------------------------------------------------------------------------------------------------------------------------------------------7
Business ------------------------------------------------------------------------------------------------------------------------------------------------ 18
Business description -------------------------------------------------------------------------------------------------------------------------------------------- 18
Business strategy ------------------------------------------------------------------------------------------------------------------------------------------------ 21
Pipeline ------------------------------------------------------------------------------------------------------------------------------------------------------------- 25
Earnings structure ----------------------------------------------------------------------------------------------------------------------------------------------- 37
Strengths and weaknesses------------------------------------------------------------------------------------------------------------------------------------ 39
Market and value chain---------------------------------------------------------------------------------------------------------------------------- 40
Market overview ------------------------------------------------------------------------------------------------------------------------------------------------- 40
Historical performance ---------------------------------------------------------------------------------------------------------------------------- 43
Income statement ----------------------------------------------------------------------------------------------------------------------------------------------- 58
Balance sheet ----------------------------------------------------------------------------------------------------------------------------------------------------- 59
Cash flow statement -------------------------------------------------------------------------------------------------------------------------------------------- 60
Other information ---------------------------------------------------------------------------------------------------------------------------------- 61
Claim for damages ---------------------------------------------------------------------------------------------------------------------------------------------- 61
History -------------------------------------------------------------------------------------------------------------------------------------------------------------- 61
News and topics ------------------------------------------------------------------------------------------------------------------------------------------------- 63
Major shareholders --------------------------------------------------------------------------------------------------------------------------------------------- 68
Top management ----------------------------------------------------------------------------------------------------------------------------------------------- 68
Employees --------------------------------------------------------------------------------------------------------------------------------------------------------- 68
Other ---------------------------------------------------------------------------------------------------------------------------------------------------------------- 69
Company profile ------------------------------------------------------------------------------------------------------------------------------------------------- 72

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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

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 rare diseases, 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 2020, 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, untreated (first-line treatment) andrelapsed or refractory low-grade NHL and MCL, and chronic lymphocytic leukemia (CLL). Treakisym® is listed 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®, rigosertib (anticancer agent for myelodysplastic
syndromes) IV and oral formulations, and the antiviral drug brincidofovir.

Earnings◤ FY12/19 sales were JPY2.8bn (-26.0% YoY). Product sales totaled JPY2.8bn (-26.2% YoY) and royalty revenue totaled JPY26mn(JPY26mn in FY12/18). The operating loss totaled JPY4.3bn (loss of JPY2.7bn). The company also reported a recurring loss of
JPY4.4bn (loss of JPY2.7bn). Net loss was JPY4.4bn (loss of JPY2.8bn).

◤ SymBio forecasts FY12/20 sales of JPY3.4bn (+20.0% YoY), an operating loss of JPY5.1bn (operating loss of JPY4.3bn in

FY12/19), a recurring loss of JPY5.1bn (recurring loss of JPY4.4bn), and a net loss of JPY4.8bn (net loss of JPY4.4bn).

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

JPY10.8bn and a net income of JPY1.7bn in FY12/22. The company expects higher sales from increased market penetration ofTreakisym® for approved indications, as well as 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 wellas 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 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 inaddition 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
LAST UPDATE: 2020.06.16

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

Key financial data
Income statement(JPYmn)Sales

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

FY12/19
Par.
2,838

Gross profit

1,212

658

593

318

527

583

904

1,031

1,173

865

Operating profit-613-2,067-1,700-1,681-1,303-2,552-2,127-3,947-2,656-4,302-5,090-638-2,095-1,729-1,601-1,110-2,630-2,317-3,977-2,749-4,377-5,134

YoY

-

-

-

-

-

-

-

-

-

-

-

RPM

-

-

-

-

-

-

-

-

-

-

-

-642

-2,105-1,733-1,605-1,116-2,632-2,313-3,978-2,753-4,376-4,803

YoY

-

-

-

-

-

-

-

-

-

-

-

Net margin

-

-

-

-

-

-

-

-

-

-

-

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

20,560-165.5212.2

26,438-189.0
143.1

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

3,911
4,887
75
70
241
5,274
121
872
2
874
4,400

-

-

-

-

-

-

-

-

-

-

-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
4,272-4,351-216
3,740-15.1%-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%-76.0%-107.4%
83.4%

YoY

YoY
GPM

YoY
OPM

Recurring profit

Net income

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%
-

-26.0%-26.3%
30.5%-

FY12/20
Est.
3,404
20.0%

-

-181.8-Source: Shared Research based on company data
Note: Figures may differ from company materials due to differences in rounding methods.
Note: The company conducted a four-to-one reverse stock split in July 2019. Earnings per share in the FY12/19 earnings forecast reflects the effect of the reverse stock
split.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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

Recent updates
Highlights
On June 16, 2020, Shared Research updated the report following interviews with SymBio Pharmaceuticals Ltd.

On May 12, 2020, the company announced earnings results for Q1 FY12/20; see the results section for details.

On May 11, 2020, the company announced the completion of approval filing regarding the combination therapy of Treakisym®
and rituximab for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
The company filed for approval of partial change to the manufacturing and marketing authorization of anticancer drug
Treakisym® (generic name: bendamustine), which will allow the drug to be used in combination with rituximab to treat relapsed
or refractory diffuse large B-cell lymphoma.

On March 26, 2020, Shared Research updated the report following interviews with the company.

On March 25, 2020, the company announced the completion of patient enrollment for the global phase III INSPIRE study
concerning anticancer agent rigosertib.
On March 24, 2020, Onconova Therapeutics, Inc., which provides licenses for rigosertib, an anticancer agent currently being
developed by SymBio, announced the achievement of the target number of 360 patient enrollments for rigosertib’s global phase
III INSPIRE study.
Out of the 360 patient enrollments, 48 were enrolled in Japan. The company expects that the fulfillment status of the study’s
primary endpoints will become clear in Q3 or Q4 FY12/20 and plans to announce the study’s results at an academic conference
within 2020.

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

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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

Trends and outlook
Quarterly trends and results
FY12/19

Cumulative(JPYmn)FY12/20

Q1

Q2

Q3

Q4

Q1

Sales

1,611

2,005

2,008

2,838

551

YoY

81.4%

4.0%

-33.8%-26.0%-65.8%

Gross profit
YoY
GPM

609

529

563

865

128

144.0%
37.8%

-7.7%
26.4%

-39.1%
28.0%-26.3%
30.5%-79.0%
23.2%

SG&A expenses

1,205

2,545

4,099

5,166

1,090

YoY
SG&A ratio

25.0%
74.8%

34.1%
126.9%

44.8%
204.1%

34.9%
182.1%-9.6%
197.6%

Operating profit-596-2,015-3,536-4,302

-962

-

-

-

-

-

-616

-2,069-3,642-4,377

-991

-

-

-

-

-

Net income-617-2,070-3,641-4,376-992

YoY
Net margin

-

-

-

-

-

Q1

Q2

Q3

Q4

Q1

1,611
81.4%
609

394
-62.2%-793-99.7%
33

830
3.3%
302

551
-65.8%
128

144.0%
37.8%--90.5%
-

21.4%
36.4%

-79.0%
23.2%

YoY
OPM

Recurring profit
YoY
RPM

Quarterly(JPYmn)Sales
YoY

Gross profit
YoY
GPM

FY12/19

SG&A expenses

1,205

1,340

1,555

1,067

1,090

YoY
SG&A ratio

25.0%
74.8%

43.4%
340.4%

66.5%
-

7.0%
128.6%-9.6%
197.6%

Operating profit-596--1,419--1,521
-

-765
-

-962
-

-616
-

-1,453--1,573
-

-735
-

-991
-

-617
-

-1,453--1,571
-

-736
-

-992
-

YoY
OPM

-

Recurring profit
YoY
RPM

-

Net income
YoY
Net margin

-

-

-

-

-

-

-

-

-

-

Q2

FY12/20
Q3

Q4% of FY
16.2%

FY Est.
3,404
20.0%

-

-5,090---5,134---

FY12/20Q2-4,803

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
FY12/19

Cumulative(JPYmn)
SG&A expenses
YoY

FY12/20

Q1

Q2

Q3

Q4

Q1

1,205

2,545

4,099

5,166

1,090
-9.6%

25.0%

34.1%

44.8%

34.9%

R&D expenses

472

963

1,972

2,442

438

YoY

13.4%

14.8%

52.5%

33.2%

-7.1%

SG&A expenses excl. R&D
YoY

733

1,582

2,127

2,725

651

33.8%

49.3%

38.3%

36.5%

-11.1%

FY12/19

Quarterly(JPYmn)
SG&A expenses
YoY

FY12/20

Q1

Q2

Q3

Q4

Q1

1,205

1,340

1,555

1,067

1,090
-9.6%

25.0%

43.4%

66.5%

7.0%

R&D expenses

472

491

1,009

470

438

YoY

13.4%

16.2%

122.1%-13.0%-7.1%

SG&A expenses excl. R&D
YoY

Q2

733

849

546

597

651

33.8%

66.0%

13.8%

30.6%

-11.1%

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: 2020.06.16

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

Q1 FY12/20 results▷

Sales:JPY551mn (-65.8% YoY)▷

Operating loss:

JPY962mn (loss of JPY596mn in Q1 FY12/19)

Recurring loss:

JPY991mn (loss of JPY616mn in Q1 FY12/19)

Net loss:

JPY992mn (loss of JPY617mn in Q1 FY12/19)▷▷

Sales fell YoY. The company booked sales of Treakisym®. As will be described later, high product defect rates and unstabledeliveries persisted in Q1 for multiple batches of Treakisym® lyophilized injections supplied by Astellas Deutschland so sales
declined YoY due to continued supply problems.
According to disclosure by Eisai, the sales agent for Treakisym®, FY03/20 sales of the product increased 6.2% YoY to JPY8bn. On aquarterly basis, Q4 (Jan–Mar 2020) Treakisym® sales were JPY1.6bn, up from JPY1.5bn a year earlier.
Gross profit totaled JPY128mn (-79.0% YoY) while GPM was 23.2% (-14.6pp YoY). Increased inspections boosted the cost ratio
for Treakisym® lyophilized injection.
SG&A expenses fell 9.6% YoY to JPY1.1bn and R&D expenses declined 7.1% YoY to JPY438mn. This included expenses for
conducting clinical trials of intravenous and oral formulations of Treakisym® and rigosertib. Excluding R&D expenses, SG&A
expenses declined 11.1% YoY to JPY651mn. The company incurred development costs building its in-house sales structure, but it
seems expenses such as compensation payments declined YoY.
As a result, operating loss, recurring loss, and net loss widened YoY. The difference between operating loss and recurring loss
was accounted for largely by JPY30mn in non-operating expenses: mainly JPY16mn in forex losses and JPY13mn in stock issuancecosts.
Although Q1 sales reached only 16.2% of the company’s full-year target, SymBio left full-year forecast unchanged, likely because
it anticipates the supply issues concerning Treakisym® lyophilized injection formulation to be resolved in 2H.
Major pipeline progress in Q1 FY12/20 is shown below.

▷
▷

▷
▷

May 2020: filed partial revisions to the manufacturing and marketing application for BR therapy (combination of anticancer
agents Treakisym® and rituximab) to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
May 2020: an abstract on analysis of phase III BR therapy (combination of anticancer agents Treakisym® and rituximab) results
for treatment of relapsed or refractory diffuse large B-cell lymphoma was adopted for the 25th Congress of the European
Hematology Association scheduled to be held in June 2020.
March 2020: Onconova, the licensor of anticancer drug Rigosertib, announced it had completed enrollment of the target 360
patients for the international joint phase III (INSPIRE) study, 48 of whom were enrolled in Japan.
March 2020: Enrollment of trial subjects for the study to confirm safety of Treakisym® liquid formulation (rapid infusion, RI) wascompleted.

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. The company plans to transition to its in-house sales organization in January 2021. This should facilitate a move into theblack from FY12/21 and ongoing profit growth thereafter and lay the groundwork for future business development.

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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In Q1, the company hired and trained additional Treakisym® sales representatives and regional sales managers who will form thecore of its in-house marketing network. This set the stage to complete the nationwide sales structure in 1H FY12/20. SymBio
continued building its distribution and logistics capabilities with logistics centers in East and West Japan and in-houseinfrastructure including a new IT system with ERP.

Substandard products
SymBio imports lyophilized Treakisym® for injection from Astellas Deutschland (consolidated subsidiary of Astellas Pharma). Some
batches of Treakisym® 100mg vials imported from Astellas Deutschland for domestic sales in FY12/19 had impurities andappearance defects in a significantly higher percentage than stipulated in the supply agreement. In order to prevent a recurrenceof such product quality issues, the company objected to Astellas Deutschland, and demanded steps such as corrective andpreventive action (CAPA) processes to fulfil its responsibilities as the supplier. Nonetheless, there was no improvement in Q1,
with persistent supply issues. Several batches from Astellas Deutschland had high defect ratios and deliveries were irregular. Sales
fell YoY as Treakisym® inventory levels were low compared with Q1 FY12/19.
The problems with defective products and irregular deliveries are likely to persist through the rest of 1H, and SymBio expects
sales from shipments to its Treakisym® sales agent, Eisai, to be down YoY. The company is persisting with its efforts to restore
Treakisym® inventory levels, reduce defect rates, and stabilize supply through discussions with its supplier.

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 anticancer agent Treakisym® is used for the indications 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 andmantle cell lymphoma (October 2010), and chronic lymphocytic leukemia (August 2016).
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,
which applies to all of the approved indications. This has seen Treakisym® establish its position as a standard treatment for
lymphatic cancer.
Also, SymBio obtained approval for the partial revision to the marketing authorization of Treakisym® in July 2018. Treakisym® can
now be used in combination with new anti-CD20 antibodies and not just rituximab for the treatment of CD20-positive follicularlymphoma, the most common histological type of low-grade NHL. This allows the company to provide patients a new treatment
option: combination therapy with obinutuzumab (launched in August 2018). In March 2019, SymBio obtained approval for thepartial revision to its application to use Treakisym® as a pretreatment agent in tumor-specific T cell infusion therapy. This allows
Treakisym® to be used as a pretreatment agent for Kymriah® intravenous infusion, which was the first chimeric antigen receptor Tcell (CAR-T) therapy approved in Japan and on the NHI drug price list from May 2019.
Following on from the above approved indications, the company conducted a phase III clinical study for the fourth indication of
relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), with Treakisym® administered in combination with rituximab (BRtherapy). The response rate (primary endpoint) in the test results released in November 2019 was better than expected. In May
2020, the company applied for a partial revision to manufacture and marketing approval.
In May 2020, an abstract on analysis of phase III BR therapy (combination of anticancer agents Treakisym® and rituximab) results
for treatment of relapsed or refractory diffuse large B-cell lymphoma was adopted for the 25th Congress of the European
Hematology Association scheduled to be held in June 2020. The company noted the main results of the phase III (38 patients)
trial analysis were as follows:<By gene activity pattern>▷

GCB type: Overall Response Rate (ORR) of 83%, Complete Response Rate (CR) of 67%

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SymBio Pharmaceuticals / 4582
LAST UPDATE: 2020.06.16

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

Non-GCB type: ORR of 78%, CR of 39%

Divided into GCB or non-GCB type DLBCLGCB type: Geminal center B-cell type
Non-GCB type: non Geminal center B-cell type

<By age group>▷

Under 65 years of age: ORR of 86%, CR of 71%▷

Over 75 years of age: ORR of 73%, CR of 36%▷

65 to 75 years old: ORR of 75%, CR of 45%

The company concluded an exclusive licensing agreement in Japan with Eagle Pharmaceuticals (based in New Jersey, US) in
September 2017. Following consultations with the PMDA, the company filed for approval of the RTD formulation in September
2019, and plans to launch it in Q1 FY12/21. SymBio launched clinical trials for the RI formulation in November 2018 primarily toconfirm safety and completed patient enrollment in March 2020. The company will apply for approval without delay after theend of the clinical trials of the RI formulation and aims to begin sales in 2H FY12/22. The RI formulation can be administered injust 10 minutes versus 60 minutes for the current lyophilized injection and RTD formulation. This reduces the burden on patientsand healthcare professionals, providing significant value added. Multiple patent protections in the form of a liquid productlicense extended the product life of Treakisym® to 2031.

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 (50 patients enrolled as of April 2020). 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. Onconova announced that it had reached its target ofenrolling 360 patients worldwide as of March 2020. Onconova said the primary endpoint results would become clear in 2H
2020, and that it planned to announce trial results at an academic conference by the end of the year. Based on these trial 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 completed phase I/II clinical trials for the drug used in combination withazacytidine, whose results suggested the efficacy and safety of the combination therapy. To verify the tolerability and safety ofthe oral formulation of rigosertib among Japanese patients, SymBio began phase I clinical trials in Japan in June 2017 andcompleted patient enrollment in June 2019. After completing the phase I trials, the company will participate in global phase III
clinical trials of the drug used in combination with azacitidine as first-line treatment for higher-risk MDS currently planned by
Onconova. In December 2019, Onconova announced that it was considering the design of a Phase II/III adaptive trial withuntreated higher risk MDS patients based on the data presented at the 61st American Society of Hematology (ASH) Annual
Meeting in December 2019.

Antiviral drug for the treatment of infections SyB V-1901 (generic name: Brincidofovir）
In September 2019, SymBio concluded an exclusive global license agreement with Chimerix Inc. (hereafter Chimerix) for
brincidofovir (SyB V-1901, hereafter BCV IV and BCV Oral), an antiviral drug for the treatment of infections in intravenous andoral forms). The company acquired exclusive global rights to develop, manufacture, and market BCV for all diseases except
smallpox.
BCV Oral has demonstrated a strong, broad-spectrum antiviral effect in clinical trials in Europe and the US by Chimerix. The
company will design a global clinical trial based on these findings.

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The company will initially develop BCV-IV for treatment of viral hemorrhagic cystitis (vHC) occurring after hematopoietic stem
cell transplantation for the domestic market, which has high unmet medical needs. It plans to conduct clinical studies and gain
approval in Japan first so it can offer it to patients there. It also plans to market BCV IV globally after conducting international joint
clinical trials in countries including the US and Europe. As well, the company plans clinical development of BCV IV as an antiviraltreatment of infections after kidney transplants, because it is likely to be effective for transplants other than hematopoietic stem
cell transplants, including organ transplants. The company looks to expand its business in Europe, the US and Asia (including
China), where organ transplant markets are larger than Japan’s. It is also looking for partnerships that take advantage of regional
characteristics of these target diseases.

SyB P-1501, a post-operative patient-controlled analgesia
Regarding SyB P-1501 licensed by The Medicines Company, the company initiated an arbitration against The Medicines
Company, 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. SymBio argued that The Medicine Company’s
failure to provide sufficient assurance to the company regarding the performance of obligations under on the license agreement
in light of its decision to suspend and withdraw from business activities relating to SyB P-1501in the European and US markets
was a material breach of the license agreement. On November 30, 2017, the license agreement was terminated as the breach
was not corrected within the contract period and development of the product ceased in February 2018. Arbitration proceedings
against The Medicines Company are still ongoing. In January 2020, Swiss company Novartis AG announced that it had acquired
The Medicines Company. SymBio expects an arbitration judgment in 1H 2020.

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

In-licensing of drug candidates
The company is currently focusing on producing and unrolling development plans for antiviral drug brincidofovir it in-licensed in
September 2019. It is constantly looking into multiple licensing deals and looking for and evaluating promising in-licensing drugcandidates.

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

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Full-year company forecasts
FY12/19

FY12/20(JPYmn)Sales
Gross profit

1H Act.
2,005
529

2H Est.
833
335

FY Est.
2,838
865

FY Est.
3,404
1,146

GPM

33.7%

26.4%

40.3%

30.5%

SG&A expenses

2,545

2,622

5,166

6,236

SG&A ratio

126.9%

314.8%

182.1%

183.2%

Operating profit-2,015-2,287-4,302-5,090Recurring profit-2,069-2,307-4,377-5,134

Net income-2,070-2,306-4,376-4,803

-

-

-

-

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:

JPY3.4bn (+20.0% YoY)▷

Operating loss:

JPY5.1bn (loss of JPY4.3bn in FY12/19)

Recurring loss:

JPY5.1bn (loss of JPY4.4bn in FY12/19)

Net loss:

JPY4.8bn (loss of JPY4.4bn in FY12/19)▷▷

SymBio expects sales growth primarily on rising domestic product sales for Treakisym® Sales of Treakisym® should recover after
the postponement of shipments in FY12/19. That said, sales are expected to fall below the FY12/18 level as Eisai shrinks its
inventories.

▷

Recovery of Treakisym® following postponed shipments: In FY12/19, lyophilized injection formulations of Treakisym® imported
from Astellas Deutschland GmbH, a consolidated subsidiary of Astellas Pharma, were found to contain impurities andappearance defects. Consequently, shipments of Treakisym® 100mg to Japan distributor Eisai were delayed and the booking ofsome product sales was postponed until FY12/20. Once the shipment system is restored, sales should benefit from the▷postponed amount.
Lower sales due to shrinkage of Eisai inventories: 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.
Therefore, Eisai needs to shrink inventories by end-2020 to accommodate this change. SymBio plans to end shipments to Eisai
from the end of 1H even though NHI price-based sales of Treakisym® remain firm reflecting market demand; this is why thecompany expects FY12/20 Treakisym® sales to decline (compared to the FY12/18 level).

The company estimates gross profits will increase 32.5% YoY to JPY1.1bn while the GPM rises 3.2pp to 33.7%. The higher GPM isattributable to an improved product mix and cost reductions.

▷▷

The weighting of domestic sales of Treakisym®, which has a relatively high gross margin, declined in the previous fiscal year,
but is projected to increase in FY12/20, thus lifting the overall GPM.
SymBio also incurred costs as a result of impurities and appearance defects in Treakisym® 100mg injection formulations, butthese costs are expected to diminish in FY12/20.

The company forecasts SG&A expenses of JPY6.2bn (+20.7% YoY).

▷

SymBio plans R&D expenses of JPY2.7bn (+9.7% YoY) 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), oral and intravenous

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rigosertib products, and new drug brincidofovir, an antiviral drug to treat infections. An upfront fee (JPY540mn) incurred in
FY12/19 for the in-licensing of antiviral drug brincidofovir will not be repeated while the expected Q4 FY12/20 approval of▷

Treakisym® RTD formulation will incur a milestone payment.
The company forecasts SG&A expenses excluding R&D at JPY3.6bn (+30.5% YoY). Personnel expenses and sales promotion
expenses are expected to increase; In particular, personnel expenses are slated to increase as SymBio looks to expand theworkforce from 106 (FY12/19) to 152 employees. The number of sales representatives will increase from 39 to 70. Eisai’s
exclusive marketing rights to Treakisym® ends in 2020 and SymBio will take over marketing from 2021. The company aims tobuild up the nationwide sales force with 62 sales representatives by Q2 and is also considering using about 30 of the 62 sales
representatives for joint marketing activities with co-promotion partners (in collaboration with sales representatives ofpharmaceutical companies).

Consequently, profits below the operating level are expected to decline YoY.

The main pipeline development plans are as follows.

Treakisym®
▷▷

For r/r DLBCL, the company plans to continue preparations to apply for drug approval
SymBio is preparing to begin sales of the RTD formulation (which has been approved) in Q1 FY12/21 and progressing withclinical trials of the RI formulation mainly to confirm safety for Treakisym® in-licensed from Eagle Pharmaceuticals

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▷

For oral rigosertib, SymBio is preparing for participation in global phase III trials of rigosertib azacitidine combination therapy

clinical trials

that Onconova Therapeutics is planning

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Long-term outlook
Medium-term plan (FY12/20–FY12/22)
SymBio announced a three-year medium-term plan for FY12/20 through FY12/22 along with the FY12/19 results announcement.
The company reduced the Treakisym® sales target compared to the previous medium-term plan after reassessing market shareassumptions and accordingly revised down operating and recurring profit estimates. In contrast, the company revised up net
income estimates to reflect tax effect accounting.
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®. The two main changes in themedium-term plan were a reduction in the end-2020 Treakisym® market share assumption for first-line treatment of low-grade
non-Hodgkin’s lymphoma from 70% to 64% and a more accelerated pace of market penetration for Treakisym® liquid
formulations.

▷

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 thestart 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 and dedicated training system by 1H FY12/20.
Grow sales of Treakisym® from already approved indications: The company seeks to increase market share to 64% by the endof 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 95% of the way toward a switch from the current lyophilized powder formulation to aliquid formulation by the end of 2021 and 100% by the beginning of 2022.

Targets in medium-term plan (FY12/20–FY12/22)
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
FY12/19

FY12/20

FY12/21(JPYmn)

Act.

Est.

MTP

FY12/22
MTP

Sales

2,811

3,404

9,008

10,816

Operating profit (loss)-4,302-5,090

1,031

1,482

Recurring profit (loss)-4,377-5,134987

1,438

Net income (loss)-4,376-4,803

1,356

1,717

Source: Shared Research based on company data.

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Medium-term plan sales target
SymBio expects product sales of Treakisym® to account for the bulk of sales. Product sales targets reflect the recent pace ofmarket penetration and sales trends, which feed into the company’s revised sales growth rates calculated over the medium-termplan period. As of February 2020, 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 salesorganization.
In estimating sales in FY12/21 and FY12/22, SymBio disclosed targets assuming increased product sales of Treakisym® as it
expects to gain approval of the drug as a treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in Q2
FY12/21.

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 nonHodgkin’s lymphoma (NHL), and in Q3 FY12/18 Treakisym® accounted for 56% of drugs used for the first-line treatment of lowgrade NHL. On an NHI drug reimbursement price basis, Treakisym® sales have increased from JPY4.8bn in FY12/16 to 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 64% 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,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 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 62 in Q2 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 pricethat 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.

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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%.
Shared Research also sees potential for SymBio to further boost 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 the medium-term plan
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®,▷

The company has not factored in upfront payments for in-licensing drug candidates outside its existing pipeline after

rigosertib IV and oral formulations, and brincidofovir, an antiviral drug for the treatment of infections.

brincidofovir, an antiviral drug for the treatment of infections, although it will continue to evaluate and investigate them.

R&D expenses▷

For FY12/20, the company forecasts R&D spending will increase 9.7% YoY to JPY2.7bn centered on Treakisym® for treatment ofrelapsed and refractory diffuse large B-cell lymphoma (r/r DLBCL), Treakisym® liquid formulations (RTD and RI), intravenous
and oral formulations of rigosertib, and development of new antiviral agent brincidofovir. The upfront licensing fee(JPY540mn) paid in FY12/19 for in-licensing antiviral agent brincidofovir will not be repeated, but it expects to make a▷milestone payment in Q4 FY12/20 in line with approval of Treakisym® RTD.
In FY12/21, the R&D budget is expected to decline YoY while the milestone payment for Treakisym® RTD should diminish. In
FY12/22, R&D spending is expected to increase YoY due to some one-time costs.

Other SG&A expenses
Other SG&A expenses comprise primarily Treakisym® sales and marketing, production and distribution, business development, dmanagement related costs. SymBio is factoring in costs associated with building and operating its own sales organization from
FY12/20 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.

▷

In FY12/20, other SG&A expenses, excluding R&D spending, are projected to increase 30.5% YoY to JPY3.6bn on higher
personnel expenses and sales promotion expenses. The company aims to expand its workforce from 106 to 152 employees, so
personnel expenses are expected to rise. SymBio plans to increase the number of sales representatives from 39 to 70. Eisai’s
marketing agreement for exclusive distribution rights to Treakisym® ends in 2020 and SymBio will take over marketing from

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2021. Management looks to build a nationwide marketing force of 62 sales representatives by Q2 FY12/20 and is considering
joint marketing activities with co-promotion partners (collaborating with sales representatives from pharmaceutical▷companies) for about 30 of the 62 sales representatives.
It looks like the company will maintain other SG&A expenses at FY12/20 levels from FY12/21 onward. Large changes to the inhouse sales force are not expected after it is expanded to 62 sales representatives in Q2.

Net income
The company forecasts net income exceeding recurring profit in FY12/21 and FY20/22 to reflect the reduction of loss carried overfrom the previous fiscal year from FY12/21 (when it is expected to turn profitable) onward on tax effect accounting.

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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 rare diseases—andsmaller patient populations. Larger pharmaceutical companies may be reluctant to develop drugs in niche markets due tolimited sales potential—SymBio sees an opportunity to avoid intense competition in the marketplace by focusing on thedevelopment 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 joint global phase III
clinical trials. 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 forthe commercialization 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), rigosertib (IV and oral), andbrincidofovir
Treakisym® (FD)For patients that have developed resistance to other drugs, Treakisym® (FD) is safer and more efficacious than existingtreatments. 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 nonHodgkin’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 thisto be added as indication for Treakisym® in December 2016.

As of February 2020, phase III clinical trials for the fourth indication of relapsed or refractory diffuse large B-cell lymphoma(DLBCL) were under way. In November 2019, the trial confirmed a positive overall response rate (the primary endpoint of thestudy) exceeding expectations and the company is currently preparing for an approval filing in 1H FY12/20.

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 basisof results 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 initiated the phase I clinical trial for higher-risk MDS in Japan to evaluate safety from June2017 and completed enrollments in June 2019. The company plans to begin a clinical trial in combination with azacitidine after
confirming safety in the phase I clinical trials, and participate in global phase III trials of rigosertib azacitidine combination therapy
targeting first-line treatment of higher-risk MDS that Onconova plans to launch.

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Brincidofovir
Brincidofovir is an antiviral drug formed by conjugating a lipid chain (hexadecyloxypropyl, or HDP) of specified length tocidofovir (an antiviral drug already approved and marketed in the EU and the US, but not approved in Japan). It has a novel
mechanism of action, which is attributed to its being a lipid conjugate, and can be taken up into cells with enhanced efficiency
compared to cidofovir (i.e., brincidofovir has higher cell membrane permeability). Once inside a cell, brincidofovir transforms
into a direct-acting agent and inhibits viral replication, demonstrating high antiviral effect. It is also easy to use as it has a low riskof nephrotoxicity, which is a side effect of cidofovir, hence making brincidofovir a novel, highly active anti-multiviral drug. It is
expected to become an effective treatment for a wide spectrum of infectious diseases caused by DNA viruses, including
cytomegalovirus (CMV) and other herpes viruses, adenoviruses, BK virus, papillomaviruses, and smallpox virus.
In September 2019, SymBio entered an exclusive global license agreement with Chimerix Inc. for brincidofovir. As a result, thecompany acquired exclusive worldwide rights to develop, market, and manufacture brincidofovir for all indications except
smallpox.
The company will initially develop brincidofovir for the indications of viral hemorrhagic cystitis (vHC) and HHV-6 encephalitis(HHV-6) after hematopoietic stem cell transplantation and kidney transplantation, areas with high unmet medical needs, with thegoal of commercializing the product in Japan by mid 2020s.

Revenue: milestone payments and Treakisym®
Revenue comes from milestone payments and product sales. Operating losses have persisted since the company’s founding withthe exception of FY12/08 when the company booked an operating profit due to a one-time contract payment from Eisai for an
exclusive domestic right to sell Treakisym®.
For FY12/20, the company expects a JPY5.1bn operating loss, JPY5.1bn recurring loss, and net loss of JPY4.8bn. Over the courseof the medium-term plan (FY12/20–FY12/22), the company expects to post an operating profit of JPY1.0bn in FY12/21 and
JPY1.5bn in FY12/22 and plans to remain 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 obtain approval andstart 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 thefollowing 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 efficacy and safety of a new drugcandidate through administration to animals or humans) 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
and improving 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 the inlicensing 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 February2020). 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 and antiviral agent brincidofovir.

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 inhouse 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;

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

Chief Scientific Officer, Cell Therapeutics; Head of Discovery Research,
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.

Honorary President, National Cancer Center
Honorary Director, Nagoya Medical Center

Makoto Ogawa, M.D., Ph.D.

Honorary President, Aichi Cancer Center

Tatsutoshi Nakahata, M.D.,
Ph.D.

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

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

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

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

Professor, Cancer Science Institute of Singapore, National University of Singapore
Vice President, The Japanese Society of Hematology in 2012
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
Medicine Cellular Transplantation Biology (Hematology/Respirology)
Executive Director, The Japanese Society of Hematology in 2012

Koichi Takahashi, M.D.

Assistant Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center,
The University of Texas

Source: Shared Research based on company data

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Drug candidate selection process

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

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 2020, marketing rights
are granted to outside partners.

Focusing on niche markets: oncology, hematology, and rare diseases
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 rare diseases.
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. In July 2018, Treakisym® was newly included as a standard option for first-line treatment of low-grade NHL andmantle cell lymphoma in the Guidelines for Hematological Malignancies 2018 issued by the Japan Society of Hematology in July
2018.

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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. Also, it acquired exclusive worldwide rights to develop, manufacture,and market brincidofovir.

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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

Preparing for approval filing(co-developed: exclusive sales rights
granted to Eisai)

DLBCL (aggressive NHL)
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 lowgrade 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

Filed for approval (Sep 2019)

—

Japan

All indications

Clinical trials underway

—

Japan

Systemic lupus erythematosus Phase I clinical trials

CLLSouth Korea

TaiwanTreakisym®
SyB L-1701

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

—

(SLE)

completed

Relapsed or refractory

Global phase III clinical trials

higher-risk MDS

underway

Relapsed or refractory higherrisk MDS

Phase I clinical trials underway —(oral)
Rigosertib

Japan

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

Japan

—

(single drug)
Untreated higher-risk MDS

Preparing for phase I clinical(with azacitidine)

trials
Preparing for global phase III

Viral hemorrhagic cystitis——

clinical trials
Brincidofovir
SyB V-1901

Worldwide—(vHC) and HHV-6 encephalitis(HHV-6) after hematopoietic
stem cell and kidneytransplantation

Source: Shared Research based on the company website

As of February 2020, the main drugs for which SymBio was preparing filing for approval or in the development pipeline were as
follows:

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Treakisym®, for the indication of relapsed or refractory DLBCL (aggressive NHL): Completed enrollment of patients for thephase III clinical trial (April 2019). Preparing to file approval application in 1H FY12/20
Treakisym®, preparing to file for approval of RTD formulation and conducting clinical trials on RI formulation: Filed for approvalfor RTD formulation in September 2019, and clinical trials on RI formulation initiated in November 2018
Rigosertib (intravenous formulation), for the indication of relapsed or refractory higher-risk myelodysplastic syndrome (MDS):
Enrolling patients for global phase III clinical trials
Rigosertib (oral formulation), for the indication of higher-risk MDS: Completed patient enrollment for the phase I clinical trial inJune 2019, in preparations for the phase I clinical trial of the combination therapy with azacitidine, in preparations for global
clinical trials of the combination therapy with azacitidine
Antiviral drug brincidofovir: Acquired exclusive global rights to develop, market, and manufacture brincidofovir for all
indications except smallpox from Chimerix, Inc. in September 2019

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.
As of February 2020, the company initiated phase III clinical studies of Treakisym® for an additional indication of relapsed or
refractory DLBCL (aggressive NHL) and is preparing for a label expansion filing in 1H FY12/20.

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).

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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)

Five-year relative survival rate for lymphatic malignancies (in patients diagnosed between 2001 and 2005)
Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma

Number of cases

Number of casesⅠ

5-year relative
survival rate (%)

5-year relative
survival rate (%)

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

Stage

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). The
marketing agreement with Eisai expires in December 2020, after which SymBio plans to independently market Treakisym® inJapan.
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 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.

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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.
As of February 2020, the company is preparing to file for the expanded approval of Treakisym® to treat relapsed or refractory
DLBCL (aggressive NHL) in 1H 2020.
Market for Treakisym® and number of patients
Non-Hodgkin's Lymphoma
Low-grade B-cell

First-line

Chronic
Lymphatic
Leukemia

Moderate- tohigh-grade

Number of patients

6,967

656

Approval

Obtained

Obtained

Development status

Obtained approval(Aug. 2016)

Number of patients

Obtained approval(Dec. 2016)
9,336

Approval

Obtained

Completed patient
enrollment forphase III clinical
trials in Japan

Development status

Obtained approvalin Japan(Oct. 2010)

Preparing for
approval

Relapsed andrefractory

18,672

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 lowgrade 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 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 lowgrade NHL and MCL. 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)
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 themajority 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®.

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R&D status: Preparing for filing of Treakisym® to treat relapsed or refractory DLBCL
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. Enrollmentof 60 patients was completed in April 2019. 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.
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)

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Dilution

Dilute with 250ml physiologicalsalineDilute with 50ml physiologicalsalineDilute with 250ml physiologicalsalineAdministration time

60 minutes

10 minutes

60 minutes

Dosage form

100mg/4mL

100mg/vial
25mg/vial

Storage

Refrigerated storage (2–8°C)

Room temperature

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 2020, the company is respectively preparing to file for approval and conducting clinical trials for the
bendamustine hydrochloride RTD and RI products.
SymBio was 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. After consultations with PMDA, the company completed the approval filing in September 2019. Basedon 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 explored 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 completed a phase I clinical
trial to confirm efficacy against progressive solid tumors and pre-clinical studies for systemic lupus erythematosus (SLE), butdevelopment was halted even though the studies achieved their initial objectives. This is because SymBio has decided tomaximize management resources by concentrating on domestic and overseas development of antiviral drug brincidofovir.

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®.
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.

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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
with other anticancer drugs. It is being developed in both intravenous and oral forms.
Rigosertib inhibits the action of multiple kinases such as phosphatidyl inositol 3-kinase (PI3K) by blocking the action of the Ras gene, a cancer-related
gene product. It is a small molecule anticancer agent with a new mechanism of action that kills cells by suppressing transmission of intracellular signals
required for cancer survival and growth.
The PI3K pathway is activated by various gene mutations in cancer, and is thought to be deeply involved in cancer survival, differentiation, andproliferation.
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, intermediate1, intermediate-2, and high. Lower-risk MDS refers to low and intermediate-1 patients, while higher-risk MDS refers tointermediate-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 2020, 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.

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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 withresumption of study drug supply SymBio restarted phase I clinical trials in Japan in June 2017 and completed patient enrollment
in June 2019, to verify the tolerability and safety of the oral formulation of rigosertib among Japanese patients. After establishingsafety in phase I clinical trials, the company plans to 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
Low-risk MDSHigh risk MDS

Number of patients

Relapsed andrefractory
3,200

Approval

TBC

Development status

Global phase III
trials underway

First-line

First-line

Intravenous

Number of patients

7,800

3,200

Approval

TBC

TBC

Development status

Phase II trials
Global clinical trials
underway in the US being reviewed by
Onconova
Phase I clinical
trials underway in
Japan

Oral

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
2020.

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
for those 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 48 patients had been registered as of end December 2019 versus the target of 50. 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. According to a press release by Onconova made in
December 2019, worldwide patient enrollment had exceeded 90% of the 360 target. Top-line (primary endpoint) results areslated for release in 1H 2020.

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 2020, 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 thesafety of the drug at high doses (an additional requirement for phase III clinical trials conducted by Onconova in the US for theindication of untreated and relapsed or refractory higher-risk MDS). The patient enrollment for the study was completed in June
2019. After establishing safety in the phase I clinical trial, the company plans to resume the trial of the drug in combination withazacitidine and participate in global phase III clinical trials conducted by Onconova. In December 2019, Onconova issued a press
release announcing it was considering a phase II/III adaptive trial for untreated high-risk MDS patients based on data presented at
the 61st American Society of Hematology Annual Meeting and Exposition in December 2019.

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 JPY14.5bn for FY03/19 (+11.1% YoY) andforecast to reach JPY15.4bn in FY03/20. Shared Research thinks that sales of the intravenous and oral forms of rigosertib could

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match or exceed sales of Vidaza, used for patients who have not received treatment with Vidaza or in combination therapy withVidaza.

SyB V-1901 (antiviral drug brincidofovir)
In September 2019, SymBio concluded an exclusive global license agreement with Chimerix Inc. for the antiviral drug
brincidofovir (SyB V-1901). The company acquired exclusive global rights to develop, manufacture, and market brincidofovir for
all diseases except smallpox. Under the terms of the agreement, the company will pay Chimerix an upfront payment of USD5mn,
milestone payments on future developments of USD180mn, and royalties on the product sales. Shared Research thinks
brincidofovir differs from other candidates in SymBio’s pipeline in that it targets the global market and that the company had
acquired not only development and marketing rights but also manufacturing rights to the drug.
According to the company, Chimerix had been developing oral formulation of brincidofovir, but suspended development due tothe failure of the phase III clinical trial. SymBio determined that the failure of the oral formulation was due to its low intestinal
absorption rate and side effects arising from toxicity, and thought that it could circumvent such problems if it worked on
developing brincidofovir as an intravenous formulation. The company commented that one of the reasons it entered the license
agreement with Chimerix was the latter’s policy of focusing on cancer.

Mechanism of action and indications of brincidofovir
Brincidofovir is an antiviral drug formed by conjugating a lipid chain (hexadecyloxypropyl, or HDP) of specified length tocidofovir (antiviral drug already approved and marketed in the EU and the US, but not approved in Japan). As a lipid conjugate, it
has a novel mechanism of action and can be taken up by cells at enhanced efficiency compared to cidofovir (i.e., brincidofovir
has higher cell membrane permeability). Once inside a cell, brincidofovir transforms into a direct-acting agent and inhibits viral
replication, demonstrating high antiviral efficacy. It is also easy to use as it has a low risk of nephrotoxicity, which is a side effect of
cidofovir, hence making it a novel, highly active anti-multiviral drug. It is expected to become an effective treatment against awide array of infectious diseases caused by DNA viruses, including cytomegalovirus (CMV) and other herpes viruses,
adenoviruses, BK virus, papillomaviruses, and smallpox virus.

Cidofovir (CDV): Approved by FDA in 1996 as a treatment for cytomegalovirus retinitis in AIDS patients. It inhibits replication of multiple families of
DNA viruses other than herpes viruses, including adenoviruses, papillomaviruses, and polyomaviruses.
CDV is taken up by renal tubular epithelial cells through organic anion transporter 1 (OAT1), and its accumulation in the cells cause nephrotoxicity.
Brincidofovir is expected to have a low risk of nephrotoxicity as its lipid chain prevents it from being taken up by OAT1 and accumulating in renal
tubular epithelial cells.

Development status: targeting commercialization by mid-2020s
The US-based phase I clinical trial of intravenous formulation of brincidofovir has been completed. It has been reported that noserious side effects were observed in the study.
SymBio will initially develop brincidofovir toward commercialization in Japan for treatment of viral hemorrhagic cystitis (vHC)*1
and HHV-6 encephalitis*2 occurring after hematopoietic stem cell and kidney transplantation, which have high unmet medical
demand. The company also looks to expand its business in Europe, the US, and Asia (including China), where organ transplant
markets are large. It will also consider forming partnerships that take advantage of regional characteristics of these target
diseases. The company will explore all options for maximizing business value, including the utilization of wholly-owned
subsidiary SymBio Pharma USA, Inc. established in May 2016. It aims to commercialize the product by mid 2020s.
Hematopoietic stem cell transplantation is one of the therapies aimed at completely curing diseases such as blood cancer andimmunodeficiency disorders that are difficult to treat with conventional chemotherapy. In Japan, there are about 4,000 patients
who have undergone allogeneic hematopoietic stem cell transplantation, and about 60% of them have contacted viral

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hemorrhagic cystitis (vHC) or HHV-6 encephalitis. For vHC, cidofovir is used as first-line treatment in the EU and US. For
encephalitis, foscavir and denocin are designated as the first-line drugs, and cidofovir as the second-line drug.

1.

Viral hemorrhagic cystitis (vHC): Among viral infections that frequently occur following hematopoietic stem cell transplantation, adenovirus
infections causing hemorrhagic cystitis are particularly refractory in nature. When severe, they can cause disseminated infection and become fatal.
Cases of adenovirus spreading to the kidney and causing kidney failure and ultimately death have been reported. These infections are especiallylikely to occur in unrelated donor transplantation and in umbilical cord blood transplantation, which are relatively common in Japan. The
infections are likely to be refractory, as they are further complicated by the length of time required for reconstruction of the immune system.
Drugs currently used in treatment, including cidofovir (CDV), are either unapproved or off-label in Japan.

2.

HHV-6 encephalitis: HHV-6 (Human Herpesvirus 6) is the sixth human herpesvirus to be discovered. It reactivates in 30–70% of patients after
allogenic hematopoietic stem cell transplantation and can cause HHV-6 encephalitis. Most cases of HHV-6 encephalitis develop within 2–6 weeks
after transplantation, most frequently in the third week after transplantation. It is characterized by the three major symptoms of impaired
memory, disordered consciousness, and convulsions, which in typical cases gradually appear in the same order (convulsions occur in 30–70% of
patients). In rapidly progressing cases, which are not uncommon, neurological symptoms worsen by the hour, often requiring respirator
management for repeated convulsions and respiratory depression. The conditions of HHV-6 encephalitis patients often deteriorate rapidly over ashort period of time, making early treatment important. According to guidelines edited and issued by the Japan Society for Hematopoietic Cell
Transplantation (February 2018), the first-line drugs are foscarnet (FOS) and ganciclovir (GCV), followed by the second-line drug cidofovir(CDV). CDV is not the preferred first-line drug due to nephrotoxicity and because it transfers poorly into cerebrospinal fluid (CSF). All three ofthese drugs have been found to be effective in vitro, but no trials have been conducted yet to confirm their clinical efficacy in patients with HHV6 encephalitis.

Number of patients and estimated sales
As previously mentioned, the company will initially develop brincidofovir for the indications of viral hemorrhagic cystitis (vHC)and HHV-6 encephalitis after hematopoietic stem cell and kidney transplantation toward commercialization in Japan. In Japan,
there are about 4,000 patients who have received allogeneic hematopoietic stem cell transplants, and about 60% of them havecontracted vHC or HHV-6 encephalitis.
In addition to vHC and HHV-6 encephalitis after hematopoietic stem cell transplantation in Japan, the company expects
indications of brincidofovir to be expanded to include infectious diseases that occur after kidney transplantation (about 40% of
patients suffer from infectious diseases caused by BK virus or cytomegalovirus after kidney transplantation) in China, the EU, andthe US. Based on such factors, the company estimates global sales of brincidofovir, including sales from emerging markets, toreach JPY100.0bn.

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Earnings structure(JPYmn)FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

FY12/18

Sales

1,450

1,883

1,955

1,532

1,955

1,933

2,368

3,444

3,836

2,838

YoY

21.7%

29.8%

3.9%

-21.6%

27.6%

-1.1%

22.5%

45.4%

11.4%

-26.0%

Product sales
YoY
Treakisym sales (NHI price basis; reference)
Product sales / Sales (NHI price basis)

Royalty revenue
Sales to Eisai
YoY

Sales to other partners

FY12/19

326

1,632

1,955

1,432

1,940

1,933

2,137

3,444

3,810

2,811

-

401.3%

19.8%-26.8%

35.5%

-0.3%

10.6%

61.1%

10.6%

-26.2%
-

644

3,390

3,940

4,230

4,320

4,760

4,720

7,600

8,500

50.6%

48.2%

49.6%

33.9%

44.9%

40.6%

45.3%

45.3%

44.8%

-

1,124

250

-

100

15

-

231

-

26

26

1,446

1,872

1,930

1,486

1,908

1,852

2,265

3,382

3,648

2,831

33.2%

29.5%

3.1%

-23.0%

28.4%

-2.9%

22.3%

49.4%

7.9%

-22.4%

4

10

26

46

47

81

104

62

187

6

238

1,224

1,362

1,214

1,428

1,350

1,464

2,413

2,663

1,973

CoGS / Product sales

73.1%

75.0%

69.7%

84.8%

73.6%

69.8%

68.5%

70.1%

69.9%

70.2%

CoGS / Sales (NHI price basis)

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

1,684
865

CoGS

Product procurement
Gross profit

1,212

658

593

318

527

583

904

1,031

1,173

Product gross profit

87

408

593

218

512

583

673

1,031

1,147

838

Gross profit margin

26.9%

25.0%

30.3%

15.2%

26.4%

30.2%

31.5%

29.9%

30.1%

29.8%

Royalty revenue
SG&A expenses
Personnel expenses
R&D expenses
Other
Operating profit

1,124

250

-

100

15

-

231

-

26

26

1,825

2,725

2,293

1,999

1,830

3,135

3,031

4,978

3,829

5,166

343

365

413

441

479

488

541

554

504

506

1,118

1,945

1,438

1,053

774

2,035

1,667

3,018

1,833

2,442

364

415

442

505

577

612

823

1,406

1,492

2,219

-613

-2,067-1,700-1,681-1,303-2,552-2,127-3,947-2,656-4,302

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.
FY12/19 product sales declined YoY. A lyophilized injection formulation of Treakisym® imported from Astellas DeutschlandGmbH, a consolidated subsidiary of Astellas Pharma, was found to contain impurities and appearance defects, and as a result,shipments of Treakisym® 100mg to Japan distributor Eisai were postponed. Consequently, booking of some product sales wasdelayed until the following fiscal year, resulting in a YoY decline in sales.

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.

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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.

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 ofcontacts in the pharmaceutical industry built during his tenure at Amgen Japan and Amgen Inc. is a significant hurdle forcompetitors 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 the company in December 2010, is being used by a number of Japanese physicians and is considered to be an
essential drug for the 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 rarediseases. The company takes advantage of a less competitive environment by developing drugs for indications that serve a
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 JPY3.9bn at end-FY12/19, but the company expects a
total net loss of JPY4.8bn for FY12/20. SymBio aims to secure a total of JPY5.5bn through its February 2020 issue of the 50thand 51st stock acquisition rights with exercise price revision clauses. 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 overview
Lymphatic cancer: patient population, market size, drugs
Newly diagnosed patients with lymphatic cancer
In 2015, the number of people diagnosed with lymphatic cancer in Japan was 30,103 (+5.7% YoY; average annual increase inpast 10 years is 5.9%), according to the Center for Cancer Control and Information Services. Of these, 23,782 (+5.4% YoY), or
79.0% (79.2% in the previous year), were 60 years or older. Of the 903,914 (+3.1% YoY) people diagnosed with cancer, thosediagnosed with lymphatic cancer accounted for only 3.3% (3.2% in 2014), but their number increased 77.2% between 2005
and 2015 versus a 39.8% increase in the number of people newly diagnosed with cancer.
Patients newly diagnosed with lymphatic malignancy
35,00030,00025,00020,00015,00010,000
5,000
0

1975

1980

Number of patients
Incidence rate (per 100,000)

1985

1990

1995

2000

2005

2010

2015

1975

1980

1985

1990

1995

2000

2005

2010

2015

4,013

4,741

6,635

9,297

11,195

13,307

16,991

23,91930,103

3.6

4.1

5.5

7.5

8.9

10.5

13.3

18.7

23.7

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

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.
Treakisym® indications and number of patients
Indications

Patients

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

CLL
Relapsed or refractory NHL

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

656 Approval granted
18,672 Clinical trials underway

Source: Shared Research based on company data
*Sales based on NHI prices.

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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
JPY11.9bn (-44.1% YoY) in FY12/19.

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

Drugs competing with rigosertib
According to the company, as of February 2020, 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

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use of hypomethylating agents such as azacitidine and decitabine (Dacogen) in the treatment of MDS has improved the outcomeof patients 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 JPY14.5bn in
FY03/19 and expects sales of JPY15.4bn in FY03/20.

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Historical performance
Full-year FY12/19 results▷

Sales:

JPY2.8bn (-26.0% YoY)▷

Operating loss:

JPY4.3bn (loss of JPY2.7bn in FY12/18)

Recurring loss:

JPY4.4bn (loss of JPY2.7bn in FY12/18)

Net loss:

JPY4.4bn (loss of JPY2.8bn in FY12/18)▷▷

Sales declined YoY. As per the reason for earnings forecast revisions announced in August 2019, foreign matter contamination
and appearance defects were discovered in lyophilized injection agents imported from Astellas Deutschland GmbH, a subsidiaryof Astellas Pharma Inc. The extent of contamination and defects significantly exceeded limits permitted by quality standards
stipulated in the supply agreement, and as a result, the shipments of Treakisym® 100mg vials to its domestic distributor Eisai wasdelayed with some product sales expected to be booked in FY12/19 postponed to the next fiscal year. Reviewing the quarterly
sales trend, sales increased 81.4% YoY to JPY1.6bn in Q1 (January–March 2019), declined 62.2% YoY to JPY394mn in Q2 (April–June), dropped 99.7% YoY to JPY3mn in Q3 (July–September), and increased 3.3% YoY to JPY830mn in Q4 (October–
December). There were practically no sales in Q3 due to the aforementioned factors, but the company posted sales in Q4 once
shipments to Eisai resumed following rigorous quality inspections.
Gross profit declined 26.3% YoY to JPY865mn while the gross profit margin declined 0.3pp to 29.8%.
SG&A expenses rose 34.9% YoY to JPY5.2bn and R&D expenses increased 33.2% YoY to JPY2.4bn. This included upfront
payments (JPY540mn) for new drug brincidofovir (an antiviral drug for the treatment of infections), and expenses for conducting
clinical trials of intravenous and oral formulations of Treakisym® and rigosertib. Excluding R&D expenses, SG&A expenses
increased by 36.5% YoY to JPY2.7bn.
As a result, operating loss, recurring loss, and net loss widened YoY.
Major progress in cumulative Q3 FY12/19 was as follows:▷

In November 2019, the company announced that in the phase III study of the anticancer drug Treakisym® administered in
combination with rituximab (BR therapy) targeting relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), the response
rate, which was the primary endpoint of the study, exceeded expectations. The company plans to compile final analysis results▷of the study and apply for approval during 1H FY12/20.
In October 2019, Onconova Therapeutics, Inc. announced that it was approaching enrollment of 90% of the target 360
patients for its INSPIRE trial evaluating intravenous formulation of rigosertib in higher-risk myelodysplastic syndrome (MDS)
patients who had failed to respond to or relapsed after previous treatment with a hypomethylating agent, the current standardof care for MDS, and that it planned to report primary endpoint results of the study during 1H 2020. Further, regarding the oral
formulation of rigosertib, Onconova announced that based on the result of its consultation with the FDA on Special Protocol
Assessment (SPA), it would consider conducting a phase II clinical trial targeting untreated higher-risk MDS patients. The
purpose of the trial would be to compare the combination therapy of rigosertib and azacitidine with the azacitidine▷

monotherapy.
In October 2019, the company entered a global license agreement with the US-based Chimerix Inc. to acquire exclusive
worldwide rights to the antiviral drug brincidofovir. Under the terms of the agreement, Chimerix will grant global exclusive
rights to develop, market, and manufacture brincidofovir for all indications except smallpox to the company.

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In September 2019, the company filed for manufacturing and marketing approval of the ready-to-dilute (RTD) liquid
formulation of Treakisym®. The application covers all indications for which Treakisym® has already been approved; if the RTD
formulation is approved for the additional indication of r/r DLBCL, which is currently in a clinical trial stage, it can also be used▷

to treat r/r DLBCL. Once the company obtains approval for the RTD formulation, it plans to launch the product in Q1 FY12/21.
In June 2019, the US Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq, a
CD79b-directed antibody-drug conjugate, in combination with bendamustine (product name: Treakisym®) and rituximab (BRtherapy) for patients with relapsed or refractory DLBCL who are not eligible for transplant. Polatuzumab vedotin-piiq was
discovered by Roche Group company Genentech and is being developed in Japan by Chugai Pharmaceutical, another▷▷member of the Roche Group.
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 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 forthe 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.
The company increased Treakisym® sales representatives (highly specialized sales representatives) and conducted training toform the core of its in-house marketing network. Information provision activities were started from July 2019 by the Treakisym®
sales representatives dispatched to each region to promote the shift to a nationwide operation with close local ties. The company
made progress toward completing the formation of its nationwide sales structure (planned in 1H FY12/20). In Q4 FY12/19(October to December 2019) it hired additional regional sales managers and Treakisym® managers necessary to complete thesales structure, as well as moving ahead with business alliances with pharmaceutical wholesalers and establishing logistics centersin East and West Japan to provide a distribution and logistics function. It also prepared a new IT system that includes ERP to
upgrade its IT infrastructure.

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).
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,
which applies to all of the approved indications. This has seen Treakisym® establish its position as a standard treatment for
lymphatic cancer. By switching to its own sales structure in 1H FY12/20, the company plans to attain a large market share as inmarkets in Europe and the US.
In addition to the above three approved indications, the company is conducting a phase III clinical trial for the fourth indicationof relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). The response rate (primary endpoint) in the test results

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released in November 2019 was better than expected. As of February 2020, the company is preparing to apply for approval in 1H
FY12/20.
SymBio is targeting a transition to Treakisym® liquid formulation (RTD and RI formulations), for which it concluded an exclusive
licensing agreement in Japan with Eagle Pharmaceuticals (based in New Jersey, US) in September 2017. The company has alreadyconsulted with PMDA and filed for approval of the RTD formulation in September 2019 with an eye towards commercialization
by Q1 FY12/21. SymBio launched clinical trials for the RI formulation in November 2018 primarily to confirm safety, and has madesteady progress with patient enrollments since enrolling the first patient in April 2019, having enrolled 31 patients as of end
January 2020. The company will apply for approval without delay after the end of the clinical trials of the RI formulation and aims
to begin sales in 1H FY12/22. Liquid formulations of Treakisym® will offer significant value added (reduced burden) to patientsand healthcare professionals, and patent protection in the form of a liquid product license makes it possible to extend the
product life of Treakisym® until 2031.
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. This will allow
combination therapy with obinutuzumab (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, the company obtained approval for the partial revision to its application concerning the use of
Treakisym® as a pretreatment agent in tumor-specific T cell infusion therapy. This will allow Treakisym® to be used as apretreatment agent for Kymriah® intravenous infusion, which was approved as the first chimeric antigen receptor T-cell (CAR-T)
therapy in Japan and listed on the NHI drug price list in May 2019.
The Phase I clinical trial of Treakisym® as a treatment for progressive solid tumors and preclinical study to verify the efficacy ofTreakisym® in the treatment of systemic lupus erythematosus (SLE), which were conducted to explore further potential
indications of the drug, have been completed. However, the company decided to suspend development despite the initial
objectives of the studies being met. Its policy is to prioritize development in Japan and overseas of antiviral drug candidate
brincidofovir (for which it has obtained a license) to utilize its management resources most effectively.

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 (48 patients enrolled as of December 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. In December 2019, Onconova announced that it hadreached over 90% of its target of enrolling 360 patients worldwide as of November 2019. The company plans to report top-line(primary endpoint) results in 1H 2020. Based on these trial results, the company plans to apply for approval in Japan at the sametime as in the US and Europe.
Regarding the oral formulation of rigosertib, Onconova completed phase I/II clinical trials for the drug used in combination withazacytidine, whose results suggested the efficacy and safety of the combination therapy. To verify the tolerability and safety ofthe oral formulation of rigosertib among Japanese patients, SymBio began phase I clinical trials in Japan in June 2017, enrolled thefirst patients in October 2017, and completed patient enrollment in June 2019. After completing the phase I trials, the company
will consider phase I 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 currently planned by Onconova, andapply for approval of the oral formulation of the drug in Japan at the same time as in the US and Europe. In December 2019,
Onconova announced that it was considering the design of a Phase II/III adaptive trial with untreated higher risk MDS patients
based on the data presented at the 61st American Society of Hematology (ASH) Annual Meeting in December 2019.

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Antiviral drug for the treatment of infections SyB V-1901 (generic name: Brincidofovir）
In September 2019, SymBio concluded an exclusive global license agreement with Chimerix Inc. (hereafter Chimerix) for
brincidofovir (SyB V-1901, hereafter BCV IV and BCV Oral), an antiviral drug for the treatment of infections in intravenous andoral forms). The company acquired exclusive global rights to develop, manufacture, and market BCV for all diseases except
smallpox.
The company will initially develop BCV-IV for treatment of viral hemorrhagic cystitis (vHC) occurring after hematopoietic stem
cell transplantation, which have high unmet medical demand. It also plans to market BCV IV globally after conducting
international joint clinical trials in countries including the US and Europe. As well, the company plans clinical development of BCV
IV as an antiviral treatment of infections after kidney transplants, because it is likely to be effective for transplants other thanhematopoietic stem cell transplants, including organ transplants. The company looks to expand its business in Europe, the US
and Asia (including China), where organ transplant markets are large. It will also consider forming partnerships that takeadvantage of regional characteristics of these target diseases. The company will explore all options for maximizing business value,
including the strategic utilization of wholly-owned subsidiary SymBio Pharma USA, Inc. established in May 2016. The company isworking on a development plan (including improvement of the formulation) for BCV Oral. BCV Oral has demonstrated a strong,
broad-spectrum antiviral effect in clinical trials in Europe and the US by Chimerix. The company will design a global clinical trialbased on these findings.

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 learned of an event 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 company initiated an arbitration against The Medicines Company, under the rules of the International Chamber ofCommerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s repudiation of thelicense agreement. SymBio argued that The Medicine Company’s failure to provide sufficient assurance to the company
regarding the performance of obligations under on the license agreement in light of its decision to suspend and withdraw frombusiness activities relating to SyB P-1501in the European and US markets was a material breach of the license agreement.
Arbitration proceedings against The Medicines Company are still ongoing, and an arbitration ruling is expected in 1H FY12/20.
On January 6, 2020, Swiss company Novartis AG announced that it had acquired The Medicines Company.

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

Q3 FY12/19 results▷

Sales:

JPY2.0bn (-33.8% YoY)▷

Operating loss:

JPY3.5bn (loss of JPY1.9bn in Q3FY12/18)

Recurring loss:

JPY3.6bn (loss of JPY1.9bn in Q3 FY12/18)

Net loss:

JPY3.6bn (loss of JPY1.9bn in Q3 FY12/18)▷▷

Cumulative Q3 sales fell YoY. By quarter, sales increased 81.4% YoY to JPY1.6bn in Q1 (Jan–Mar 2019), but fell 62.2% YoY to
JPY394mn in Q2 (Apr–Jun 2019) and dropped again by 99.7% YoY to JPY3mn in Q3 (Jul–Sep 2019). As the company explained
as its reason for earnings forecast revisions announced in August 2019, foreign matter contamination and appearance defects
were discovered in lyophilized injection agents imported from Astellas Deutschland GmbH, a subsidiary of Astellas Pharma Inc.
The extent of contamination and defects significantly exceeded limits permitted by quality standards stipulated in the supply
agreement, and as a result, the initially scheduled shipment of Treakisym® 100mg vials to its domestic distributor Eisai wasdelayed.

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Gross profit was JPY563mn (-39.1% YoY), with the GPM down 2.5pp YoY to 28.0%. By quarter, while gross profit jumped
144.0% YoY to JPY609mn and GPM rose 9.7pp YoY to 37.8% in Q1, gross profit plunged to -JPY79mn in Q2. The sharp decline ingross profit was attributed to weak sales in Q2, combined with a JPY188mn loss on valuation of inventories due to quality defects
found in some batches of Treakisym® 100mg. In Q3, gross profit declined 90.5% YoY to JPY33mn.
SG&A expenses rose 44.8% YoY to JPY4.1bn and R&D expenses increased 52.5% YoY to JPY2.0bn. This included upfront
payments for new antiviral drug candidate brincidofovir, and expenses for conducting clinical trials of intravenous and oral
formulations of Treakisym® and rigosertib. Excluding R&D expenses, SG&A expenses increased by 38.3% YoY to JPY2.1bn.
As a result, operating loss, recurring loss, and net loss widened YoY.
Major progress in cumulative Q3 FY12/19 was as follows:▷

In November 2019, the company announced that in the phase III study of the anticancer drug Treakisym® administered in
combination with rituximab (BR therapy) targeting relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), the response
rate, which was the primary endpoint of the study, exceeded expectations. The company plans to compile final analysis results▷of the study and apply for approval during 1H FY12/20.
In October 2019, Onconova Therapeutics, Inc. announced that it was approaching enrollment of 90% of the target 360
patients for its INSPIRE trial evaluating intravenous formulation of rigosertib in higher-risk myelodysplastic syndrome (MDS)
patients who had failed to respond to or relapsed after previous treatment with a hypomethylating agent, the current standardof care for MDS, and that it planned to report primary endpoint results of the study during 1H 2020. Further, regarding the oral
formulation of rigosertib, Onconova announced that based on the result of its consultation with the FDA on Special Protocol
Assessment (SPA), it would consider conducting a phase II clinical trial targeting untreated higher-risk MDS patients. The
purpose of the trial would be to compare the combination therapy of rigosertib and azacitidine with the azacitidine▷▷

monotherapy.
In October 2019, the company entered a global license agreement with the US-based Chimerix Inc. to acquire exclusive
worldwide rights to the antiviral drug brincidofovir. Under the terms of the agreement, Chimerix will grant global exclusive
rights to develop, market, and manufacture brincidofovir for all indications except smallpox to the company.
In September 2019, the company filed for manufacturing and marketing approval of the ready-to-dilute (RTD) liquid
formulation of Treakisym®. The application covers all indications for which Treakisym® has already been approved; if the RTD
formulation is approved for the additional indication of r/r DLBCL, which is currently in a clinical trial stage, it can also be used▷

to treat r/r DLBCL. Once the company obtains approval for the RTD formulation, it plans to launch the product in Q1 FY12/21.
In August 2019, SymBio announced a revision to its FY12/19 earnings forecast. In Q2 FY12/19, impurities and appearance
defects were found in Treakisym® 100mg vials imported from Astellas Deutschland, which led to the company returning thewhole batch. Thus only a fraction of the batches scheduled for shipment in 2Q FY12/19 onward can be shipped by the end of
the year, with shipments possibly being delayed until Q1 FY12/20. The company therefore revised down its FY12/19 earnings▷

forecast.
In June 2019, the US Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq, a
CD79b-directed antibody-drug conjugate, in combination with bendamustine (product name: Treakisym®) and rituximab (BRtherapy) for patients with relapsed or refractory DLBCL who are not eligible for transplant. Polatuzumab vedotin-piiq was
discovered by Roche Group company Genentech and is being developed in Japan by Chugai Pharmaceutical, another▷member of the Roche Group.
In 1H FY12/19, capital stock and capital surplus each increased by JPY1.3bn YoY, reflecting proceeds from the issuance ofshares resulting from exercise of the 46th stock acquisition rights.

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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 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 forthe chimeric antigen receptor T-cell (CAR-T) therapy Kymriah® intravenous infusion.

Introduction of new pipeline candidate
SymBio concluded an exclusive global license agreement with Chimerix Inc. for the antiviral drug brincidofovir (SyB V-1901,
hereafter BCV)*1. The company acquired exclusive global rights to develop, manufacture, and market BCV for all diseases except
smallpox.
The company will initially develop BCV for treatment of viral hemorrhagic cystitis (vHC)*2 and HHV-6 encephalitis*3 occurring
after hematopoietic stem cell and kidney transplantation, which have high unmet medical demand. The company also looks toexpand its business in Europe, the US and Asia (including China), where organ transplant markets are large. It will also consider
forming partnerships that take advantage of regional characteristics of these target diseases. The company will explore all options
for maximizing business value, including the strategic utilization of wholly-owned subsidiary SymBio Pharma USA, Inc.
established in May 2016.

1. Brincidofovir (BCV) has a structure in which cidofovir (CDV, an antiviral drug already approved and marketed in the US and Europe but not
approved in Japan) is bound to a lipid chain (hexadecycloxypropyl, HDP). It is absorbed into the lipid bilayer membrane and transferred into cells,
where the bound lipid chain (HDP) is metabolized and separated from the structure by intracellular phospholipases. This process generates an activator(CDV diphosphate [CDV-PP]) that is retained in the cells for a long period of time, raising the compound's antiviral activity. Furthermore, BCV avoids
nephrotoxicity, a fundamental issue plaguing CDV, since HDP conjugation prevents the accumulation of the compound in renal tubular epithelial cells
through organic anion transporter 1 (OAT 1) and CDV is released at low levels into the bloodstream.
2. Viral hemorrhagic cystitis (vHC): Among viral infections that frequently occur following hematopoietic stem cell transplantation, adenovirus
infections causing hemorrhagic cystitis are particularly refractory in nature. When severe, they can cause disseminated infection and become fatal.
Cases of adenovirus spreading to the kidney and causing kidney failure and ultimately death have been reported. These infections are especially likely
to occur in transplantation between unrelated donors and in umbilical cord blood transplantation, which are relatively common in Japan. The infections
are likely to be refractory, as they are further complicated by the length of time required for reconstruction of the immune system. Drugs currently usedin treatment, including cidofovir (CDV), are either unapproved or off-label in Japan.
3. HHV-6 encephalitis: HHV-6 (Human Herpesvirus 6) is the sixth human herpesvirus to be discovered. It reactivates in 30–70% of patients after
allogenic hematopoietic stem cell transplantation and can cause HHV-6 encephalitis. Most cases of HHV-6 encephalitis develop within 2–6 weeks after
transplantation, most frequently in the third week after transplantation. It is characterized by the three major symptoms of impaired memory,disordered consciousness, and convulsions, which in typical cases gradually appear in the same order (convulsions occur in 30–70% of patients). In
rapidly progressing cases, which are not uncommon, neurological symptoms worsen by the hour, often requiring respirator management for repeatedconvulsions and respiratory depression. The conditions of HHV-6 encephalitis patients often deteriorate rapidly over a short period of time, making
early treatment important. According to guidelines edited and issued by the Japan Society for Hematopoietic Cell Transplantation (February 2018), thefirst-line drugs are foscarnet (FOS) and ganciclovir (GCV), followed by the second-line drug cidofovir (CDV). CDV is not the preferred first-line drug
due to nephrotoxicity and because it transfers poorly into cerebrospinal fluid (CSF). All three of these drugs have been found to be effective in vitro,
but no trials have been conducted yet to confirm their clinical efficacy in patients with HHV-6 encephalitis.

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.
The company increased Treakisym® sales representatives and conducted training needed to form the core of its in-housemarketing network. Information provision activities were started from July 2019 by the Treakisym® sales representatives

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dispatched to each region to promote the shift to a nationwide operation with close local ties. The company also made steadyprogress with preparation of 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).
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. According to the company, market share in the area of firstline treatment increased to 55%.
In addition to the above three approved indications, the company is conducting a phase III clinical trial for the fourth indicationof relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), and the trial is progressing well with an aim to obtainapproval. In response to strong medical needs, the company began a phase III clinical trial in August 2017. With the enrollmentof the first patient in January 2018, the company made steady progress and completed enrollments in April 2019. The
observational period for all patients (Last Patient Last Visit, LPLV) was completed in September 2019. Results of the trial indicatedthat the primary endpoint of response rate exceeded initial expectations. Going forward, the company will prepare for theapproval filing, projected for Q2 2020.
SymBio is targeting a transition to Treakisym® liquid formulation (RTD and RI formulations), for which it concluded an exclusive
licensing agreement in Japan with Eagle Pharmaceuticals (based in New Jersey, US) in September 2017. The company has alreadyconsulted with PMDA and filed for approval of the RTD formulation in September 2019 with an eye towards commercialization
by Q1 2021. SymBio launched clinical trials for the RI formulation in November 2018 primarily to confirm safety, and has madesteady progress with patient enrollments since enrolling the first patient in April 2019, having enrolled 26 patients as of end
October 2019. Liquid formulations of Treakisym® will offer significant value added (reduced burden) to patients and healthcare
professionals, and liquid formula patent protection makes it possible to extend the product life of Treakisym® until 2031.
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. This will allow
combination therapy with obinutuzumab (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, the company obtained approval for the partial revision to its application concerning the use of
Treakisym® as a pretreatment agent in tumor-specific T cell infusion therapy. This will allow Treakisym® to be used as apretreatment agent for Kymriah® intravenous infusion, which was approved as the first chimeric antigen receptor T-cell (CAR-T)
therapy in Japan and listed on the NHI drug price list in May 2019.
To reinforce the position of Treakisym® at the core of its business to strengthen its business foundation, SymBio is looking at thepossibility of developing Treakisym® for other disorders such as solid tumors and autoimmune diseases. 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. With the enrollment of the first patient in May 2018, the company is currently working on enrolling morepatients for the trial. 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 performed a preclinical study to verify the efficacy of the oral
formulation of Treakisym® in treating systemic lupus erythematosus (SLE), a form of autoimmune disease. The company is

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currently compiling study results and after evaluating the findings will consider the next stage of this research project (including
clinical trials).

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 (48 patients enrolled as of October 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. In October 2019, Onconova announced that it hadreached 90% of its target of enrolling 360 patients worldwide. The company plans to report top-line (primary endpoint) resultsin 1H 2020. Based on these trial results, the company plans to apply for approval in Japan at the same time as in the US andEurope.
Regarding the oral formulation of rigosertib, Onconova has completed 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, enrolled the first patients in October 2017, and completed patient enrollment in June 2019.
After completing the phase I trials, the company will consider phase I clinical trials for rigosertib used in combination withazacitidine, participate in global clinical trials of the drug used in combination with azacitidine as first-line treatment for higherrisk MDS currently planned by Onconova, and apply for approval of the oral formulation of the drug in Japan at the same time asin the US and Europe. In December 2018, Onconova submitted a Special Protocol Assessment (SPA) request to the US Food andDrug Administration (FDA) to speed up the approval review for the global trials. Onconova announced in October 2019 that itwas considering a phase II controlled study comparing rigosertib + azacitidine to azacitidine stand-alone therapy for untreatedpatients with higher-risk MDS. 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 learned of an event 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 company initiated an arbitration against The Medicines Company, under the rules of the International Chamber ofCommerce, seeking damages of USD82mn (approximately JPY9.0bn) arising from The Medicines Company’s repudiation of thelicense agreement. SymBio argued that The Medicine Company’s failure to provide sufficient assurance to the company
regarding the performance of obligations under on the license agreement in light of its decision to suspend and withdraw frombusiness activities relating to SyB P-1501in the European and US markets was a material breach of the license agreement.
Arbitration proceedings against The Medicines Company are still ongoing.

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

1H FY12/19 results▷

Sales:

JPY2.0bn (+4.0% YoY)▷

Operating loss:

JPY2.0bn (loss of JPY1.3bn in 1H FY12/18)

Recurring loss:

JPY2.1bn (loss of JPY1.4bn in 1H FY12/18)

Net loss:

JPY2.1bn (loss of JPY1.4bn in 1H FY12/18)▷▷

Sales rose on domestic product sales of Treakisym®.

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On a quarterly basis, sales grew 81.4% YoY to JPY1.6bn in Q1 (Jan–Mar 2019), but fell 62.2% YoY to JPY394mn in Q2 (Apr–Jun2019). In Q2, impurities and appearance defects were found in Treakisym® 100mg vials imported from Astellas Deutschland,
which led to the company returning the whole batch. For this reason, Q2 sales were low relative to Q1 as well as Q2 FY12/18. In
order to resolve this problem, SymBio says that all parties involved are working to return supplies to normal; it has requested that
Astellas Deutschland take steps to improve its manufacturing and quality control arrangements for Treakisym® 100mg.
Gross profit fell 7.7% YoY to JPY529mn, and the gross profit margin narrowed by 3.3pp YoY to 26.4%. On a quarterly basis, grossprofit was 144.0% higher YoY at JPY609mn in Q1, for a gross profit margin of 37.8% (+9.7pp YoY), but dropped to a loss of
JPY79mn in Q2. In addition to weak sales in Q2, SymBio booked a JPY188mn inventory valuation loss under CoGS, in connection
with the aforementioned quality issues associated with a particular batch of Treakisym® 100mg.
SG&A expenses rose 34.1% YoY to JPY2.5bn and R&D expenses increased 14.8% YoY to JPY963mn, which included expenses for
conducting clinical trials of intravenous and oral formulations of Treakisym® and rigosertib. Excluding R&D expenses, SG&A
expenses increased by 49.3% YoY to JPY1.6bn. Fees and commissions paid for expert consultations rose 85.5% YoY to JPY542mn.
On the other hand, personnel expenses (total for directors’ remuneration and salaries) were 3.0% lower YoY at JPY248mn, as
although the company hired more Treakisym® managers in the process of building an in-house sales organization, someadministrative staff retired.
As a result, operating loss, recurring loss, and net loss widened YoY.
Major progress in 1H FY12/19 was as follows:▷

In August 2019, SymBio announced a revision to its FY12/19 earnings forecast. In Q2 FY12/19, impurities and appearance
defects were found in Treakisym® 100mg vials imported from Astellas Deutschland, which led to the company returning thewhole batch. Thus only a fraction of the batches scheduled for shipment in 2Q FY12/19 onward can be shipped by the end of
the year, with shipments possibly being delayed until Q1 FY12/20. The company therefore revised down its FY12/19 earnings▷▷▷

forecast.
Progress was made in Q2 in the company’s arbitration against The Medicines Company, and SymBio expects a conclusion to
be reached by the end of 2019.
In July 2019, the company agreed upon basic terms for a new license.
In June 2019, the US Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq, a
CD79b-directed antibody-drug conjugate, in combination with bendamustine (product name: Treakisym®) and rituximab (BRtherapy) for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for transplant.
Polatuzumab vedotin-piiq was discovered by Roche Group company Genentech and is being developed in Japan by Chugai
Pharmaceutical, another member of the Roche Group.

▷

In 1H FY12/19, capital stock and capital surplus each increased by JPY1.3bn YoY, reflecting proceeds from the issuance of▷

In April 2019, the first patient was enrolled in the clinical trial of the liquid formulation of Treakisym® (rapid infusion [RI]▷

shares resulting from exercise of the 46th stock acquisition rights.

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.

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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 forthe 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 and training activities, and prepared for deployment to each region of responsibility asplanned by the end of 1H. In Q3, SymBio intends to deploy Treakisym® managers across Japan. The company is also making
steady progress with preparation of 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).
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. According to the company, market share in the area of firstline treatment increased to 55% (from 52% in Q2 FY12/18). SymBio expects market share in the area of first-line treatment togrow further from 2H FY12/19, as the aforementioned Treakisym® managers become fully operational.
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.
SymBio is targeting a transition to Treakisym® liquid formulation (RTD and RI formulations), for which it concluded an exclusive
licensing agreement in Japan with Eagle Pharmaceuticals (based in New Jersey, US) in September 2017. The company has alreadyconsulted with PMDA and is preparing to file for approval of the RTD formulation in 2H FY12/19. SymBio launched clinical trials
for the RI formulation in November 2018 primarily to confirm safety, and has made steady progress with patient enrollments
since enrolling the first patient in April 2019. Liquid formulations of Treakisym® will offer significant value added (reduced
burden) to patients and healthcare professionals, and liquid formula patent protection makes it possible to extend the productlife of Treakisym® until 2031.
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. This will allow
combination therapy with obinutuzumab (launched in August 2018) for the treatment of CD 20-positive follicular lymphoma

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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp(FL), the most common histological type of low-grade NHL, enabling the company to provide patients with a new treatment
therapy. In March 2019, the company obtained approval for the partial revision to its application concerning the use of
Treakisym® as a pretreatment agent in tumor-specific T cell infusion therapy. This will allow Treakisym® to be used as apretreatment agent for Kymriah® intravenous infusion, which was approved as the first chimeric antigen receptor T-cell (CAR-T)
therapy in Japan and listed on the NHI drug price list in May 2019.
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 performed a preclinical study to verify the efficacy of the oral formulation ofTreakisym® in treating systemic lupus erythematosus (SLE), a form of autoimmune disease. The company will consider the nextstage of this research project (including clinical trials) after evaluating the results of the preclinical study.

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 (44 patients enrolled as of July 2019, versus a target of 50). The global phase III trial addresses
higher-risk myelodysplastic syndromes (higher-risk MDS), which do not respond to the current standard treatment withhypomethylating agents, which relapse after treatment under the current standard of care, or which are intolerant tohypomethylating agents, and is under way at clinical trial sites in more than 20 countries worldwide. As of March 2019, thecompany had reached 75% of its target of enrolling 360 patients worldwide. Based on these trial results, the company plans toapply for approval in Japan at the same time as in the US and Europe.
Regarding the oral formulation of rigosertib, Onconova has completed 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, enrolled the first patients in October 2017, and completed patient enrollment in June 2019.
After completing the phase I trials, the company plans to start phase I clinical trials for rigosertib used in combination withazacitidine, participate in global phase III clinical trials of the drug used in combination with azacitidine 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 plans to begin phase III clinical
trials as soon as it receives approval from the FDA. In regards to development 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 learned of an event 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.
In October 2017, SymBio initiated an arbitration against The Medicines Company, under the rules of the International Chamberof 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. According to SymBio, progress
was made in Q2 in the company’s arbitration against The Medicines Company, and the company expects that a conclusion will
be reached by end-2019.

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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
and profitability. The company is considering licensing rights for several drug candidates. In July 2019, the company agreed
upon basic terms for a new license.
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 licensing rights overnew drug development candidates globally, and engage in development and commercialization in major markets including theUS, 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.

Q1 FY12/19 results▷

Sales:

JPY1.6bn (+81.4% YoY)▷

Operating loss:

JPY596mn (loss of JPY715mn in Q1 FY12/18)

Recurring loss:

JPY616mn (loss of JPY749mn in Q1 FY12/18)

Net loss:

JPY617mn (loss of JPY760mn 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 forthe chimeric antigen receptor T-cell (CAR-T) therapy Kymriah® intravenous infusion.

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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).
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.

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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 (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.
Regarding the oral formulation of rigosertib, Onconova has completed 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 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 withazacitidine, participate in global Phase III clinical trials of the drug used in combination with azacitidine 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
and profitability. 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 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.

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

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Income statement
FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

FY12/18

FY12/19(JPYmn)
Sales

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

Par.
2,838

CoGS
Gross profit

238
1,212

1,224
658

1,362
593

1,214
318

1,428
527

1,350
583

1,464
904

2,413
1,031

2,663
1,173

SG&A expenses

1,825

3,031

4,978

3,829

Income statement

YoY

GPM

SG&A ratio

Operating profit

21.7%

29.8%

3.9%

-21.6%

27.6%

-1.1%

22.5%

83.6%

35.0%

30.3%

20.8%

26.9%

30.2%

38.2%

125.8%

144.8%

117.3%

130.4%

93.6%

162.1%

128.0%

Non-operating income
Non-operating expenses
Recurring profit
YoY
RPM

3,135

29.9%

144.5%

30.6%

30.5%

99.8%

182.1%

5,166-1,681-1,303-2,552-2,127-3,947-2,656-4,302

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
95-2,7494
79-4,377

0
4

5
4

0
4

4

2
3
4

3
1
4

9
1
4

17
15
4

10
10
4

4
4

-642

-2,105-1,733-1,605-1,116-2,632-2,313-3,978-2,753-4,376-

YoY
Net margin

1,830

1,973
865

-1,700Extraordinary gains
Extraordinary losses
Tax charges
Net income

1,999-26.0%-2,067-

Implied tax rate

2,293

11.4%

-613

-

YoY
OPM

2,725

45.4%

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

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.

FY12/10Par.
-

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-

FY12/19
Par.
4,465
2,838
-36.4%-3,587-4,302-3,612-4,377-3,612-4,376-

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

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

FY12/17

FY12/18

FY12/19

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

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

3,911
549
1
427
4,887
47
19
75
70
95
146
241
386
5,274

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

121
639
112
872
2
2
874

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
180

5
5
651

4
4
602

3
3
254

2
2
490

320
184
47
551
2
2
552

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

14,871
14,841-25,919
-15
621
4,400

Working capital
Total interest-bearing debt
Net debt

5-2,31461-4,559-17-4,540125-6,163212-5,692

114-4,261439-5,719249-2,947220-4,821429-3,911

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 stock and capital surplus 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
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.
-2,325-26-2,3514,272

FY12/19
Par.
-4,351-216-4,5673,740

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

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
325-2,64030-57-190-3,81535-40-29-2,72938-217
209-4,764

Cash and cash equivalents (year-end)

3,916

6,311

4,240

5,294

5,092

4,261

5,719

2,947

4,821

3,911

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
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.
Main sources of funding
Date

Change inshares issued

Total sharesissuedChange in capital Capital stock andstock and capital capital 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 toconvertible corporate bonds and otherstock options

Dec. 2013

6,720,200

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

54,049,224

1,627

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

Apr. to Dec. 2018

28,349,700

82,398,924

4,422

25,915 Exercise of stock options

Jan. to Dec. 2019

1,726,800

26,437,681

3,796

29,711 Exercise of stock options

Source: Shared Research based on company data
Note: In July 2019, the company conducted a 4:1 reverse stock split, reducing the number of shares outstanding by 73,088,043.

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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.
SymBio claims that when MDCO decided to suspend or withdraw its business related to SyB P-1501 in Europe and the US it failed
to provide sufficient guarantees to fulfill its obligations under the license agreement, which was a material breach. Arbitration
proceedings with MDCO are still ongoing, and an arbitration ruling is expected in 1H FY12/20. Novartis AG (Switzerland)announced on January 6, 2020 that it has completed the acquisition of MDCO.

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 more than 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.

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As of February 2020, 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® indications, RTD and RI
formulations of Treakisym®, and anticancer drug rigosertib for myelodysplastic syndromes. In addition, after acquiring exclusive
worldwide rights from Chimerix in September 2019 to develop, manufacture, and market brincidofovir for all indications except
smallpox, SymBio looks to commercialize it by the mid-2020s.

March 2005
December 2005

SymBio Pharmaceuticals Limited established with JPY30mn in capital.
License Agreement finalized with Astellas Pharma GmbH for SyB L-0501 (bendamustine) development andcommercialization rights in Japan.

March 2006

Manufacturer’s License (packaging, labeling and storage) obtained from Tokyo Metropolitan Government (License#13AZ200010).

March 2007

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

Launched Symbenda® (bendamustine hydrochloride) in South Korea for the treatment of Chronic Lymphocytic
Leukemia and multiplemyeloma.

October 2011

Listed on Osaka Securities Exchange JASDAQ Growth Market.

February 2012
October 2015

Launched Innomustine® (bendamustine hydrochloride) in Taiwan for the treatment of Low-grade Non-Hodgkin’s
Lymphoma and Chronic Lymphocytic Leukemia.
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.

September 2019Concluded license agreement with Chimerix Inc. (US), granting SymBio exclusive worldwide rights to develop,
manufacture, and market antiviral brincidofovir for all indications except smallpox.

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News and topics
February 2020
On February 27, 2020, the company announced the issuance of the 50th and 51st stock acquisition rights with exercise pricerevision clauses and the conclusion of a third-party allotment agreement (commit issue program).
The company agreed with EVO FUND (the allottee) to issue the 50th and 51st stock acquisition rights and to enter with theallottee into a third-party allotment agreement on stock acquisition rights (commit issue program), on condition of becoming
effective via notification in accordance with the Financial Instruments and Exchange Act.
Summary of subscription
Date of allotment

March 16, 2020

Number of stock acquisition rights

10,000,000 units(50th stock acquisition rights: 7,000,000 units; 51st stock acquisition rights: 3,000,000 units)

Issue price

JPY11mn(50th stock acquisition rights: JPY1.06 per unit; 51st stock acquisition rights: JPY1.04 per unit)

Number of dilutive shares from the

10,000,000 shares (one share per unit; corresponds to a dilution rate of 37.8% against total number ofissuance

shares outstanding as of December 31, 2019)
No maximum exercise price.
While the minimum exercise price is JPY291, even at the minimum exercise price, the number ofdilutive shares is 10,000,000.

Amount of funding

JPY5,450mn

Exercise price and conditions for

The initial price is set at JPY547.

revising the exercise price

The initial revision of the exercise price on the 50th and 51st stock acquisition rights will take place on
March 17, 2020, and further revisions will take place after the passage of each subsequent five tradingday period. In the event the exercise price is revised, on the next trading day following the fifth trading
day counted from the date on which the exercise price was previously revised (the revision date), theexercise price will be revised to an amount obtained by multiplying the simple average value of thevolume weighted average price (VWAP) of SymBio’s common shares in regular trading announced by
the Tokyo Stock Exchange on each trading day for the five consecutive trading days prior to therevision date by 94%. However, the price will be revised to the minimum exercise price if such pricefalls below the minimum exercise price.

Method for subscription or

All of the stock acquisition rights will be allotted to EVO FUND through third-party allotment.

allotment (allottee)

Characteristics of the 50th and 51st stock acquisition rights and specific uses of the funds to be raised▷

50th stock acquisition rights: The exercise period begins on the trading day immediately following issuance. Once the exercise
period begins, the allottee shall in principle exercise all of the 50th stock acquisition rights (7,000,000 shares) within 106
trading days. Furthermore, the allottee commits in principle to the exercise of the 50th stock acquisition rights, a number▷

corresponding to 2,800,000 shares or more, within 56 trading days on or after the trading day following the issuance date.
51st stock acquisition rights: The allottee shall in principle exercise all of the 51st stock acquisition rights up to the maximum
amount issued within 46 trading days starting from the trading day immediately following the date the company gives aninstruction to exercise. The 51st Stock acquisition rights are designed so that it cannot be exercised until the company issues aninstruction to exercise. Conditions for issuing an instruction to exercise are that SymBio does not continue to possess
undisclosed insider information at the time it issues an instruction to exercise and at the start of the exercise period, and that no
portion of the 50th Stock Acquisition Rights is remaining.

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50th stock acquisition rights

51st stock acquisition rights

Number of stock acquisition rights
issued7,000,000 units

3,000,000 units

Total issue price

JPY7mn

JPY3mnTotal exercise price

JPY3,829mn

JPY1,641mn

Expected exercise period (in principle,
except if reasons for extension ofcommitment period occur)

Approximately five months after issuanceRoughly two months from the date specified by
SymBio after it issues an instruction to exercise

Number of revisions (revised every five
trading days in principle)

Total of 21 (planned)

Total of nine (planned)

Exercise price

94% of simple average value of VWAP of SymBio’s common shares in regular trading over fiveconsecutive trading days

Commitment

Commitment, in principle, to exercise all of theCommitment, in principle, to exercise thestock acquisition rights issued within 106
trading days (full commitment)complete number of stock acquisition rights
specified within 46 trading days

Commitment, in principle, to exercise at least
40% of the stock acquisition rights issued
within 56 trading days (first-half commitment)
Expected start date of initial exercise

March 17, 2020

To be determined

Expected final date of commitment

Full commitment: August 21, 2020

To be determinedFirst-half commitment: June 9, 2020
Specific uses of the funds to be raised(JPYmn)Funds to be raisedFunds to be raised

Total amount of

Expected timing ofthrough the 50th
stock acquisition

through the 51st
stock acquisition

funds to be raised

expenditurerightsrightsDevelopment of in-licensed drugs

2,375

55

2,430

March 2020 to June 2021

Establishment of the company’s
own salesforce

1,431

54

1,485

March 2020 to June 2021

0

1,535

1,535

October 2020 to June 2021

3,806

1,644

5,450

Investment in new in-licensing and
M&A
Total

Duty to discuss in case of change in funding requirements due to arbitration award
SymBio initiated an arbitration against The Medicines Company on October 11, 2017 under the rules of the International
Chamber of Commerce, seeking damages of USD82mn (equivalent to approximately JPY9.0bn), arising out of The Medicines
Company’s repudiation of the license agreement. This arbitration is ongoing.
Hearing procedures commenced in New York in June 2019, and both parties had finished submitting their final documents as ofthe end of December 2019. Currently, a panel comprising three arbitrators is preparing an arbitration judgment. Assuming
typical submission procedures, SymBio expects to receive an arbitration judgment between March and June 2020. The company
intends to establish a provision to the effect that it will be able to request the allottee, after discussions with the allottee, not toexercise more stock acquisition rights than a number specified by the company, in case of an award by the arbitration panel, andthat the allottee will discuss any such request with SymBio in good faith.
On February 6, 2020, the company announced a medium-term plan covering FY12/20–FY12/22.
Medium-term plan targets
FY12/19

FY12/20

FY12/21(JPYmn)

Act.

Est.

MTP

FY12/22
MTP

Sales

2,811

3,404

9,008

10,816

Operating profit (loss)-4,302-5,090

1,031

1,482

Recurring profit (loss)-4,377-5,134987

1,438

Net income (loss)-4,376-4,803

1,356

1,717

Source: Shared Research based on company data

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Targets in medium-term plan (FY12/20–FY12/22)
Sales
SymBio expects product sales of Treakisym® to account for the bulk of sales. Product sales targets reflect the recent pace ofmarket penetration and sales trends, which feed into the company’s revised sales growth rates calculated over the medium-termplan 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 salesorganization.
In estimating sales in FY12/21 and FY12/22, SymBio disclosed targets assuming increased product sales of Treakisym® as it
expects to gain approval of the drug as a treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in Q2
FY12/21.

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®,▷

The company has not factored in upfront payments for in-licensing drug candidates outside its existing pipeline after▷

rigosertib IV and oral formulations, and brincidofovir, an antiviral drug for the treatment of infections.

brincidofovir, an antiviral drug for the treatment of infections, although it will continue to evaluate and investigate them.
Other SG&A expenses comprise primarily Treakisym® sales and marketing, production and distribution, business development,
and management related costs. SymBio is factoring in costs associated with building and operating its own sales organizationfrom FY12/20 onward ahead of the move to sell Treakisym® in-house from FY12/21. It forecasts an increase primarily inpersonnel costs due to a higher medical representative headcount and higher costs due to more activities.

Net income
The company forecasts net income exceeding recurring profit in FY12/21 and FY20/22 to reflect the reduction of loss carried overfrom the previous fiscal year from FY12/21 (when it is expected to turn profitable) onward on tax effect accounting.

Personnel plans
SymBio assumes it will complete the formation of its 62-member nationwide sales structure by Q2 FY12/20 and transition tooperating its own sales force in FY12/21. It plans to allocate the bare minimum of necessary personnel in other parts of theorganization and is budgeting for personnel expenses accordingly. Regarding plans to increase personnel expenses for global
expansion of brincidofovir, an antiviral drug to treat infections, the company noted that as of February 2020, it was considering aclinical trial plan and would not need extra personnel during the plan period. Accordingly, it has not booked related personnel
expenses.

Funding plans
In April 2018, the company decided to issue its 45th through 47th stock acquisition rights to secure funds needed to operate.

November 2019
On November 12, 2019, the company announced that it would bring forward the exercise date of its 47th stock acquisitionrights and that it had concluded an amendment agreement to this effect.
The company decided to instruct the bringing forward of the exercise date of its 47th stock acquisition rights with exercise pricerevision clauses, which were issued in April 2018 by third-party allotment to EVO FUND, under the terms of the third-party
allotment agreement between the two companies. On the same day, the company and EVO FUND also concluded an agreement
to amend the third-party allotment agreement. As a result of concluding the amendment agreement, the company can specify
the date on which the rights can be exercised and the start date of the full commitment period.

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The company’s business is progressing more or less on track to turn profitable in FY12/21, but profits in FY12/19 will likely fallshort of the company forecast at the time the 47th stock acquisition rights were issued. The expected shortfall is due to delayed
product shipments caused by defects discovered in lyophilized injection agents imported from Astellas Deutschland GmbH. The
company must purchase and build up inventory in order to begin sales of its own products in FY12/20. It also decided that itneeded additional funds to in-license (on a global license agreement) and develop brincidofovirName of issue: SymBio Pharmaceuticals 47th stock acquisition rights▷

Number of rights issued:

15,000,000▷

Number of shares issued:

3,750,000

Date of instruction to bring forward exercise date: November 12, 2019▷▷

Exercise start date: November 14, 2019

On November 5, 2019, the company announced that primary endpoints (response rates) were met in its phase III study of the
anticancer drug Treakisym® targeting relapsed/refractory diffuse large B-cell lymphoma (“r/r DLBCL”).
The company stated that the results of the phase III study, the objective of which was to confirm the efficacy and safety ofTreakisym used in combination with rituximab (bendamustine-rituximab combination therapy or BR therapy) for treatment ofpatients with r/r DLBCL, exceeded expected primary endpoints for response rate. The company will compile the results of thisstudy’s final analyses and plans to submit an application for the treatment’s approval in 1H FY12/20.

October 2019
On October 25, 2019, the company announced an update on the global phase III INSPIRE study of the anticancer agent
rigosertib, and on future clinical trial plans.
On October 24, 2019, the licensor for the anticancer agent rigosertib sodium (hereafter, rigosertib), Onconova Therapeutics, Inc.
(hereafter, Onconova), provided an update on the global phase III INSPIRE study of rigosertib, and on future clinical trial plans.
The INSPIRE trial is investigating the efficacy of rigosertib in higher-risk myelodysplastic syndrome (“HR-MDS”) patients who had
progressed on, failed to respond to, or relapsed after previous treatment with a hypomethylating agent, the standard of care for
MDS (such patients are described as “HMA-refractory”). Onconova is approaching enrollment of 90% of the required 360
patients for the INSPIRE trial, and anticipates reporting top-line data in the first half of 2020.
Regarding the development of oral rigosertib, as a result of Onconova’s consultations with the FDA on SPA (Special Protocol
Assessment), Onconova plans to conduct a randomized controlled phase II trial with a control arm of single agent azacitidine forthe continued development of oral rigosertib plus azacitidine in untreated HR-MDS patients.
On October 1, 2019, the company announced the signing of an exclusive global license agreement for the highly active
antiviral drug, brincidofovir (BCV).
On October 1, SymBio said it had entered into a license agreement with US-based Chimerix Inc., for the purpose of acquiringglobal rights for the antiviral drug, brincidofovir (BCV). Under the terms of the agreement, Chimerix has granted SymBio
exclusive worldwide rights to develop, manufacture, and commercialize BCV in all human indications, excluding the prevention
and treatment of smallpox. Acquiring the exclusive worldwide license to BCV will aid SymBio in its transition into a global
business.
Chimerix Inc. (NASDAQ: CMRX) is headquartered in the US state of North Carolina, and has developed two types of nucleotide compounds using its
own lipid technology. Chimerix was developing brincidofovir (CMX001) as the world’s first drug with strong and broad activity against viral diseases(such as AdV, BKV, EBV, and HHV-6) for which there is currently no effective treatment. In order to concentrate on businesses centering on the
oncology field, however, Chimerix out-licensed a global license excluding smallpox to SymBio in September 2019.

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Based on BCV’s strong data, SymBio will initially target treatment of viral hemorrhagic cystitis (vHC) and HHV-6 encephalitis(HHV-6) after allogeneic hematopoietic stem cell transplantation and kidney transplantation, to address critically underserved
therapeutic areas. Although other antiviral drugs are currently used for these diseases, there is a long-standing and significant
medical need for a treatment that is both effective and safe.
BCV is a lipid conjugate of cidofovir (CDV), which is an antiviral drug already approved and marketed in the US and the EU, but
unapproved in Japan. As BCV has not only higher antiviral activity, but also a superior safety profile in comparison with CDV, thecompany expects BCV to be an effective treatment against a wide spectrum of infectious diseases caused by DNA viruses,
including herpes viruses (including CMV), adenovirus, BK virus, papilloma virus, and smallpox virus. BCV’s innovative mechanismof action, which is based on conjugating a lipid chain of specified length to a CDV base, dramatically improves efficiency of
uptake into the cells where BCV is converted into a direct-acting agent in the cell, resulting in high antiviral effect. Furthermore,
BCV is easy to use due to its low risk of nephrotoxicity, which is a serious side effect of CDV. This makes BCV a novel highly active
anti-multiviral drug.

September 2019
On September 26, 2019, the company announced filing of an approval application for the RTD formulation of Treakisym®.
The company applied for approval to manufacture and market the ready-to-dilute (RTD) liquid formulation of Treakisym®. If
approved, the RTD formulation can be used for the indication of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), forwhich clinical trial is currently under way, in addition to all previously approved indications. The company plans to launch the
product in Q1 FY12/21 after obtaining approval.
On September 18, 2019, the company announced achievement of LPLV in phase III clinical trials of anticancer agent
Treakisym® targeting relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The company announced completion of Last Patient Last Visit (LPLV) in its phase III clinical trials of anticancer agent Treakisym®
(generic name: bendamustine hydrochloride) for the additional indication of relapsed or refractory DLBCL.
The company plans to announce topline data of the drug’s efficacy in Q4 FY12/19 (October–December 2019). Having received
the topline results, the company will prepare to file for approval for the additional indication of relapsed or refractory DLBCL in
Q2 FY12/20 (April–June 2020).

August 2019
On August 7, the company announced a revision to its full-year FY12/19 earnings forecast and medium-term plan.

Revised FY12/19 earnings forecast▷

Sales:

JPY3.1bn (previous forecast: JPY4.5bn)▷

Operating loss:

JPY3.8bn (JPY3.6bn)

Recurring loss:

JPY3.9bn (JPY3.6bn)

Net loss:

JPY3.9bn (JPY3.6bn)

Loss per share:

JPY167.66 (JPY175.52)▷▷▷

Reasons for revision
SymBio imports lyophilized Treakisym® for injection from Astellas Deutschland GmBH (consolidated subsidiary of Astellas PharmaInc.), which it supplies to the market for sale in Japan through its business partner, Eisai Co., Ltd. after quality inspection andpackaging. In Q2 FY12/19, impurities and appearance defects were found in Treakisym® 100mg vials imported from Astellas
Deutschland, which led to the company returning the whole batch. Thus only a fraction of the batches scheduled for shipment in
2Q FY12/19 onward can be shipped by the end of the year, with shipments possibly being delayed until Q1 FY12/20. The
company therefore revised down its FY12/19 earnings forecast. Lower operating profit stems from the sales decline, but the

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impact on operating profit is mitigated by SG&A expenses (including R&D expenses) being revised down by JPY294mn from
JPY5.1bn to JPY4.8bn.
The company is reviewing the impact of the FY12/19 earnings forecast revision on medium-term plan targets for FY12/20,
FY12/21, and FY12/22 and intends to announce revised plan targets once it has confirmed the figures.

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

Details of change (resigning representative director)
Name

Current position

Kazuo Asakawa

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.

Major shareholders
Top shareholders

Shares held

Fuminori Yoshida
Cephalon, Inc.
SMBC Nikko Securities Co., Ltd.
Daiwa Securities Co., Ltd.
Eisai Co., Ltd.
Matsui Securities Co., Ltd.
Goldman Sachs International
Japan Securities Finance Co., Ltd.
Kazuyuki Ota
Nomura Securities Co., Ltd.

862,750647,250
538,300
293,350
208,350
189,300
185,075
183,900
157,700
155,622
3,421,597

SUM

Source: Shared Research based on company data
As of December 31, 2019
Note: Shareholding ratio calculated excluding treasury shares from shares issued.

Shareholding
ratio
3.30%
2.50%
2.00%
1.10%
0.80%
0.70%
0.70%
0.70%
0.60%
0.60%
13.00%

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 107 employees as of December 31, 2019.
Employees
No. of employees

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

FY12/19
Par.
107

4

15

5

-4

-3

5

3

1

12

17

YoY change

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 II clinical trials: 19%▷▷▷

Phase I clinical trials: 46%

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.

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.

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 typically

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leads 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 approvalis reduced). 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 berevised 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.

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

SymBio Pharmaceuticals Limited

3-2-2 Toranomon, Minato-ku
Tokyo, JAPAN 105-0001

Phone

Exchange listing+81-3-5472-1125

TSE JASDAQ GrowthEstablished

Listed on

March 25, 2005

October 20, 2011

WebsiteFiscal year-end

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

December

IR webhttp://www.symbiopharma.com/ir_e/01.html

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Current Client Coverage of Shared Research Inc.
Accordia Golf Trust

Digital Arts Inc.

Kawanishi Holdings, Inc.

RYOHIN KEIKAKU CO., LTD.

Advance Create Co., Ltd.

Digital Garage Inc.

KFC Holdings Japan, Ltd.

SanBio Company Limited

ADJUVANT COSME JAPAN CO., LTD.

Doshisha Corporation

KI-Star Real Estate Co., Ltd.

SANIX INCORPORATED

Aeon Delight Co., Ltd.

Dream Incubator Inc.

Kondotec Inc.

Sanrio Company, Ltd.

Aeon Fantasy Co., Ltd.

Earth Corporation

Kumiai Chemical Industry Co., Ltd.

SATO HOLDINGS CORPORATIONAi Holdings Corporation

Edion Corporation

Lasertec Corporation

SBS Holdings, Inc.

AirTrip Corp.

Elecom Co., Ltd.

Locondo, Inc.

Seikagaku Corporationand factory, inc.

en-Japan Inc.

LUCKLAND CO., LTD.

Seria Co.,Ltd.

ANEST IWATA Corporation

euglena Co., Ltd.

MATSUI SECURITIES CO., LTD.

SHIFT Inc.

AnGes Inc.

FaithNetwork Co., Ltd.

Media Do Holdings Co., Ltd.

Shikigaku Co., Ltd

Anicom Holdings, Inc.

Ferrotec Holdings Corporation

Medical System Network Co., Ltd.

SHIP HEALTHCARE HOLDINGS, INC.

Anritsu Corporation

FIELDS CORPORATIONMEDINET Co., Ltd.

SIGMAXYZ Inc.

Apaman Co., Ltd.

Financial Products Group Co., Ltd.

MedPeer,Inc.

SMS Co., Ltd.

ARATA CORPORATIONFirst Brothers Col, Ltd.

Mercuria Investment Co., Ltd.

Snow Peak, Inc.

Artspark Holdings Inc.

FreeBit Co., Ltd.

Micronics Japan Co., Ltd.

Solasia Pharma K.K.

AS ONE CORPORATIONFRONTEO, Inc.

MIRAIT Holdings Corporation

SOURCENEXT Corporation

Ateam Inc.

Fujita Kanko Inc.

Monex Goup Inc.

Star Mica Holdings Co., Ltd.

Aucfan Co., Ltd.

Gamecard-Joyco Holdings, Inc.

MORINAGA MILK INDUSTRY CO., LTD.

Strike Co., Ltd.

AVANT CORPORATION

GameWith, Inc.

Mortgage Service Japan Limited.

SymBio Pharmaceuticals Limited

Axell Corporation

GCA Corporation

NAGASE & CO., LTD

Synchro Food Co., Ltd.

Azbil Corporation

Good Com Asset Co., Ltd.

NAIGAI TRANS LINE LTD.

TAIYO HOLDINGS CO., LTD.

AZIA CO., LTD.

Grandy House Corporation

NanoCarrier Co., Ltd.

Takashimaya Company, Limited

AZoom, Co., Ltd.

Hakuto Co., Ltd.

Net Marketing Co., Ltd.

Take and Give Needs Co., Ltd.

Base Co., Ltd

Hamee Corp.

Net One Systems Co.,Ltd.

Takihyo Co., Ltd.

BEENOS Inc.

Happinet Corporation

Nichi-Iko Pharmaceutical Co., Ltd.

TEAR Corporation

Bell-Park Co., Ltd.

Harmonic Drive Systems Inc.

Nihon Denkei Co., Ltd.

Tenpo Innovation Inc.

Benefit One Inc.

HOUSEDO Co., Ltd.

Nippon Koei Co., Ltd.

3-D Matrix, Ltd.

B-lot Co.,Ltd.

H2O Retailing Corporation

NIPPON PARKING DEVELOPMENT Co., Ltd.

TKC Corporation

Broadleaf Co., Ltd.
CanBas Co., Ltd.

IDOM Inc.
IGNIS LTD.

NIPRO CORPORATION
Nisshinbo Holdings Inc.

TKP Corporation
Tsuzuki Denki Co., Ltd.

Canon Marketing Japan Inc.

i-mobile Co.,Ltd.

NS TOOL CO., LTD.

TOCALO Co., Ltd.

Career Design Center Co., Ltd.

Inabata & Co., Ltd.

OHIZUMI MFG. CO., LTD.

TOKAI Holdings Corporation

Carna Biosciences, Inc.

Infocom Corporation

Oisix ra daichi Inc.

Tokyu Construction Co., Ltd.

CARTA HOLDINGS, INC

Infomart Corporation

Oki Electric Industry Co., Ltd

TOYOBO CO., LTD.

CERES INC.

Intelligent Wave, Inc.

ONO SOKKI Co., Ltd.

Toyo Ink SC Holdings Co., Ltd

Chiyoda Co., Ltd.

ipet Insurance CO., Ltd.

ONWARD HOLDINGS CO.,LTD.

Toyo Tanso Co., Ltd.

Chori Co., Ltd.

Itochu Enex Co., Ltd.

Pan Pacific International Holdings Corporation

Tri-Stage Inc.

Chugoku Marine Paints, Ltd.

JSB Co., Ltd.

PARIS MIKI HOLDINGS Inc.

TSURUHA Holdings

cocokara fine Inc.

JTEC Corporation

PIGEON CORPORATIONVISION INC.

COMSYS Holdings Corporation

J Trust Co., Ltd

QB Net Holdings Co., Ltd.

VISIONARY HOLDINGS CO., LTD.

COTA CO.,LTD.

Japan Best Rescue System Co., Ltd.

RACCOON HOLDINGS, Inc.

WirelessGate, Inc.

CRE, Inc.

JINS HOLDINGS Inc.

Raysum Co., Ltd.

YELLOW HAT LTD.

CREEK & RIVER Co., Ltd.

JP-HOLDINGS, INC.

RESORTTRUST, INC.

YOSHINOYA HOLDINGS CO., LTD.

Daiichi Kigenso Kagaku Kogyo Co., Ltd.

KAMEDA SEIKA CO., LTD.

ROUND ONE Corporation

YUMESHIN HOLDINGS CO., LTD.

Daiseki Co., Ltd.

Kanamic Network Co.,LTD

RVH Inc.

Yushiro Chemical Industry Co., Ltd.

Demae-Can CO., LTD

ZAPPALLAS, INC.

DIC Corporation

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