R

SymBio Pharmaceuticals / 4582
COVERAGE INITIATED ON:

2014.10.31

LAST UPDATE:

2017.10.16

Shared Research Inc. has produced this report by request from the company discussed in the report. The aim is toprovide an “owner’s manual” to investors. We at Shared Research Inc. make every effort to provide an accurate,
objective, and neutral analysis. In order to highlight any biases, we clearly attribute our data and findings. We will
always present opinions from company management as such. Our views are ours where stated. We do not try toconvince or influence, only inform. We appreciate your suggestions and feedback. Write to us at
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R SymBio Pharmaceuticals / 4582
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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 ------------------------------------------------------------------------------------------------------------------------------------- 4
Recent updates ---------------------------------------------------------------------------------------------------------------------------------------- 5
Highlights ------------------------------------------------------------------------------------------------------------------------------------------------------------5
Trends and outlook -----------------------------------------------------------------------------------------------------------------------------------------------9
Business ------------------------------------------------------------------------------------------------------------------------------------------------ 18
Business description -------------------------------------------------------------------------------------------------------------------------------------------- 18
Business strategy ------------------------------------------------------------------------------------------------------------------------------------------------ 20
Pipeline ------------------------------------------------------------------------------------------------------------------------------------------------------------- 23
Earnings structure ----------------------------------------------------------------------------------------------------------------------------------------------- 33
Strengths and weaknesses------------------------------------------------------------------------------------------------------------------------------------ 34
Market and value chain---------------------------------------------------------------------------------------------------------------------------- 35
Market strategy -------------------------------------------------------------------------------------------------------------------------------------------------- 35
Historical performance ---------------------------------------------------------------------------------------------------------------------------- 38
Income statement ----------------------------------------------------------------------------------------------------------------------------------------------- 46
Balance sheet ----------------------------------------------------------------------------------------------------------------------------------------------------- 48
Cash flow statement -------------------------------------------------------------------------------------------------------------------------------------------- 49
Other information ---------------------------------------------------------------------------------------------------------------------------------- 50
History -------------------------------------------------------------------------------------------------------------------------------------------------------------- 50
News and topics ------------------------------------------------------------------------------------------------------------------------------------------------- 51
Major shareholders --------------------------------------------------------------------------------------------------------------------------------------------- 58
Top management ----------------------------------------------------------------------------------------------------------------------------------------------- 58
Employees --------------------------------------------------------------------------------------------------------------------------------------------------------- 58
Other ---------------------------------------------------------------------------------------------------------------------------------------------------------------- 58
Company profile ------------------------------------------------------------------------------------------------------------------------------------------------- 62

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R SymBio Pharmaceuticals / 4582
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Executive summary
SymBio in-licenses drugs for development and sale
◤ SymBio is a specialty pharmaceutical company that buys the right to develop and commercialize drug candidates in order toaddress the underserved medical needs of patients in Japan and the rest of Asia. With its main focus on the areas of oncology,
hematology, and pain management, the company typically seeks in-licensing opportunities for niche markets frompharmaceutical 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 August 2017, the company had received approval for Treakisym (anticancer agent for hematologic malignancies) for theindications of relapsed or refractory low grade NHL and MHL, first-line treatment of relapsed or refractory low grade NHL and
MHL, and chronic lymphocytic leukemia (CLL). Drugs in the development pipeline include Treakisym for the indication of
relapsed or refractory aggressive NHL, rigosertib (anticancer agent for myelodysplastic syndromes) IV and oral formulations,and SyB P-1501 (patient-controlled analgesia for pain management).

Earnings◤ FY12/16 sales were JPY2.4bn (+22.5% YoY). Product sales totaled JPY2.1bn (+10.6% YoY) and milestone payments totaled

JPY230mn (no milestone payments in FY12/15). Operating loss totaled JPY2.1bn (loss of JPY2.6bn in FY12/15). The company
also reported a recurring loss of JPY2.3bn (loss of JPY2.6bn last year). Net loss was JPY2.3bn (loss of JPY2.6bn).

◤ As a result of sales growth of Treakisym, SymBio forecasts FY12/17 sales of JPY2.9bn (+22.6% YoY), an operating loss of

JPY3.2bn (operating loss of JPY2.1bn in FY12/16), a recurring loss of JPY3.3bn (recurring loss of JPY2.3bn in FY12/16), and a
net loss of JPY3.3bn (net loss of JPY2.3bn in FY12/16).

◤ In its mid-term plan, SymBio projects sales of JPY3.6bn–JPY4.6bn and a net loss of JPY1.9bn–JPY2.3bn in FY12/19. The

company obtained regulatory approval for first-line treatment for low-grade NHL and MCL in FY12/16, and aims for additional
indication of Treakisym for chronic lymphocytic leukemia (CLL), which will result in higher sales.

◤ Shared Research thinks sales of JPY10bn and OPM of over 20% is achievable in FY12/21 and beyond. We have identified thefollowing four growth drivers. 1) Sales growth due to progress with market penetration of Treakisym® as a first-line treatmentof low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL). 2) Sales growth spurred by indication forrelapsed or refractory DLBCL going on sale. 3) Profit margin improvement as a result of starting own sales. 4) Establishing acompetitive advantage over generics by putting ready-to-dilute (RTD) and rapid infusion (RI) injection products on themarket (see Long-term outlook section).

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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Key financial data
Income statement(JPYmn)Sales
YoY

Gross profit

FY12/09Par.
1,191

FY12/10Par.
1,450

FY12/11Par.
1,883

FY12/12Par.
1,955

FY12/13Par.
1,532

FY12/14Par.
1,955

FY12/15Par.
1,933

FY12/16
Par.
2,368

1,191

1,212

658

593

318

527

583

904

-208

-613

-2,067-1,700-1,681-1,303-2,552-2,127-3,932-26.9%

YoY
GPM-26.9%
100.0%YoY
OPM-

Operating profit
Recurring profit

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%
-

FY12/17
Est.
3,583
51.3%

-

-214

-638

-2,095-1,729-1,601-1,110-2,630-2,317-4,009

YoY

-

-

-

-

-

-

-

-

-

RPM

-

-

-

-

-

-

-

-

-

-218

-642

-2,105-1,733-1,605-1,116-2,632-2,313-4,009Net income
YoY

-

-

-

-

-

-

-

-

-

Net margin

-

-

-

-

-

-

-

-

-

101
-32.5
402.8

112
-59.3
365.4

19,131-143.6345.3

19,131-90.6
254.7

30,634-69.3
239.5

30,634-36.3
208.8

32,391-81.3
127.6

46,531
-58.8
108.6

-82.2
-

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

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

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

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

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

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

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

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

-

-

-

-

-

-

-

-

-211
-4
2,963

-754
-116
663

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

-7.6%
-8.1%
95.1%

-15.1%-15.8%
95.8%-36.5%-39.4%
91.0%-27.2%-30.2%
89.1%-24.3%-26.3%
96.7%-14.7%-15.8%
93.4%-42.3%-48.3%
88.9%-39.0%-50.4%
79.7%

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
Investment 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

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

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R SymBio Pharmaceuticals / 4582
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LAST UPDATE: 2017.10.16

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Recent updates
Highlights
On October 16, 2017, Shared Research updated the report on the company following interviews with SymBio Pharmaceuticals
Ltd.

On October 10, 2017, the company announced that it had enrolled the first patient in a domestic phase I clinical trial of
anticancer agent rigosertib monotherapy for high-risk myelodysplastic syndrome (MDS).
SymBio registered the first patient in its domestic phase I clinical trial of anticancer agent rigosertib (oral formulation)
monotherapy for high risk myelodysplastic syndrome (MDS) started in June 2017.
The purpose of the trial is to confirm safety of high-dose oral rigosertib –an additional requirement in the phase II clinical trial
conducted by Onconova Therapeutics, Inc. in the US with relapsed and refractory MDS patients. Once safety has been confirmed,
SymBio plans to perform a domestic trial of combination therapy with azacitidine and participate in the global phase III study ofrigosertib-azacitidine combination therapy with untreated higher-risk MDS patients planned by Onconova.
The company has not made any revisions to its FY12/17 earnings forecast associated with the start of the domestic phase I clinical
trial.

On September 21, 2017, the company announced revisions to its full-year FY12/17 earnings forecasts.

Revised FY12/17 company earnings forecasts▷ Sales:

JPY3.6bn (previous forecast: JPY2.9bn)▷ Recurring loss:

JPY4.0bn (JPY3.3bn)▷ Operating loss:▷ Net loss:

JPY3.9bn (JPY3.2bn)

JPY4.0bn (JPY3.3bn)

Reasons for revisions
The company expects sales of JPY3.6bn, exceeding its previous forecast by JPY680mn, because sales of Treakisym® in Japan grewfaster than expected following approval for the new indication of first-line treatment of low-grade non-Hodgkin’s lymphoma(NHL) and mantle cell lymphoma (MCL) in December 2016. The company expects operating profit, recurring profit, and net
profit to be lower than its previous forecast due to the upfront payment relating to the license agreement with Eagle
Pharmaceuticals, Inc., for the liquid formulation products of bendamustine hydrochloride, although SG&A expenses have beensolidly controlled within budget.
On the same day, the company announced that it had concluded a license agreement with Eagle Pharmaceuticals, Inc., for the
bendamustine hydrochloride ready-to-dilute (RTD) and rapid infusion (RI) injection products.
On September 20, 2017, Eagle Pharmaceuticals and SymBio concluded a license agreement that licenses to SymBio rights todevelop, market, and sell Eagle’s bendamustine hydrochloride RTD and RI injection products (marketed in the US by Teva
Pharmaceutical Industries as BENDEKA®) in Japan.
SymBio received approval for the new indication of first-line treatment of low-grade B-cell non-Hodgkin’s lymphoma (NHL) andmantle cell lymphoma (MCL) in December 2016. As a result of patent protection conferred by the license agreement with Eagle

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Pharmaceuticals for the liquid formulation products of bendamustine hydrochloride, the company will be able to extend the
product life cycle of Treakisym® until 2031. Switching from the currently available freeze-dried (FD) powder injection to the RTD
product (which is already liquidized) will reduce the dispensing workload. The company also plans to develop a RI product toshorten the administration time from 60 minutes to 10 minutes. SymBio aims to begin selling the RTD product in early 2021,
followed by the RI product.
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 bendamustine products are marketed in the US by Teva Pharmaceutical Industries as BENDEKA®, which accounts for
97% of the bendamustine market. Teva estimates that the North American market for bendamustine products at around
USD600mn–USD660mn.

RTD and RI products: RTD products are ready to dilute, which eliminates the time-consuming process of reconstitution and substantially reduces theworkload of healthcare professionals. Rapid infusion (RI) products can be administered by intravenous infusion in 10 minutes instead of 60 minutes,
which reduces stress on patients.

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

RTD and RI products
bendamustine hydrochloride
LiquidNot required
60 minutes (RTD product)
10 minutes (RI product)
100mg/4mL

Storage

Refrigerated storage (2°C–8°C)

Generic name
Dosage form
Reconstitution
Administration time

Currently available products
Freeze-dried powder injection
Required
60 minutes
100mg/vial
25mg/vial
Room temperature

On August 31, 2017, the company announced the initiation in Japan of the Phase III clinical trial of the anti-cancer drug
TREAKISYM® for the indication of relapsed/refractory diffuse large B-cell lymphoma.
The company announced that it initiated a phase III study in Japan of the anti-cancer drug Treakisym® (non-proprietary name:bendamustine hydrochloride) for the indication of relapsed/refractory DLBCL.
Although DLBCL accounts for about one-third of malignant lymphoma in terms of the number of patients, a standard
chemotherapy for treatment of DLBCL is currently not available, thus multiple drug therapies are administered. Multiple drug
therapies, however, tend to have strong adverse effects, placing a burden on patients, and accordingly a new therapy ismuch-awaited.
Having completed a phase II study for bendamustine-rituximab (BR) therapy, SymBio obtained clinical trial results for thetreatment of patients with relapsed/refractory DLBCL.

Based on the achievements of this clinical study, BR therapy has been recommended in the NCCN (National Comprehensive
Cancer Network) Guidelines in the US, the standard for clinical policy in oncology, since 2012. After consultation with
Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, SymBio has now initiated a phase III study. The objective of thestudy is to confirm the efficacy and safety of BR therapy. The disease, relapsed/refractory DLBCL, falls under a therapeutic areawith high unmet medical needs, where a new drug therapy is much-awaited, as the strong need for the development of BR
therapy has been voiced by a patient group and relevant academic societies.

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Swiftly enrolling patients in the study, SymBio aims to file an NDA (new drug application) for relapsed/refractory DLBCL in thesecond half of 2019. This event will not impact the company’s FY12/17 forecasts.

On August 9, 2017, the company announced the issuance of the 42nd stock acquisition rights by third-party allotment.
The company resolved to issue its 42nd stock acquisition rights (placement through third-party allotment) as outlined below.

42nd stock acquisition rights▷ Allotment date:August 25, 2017

▷ Issue price:

JPY32,560,000 (JPY370 per unit)▷ Total funding amount:

JPY1,910mn (net of cost)▷ Number of stock acquisition rights issued:▷ Number of underlying shares:▷ Exercise price and exercise priceamendment provisions:

88,000 units

8,800,000 (17.97% of all issued shares)

Initial exercise price: JPY215

On February 26, 2018, the exercise price shall be amended to an amount equivalent to 90% of the closing price of SymBio’s
common shares on February 23, 2018, but in the event that the price falls below the minimum exercise price, the minimum
exercise price shall be the exercise price after amendment.

Uses of proceeds to be raised
Specific use of funds to be raised

AmountScheduled disbursement timing

Expenses for the development of TREAKISYM®
（SyB L-0501）for relapsed/refractory aggressive
non-Hodgkin lymphoma (diffuse large B-cell
lymphoma, or DLBCL)

JPY900mn

August 2017-December 2018

Expenses related to acquisition of rights andsubsequent development of the oral form of
TREAKISYM®

JPY1,009mn

August 2017-December 2018

Phase II clinical trials for TREAKISYM (SyB L-0501) for the additional indication of relapsed/refractory aggressive NHL (DLBCL) havebeen completed with favorable results, and SymBio has considered applying for approval in order to further enhance the productvalue of TREAKISYM® through additional indications. SymBio is currently formulating the details of a phase III clinical trial plan, andplans to submit a trial plan within 2017 and begin the trials. Of the total development period for these phase III clinical trials, theamount of expenditure expected until the end of December 2018 is stated.
With regard to the acquisition of rights for the oral form of TREAKISYM, SymBio will expand the rights it holds on TREAKISYM® inorder to promote indications in addition to blood cancer, such as for solid cancer and autoimmune diseases. Expenses related tothe acquisition of rights and expenses related to the implementation of phase I clinical trials currently under consideration are stated.
On the same day, the company announced the current status of the domestic phase III clinical trial of the patient-controlled pain
management drug SyB P-1501.
On May 11, 2017, SymBio announced temporary suspension of new patient enrollment in the domestic phase III clinical trial of
the patient-controlled pain management drug “SyB P-1501.” On June 5, 2017, the company announced that The Medicines
Company, the licensor of SyB P-1501, had filed a report (Form 8-K) with the US Securities and Exchange Commission.

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In an update on the current status of the domestic phase III clinical trial of the drug, SymBio said that it is continuing to discusswith The Medicines Company (MDCO) the effects of MDCO’s decision to discontinue and withdraw IONSYS® (the product namefor SyB P-1501 in the US) from the US market, in particular on the SyB P-1501 clinical trial and commercialization in Japan. SymBio
will make a timely disclosure once it makes a decision pending the results of the ongoing discussions with MDCO.

On August 3, 2017, the company announced earnings results for 1H FY12/17; see the results section for details.

For corporate releases and developments more than three months old, see the News and topics section.

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Trends and outlook
Quarterly trends and results
FY12/16

Cumulative

FY12/17(JPYmn)

Q1

Q2

Q3

Q4

Q1

Q2

Sales

193

1,211

1,408

2,368

870

1,786

YoY

-52.7%

24.0%

5.6%

22.5%

350.2%

47.5%

Gross profit

FY12/17
Q3

Q4% of FYFY Est.

49.8%

3,583
51.3%

57

405

478

904

239

510

YoY

-53.1%

43.2%

21.1%

55.1%

323.0%

26.0%

GPM

29.2%

33.4%

34.0%

38.2%

27.5%

28.5%

575

1,225

2,011

3,031

764

1,746

YoY

27.0%

31.6%

45.4%

-3.3%

32.9%

42.5%

SG&A-to-sales ratio

297.6%

101.2%

142.8%

128.0%

87.9%

97.7%

-518

-820

-1,532-2,127-525-1,236

YoY

-

-

-

-

-

-

-

OPM

-

-

-

-

-

-

-

SG&A expenses

Operating profit

Recurring profit--3,932-655-1,177-1,917-2,317-583-1,268

YoY

-

-

-

-

-

-

-

RPM

-

-

-

-

-

-

-

Net income--4,009-653-1,175-1,916-2,313-583-1,266

YoY

-

-

-

-

-

-

-

Net margin

-

-

-

-

-

-

-

FY12/16

Quarterly(JPYmn)

Q2

Q3

Q4

Q1

Q2

Gross profit

193-52.7%
57

1,018
79.2%
348

197
-44.7%
74

960
59.9%
426

870
350.2%
239

916
-9.9%
271

YoY

-53.1%

114.8%-34.6%

126.6%

323.0%-22.2%

GPM

29.2%

34.2%

37.4%

44.3%

27.5%

29.6%

575

650

786

1,021

764

982

YoY

27.0%

36.0%

73.8%

-41.7%

32.9%

51.1%

SG&A-to-sales ratio

297.6%

63.9%

399.2%

106.2%

87.9%

107.1%

-518
-

-302
-

-712
-

-595
-

-525
-

-711
-

-655
-

-522
-

-740
-

-400
-

-583
-

-685
-

-653
-

-523
-

-741
-

-397
-

-583
-

-684
-

YoY

SG&A expenses

Operating profit
YoY
OPM

Recurring profit
YoY
RPM

Net income
YoY-4,009FY12/17

Q1

Sales

-

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

Q3

Q4

1H FY12/17 results
1H FY12/17 sales totaled JPY1.8bn (+47.5% YoY) thanks to sales of Treakisym. Product sales totaled JPY1.8bn (+51.4% YoY) andother sales were JPY0mn (JPY30mn in FY12/16).
In December 2016, Treakisym was approved for the additional indication of first-line treatment for low-grade NHL and MCL. Salesof Treakisym indicated for untreated low-grade NHL and MCL increased in Q2 FY12/17.
Due to the sales increase, gross profit came to JPY510mn (+26.0% YoY). Gross profit margin was 28.5% (-4.9pp).
SG&A expenses rose 42.5% YoY to JPY1.7bn. R&D expenses increased 62.0% to JPY840mn. There were expenses for clinical trials
for the intravenous and oral formulations of Rigosertib Sodium and SyB P-1501. SG&A expenses excluding R&D expenses wereup 28.3% at JPY906mn.
As a result, operating loss totaled JPY1.2bn (loss of JPY820mn in 1H FY12/16). The company also reported a recurring loss of
JPY1.3bn (loss of JPY1.2bn in 1H FY12/16) partly due to non-operating expenses of JPY34mn (mainly on forex losses of JPY27mn).
Net loss was JPY1.3bn (loss of JPY1.2bn in 1H FY12/16).

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Progress toward the company’s full-year forecast was 61.5% for sales (51.1% in 1H FY12/16). Sales volume in 1H FY12/17 was
34,633 vials, exceeding the company’s assumption of 30,289 vials. Sales so far in FY12/17 are trending at a pace of 75,000 vials
for the full year, ahead of the company’s target of 66,000 vials. The company assumes a market penetration rate of 35% forTreakisym indicated for untreated NHL and MCL (first-line treatment), but the actual rate appears to be exceeding this level.
Progress made in 1H FY12/17 is as follows.

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

▷ In June 2017, the company restarted domestic phase I clinical trials for oral Rigosertib, because the supply of the study drug had
resumed.

▷ The Medicines Company had filed a report (Form 8-K) with the US Securities and Exchange Commission in June 2017 stating that
it would withdraw the patient-controlled pain management drug IONSYS® (SyB P-1501) from the US market and suspendcommercial activities. In May 2017, SymBio announced temporary suspension of new patient enrollment in the domestic phase
III clinical trial of SyB P-1501. As of August 2017, SymBio said that it is continuing to discuss with The Medicines Company(MDCO) the effects of MDCO’s decision to discontinue and withdraw IONSYS® from the US market, in particular on the SyB
P-1501 clinical trial and commercialization in Japan. SymBio will make a timely disclosure once it makes a decision pending theresults of the ongoing discussions with MDCO.

▷ In August 2017, the company announced the subscription for its 42nd stock acquisition rights by third-party allotment(8,800,000 residual shares corresponding to 17.97% of outstanding shares) to raise JPY1.9bn on an estimated net proceeds basis.

The funds are mainly to be used for expenses related to development of Treakisym indicated for relapsed or refractory DLBCL(aggressive NHL) totaling JPY900mn and expenses for obtaining rights to the oral formulation of Treakisym and development
after obtaining the rights totaling JPY1.0bn.

Domestic
Treakisym (SyB L-0501; 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 refractory or relapsed low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL), untreatedlow-grade NHL and MCL, and chronic lymphocytic leukemia (CLL).
In 1H FY12/17, sales of Treakisym based on the National Health Insurance (NHI) drug price grew 42.9% YoY, and accordingly
product sales to Eisai increased 44.6%.
In addition to the above three approved indications, the company is working to gain approval for a fourth indication to help
patients who need new treatments and maximize the value of the product.
The company has completed phase II clinical trials for relapsed or refractory diffuse large B-cell lymphoma (DLBCL, or aggressiveNHL). In response to strong medical needs, the company finished consultation with the Pharmaceuticals and Medical Devices
Agency in June 2017 and announced on August 31, 2017 that it had commenced phase III clinical trials toward the addition of an
indication, aiming to file an NDA in 2H 2019.
SymBio is exploring further expansion of the Treakisym business by developing an oral formulation in addition to the injection
currently under development or on sale to treat solid tumors and autoimmune diseases.

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. The global Phase III trial addresses higher risk myelodysplastic syndrome (MDS) patients who do
not respond to treatment or relapsed after treatment with hypomethylating agents (HMAs), the current standard of care

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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp(“Primary HMA Failure”); the trial is underway in more than ten countries worldwide. The company completed the first patient
enrollment in July 2016. Of the total enrollment target of 225, 25 are slated for Japan and as of August 2017, 20 patients havebeen enrolled.
SymBio started domestic Phase I clinical trials for the oral form of Rigosertib Sodium (used in combination with azacitidine) for
higher-risk myelodysplastic syndrome (MDS) in December 2015. Due to delays in the supply of drugs for the joint trials, however,patient enrollment did not make progress. Since Onconova resumed the supply of clinical trial materials, SymBio initiated a phase
I clinical trial in Japan in June 2017. The purpose of the Japanese phase I study is to confirm the safety of high-dose oral rigosertib,
which was added to the ongoing US phase II study by Onconova in untreated or relapsed/refractory patients with higher-risk
MDS. After demonstrating the safety of high-dose oral rigosertib, SymBio intends to immediately recommence an oral
rigosertib/azacitidine combination trial in Japan, and participate in the global phase III study in untreated higher-risk MDS patientsthat Onconova is planning.

SyB P-1501, a post-operative patient-controlled analgesia
In June 2016, the company started a domestic phase III clinical trial for SyB P-1501—licensed by The Medicines Company(through its wholly owned subsidiary Incline Therapeutics)by n untreated higher-risk MDS patients that Onconova is planning. y
by Onconova i. The company enrolled the first patient in November 2016 and was making progress with case accumulation.
However, facts raising concerns about the continuity of SyB P-1501 business at The Medicines Company surfaced, and in theinterest of patient welfare, SymBio temporarily suspended further patient enrollment in April 2017. As of August 2017, SymBio
said it was in discussions with The Medicines Company, and planned to make a timely disclosure once it determined how the SyB
P-1501 clinical trial and commercialization in Japan would be affected.

New drug candidates
From a long-term perspective, SymBio continues to search for and evaluate promising drug candidates, in a bid to acquire global
licensing rights for these drugs and grow into a sustainable and profitable biopharmaceutical company with growth potential andprofitability. As of August 2017, talks were underway regarding licensing rights for three drug candidates.
In May 2016, the company established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic base foroverseas business development. The company looks to leverage this subsidiary to actively acquire rights over new drug
development candidates globally, and engage in development and commercialization in major markets including the US, Japan,
and Europe to transition to a global specialty pharmaceutical company.

Overseas
The company marketed SyB L-0501 in Korea, Taiwan, and Singapore, and overseas sales were steady.

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

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Full-year company forecasts(JPYmn)Sales
Milestone revenue
Product sales
Domestic
Overseas
CoGS

CoGS ratio (% of product sales)

FY12/16FY Act.
2,368
230
2,137
2,014
123
1,464

FY12/17
Init. Est.
2,903
0
2,903
2,715
187
2,080

904

823

Gross profit

68.5%

71.7%

GPM

38.2%

28.3%

SG&A-to-sales ratio

128.0%

139.9%

SG&A expensees

R&D expenses
SG&A excluding R&D
Operating profit
OPM

3,031

1,667
1,364
-2,127

-

YoY
22.6%
35.8%
34.8%
52.0%
42.1%

FY12/17
Rev. Est.
3,583
-

51.3%
-

-9.0%

-

-

-

-

-

34.0%

-

-

2,286
1,775
-3,238

37.1%
30.1%
-

-3,932--4,009--4,009----2,317-3,303-

Net income-2,313-3,306

-

-

-

-

4,061

Recurring profit
RPM

-

YoY

-

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

-

-

-

-

-

-

-

-

Earnings outlook
The company announced a revision to its FY12/17 earnings forecast on September 21, 2017. The revised forecasts are sales of
JPY3.6bn (+51.3% YoY), operating loss of JPY3.9bn (operating loss of JPY2.1bn in FY12/16), recurring loss of JPY4.0bn (JPY2.3bnloss), and net loss of JPY4.0bn (JPY2.3bn loss).
The company expects sales of JPY3.6bn, exceeding its previous forecast by JPY680mn, because sales of Treakisym® in Japan grewfaster than expected following approval for the new indication of first-line treatment of low-grade non-Hodgkin’s lymphoma(NHL) and mantle cell lymphoma (MCL) in December 2016. The company expects operating profit, recurring profit, and net
profit to be lower than its previous forecast due to the upfront payment relating to the license agreement with Eagle
Pharmaceuticals, Inc., for the liquid formulation products of bendamustine hydrochloride, although SG&A expenses have beensolidly controlled within budget.
The following is based on information obtained before the company’s earnings forecast revision. Shared Research plans to update
the report after interviewing the company.

Higher sales forecast from Treakisym
Sales are expected to reach JPY2.9bn (+22.6% YoY), attributable to higher sales from Treakisym, breaking down into JPY2.9bn(+35.8% YoY) in product sales and JPY0 in milestone payments (JPY230mn in FY12/16).
For product sales, we assume Treakisym’s market share will be 58% (unchanged from FY12/16) for the indications of relapsed or
refractory low-grade NHL and MCL and 35% for first-line therapy for low-grade NHL and MCL. We note that approval of
Treakisym for the additional indication of first-line therapy for low-grade NHL and MCL in December 2016 will likely make acontribution to sales in FY12/17.

SG&A expense to increase (including R&D expense)
R&D expense is expected to total JPY2.3bn (up from JPY1.7bn in FY12/16), while total SG&A expense–including R&D–isprojected to reach JPY4.1bn (up from JPY3.0bn). R&D spending is slated to increase with a global phase III clinical study ofrigosertib IV, phase I trials of oral rigosertib azacitidine combination therapy, and phase III trials of SyB P-1501. The company will
also consider expanding indications of Treakisym. In a bid to boost its enterprise value for the long term, SymBio plans to
consider introducing candidates for newly developed drug products and enhancing the overall value of its pipeline.

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Higher losses forecast
As a result, SymBio forecasts an operating loss of JPY3.2bn (operating loss of JPY2.1bn in FY12/16), a recurring loss of JPY3.3bn(recurring loss of JPY2.3bn in FY12/16), and a net loss of JPY3.3bn (net loss of JPY2.3bn in FY12/16).

Pipeline
Treakisym
The company has finished the phase II trial for relapsed or refractory moderate to high-grade non-Hodgkin lymphoma (NHL) andcontinues considering expansion of indications. In August 2017, SymBio began phase III clinical trials in Japan for anticancer agent
Treakisym to add the indication for relapsed or refractory DLBCL (aggressive NHL).

Intravenous and oral rigosertib
The company is moving ahead with the accumulation of cases in Japan in the global phase III trial for the intravenous version ofrigosertib. SymBio submitted a clinical trial notification in December 2015, enrolled the first patient in July 2016, and hadenrolled 20 patients as of end-August 2017. The company aims to complete enrollment of the target 25 patients by the end of
FY12/17.
In December 2016, SymBio began a phase I trial of the oral version of rigosertib for use in combination with azacitidine for theindication of high-risk MDS. However, the company did not begin patient enrollment because of delayed supply of the study
drug from Onconova Therapeutics. SymBio restarted the domestic phase I trial in June 2017 after supply of the study drug
resumed. The company plans to resume the study of the combination therapy with azacitidine after establishing safety in thephase I trial and plans to participate in an international phase III clinical study planned by Onconova Therapeutics of the
combination therapy for the first-line treatment of high-risk MDS. Regarding development with transfusion-dependent low-risk
MDS as the target efficacy, SymBio will consider it while watching development progress at Onconova Therapeutics.

SyB P-1501, a post-operative patient-controlled analgesia
SymBio reached an in-licensing agreement for SyB P-1501 in FY12/15. The company submitted a clinical trial notification forphase III trials in June 2016 and registered the first patient in November 2016.
In June 2017, The Medicines Company filed a report (Form 8-K) with the US Securities and Exchange Commission, stating that it
would withdraw IONSYS® (the product name for SyB P-1501 in the US) from the US market and discontinue commercial activities.
Prior to the event, in April 2017 SymBio suspended further enrollment of patients for its domestic phase III clinical trials for SyB
P-1501. As of August 2017, SymBio said it was in talks with The Medicines Company, and planned to make a timely disclosure
once it determined how the SyB P-1501 clinical trial and commercialization in Japan would be affected.

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Long-term outlook
Mid-term Plan (FY12/17–FY12/19)
When it released its FY12/16 results, SymBio also announced a mid-term plan for FY12/17 through FY12/19.
Mid-term Plan
FY12/16

FY12/17

FY12/18(JPYmn)

Act.

Est.

TargetFY12/19
Target

Sales

1,933

2,339

3,926 to 3,401

4,605 to 3,586

Operating profit (losses)-2,551-2,778-2,309 to -2,509-1,872 to -2,261

Recurring profit (losses)-2,630-2,811-2,373 to -2,573-1,936 to -2,325

Net income (losses)-2,632-2,815-2,377 to -2,577-1,940 to -2,329

Source: Shared Research based on company data.

Main pipeline schedule
Major pipelines

FY12/16

Treakisym®
(relapsed or refractory low-grade NHL
and MCL)

Obtained
approval(Oct-10)Treakisym®
(first-line treatment of low-grade NHL
and MCL)

Obtained
approval(Dec-16)

Treakisym®
(CLL)

Obtained
approval(Aug-16)

Treakisym®
(relapsed or refractory moderate- andhigh-grade NHL)

Completedphase II clinical
trialsRigosertib (IV)(relapsed and refractory high-risk MDS)

Global phase III
clinical trials
underway

Rigosertib (oral)(high-risk MDS [in combination withazacitidine])

Phase I clinical
trial underway

SyB P-1501
Patient-controlled analgesia for pain
management

Phase III clinical
trials underway

FY12/17

FY12/18

FY12/19

Apply forapproval

Obtain approval(planned)

FY12/20

Complete phase Phase III clinicalI clinical trials
trialsApply forapproval

Obtain approval(planned)

Source: Shared Research based on company data

Earnings targets of Mid-term Plan (FY12/17–FY12/19)
Sales
Based on the assumptions below, the company’s mid-term plan calls for an increase in Treakisym sales by securing a larger market
share alongside an expansion of its applications (additional indication for first-line therapy for low-grade NHL and MCL).
SymBio expects Treakisym to maintain the FY12/16 market share of 58% as a treatment for relapsed or refractory low-grade NHL
and MCL.
Sales of Treakisym for the indication of first-line low-grade NHL and MCL will likely affect the upper and lower estimates for overallsales in FY12/18 and FY12/19. The company assumes market share of between 50% and 80% in FY12/19. The lower sales estimate
is based on a 50% market share and the upper estimate on an 80% share.
SymBio estimates that there are 4,700 patients with relapsed or refractory low-grade NHL and MCL and 7,100 patients withuntreated low-grade NHL and MCL. The standard first-line therapy for low-grade NHL and MCL in Japan is a combination ofrituximab and CHOP chemotherapy (R-CHOP). CHOP is a combination of four agents (cyclophosphamide, hydroxydaunorubicin(doxorubicin), oncovin (vincristine), and prednisone). However, results of studies in Europe demonstrating that the efficacy ofrituximab and Treakisym combination therapy (BR therapy) is significantly higher than R-CHOP as a first-line treatment were

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presented at the American Society of Hematology Annual Meeting in 2012. Treatment guidelines in the US and Europe
recommend BR therapy as a first-line treatment and an estimated 80% of patients outside Japan now receive BR therapy.
The company targets NDA for post-operative patient-controlled analgesia SyB P-1501 within the medium-term plan period, but
has not included any sales in numerical plan targets.

SG&A expenses
SG&A expenses, including R&D costs, are expected to increase in FY12/17 under the medium-term management plan as thecompany pursues clinical trials of SyB P-1501 and the IV and oral forms of rigosertib. SymBio expects R&D expenses to decline
YoY in FY12/18, because it will complete the case series study in FY12/17. SymBio intends to continue with evaluations anddeliberations regarding new product development candidates, but any expenses related to the launch and development of thesecandidates are not included in medium-term plan estimates.
Concerning other SG&A expenses, most of which comprises marketing expenses for Treakisym, the company has an agreementwith Eisai to share the cost 50/50. Thus SymBio books 50% of the estimated amount as an expense.

Mid-term plan assumptions
Pipeline progress
Treakisym◤ Treakisym’s market share has reached a high level as a treatment for relapsed or refractory low-grade NHL and MCL. SymBio’s

medium-term plan assumes that market share will trend at around 58%.

◤ SymBio received approval for the manufacturing and sale of Treakisym as a first-line treatment for refractory/relapsed

low-grade NHL and MCL in December 2016 and for CLL in August 2016. The company is strengthening its marketing
partnership with Eisai to grow sales of Treakisym, focusing on increasing market share and optimal use of Treakisym indicatedfor untreated refractory/relapsed low-grade NHL and MCL to establish its position as a first-line treatment, thereby maximizing
its product value. The company’s medium-term plan assumes market share of Treakisym for these indications of 35% in
FY12/17 and 50–80% in FY12/19.

◤ Concerning the use of Treakisym for relapsed or refractory aggressive NHL, phase II clinical trials have been completed, anddeliberations aimed at winning approval will continue. Sales and expenses related to these indications have not been
incorporated into the medium-term plan.

Rigosertib◤ Rigosertib (IV) for relapsed and refractory high-risk MDS is slated to undergo Japanese clinical trials as part of global phase III

trials being undertaken in cooperation with Onconova. The company aims for approval during FY12/19.

◤ As of February 2017, patient enrollment for Phase I clinical trials of oral rigosertib for high-risk MDS (in combination withazacitidine) had been interrupted because of delayed supply of the study drug from Onconova Therapeutics. The company
plans to resume the trials in FY12/17 for completion in FY12/18 before taking part in global phase III trials planned by
Onconova in FY12/19.

◤ Regarding development with transfusion-dependent low-risk MDS as the target efficacy of oral rigosertib, SymBio willconsider it while watching development progress at Onconova Therapeutics.

SyB P-1501: Patient-controlled analgesia for pain management
Phase III clinical trials for short-term management of acute postoperative pain began in June 2016 and the first patient was
registered in November 2016. The company plans to file NDA in FY12/18.

Plans to establish own sales force
In August 2008, the company established an exclusive partnership with Eisai for Treakisym. Eisai agreed to cover one-time
payments, milestone payments in accordance with clinical trial stage, and half of R&D expenses, as well as 100% of sales and

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marketing costs. Shared Research estimates that Eisai takes a margin of about 50% on domestic Treakisym sales at the National
Health Insurance (NHI) drug price - SymBio’s margin is just under 20%. The company also expects its margin to improve as
procurement costs fall in line with higher sales.
As of February 2017, SymBio had not entered into an exclusive domestic sales agreement for SyB P-1501 or rigosertib (IV) withany company. According to its medium-term plan, the company will consider the creation of its own sales framework to coincidewith approval to manufacture and sell SyB P-1501 or rigosertib in IV form and the timing of licensing-in new drug candidates.
Labor costs would increase if SymBio were to create its own sales force, but the company could realize a significantly higher profit
margin on product supply as well as sales. Assuming the company establishes its own sales force, Shared Research sees potential
for a significantly higher profit margin than Treakisym.

Introduction of new drug candidates
According to the medium-term plan, the company will continue to evaluate numerous candidate drugs, and will move to acquire
promising candidates that enhance its corporate value. Shared Research expects the company to spend between JPY500mn and
JPY1bn in one-time payments per new drug candidate and incur additional R&D expenses.

Long-term outlook
Shared Research thinks sales of JPY10bn and OPM of over 20% is achievable in FY12/21 after the completion of the current
mid-term management plan (FY12/17–FY12/19), and beyond, with additional indications for Treakisym® driving sales growth and
OPM improvement. We have identified the following four growth drivers:◤ Sales growth due to progress with market penetration of Treakisym® as a first-line treatment of low-grade non-Hodgkin’s

lymphoma (NHL) and mantle cell lymphoma (MCL)◤ Sales growth spurred by Treakisym® indicated for relapsed or refractory DLBCL going on sale
◤ Profit margin improvement as a result of starting own sales◤ Establishing a competitive advantage over generics by putting ready-to-dilute (RTD) and rapid infusion (RI) injection productson the market

Sales growth due to progress with market penetration of Treakisym® as a first-line treatment of low-grade non-Hodgkin’s lymphoma(NHL) and mantle cell lymphoma (MCL)
R-CHOP therapy—a combination of rituximab with CHOP chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, andprednisolone)—was standard first-line treatment for low-grade NHL and MCL in Japan prior to December 2016.
Clinical trials conducted overseas have demonstrated that rituximab in combination with bendamustine (BR therapy) was safer
and more efficacious than standard R-CHOP therapy in all endpoints including progression-free survival (PFS), time to next
treatment, overall survival, and safety. Based on these results, the National Comprehensive Cancer Network (NCCN) andEuropean Society for Medical Oncology (ESMO) guidelines recommend the use of BR therapy as first-line therapy for patientswith untreated low-grade NHL and MCL.
SymBio received permission to add first-line low-grade NHL and MCL as indications in December 2016. The company expects
market penetration of Treakisym to progress for the new indication in FY12/17 onward. The mid-term plan targets a market
penetration rate of 35% for the new indication in FY12/17 and 50–80% in FY12/19. Based on this assumption, SymBio estimates
FY12/19 sales of Treakisym (NHI drug reimbursement price basis; total including relapsed or refractory low-grade NHL and MCL
indications) at around JPY10bn versus over JPY4bn n FY12/16.

Sales growth due to Treakisym® indicated for relapsed or refractory DLBCL going on sale
In August 2017, SymBio began Phase III clinical trials of Treakisym for an additional indication for relapsed or refractory DLBCL(aggressive NHL). The trials are scheduled to take 24 months. The company plans to file for approval for the additional indicationfor elapsed or refractory DLBCL (aggressive NHL) in 2H 2019.

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The company estimates that there are 6,700 patients with relapsed or refractory DLBCL (aggressive NHL) in Japan. This number isclose to the number of patients with untreated NHL and MCL (7,100). We estimate that the company will add around JPY6bn insales of Treakisym (NHI drug reimbursement price basis) if it can obtain approval for the additional indication.

Profit margin improvement as a result of starting own sales
As of September 2017, SymBio has an exclusive partnership with Eisai for the marketing of Treakisym in Japan. We estimate that
Eisai makes roughly 50% profit from sales of the product based on the NHI drug reimbursement price, while SymBio’s profit
margin on the same basis is slightly under 20%.
SymBio stated in its midterm plan that it would make management decisions to establish its own sales structure. That being said,
the company was having problems formulating a strategy based on a long-term sales outlook, because the re-examination term
for the currently available freeze-dried (FD) powder injection product ends in 2020.
In September 2017, the company extended the product life cycle of Treakisym (bendamustine hydrochloride) until 2031 byconcluding a license agreement with Eagle Pharmaceuticals that grants SymBio rights to develop, market, and sell Eagle’s
bendamustine hydrochloride RTD and RI injection products in Japan (see below). In our view, the agreement has increased thelikelihood of SymBio continuing to expand sales of Treakisym after 2020 and accordingly, that of the company deciding to set up
its own sales structure.
If the company does establish its own sales structure, sales-related expenses will increase as the company hires medical reps andother employees. However, it will also allow the company to take a bigger share of profits and is therefore likely to boost profit
margins on Treakisym.
SymBio does not yet have its own sales force as of September 2017, but a team of five product managers in the company
supports sales at Eisai. We think that in the longer term, SymBio will gradually increase the number of product managers andtransition to its own sales structure in or around December 2020, when the exclusive marketing agreement with Eisai comes to an
end.

Establishing a competitive advantage over generics by putting RTD and RI bendamustine hydrochloride products on the market
As of September 2017, the company sells bendamustine hydrochloride (brand name in Japan: Treakisym® ) as a freeze-dried (FD)powder injection through Eisai. The re-examination term for the product ends in 2020, after which generics can go on themarket.
In September 2017, the company concluded a license agreement with Eagle Pharmaceuticals, Inc., for the development andmarketing of bendamustine hydrochloride ready-to-dilute (RTD) and rapid infusion (RI) injection products in Japan. Since the
RTD and RI products are already liquidized, they do not require the time-consuming process of reconstitution and substantiallyreduce the workload of healthcare professionals. RI products also do not require reconstitution and can be administered byintravenous infusion in 10 minutes instead of 60 minutes, which reduces stress on patients. The exclusive sales period for theseproducts extends to 2031.
SymBio believes that by selling the RTD and RI products that offer the advantages of reducing healthcare professionals’ workload
and stress on patients will limit the spread of generics after the re-examination term for Treakisym (FD product) ends.
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.

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

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

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

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

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

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

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

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

As of March 2016, the company had evaluated some 500 drug candidates since its establishment in March 2005, signing on four
deals.
According to the company, the development of a drug—from preclinical studies to approval—usually takes 10 to 17 years. A
newly developed chemical compound has a 1/100,000 chance of securing regulatory approval. By contrast, the company’s first
product, Treakisym, received approval for domestic production only five years after signature of the License Agreement. The
company achieved sales of JPY4.2bn in Japan in the third year after launch (FY12/13), equivalent to a market share of over 50%.
An example of the company’s ability to identify and pursue quality in-licensing opportunities with proof-of-concept established isthe license agreement signed for the development and commercialization right to rigosertib—currently in phase I clinical trials inJapan. In July 2011, once phase II clinical trials in the US established the drug’s proof-of-concept, SymBio secured an exclusive
right to all indications for rigosertib in Japan and South Korea from Onconova within seven months from the initial meeting
between the two companies. The following year, Baxter International Inc. entered into an agreement with Onconova for thecommercialization rights to rigosertib in Europe with a USD50mn upfront payment and USD337.5mn in pre-commercial
milestones tied to MDS and pancreatic cancer indications (in addition to an existing equity investment with Onconova of
USD55mn), a market that is approximately twice the size of Japan.

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Four products under development: Treakisym, rigosertib (IV and oral), and SyB P-1501
Treakisym
For patients that have developed resistance to other drugs, Treakisym is safer and more effective than existing treatments. In
October 2010, SymBio received approval to use the drug in Japan for relapsed or refractory low-grade NHL and MCL, having
previously received orphan drug designation and priority review for these two indications.
Refractory conditions are difficult to treat, or do not respond to treatment.

The company received permission to add CLL as an indication for Treakisym in August 2016, followed by permission to add
first-line low-grade NHL and MCL as indications in December 2016.
In August 2017, SymBio announced it had commenced phase III clinical trials for an additional indication of relapsed or refractoryhigh-grade DLBCL (aggressive NHL).

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). Within Japan, the company
has been conducting joint global phase III clinical trials in cooperation with Onconova.
For the oral form of the drug, SymBio is conducting a phase I clinical trial for high-risk MDS (with azacitidine) in Japan. It may
participate in global phase III trials that Onconova plans to launch in FY12/20.

SyB P-1501
Patient-controlled analgesia for pain management SyB P-1501 (known as IONSYS in the US) is a drug delivery system allowing
post-operative patients to manage their pain. As a needle-free alternative, SyB P-1501 is anticipated to improve treatment
satisfaction as it lessens the physical and psychological burden on patients. It is also expected to offer increased safety andconvenience for medical institutions, decreasing the labor and costs required to manage electric pumps. SymBio obtained
exclusive development and marketing rights for the drug in Japan from The Medicines Company in October 2015.
The Medicines Company received approval for IONSYS from the US Food and Drug Administration (FDA) in April 2015. It has
already begun marketing the drug in the US. The European regulatory agency also granted approval to the drug in November
2015. In Japan, safety of the drug has already been established in a phase I clinical trial on healthy adults, and SymBio beganphase III clinical trials in June 2016. However, facts raising concerns about the continuity of SyB P-1501 business at The Medicines
Company surfaced, and in the interest of patient welfare, SymBio temporarily suspended further patient enrollment in April 2017.

Revenue: milestone payments and Treakisym
Revenue comes from milestone payments and product sales. Operating losses have persisted since the company’s foundation
with the exception of FY12/08 when the company booked an operating profit due to a one-time contract payment from Eisai foran exclusive domestic right to sell Treakisym (see Historical performance). For FY12/17, the company expects a JPY3.2bn
operating loss, JPY3.3bn recurring loss, and net loss of JPY3.3bn. Over the course of the mid-term plan (FY12/16–FY12/18), thecompany expects to post annual operating losses of JPY1.8–3.3bn.
SymBio expects operating losses of JPY7.4–8.0bn in total between FY12/17 and FY12/19. To achieve medium-term growth, thecompany needs to continue considering the in-licensing of new drug candidates for development and commercialization. As ofthe end of FY12/16, the company had cash and deposits plus securities of about JPY5.7bn.

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

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

Source: Shared Research based on company data.

It may be possible for the company to file NDAs in Japan by bridging Japanese phase I clinical trials with foreign data through its
participation in global phase III studies, thereby avoiding the need to complete domestic phase II and/or phase III studies formarketing approval.

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

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

Only four drugs out of 500+ have met the company’s stringent criteria since its foundation
As of March 2016, the company had screened over 500 candidates. It acquired four. The first was Treakisym, which Eisai Co., Ltd.
(TSE1: 4523) sells in Japan. Clinical trials for additional Treakisym indications are underway. In addition to Treakisym, thecompany is also developing intravenous and oral versions of rigosertib, an anti-cancer drug for myelodysplastic syndromes, and
SyB P-1501, a patient-controlled analgesia for pain management.
Drug candidate selection process

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

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

Presently Chairman GBS Venture Capital firm, Deputy Chairman Victorian Comprehensive Cancer Centre,
Director of Co-operative Research Centre for Cancer Therapeutics and Proacta.
Former Senior Vice-President of Development and CMO at Amgen Inc..

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

Former Senior Vice-President of US R&D, Aventis Pharmaceuticals;
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.

Deputy Director and Professor of Center for iPS Cell Research andApplication (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University
Honorary member, The Japanese Society of Hematology

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

Professor, Keio University School of Medicine(Chair in Developmental and Differential Biology)
Guest Professor, Institute of Molecular Embryology and Genetics, Kumamoto University
Vice President, The Japanese Society of Hematology in 2012

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

Professor of Medicine, Keio University, School of Medicine(Division of Rheumatology, Clinical Immunology, Department of Internal Medicine)

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

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.

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), but as ofFebruary 2017, marketing rights are granted to outside partners.

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

Strategy for global expansion
The company is seeking to develop new drugs that are complementary to Treakisym and rigosertib to sell in China/Hong Kong,
Taiwan, South Korea, and Singapore, as well as in Japan. In the medium-term plan announced in February 2016 and updated in
February 2017, the company maintains that it will not limit itself to the Japan and Asia regions, but will always look to acquiringglobal rights when discovering, evaluating, and negotiating terms for new drug development candidates.

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Pipeline
Licensedcountry

Name/Code

Category

Treakisym
SyB L-0501

Anti-cancer agent Japan

Indications

Development stage

Sales partner

Refractory/relapsed
low-grade NHL and MCL

Approval obtained (Oct.
2010)

Eisai Co., Ltd.
(co-developed: exclusive

Refractory/relapsed
DLBCL (aggressive NHL)

Phase III clinical trials
underwaysales rights granted to Eisai)

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

Approval granted(Aug. 2016)Low-grade B-cell NHL

Approval granted(Jan. 2010)

Eisai Co., Ltd.
(Exclusive development andsales rights granted to Eisai)

CLLMMApproval granted(May 2011)

Eisai Co., Ltd.
(Exclusive development andRefractory/relapsed
low-grade NHL

Approval granted(Jun. 2014)

China

Low-grade NHL

Clinical trials underway

Hong Kong

Low-grade NHL

Approval granted(Dec. 2009)

Singapore

CLL
South Korea

sales rights granted to Eisai)

Cephalon, Inc. (US)(Exclusive development andsales rights granted to Eisai)

CLL
TaiwanLow-grade NHL

Approval granted(Oct. 2011)

CLL
Rigosertib(IV)
SyB L-1101

Anti-cancer agent Japan(IV)

Refractory/relapsed
high-risk MDS

Global phase III clinical
trials underway

Rigosertib(oral)SyB C-1101

Anti-cancer agent Japan(oral)High risk MDS(single drug)

Completed phase I
clinical trials(Jun. 2015)

High-risk MDS (withazacitidine)

Phase I clinical trials

Management of acutepostoperative pain

Completed phase I
clinical trials
Phase III clinical trials

SyB P-1501

Patient-controlled Japanpain
management

InnoPharmax, Inc. (Taiwan)(Exclusive development andsales rights granted to Eisai)
―

―
―
―

Source: Shared Research based on the company website
The company is preparing to file for approval of a liquid ready-to-dilute (RTD) formulation and developing a rapid infusion (RI) formulation of Treakisym.

As of September 2017, the main drugs for which SymBio was preparing filing for approval or in the development pipeline were as
follows:▷ Treakisym, targeting indication for refractory or relapsed DLBCL (aggressive NHL)▷ Treakisym, preparing to file for approval of RTD formulation and developing RI formulation▷ Rigosertib (intravenous form), targeting indication for relapsed or refractory higher-risk myelodysplastic syndrome (MDS)▷ Rigosertib (oral form, in combination with azacitidine), targeting indication for high-risk MDS▷ SyBP-1501, patient controlled analgesia for pain management

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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 effective than existing treatments for target indications. In October 2010,
SymBio received regulatory approval in Japan to market the drug for relapsed or refractory low-grade NHL and MCL. Eisai has
been selling the drug since its launch in December 2010. The company received permission to add CLL as an indication for
Treakisym in August 2016, and first-line treatment of low-grade NHL and MCL in December 2016.
In August 2017, the company announced the initiation of phase III clinical studies of Treakisym for an additional indication of
relapsed or refractory DLBCL (aggressive NHL).

Lymphatic cancer
Lymphatic cancer is a malignant growth of lymphatic corpuscles in white blood cells. It causes inflammation of the lymphatic
nodes. 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. Physicians examine tissue and determine the method of treatment depending on the type of cancerous cells
observed: they look at the grade (high, intermediate, or low, depending on the aggressiveness of the disease) and clinicalstaging, which shows to what extent the cancer has spread.
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)

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. (“Eisai”) 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 a particular 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 Earnings structure).
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.

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Approval for relapsed or refractory low-grade NHL, MCL in October 2010
In October 2010, five years after acquiring the right to Treakisym, SymBio received marketing approval in Japan for relapsed or
refractory low-grade NHL and MCL. In FY12/16—six years after the domestic launch of the drug in December 2010—Treakisym
sales to end users reached JPY4.7bn on a 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 JPY4.5bn-JPY5.0bn.

Treakisym: additional indications
Approval for first-line treatment of low-grade NHL, MCL in December 2016 and additional indication for CLL in
August 2016
In December 2016, Treakisym was approved in Japan for first-line treatment of low-grade NHL/MCL and for CLL in August 2016.
In August 2017, the company announced the start of phase III clinical studies for relapsed or refractory DLBCL (aggressive NHL)as part of its plans to add indications
Market for Treakisym and number of patients
Non-Hodgkin's Lymphoma
Low-grade B-cell
First-line

Relapsed andrefractory

Number of patients

Chronic Lymphatic Leukemia
Moderate- to high-grade

7,100

700

Approval

Obtained

Obtained

Development status

Dec. 2016 approval obtained

Aug. 2016 approval obtained

Number of patients

4,700

6,700

Approval

Obtained

Completed phase II clinical trials in Japan

Development status

Approval obtained in Japan in Oct. 2010
Sales launched in Japan in Dec. 2010

Phase III clinical trials underway in Japan

Source: Shared Research based on company data.

First-line treatment of low-grade NHL and MCL
According to the company, R-CHOP therapy—a combination of rituximab with CHOP chemotherapy drugs (cyclophosphamide,
doxorubicin, vincristine, and prednisolone)—was standard first-line treatment for low-grade NHL and MCL in Japan prior to
December 2016.
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.

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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.

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

Source: Company data

Treakisym approved in December 2016 for first-line treatment of low-grade NHL and MCL
In December 2016, SymBio received approval to manufacture and sell in Japan Treakisym targeting first-line treatment of
low-grade NHL and MCL. The company expects the shift from R-CHOP to BR therapy to progress domestically in the medium
term.

Untreated low-grade NHL and MCL: Patient population
SymBio estimates that there are 7,100 first-line low-grade NHL and MCL patients in Japan—1.5 times the number of patients withrelapsed or refractory low-grade NHL and MCL. Treakisym sales could reach JPY5.5bn–JPY7bn as the Japanese population
continues to age.

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

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

Potential patient population, expected sales
SymBio estimates that there are about 700 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 anti-cancer drugs are effective. R-CHOP is the standard initial therapy for relapsed or refractory DLBCL, the most common
type of NHL.

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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 effective method of treatment such as Treakisym.

R&D status: Began phase III clinical trial of Treakisym to treat relapsed or refractory DLBCL in August 2017
In March 2012, the company completed final analysis and evaluation of data from its phase II clinical trial using Treakisym in
combination 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.
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 DLBL. The purpose of the study is to test
the efficacy and safety of BR therapy, with the overall response rate (ORR; antitumor effect) as the primary endpoint and anenrollment target of 60 patients. The company plans to conduct the study over 24 months and aims to file NDA in 2H 2019.

Potential patient population
According to SymBio, the number of relapsed or refractory DLBCL (aggressive NHL) patients in Japan is approximately 6,700.

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

RI products

Currently available products

Generic namebendamustine hydrochloride

Dosage form

LiquidReconstitution

Not required

Dilution

Dilute with 250ml physiologicalsalineDilute with 50ml physiologicalsalineAdministration time

60 minutes

10 minutes

Dosage form

100mg/4mL

100mg/vial
25mg/vial

Storage

Refrigerated storage (2°C–8°C)

Room temperature

Freeze-dried powder injection
Required (manual reconstitution)
Dilute with 250ml physiologicalsaline60 minutes

Can extend life cycle of Treakisym® until 2031
The re-examination term for the FD product of Treakisym ends in 2020, after which generics can go on the market. SymBio
believes that by selling the RTD and RI products that offer the advantages of reducing healthcare professionals’ workload andstress on patients after 2020, it can extend the exclusive sales period until 2031. This increases the possibility of prolonging thelife cycle of Treakisym and limiting the spread of generics.

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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: Aim to begin selling bendamustine hydrochloride RTD product in 1H 2021
As of September 2017, the schedule for filing for approval of the bendamustine hydrochloride RTD product and development of
the RI product were under discussion.
SymBio commented that it is likely to be allowed to file for approval of the RTD product without conducting clinical trials,
because the ingredients, efficacy, and administration time are identical to the Treakisym FD product; the only difference beingthat it does not need reconstitution. The company aims to begin selling the RTD product in 1H 2021, based on the estimatedtime required to prepare filing documentation and review period from filing to approval.
However, the company expects clinical trials will be required for the RI product, because the administration time is different fromthe FD product. Given that the trials will only be comparing the safety and efficacy of the RI product and the FD product (which
has already been approved) rather than the usual phase III clinical trial of a new drug, SymBio expects that the required numberof patients in the study will be small. The company plans to begin preparing for the sale of the RI product after the RTD productgoes on sale.

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

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

Acquired rights from Onconova to develop and sell rigosertib in Japan, 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.

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Development status of rigosertib
As of February 2017, SymBio is developing the IV form of rigosertib for the indication of relapsed or refractory high-risk MDS, andthe oral form for high-risk MDS (in combination with azacitidine).
Onconova has been conducting joint global phase III clinical trials in over 10 countries since August 2015 for the intravenous
form of rigosertib in high-risk MDS patients who had failed or relapsed after prior therapy with hypomethylating agents (HMAs).
In the Japanese market, the company has been conducting the joint global phase III clinical trials in cooperation with Onconova
since December 2015.
The company had started phase I clinical trials for the oral form of rigosertib for the indications of high-risk MDS (in combination
with azacitidine) in December 2015. The supply of the study drug from Onconova had been delayed, but SymBio restarted phase
I trials in Japan in June 2017. After establishing safety in phase 1 trials, the company plans to resume the trial of rigosertib in
combination with azacitidine and participate in an international phase III study planned by Onconova in FY12/20.
Market for Rigosertib (oral form) and number of patients

Intravenous

Oral

Low-risk MDSHigh risk MDSFirst-line

First-line

Relapsed and refractory

Number of patients

3,200

Approval

Obtain approval in FY12/19 (expected)

Development status

Global phase III trials

Number of patients

7,800

3,200

Approval

Obtain approval in FY12/19 or FY12/20(expected)

TBC

Development status

Phase II trials underway in the US

Phase II clinical trials underway in the US
Phase I clinical trials underway in Japan(with azacitidine)

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
2017.

R&D status: ongoing joint international phase III clinical trial in patients with recurrent high-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.

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Of the 299 patients enrolled in the phase III clinical trial, 199 were administered rigosertib and 100 were placed in the control
group. The overall survival (OS) period for those who received rigosertib was 8.2 months, while OS for the control group (BSC)
was 5.8 months. However, with a p-value of 0.27, there was no statistically significant difference between the two groups.
Among patients whose condition had deteriorated or not responded to previous treatment using hypomethylating agents (184of 299 people, or 62%), the overall survival period for higher-risk MDS patients who received rigosertib was 8.5 months, while forthose in the control group (BSC) it was 4.7 months. The p-value was 0.022, showing a statistically significant difference. The
hematological toxicity of the conventional anti-cancer agent was approximately 60%. With rigosertib, toxicity of Grade 3 orabove did not exceed 7%, and non-hematological toxicity did not exceed 3%, confirming safety of the drug.
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
SymBio initiated its phase I clinical trial for intravenous rigosertib to treat relapsed or refractory higher-risk MDS in June 2012.
Phase I clinical trials were completed in October 2010. Based on the outcome of discussions with the FDA and European
regulatory agencies and Onconova’s future development, the company has been operating the global phase III clinical trials
within Japan since December 2015. The first patient was registered in July 2016 and 20 patients had been registered as ofend-August 2017 versus the target 25–30. SymBio aims for approval during FY12/19. Onconova is scheduled to perform aninterim analysis of the global phase III clinical trials data in Q4 FY12/17.

Oral form of rigosertib for first-line high-risk MDS (in combination with azacitidine)
R&D status: phase I and II clinical trials underway
Onconova, the anticancer drug rigosertib’s licensor, presented Phase 2 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 August 2017, Onconova is making efforts toward finalizing the design for a pivotal Phase 3 oral rigosertib/azacitidine
combination trial for higher-risk MDS patients.

Domestic phase I clinical trials
SymBio completed domestic phase I clinical trial of rigosertib (oral, without supplements) for the indication of high-risk MDS in
June 2015. In FY12/16, the company launched phase I clinical trials to confirm the safety of the drug in combination withazacitidine for treatment of high-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 thedomestic phase I clinical trial to confirm the safety of the drug at high doses (an additional requirement for phase III trials
conducted by Onconova in the US for the indication of untreated and relapsed/refractory high-risk MDS). After establishing safety
in the phase I trial, the company plans to resume the trial of the drug in combination with azacitidine and participate in global
phase III trials conducted by Onconova in FY12/20.

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Oral form of rigosertib for transfusion-dependent lower-risk MDS
Lower-risk MDS corresponds to all the low-risk categories and intermediate-1 of the IPSS with a blast-cell ratio (the ratio of blast
cells in the marrow and peripheral blood) of less than 5%. It is primarily caused by a decline in blood cells. It poses a low risk ofprogression to acute leukemia.
Patients who do not suffer a large decline in blood cells and who do not have any subjective symptoms are placed underobservation instead of being treated. Those who develop anemia receive an infusion of red blood cells in accordance with theirage. Sometimes an immunosuppressant is used to prevent lymphocyte cells from attacking hematopoietic stem cells. Depending
on a patient’s age and condition, and HLA compatibility with a donor, an allogeneic hematopoietic stem cell transplant issometimes carried out. Patients who are not suitable candidates for an allogeneic hematopoietic stem cell transplant, but who arein critical condition due to hematopoietic failure, may be given Vidaza.

R&D status
The company plans to concentrate on domestic phase I clinical trials (with azacitidine) for the oral form of rigosertib for high-risk
MDS patients. Concerning clinical trials for transfusion-dependent, lower-risk MDS patients, SymBio plans to make deliberations
based on development progress at Onconova.

Patient population, estimated sales
According to SymBio estimates, patients with lower-risk MDS in Japan number about 7,800, with 3,200 MDS patients classified as
higher-risk.
Nippon Shinyaku Co., Ltd. (TSE1: 4516) has been selling azacitidine in Japan as first-line therapy for MDS under the productname Vidaza since March 2011. According to Nippon Shinyaku, sales of Vidaza were JPY12.4bn for FY03/16 (+14.3% YoY). The
company expects to book sales of JPY13.4bn for FY03/17. Shared Research thinks that sales of the intravenous and oral forms ofrigosertib could match or exceed sales of Vidaza, used for patients who have not received treatment with Vidaza or in
combination therapy with Vidaza.

SyB P-1501 (Ionsys [US product name] for patient-controlled analgesia)
SymBio obtained exclusive development and marketing rights to SyB P-1501 (US product name: Ionsys) in Japan from The
Medicines Company (US) in October 2015. SyB P-1501 is a patient-controlled analgesia (PCA) system for post-operative pain
management. It uses a credit card-size device on the patient’s arm or chest to deliver a set dose of fentanyl (a synthetic opiate
painkiller) at the press of a button. This dose is absorbed transdermally without the need for needles or other invasive measures.

Post-operative pain management
Post-operative patients experience various forms of pain, so safe and effective forms of analgesia are key to improving treatment
satisfaction and quality of life. BB Research has estimated the worldwide market for pain management drugs and devices at
USD36.6bn in 2014, a figure expected to increase to USD44.3bn by 2020 based on 3.2% annual growth.
As of February 2017, many hospitals had begun using PCA, which allows patients to control administration of their pain
medications based on their own symptoms. The drug is delivered through an electronic pump at the touch of a button. A
cassette with diluted fentanyl is connected to an epidural or intravenous line. When necessary, the patient activates the device
and a safe, effective dose of the analgesic is delivered automatically to control pain.
Conventional PCA methods used needles and constituted a mental and physical burden on patients. The electronic pumps usedalso required maintenance, incurring high costs. Both doctors and patients were looking for a safer, more convenient PCA
method.

SyB P-1501: expected to alleviate mental and physical patient burden, improve treatment satisfaction, save on labor and costs.

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According to SymBio, this needle-less PCA system operates through using a tiny electrical current to deliver ionized fentanyl
transdermally using the principle of iontophoresis. Older generations of PCA devices required electronic pump maintenance, but
SyB P-1501 eliminates the need for programming, line installation, power cords, accessories, drug dilution, inspection, andrefilling. This results in a safer, more convenient system which also allows hospitals to save labor and costs.
SyB P-1501 (left) and conventional PCA system (right)

Source: Company data

R&D status: Marketed in the US, approved in the EU, and phase III clinical trial temporarily suspended in JapanThe Medicines Company received approval from the US Food and Drug Administration (FDA) in April 2015, and SyB P-1501 is
already marketed in the US. European regulators approved the drug in November 2015.
In Japan, domestic phase I trials have already established the drug’s safety in healthy adults, and SymBio launched phase III trials
in June 2016. The company was making progress with enrollment after the first patient was enrolled in November 2016.
The Medicines Company had filed a report (Form 8-K) with the US Securities and Exchange Commission in June 2017 stating that
it would withdraw the patient-controlled pain management drug IONSYS® (SyB P-1501) from the US market and suspendcommercial activities. In May 2017, SymBio announced temporary suspension of new patient enrollment in the domestic phase III
clinical trial of SyB P-1501. As of August 2017, SymBio said it was in talks with The Medicines Company, and planned to make atimely disclosure once it determined how the SyB P-1501 clinical trial and commercialization in Japan would be affected.

Patient population, estimated sales
According to SymBio, about 1 million patients receive PCA treatment in Japan each year, accounting for 20% of all surgeries. Of
these, the company estimates 330,000 (about 34%) patients use IV-based PCA systems. The company envisions switching ofIV-based PCA to SyB P-1501. Price for the drug is about USD200 in the US, so the company estimates annual sales of about
JPY6.6bn assuming equivalent pricing in Japan and full switching of the IV-based PCA patient population to SyB P-1501.

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Earnings structure(JPYmn)FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

1,191

1,450

1,883

1,955

1,532

1,955

1,933

2,368

-

326

1,632

1,955

1,432

1,940

1,933

2,137

Treakisym sales to end users (reference)

-

644

3,390

3,940

4,230

4,320

4,760

4,720

Product sales / Sales to end users

-

50.6%

48.2%

49.6%

33.9%

44.9%

40.6%

45.3%

Royalty revenue

1,191

1,124

250

-

100

15

-

231

Sales to Eisai

1,085

1,446

1,872

1,930

1,486

1,908

1,852

2,265

Non-Eisai sales

106

4

10

26

46

47

81

104

-

238

1,224

1,362

1,214

1,428

1,350

1,464

Sales
Product sales

CoGS
CoGS / Product sales

-

73.1%

75.0%

69.7%

84.8%

73.6%

69.8%

68.5%

CoGS / Sales to end users

-

37.0%

36.1%

34.6%

28.7%

33.1%

28.4%

31.0%
1,606

-

238

1,434

1,322

1,175

1,550

1,242

Gross profit

Product procurement

1,191

1,212

658

593

318

527

583

904

SG&A expenses

1,399

1,825

2,725

2,293

1,999

1,830

3,135

3,031

Personnel expenses

323

343

365

413

441

479

488

628

R&D expenses

817

1,118

1,945

1,438

1,053

774

2,035

1,667

Other
Operating profit

Source: Shared Research based on company data.

259

364

415

442

505

577

612

737

-208

-613

-2,067-1,700-1,681-1,303-2,552-2,127Sales
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 anti-cancer agent in December 2010. In FY12/16, product sales comprised sales of
bendamustine to Eisai and InnoPharmax. Bendamustine is supplied wholesale at the NHI price minus a percentage based on pasttransactions. Shared Research estimates this percentage to be about 40%.

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. Margins may improve as sales increase.
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 have been trending upward in line with business growth.
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 per drug, and domestic clinical trials cost
between JPY1bn and JPY2bn. Note: Eisai pays half of the development costs for Treakisym in Japan.

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Strengths and weaknesses
Strengths◤ Unique candidate selection process: SymBio makes decisions on in-licensing new drug candidates based on an initialassessment and screening process by its in-house search and evaluation team. The final decision is made by the company after
evaluation by a team of medical experts—the Scientific Advisory Board (SAB). President Yoshida’s extensive range of contacts
in the pharmaceutical industry built during his tenure at Amgen Japan and Amgen Inc. is a significant hurdle for competitors
attempting to emulate the quality of the company’s search and evaluation team, SAB panel and selection process.

◤ Strong product development: Treakisym (bendamustine hydrochloride)—the first drug the company developed—received

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

to pain management. 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 insecuring 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. The company is considering the creation of its own sales and marketing organization for rigosertib and otherdrugs approved beyond rigosertib. Such efforts could drive up costs and impact the company’s future profitability.

◤ 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 JPY5.7bn at the end of FY12/15. But the company
expects a total net loss of JPY7.6–8.2bn over the period of its mid-term plan (FY12/17–FY12/19). The company’s operations
would be affected if it fails to secure additional funding.

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

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Market and value chain
Market strategy
Lymphatic cancer: patient population, market size, drugs
Newly diagnosed patients with lymphatic cancer
In 2012, the number of people diagnosed with lymphatic cancer in Japan was 26,632 (+7.5% YoY; average annual increase inpast 10 years is 5.5%), according to the Center for Cancer Control and Information Services. Of these, 20,748 (+8.7%), or 77.9%(77.0% in 2011), were 60 years or older. Of the 865,238 (+1.6%) people diagnosed with cancer, those diagnosed withlymphatic cancer accounted for only 3.1%, but their number increased 71.3% between 2002 and 2012 versus a 51.6% increasein the number of people newly diagnosed with cancer.
Patients newly diagnosed with lymphatic malignancy
30,00025,00020,00015,00010,000

5,000

0

1975

1980

Number of patients
Incidence rate (per 100,000)

1985

1990

1995

2000

2005

2010

1975

1980

1985

1990

1995

2000

2005

2010

4,013

4,741

6,635

9,297

11,195

13,307

16,991

23,919

3.6

4.1

5.5

7.5

8.9

10.5

13.3

18.7

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

Market for anticancer drugs to expand
According to the Fuji Keizai Group, the domestic market potential for anticancer agents was JPY852.3bn in 2014. The market is
growing amid new products going on sale and additional indications, and is expected to hit JPY1.5tn by 2023 (+81.1% from2014).

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 is
4,700. Treakisym sales reached JPY4.7bn (-0.8%) in FY12/16.
The company estimates that the number of Japanese patients receiving first-line treatment for low-grade NHL and MCL is about
7,100 (additional indication approved in FY12/16). The number of Japanese patients with CLL is estimated to be about 700. Thus
the estimate for total number of users and potential users of Treakisym is 7,800. The company estimates that the number ofJapanese patients with relapsed or refractory DLBCL for which the company is considering application for approval of anadditional indication is 6,700.

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Treakisym indications and number of patients
Patients

Indications

Progress

Relapsed or refractory low-grade NHL andrelapsed or refractory MCL

4,700 Approval granted

Untreated low-grade NHL, and untreated MCL

7,100 Approval granted

Relapsed or refractory moderate- to high-gradeNHL

6,700 Clinical trials
underway

Notes
Sales: JPY4.7bn (FY12/16)

Consultation on application
underway

700 Approval granted

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

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

Rituximab (product name: Rituxan)
The drug, co-developed by the US companies IDEC Pharmaceuticals and Genentech, Inc. received US approval in November
1997 as the world’s first monoclonal antibody.
Rituxan consists of a portion of both mouse antibody and IgG, a human antibody. It attaches itself to the CD20 antigen thatappears on B cells in the body and fights tumors through complement-dependent cytotoxicity and antibody‐dependent cell‐
mediated cytotoxicity effects (source: Chugai, Zenyaku Kogyo).
In Japan, Zenyaku Kogyo and Chugai have been jointly selling the drug since September 2001. Chugai’s Rituxan sales were
JPY32.1bn (+10.7% YoY) in FY12/16.

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 effective treatment available.
Rigosertib indications and number of patients
Condition

Patients

Low-risk MDS

7,800

High-risk MDS

3,200

Source: Shared Research based on company data.

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Drugs competing with rigosertib
According to the company, as of February 2017, 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 effective after use for three to six months,
with bone marrow suppression as the main side effect (a decline in white blood cells and platelets). However, while the use of
hypomethylating agents such as azacitidine and decitabine (Dacogen) in the treatment of MDS has improved the outcome ofpatients who tend to have very poor survival, about half of MDS patients do not respond, progress, or relapse at different times
after their response on these HMAs, followed by an extremely poor prognosis.
According to Nippon Shinyaku, Vidaza is the only approved drug in Japan for the first-line treatment of higher-risk MDS, with noeffective treatment available once patients treated with Vidaza relapse. Nippon Shinyaku booked Vidaza sales of JPY12.4bn in
FY03/16 (+14.3% YoY) and expects sales of JPY13.4bn in FY03/17.

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Historical performance
Q1 FY12/17 results
Q1 FY12/17 sales totaled JPY870mn (+350.2% YoY) thanks to sales of Treakisym. The company in December 2016 obtained
approval of an additional indication for Treakisym for untreated low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell
lymphoma (MCL). Sales of Treakisym in Q1 FY12/17, just after the approval, sharply increased from Q1 FY12/16.
Due to the sales increase, gross profit came to JPY239mn (+323.0% YoY). Gross profit margin was 27.5% (-1.7pp YoY). The
decline in GPM was due to a change in the structure of distribution costs stemming from a change in the product mix.
SG&A expenses rose 32.9% YoY to JPY764mn. R&D expenses increased 76.8% to JPY395mn. There were expenses for clinical
trials for the intravenous and oral formulations of Rigosertib Sodium and SyB P-1501. SG&A expenses excluding R&D expenses
were up 5.0% at JPY369mn.
As a result, operating loss totaled JPY525mn (loss of JPY518mn in Q1 FY12/16). The company also reported a recurring loss of
JPY583mn (loss of JPY655mn in Q1 FY012/16) partly due to non-operating expenses of JPY59mn (mainly on forex losses of
JPY55mn). Net loss was JPY583mn (loss of JPY653mn).
Progress in Q1 FY12/17 is as follows.

Domestic
Treakisym (SyB L-0501; 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 refractory or relapsed low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL).
In Q1 FY12/17, sales of Treakisym based on the National Health Insurance (NHI) drug price grew 28.0% YoY, and accordingly
product sales to Eisai increased 312.4%. In December 2016, SymBio obtained approval of an additional indication of Treakisym
for untreated low-grade NHL and MCL. In Q1 FY12/17, just after receiving approval, sales of Treakisym sharply increased YoY.
In addition to the above three approved indications, the company has filed an NDA for a fourth indication to help patients whoneed new treatments and maximize the value of the product. The company has completed phase III clinical trials for relapsed or
refractory diffuse large B-cell lymphoma (DLBCL, or aggressive NHL). At the end of FY12/16, the company had said that it wasconsidering an additional indication, and in Q1 FY12/17, in response to strong medical needs, was in consultation with thePharmaceuticals and Medical Devices Agency and continues to discuss the path forward for approval.
SymBio is exploring further expansion of the Treakisym business by developing an oral formulation in addition to the injection
currently under development or on sale to treat solid tumors and autoimmune diseases.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Regarding these agents, for which a licensing agreement was entered into in July 2011, the company changed their genericname from “Rigosertib” to “Rigosertib Sodium” in accordance with the notice of decision on its Japanese Accepted Names for
Pharmaceuticals (JAN) received in October 2016.
Onconova Therapeutics, Inc., the licensor, is currently conducting a global Phase III trial and SymBio Pharmaceuticals started theJapan trial in December 2015. The global Phase III trial addresses higher risk myelodysplastic syndrome (MDS) patients who do
not respond to treatment or relapsed after treatment with hypomethylating agents (HMAs), the current standard of care(“Primary HMA Failure”) and is under way at clinical trial sites in more than ten countries worldwide. The company has taken
steps to register patients, and completed the first patient enrollment in July 2016. Enrollments are currently accumulating.

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SymBio started domestic Phase I clinical trials for the oral (IV) form of Rigosertib Sodium (used in combination with azacitidine)for higher-risk myelodysplastic syndrome (MDS) in December 2015. Due to delays in the supply of drugs for the joint trials,
patient enrollment has not started as of May 11, 2017. According to the company, however, it was resolving the issue of delays.
The company is looking to start patient registration upon resolution of this issue, and to complete joint trials in line with its plans.
SymBio is considering participating in the global clinical trial to be conducted by Onconova.

SyB P-1501, a post-operative patient-controlled analgesia
The company started a domestic phase III clinical trial for SyB P-1501—licensed by the Medicines Company (through its wholly
owned subsidiary Incline Therapeutics)—for the short-term management of acute post-operative pain during hospitalization inJune 2016. The company enrolled the first patient in November 2016 and was making progress with case accumulation. However,in a report submitted to the US Securities and Exchange Commission in May 2017, The Medicines Company said that it intends toconsider a business alliance or divestiture regarding SyB P-1501. It also said that if it fails to complete an acceptable deal during
Q2 (April–June 2017), it may choose to discontinue the commercialization of SyB P-1501. In the interests of patient welfare,
SymBio has suspended further patient enrollment since April 21, 2017 because of the concerns raised about the continuity of The
Medicines Company’s SyB P-1501 business.

New drug candidates
From a long-term perspective, SymBio will continue to search for and evaluate promising drug candidates, and acquire global
rights for these drugs to become a sustainable and profitable pharmaceutical company with growth potential and profitability.
Further, in May 2016, the company established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic basefor overseas business development. The company looks to leverage this subsidiary to actively acquire rights over new drug
development candidates globally, and engage in development and commercialization in major markets including the US, Japan,
and Europe to transition to a global specialty pharmaceutical company.

Overseas
The company marketed Treakisym in Korea, Taiwan, and Singapore, and overseas sales were steady.

FY12/16 results
FY12/16 sales totaled JPY2.4bn (+22.5% YoY) thanks to domestic sales of Treakisym (SyB L-0501). Products sales totaled JPY2.1bn(+10.6%). It also booked a royalty revenue of JPY230mn (zero in FY12/15) resulting from achieving the sales milestone of SyB
L-0501 in Taiwan.
SG&A expenses fell 3.3% YoY to JPY3.0bn. R&D expenses fell to JPY1.7bn (-18.1% YoY). There were expenses for clinical trials for
TREAKISYM®, the intravenous and oral formulations of Rigosertib Sodium, and SyB P-1501 (patient-controlled analgesia for pain
management), but declined from FY12/15, when the company booked costs for licensing-in SyB P-1501. The company set an
initial R&D expense budget of JPY2.2bn, but spent less than planned because of delays with the development of the oral
formulation of rigosertib sodium. SG&A expenses excluding R&D expenses were up 24.0% at JPY1.4bn.
As a result, operating loss totaled JPY2.1bn (loss of JPY2.6bn in FY12/15). The company also reported a recurring loss of JPY2.3bn(loss of JPY2.6bn last year) partly due to non-operating expenses of JPY196mn (mainly on forex losses of JPY159mn). Net loss was
JPY2.3bn (loss of JPY2.6bn).

Domestic
Treakisym (SyB L-0501; 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 refractory or relapsed low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL).
Though product sales based on the National Health Insurance (NHI) drug price declined slightly by 0.8% YoY, product sales toEisai were largely in line with plan.

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Regarding chronic lymphocytic leukemia (CLL), the company filed an NDA in December 2015, and obtained approval for the
additional indication in August 2016. The company developed and applied for this indication upon request of the Ministry of
Health, Labour and Welfare in Japan as one of the “Unapproved or Off-Labeled Drugs with High Medical Needs.” This is thesecond approval after the approval of an sNDA for the indication of refractory/relapsed low-grade NHL and mantle cell lymphoma
which the company has already received in October 2010.
In Japan, the company submitted a new drug application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA)
in December 2015 for a first-line treatment of low-grade NHL and MCL and obtained approval for the additional indication in
December 2016. Meanwhile, in Europe, though the company received notification on January 2016 from Astellas Pharma that its
application had been withdrawn, it continued with the domestic approval process upon consulting with the PMDA, resulting in
the approval of the additional indication.

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Regarding these agents, for which a licensing agreement was entered into in July 2011, the company changed their genericname from “Rigosertib” to “Rigosertib Sodium” in accordance with the notice of decision on its Japanese Accepted Names for
Pharmaceuticals (JAN) received in October 2016. Onconova Therapeutics, Inc., the licensor, is currently conducting a global
Phase III trial and SymBio Pharmaceuticals started the Japan trial in December 2015. The global Phase III trial addresses higher risk
myelodysplastic syndrome (MDS) patients who do not respond to treatment or relapsed after treatment with hypomethylating
agents (HMAs), the current standard of care (“Primary HMA Failure”) and is under way at clinical trial sites in more than ten
countries worldwide. The company has taken steps to register patients, and completed the first patient enrollment in July 2016.
Enrollments are currently accumulating.
SymBio started domestic Phase I clinical trials for the oral (IV) form of Rigosertib Sodium (used in combination with azacitidine)for higher-risk myelodysplastic syndrome (MDS) in December 2015. Due to delays in the supply of drugs for the joint trials,
patient enrollment has not started as of November 11, 2016. The company is looking to start patient registration upon resolutionof this issue, and complete joint trials in line with its plans. SymBio is considering participating in the global clinical trial to be
conducted by Onconova.

SyB P-1501, a post-operative patient-controlled analgesia
The company started a domestic phase III clinical trial for SyB P-1501—licensed by the Medicines Company (through its wholly
owned subsidiary Incline Therapeutics)—for the short-term management of acute post-operative pain during hospitalization inJune 2016. The company is looking to complete the phase III clinical trial quickly, and obtain regulatory approval in 2019.

New drug candidates
From a long-term perspective, SymBio will continue to search for and evaluate promising drug candidates, and acquire global
rights for these drugs to become a sustainable and profitable pharmaceutical company with growth potential and profitability.
Further, in May 2016, the company established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic basefor overseas business development. 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 accelerate the process of turning into a global specialty pharmaceutical company.

Overseas
The company marketed Treakisym in Korea, Taiwan, and Singapore, and overseas sales were steady.

Q3 FY12/16 results
Cumulative Q3 FY12/16 sales totaled JPY1.4bn (+5.6% YoY) thanks to domestic sales of Treakisym. Product sales through Eisai
were largely in line with forecasts, and products sales rose 3.3%. It also booked a non-recurring revenue resulting from achieving
the sales milestone of SyB L-0501 in Taiwan.

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In cumulative Q3 FY12/16 sales reached 60.2% of the company’s full-year target (vs. 68.9% in the same period the previous year).
In Q4 the company expects to generate product sales after gaining approval to add an indication for Treakisym®. In August 2016,
the company obtained approval to add chronic lymphocytic leukemia (CLL) as an indication and is in the process of applying forthe additional indications as a first-line treatment of low-grade malignant non-Hodgkin's lymphoma and mantle cell lymphoma as
indications. Gaining approval for these indications should significantly boost sales.
SG&A expenses rose 45.4% YoY to JPY2.0bn. R&D expenses rose to JPY981mn (+64.1% YoY) primarily due to expenses
associated with obtaining the approval for the additional indications of TREAKISYM®, the clinical trial for the intravenous and oral
formulations of Rigosertib Sodium, and preparations for the clinical trial of SyB P-1501. SG&A expenses excluding R&D expenses
were up 31.2% at JPY1.0bn on expenses for the introduction of new development candidates and expenses for acquisition ofcompanies that own the rights to new drug candidates.
As a result, operating loss totaled JPY1.5bn (loss of JPY988mn in Q3 FY12/15). The company also reported a recurring loss of
JPY1.9bn (loss of JPY1.1bn last year) due to non-operating expenses of JPY391mn (mainly on forex losses of JPY356mn). Net loss
was JPY1.9bn (loss of JPY1.1bn).

Domestic
Treakisym (SyB L-0501; 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 refractory or relapsed low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL). In Q3,
product sales to Eisai were largely in line with plan.
In Japan, the company submitted a new drug application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency(PMDA) in December 2015 for a first-line treatment of low-grade NHL and MCL. Meanwhile, in Europe, though the company
received notification on January 2016 from Astellas Pharma that its application had been withdrawn, it plans to continue
with the domestic approval process upon consulting with the PMDA.

On November 24, 2016, the Ministry of Health, Labour and Welfare hosted a meeting for Drug Section Two of the Pharmaceutical
Affairs and Food Sanitation Council. One topic at the meeting was on setting the re-examination period and on whether to allow
partial modifications to the approved manufacturing and marketing of drug products TREAKISYM® Intravenous Infusion 25 mg
and 100 mg. Shared Research understands that the council discussed the approval of additional indications and that if it isapproved, SymBio will be notified after a predetermined period of time.
According to the company, over 7,100 people have low-grade malignant non-Hodgkin's lymphoma and mantle cell lymphoma
for first-line treatment, and over 4,700 people suffer from relapsed or refractory low-grade malignant non-Hodgkin's lymphoma
and mantle cell lymphoma. With these numbers, we believe that adding indications as first-line treatment of low-grade malignant
non-Hodgkin's lymphoma and mantle cell lymphoma to Treakisym® would significantly boost product sales.
Regarding chronic lymphocytic leukemia (CLL), the company filed an NDA in December 2015, and obtained approval for the
additional indication in August 2016. The company developed and applied for this indication upon request of the Ministry of
Health, Labour and Welfare in Japan as one of the “Unapproved or Off-Labeled Drugs with High Medical Needs.” This is thesecond approval after the approval of an sNDA for the indication of refractory/relapsed low-grade NHL and mantle cell lymphoma
which the company has already received in October 2010. According to the company, there are 700 people suffering fromchronic lymphocytic leukemia (CLL).

Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: Rigosertib Sodium)
Regarding these agents, for which a licensing agreement was entered into in July 2011, the company changed their genericname from “Rigosertib” to “Rigosertib Sodium” in accordance with the notice of decision on its Japanese Accepted Names for
Pharmaceuticals (JAN) received in October 2016. Onconova Therapeutics, Inc., the licensor, is currently conducting a global
Phase III trial and SymBio Pharmaceuticals started the Japan trial in December 2015. The global Phase III trial addresses higher risk

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myelodysplastic syndrome (MDS) patients who do not respond to treatment or relapsed after treatment with hypomethylating
agents (HMAs), the current standard of care (“Primary HMA Failure”) and is under way at clinical trial sites in more than ten
countries worldwide. The company has taken steps to register patients, and completed the first patient enrollment in July 2016.
Enrollments are currently accumulating.
SymBio started domestic Phase I clinical trials for the oral (IV) form of Rigosertib Sodium (used in combination with azacitidine)for higher-risk myelodysplastic syndrome (MDS) in December 2015. Due to delays in the supply of drugs for the joint trials,
patient enrollment has not started as of November 11, 2016. The company is looking to start patient registration upon resolutionof this issue, and complete joint trials in line with its plans. SymBio is considering participating in the global clinical trial to be
conducted by Onconova.

SyB P-1501, a post-operative patient-controlled analgesia
The company started a domestic phase III clinical trial for SyB P-1501—licensed by the Medicines Company (through its wholly
owned subsidiary Incline Therapeutics)—for the short-term management of acute post-operative pain during hospitalization inJune 2016. In November 2016, the first patient completed registration. The company is looking to complete the phase III clinical
trial quickly, and obtain regulatory approval in 2019.

New drug candidates
From a long-term perspective, SymBio will continue to search for and evaluate promising drug candidates, and acquire global
rights for these drugs to become a sustainable and profitable pharmaceutical company with growth potential and profitability.
Further, in May 2016, the company established SymBio Pharma USA, Inc., a wholly owned US-based subsidiary, as a strategic basefor overseas business development. 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 accelerate the process of turning into a global specialty pharmaceutical company.

Overseas
The company marketed Treakisym in Korea, Taiwan, and Singapore, and saw overseas sales progress largely in line with plans in
Q1 because shipments to overseas clients are planned from Q3 and after.

FY12/15 results
FY12/15 sales totaled JPY1.9bn (-1.1% YoY) due to domestic and overseas sales of SyB L-0501 (Treakisym).
Treakisym domestic sales rose 24.0% YoY, but overseas sales fell 76.1% on factors including the earlier booking of orders in Korea
in FY12/14.
SG&A expenses rose 71.3% YoY to JPY3.1bn due to expenses incurred for clinical trials for oral and intravenous rigosertib andTreakisym, and the booking of R&D expenses of JPY2.0bn (+162.8%) in conjunction with the in-licensing expenses for SyB P-1501(IONSYS for post-operative patient-controlled analgesia) and “other” SG&A expenses of JPY1.1bn (+4.2%).
As a result, operating loss totaled JPY2.6bn (versus a loss of JPY1.3bn the preceding year). The company also reported a recurring
loss of JPY2.6bn (JPY1.1bn loss) due to non-operating expenses of JPY96mn (mainly on forex losses of JPY86mn). Net loss totaled
JPY2.6bn (JPY1.1bn loss the preceding year).
Progress towards FY12/16 targets is as follows.

Domestic
Treakisym (SyB L-0501; 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 refractory or relapsed low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL). Sales throughEisai increased as expected. NHI price-based sales rose 10.3% YoY.

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Phase II clinical trial of Treakisym for the first-line treatment of low-grade NHL and MCL had already been completed and thecompany submitted a new drug application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) in December
2015. Meanwhile, in Europe, review of the application by Astellas Pharma is under way by European authorities.
Regarding the phase II clinical trial for chronic lymphocytic leukemia (CLL), the company filed an NDA in December 2015.
Treakisym was designated as an orphan drug (drug for the treatment of rare diseases) for CLL in June 2012, and the Evaluation
Committee on Unapproved or Off-Labeled Drugs with High Medical Need has also submitted a development request to thecompany.
In addition to the 100mg dosage of Treakisym, SymBio Pharmaceuticals also filed in December 2015 for approval of a smaller
25mg dosage as an amount that could actually be used at medical facilities.
SymBio is still considering applying for approval for use of the drug for relapsed or refractory aggressive NHL.
Rigosertib (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent)
The company is conducting a domestic phase I clinical trial for the intravenous (IV) form of rigosertib in relapsed or refractory
higher-risk myelodysplastic syndromes (MDS), a hematological malignancy. Patient enrollment was completed in January 2015,
and the trial was completed in October 2015.
Onconova Therapeutics, Inc., the U.S. licensor, is currently conducting a global phase III trial and SymBio Pharmaceuticals started
the Japan trial in December 2015. The global phase III trial addresses higher risk MDS patients who do not respond to treatment
with hypomethylating agents (HMAs), the current standard of care (“Primary HMA Failure”) and is under way at clinical trial sites
in more than ten countries worldwide.

SyB P-1501, a post-operative patient-controlled analgesia
In October 2015 SymBio reached an in-licensing agreement with The Medicines Company (through its wholly owned subsidiary
Incline Therapeutics) for the development and commercialization of SyB P-1501, a post-operative patient-controlled analgesia
known as IONSYS in the US. SymBio acquired exclusive development and marketing rights for Japan. Preparations are under way
to start a domestic phase III clinical trial in 2016.

Overseas
The company marketed Treakisym in Korea, Taiwan, and Singapore. Product sales were mostly in line with targets.

FY12/14 results
Sales for FY12/14 totaled JPY2.0bn (+27.6% YoY) due to domestic and overseas shipments of Treakisym.
Sales of Treakisym were JPY1.9bn (+35.5% YoY). Domestic sales totaled JPY1.5bn (+12.9% YoY), while overseas sales were
JPY472mn (up 3.6x). The significant increase in overseas sales was because the company added one year of inventory (JPY273mn)
in South Korea following a change of manufacturing location.
Milestone revenues were JPY15mn (-85% YoY), which the company booked on the approval of Treakisym for the indication of
relapsed or refractory low-grade NHL in Korea.
SG&A expenses were JPY1.8bn (-8.4% YoY), including R&D expenses of JPY774mn (-26.5% YoY). Despite clinical trial expenses
for Treakisym and the oral and IV forms of rigosertib, overall R&D expenses were down year-on-year because clinical trials for
additional indications for Treakisym wound down. Other SG&A expenses totaled JPY1.1bn (+1.6% YoY).
As a result, operating loss totaled JPY1.3bn (FY12/13: loss of JPY1.7bn). The company also reported a recurring loss of JPY1.1bn(FY12/13: loss of JPY1.6bn). The recurring loss narrowed owing to non-operating gains of JPY215mn, including forex gains of

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JPY189mn, JPY16mn in interest received, and JPY8mn from interest on investment securities. Net loss totaled JPY1.1bn (FY12/13:
loss of 1.6bn).

Domestic
Treakisym
SymBio completed the phrase II clinical trial of Treakisym for the first-line treatment of low-grade NHL and MCL in February 2014.
The company is analyzing and evaluating data from the trial as it prepares to file a supplemental new drug application (sNDA) for
marketing approval. Astellas Pharma GmbH (“Astellas”; European subsidiary of Astellas Pharma Inc.; TSE1: 4503) has alreadyapplied for approval in Europe.
The company completed the patient enrollment for a phase II clinical trial for CLL in October 2014. Treakisym was designated as
an orphan drug (drug for the treatment of rare diseases) for CLL in June 2012.
The company is still considering applying for approval for use of the drug for relapsed or refractory aggressive NHL.

Rigosertib
The company is conducting a domestic phase I clinical trial for the intravenous (IV) form of rigosertib in relapsed or refractory
higher-risk myelodysplastic syndromes (MDS).
In February 2014, licensor Onconova Therapeutics, Inc. (“Onconova”; Nasdaq: ONTX) announced the results of its phase III
ONTIME clinical trial in patients with higher-risk MDS. Compared with best supportive care (BSC), the clinical trial did not show astatistically significant improvement in the overall survival period (primary outcome measures). However, group analysis showeda statistically significant difference in the survival period for patients whose condition had deteriorated or those who had not
responded to previous treatment using hypomethylating agents (HMAs).
Onconova held discussions with regulatory agencies in the US and Europe regarding the possibility of seeking approval based on
the results of the phase III trial. The regulators have confirmed that patients who had not responded to HMAs would require a
new treatment. In response, the company announced that it would develop the new treatment. SymBio will continue with its
current phase I clinical trials in Japan. Post-phase I development in Japan will depend on the development in the US and Europe.
A domestic phase I clinical trial using the oral form of rigosertib is also underway in Japan for the treatment of high-risk MDS
patients. The patient enrollment for the trial was completed in August 2014.

Overseas
Bendamustine (domestic product name: Treakisym) was approved in South Korea for the additional indication of relapsed or
refractory low-grade NHL in June 2014. The product is now sold by Eisai’s Eisai Korea Inc. unit. The subsidiary also sells the drugfor two other indications—CLL and multiple myeloma (MM).
In Taiwan, the drug is being marketed by InnoPharmax Inc. In Singapore, Eisai (Singapore) Pte. Ltd. markets the drug. Overseas
sales increased by 2.2 times the estimate after the company added one year of inventory in South Korea in connection with afactory alignment.

FY12/13 results
Treakisym sales in Japan and other parts of Asia were JPY1.5bn (-21.6% YoY) due to adjustments in distribution inventory. Sales to
end users were JPY4.2bn (+7.4% YoY). However, Treakisym sales totaled JPY1.4bn (-26.8% YoY) due to adjustments in Treakisym
distribution inventory at Eisai.
The company earned JPY100mn in royalty revenue (no such revenue was posted a year earlier). The company received milestone
payments associated with the start of the phase II clinical trial for CLL.

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The company posted R&D costs of JPY1.1bn (-26.8% YoY) due to clinical trials for additional Treakisym indications, and rigosertib
indications. R&D costs declined from a year earlier as development for Treakisym nears completion. With other expenses totaling
JPY946mn (+10.6% YoY), total SG&A expenses were JPY2.0bn (-12.9% YoY).
Operating loss was JPY1.7bn (almost unchanged from a year earlier). There were non-operating expenses of JPY35mn associatedwith payment of fees and stock issuance costs. The company posted a non-operating profit of JPY114mn due to currency gains.
Consequently, recurring loss was JPY1.6bn (a loss of JPY1.7bn a year earlier), and net loss was 1.6bn (a loss of JPY1.7bn a year
earlier).

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Income statement
Income statement(JPYmn)Total sales
YoY
CoGS
Gross profit
GPM
SG&A expenses
SG&A-to-sales ratio
Operating profit
YoY
OPM
Non-operating income
Non-operating expenses
Recurring profit
YoY
RPM
Extraordinary gains
Extraordinary losses
Tax charges
Implied tax rate
Net income
YoY
Net margin

FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

Par.
1,191-26.9%
0
1,191
100.0%
1,399
117.5%
-208
20
26
-214
4
-218
-

Par.
1,450
21.7%
238
1,212
83.6%
1,825
125.8%
-613
13
38
-638
0
4
-642
-

Par.
1,883
29.8%
1,224
658
35.0%
2,725
144.8%-2,06756
85-2,0955
4-2,105
-

Par.
1,955
3.9%
1,362
593
30.3%
2,293
117.3%-1,700737-1,7290
4-1,733
-

Par.
1,532
-21.6%
1,214
318
20.8%
1,999
130.4%-1,681114
35-1,6014-1,605
-

Par.
1,955
27.6%
1,428
527
26.9%
1,830
93.6%
-1,303215
22-1,1102
3
4-1,116
-

Par.
1,933
-1.1%
1,350
583
30.2%
3,135
162.1%-2,55217
96-2,6303
1
4-2,632
-

Par.
2,368
22.5%
1,464
904
38.2%
3,031
128.0%-2,1277
196-2,31791
4-2,313-

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

FY12/12
Sales were JPY2.0bn (+3.9% YoY). Product sales were JPY2.0bn (+19.8% YoY) due to an increase in Treakisym sales to end users,
which totaled JPY3.9bn (+16.2% YoY). The company did not receive any royalty revenue.
SG&A expenses were JPY2.3bn (-15.8% YoY). R&D costs totaled JPY1.4bn (-26.1% YoY), which included the cost of clinical trials
for additional Treakisym indications and rigosertib. The company, which made one-time payments for the acquisition ofrigosertib a year earlier, did not make such payments, slashing R&D expenses.

FY12/11
Sales were JPY1.9bn (+29.8% YoY). Product sales were JPY1.6bn (+401.3% YoY). Sales of Treakisym to end users were JPY3.4bn(JPY64mn in FY12/10). Royalty revenues were JPY250mn. The company received milestone payments associated with the start ofdomestic development of first-line low-grade non-Hodgkin’s lymphoma and mantle-cell lymphoma, plus the marketing approvalof Treakisym in South Korea and Taiwan.
SG&A expenses were JPY2.7bn (+49.4% YoY). R&D costs were JPY1.9bn (+73.9% YoY). The company conducted clinical trials for
additional Treakisym indications and SyB D-0701 (antiemetic transdermal patch for RINV). The company also made one-time
payments for the acquisition of rigosertib rights (both IV and oral).

FY12/10
Sales were JPY1.5bn (+21.7% YoY). Product sales were JPY326mn (no product sales a year earlier). The company began to postproduct sales as it started to sell Treakisym in Japan. Royalty revenue totaled JPY1.1bn. The company received milestone
payments from Eisai associated with the marketing approval of Treakisym in Japan, marketing approval of Symbenda in Singapore,and the start of the phase II clinical trial for multiple myeloma in Japan.
SG&A expenses were JPY1.8bn (+30.4% YoY). R&D costs were JPY1.1bn (+36.9% YoY), which included spending for clinical trials,
preparation for additional Treakisym indications and the clinical trial for SyB D-0701 (antiemetic transdermal patch for RINV). The
company made one-time payments for SyB 0702 (HSP32 inhibitor).

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FY12/09
Sales were JPY1.2bn (-26.9% YoY), all from royalty revenues. The pivotal phase II clinical trial for Treakisym targeting low-grade
NHL and MCL patients who had received prior treatment was completed in March 2009. The company submitted an application
for accelerated marketing approval of Treakisym in October 2009 (receiving orphan drug designation with 10-year marketingexclusivity once approved).
SG&A expenses were JPY1.4bn (-6.5% YoY). R&D costs were JPY817mn (-5.9% YoY). The company sought to develop its productpipeline with emphasis on phase II clinical trials for additional indications of Treakisym, and phase I clinical trial for the
combination therapy of Treakisym plus rituximab in first-line low-grade NHL and MCL.

FY12/08
Sales were JPY1.6bn (no sales for FY12/07). All sales were comprised of royalty revenue. In August 2008, the company enteredinto a license agreement with Eisai for the co-development and exclusive marketing right to Treakisym in Japan. SymBio received
one-time payments for the agreement. SG&A expenses: JPY1.5bn. R&D expenses: JPY868mn.

Historical forecast accuracy
Initial CE vs. results(JPYmn)Sales (Initial CE)
Sales (Results)
Initial CE versus Results

FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

-

-

1,933

2,338

1,927

1,785

1,785

2,339

FY12/16

-

-

1,883

1,955

1,532

1,955

1,933

2,368

-

-

-2.6%

-16.4%-20.5%

9.5%

8.3%

1.2%

Operating profit (Initial CE)---2,351-1,625-1,889-1,654-1,654-2,778Operating profit (Results)---2,067-1,700-1,681-1,303-2,552-2,127

Initial CE versus Results

-

-

-

-

-

-

-

-

-

-

-2,398-1,652-1,922-1,650-1,650-2,811-2,317

Recurring profit (Initial CE)
Recurring profit (Results)---2,095-1,729-1,601-1,110-2,630Initial CE versus Results

-

-

-

-

-

-

-

-

Net income (Initial CE)---2,407-1,656-1,926-1,654-1,654-2,815

Net income (Results)---2,105-1,733-1,605-1,116-2,632-2,313

Initial CE versus Results

-

-

-

-

-

-

-

-

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

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Balance sheet
FY12/09

FY12/10

FY12/11

FY12/12FY12/13

FY12/14

FY12/15

FY12/16

Par.

Par.

Par.

Par.

Par.

Par.

Par.

Par.

3,902
219
0
0
97
4,218
3
11
13
27
2
0
2
42
4,261

2,314
1,701
6
0
191
4,213
3
19
22
27
1
0
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
0
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
0
301
133
131
4,827
22
31
53
53
51
1
52
158
4,984

5,719
0
487
273
205
6,685
31
43
75
77
42
0
42
193
6,878

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

0
182
0
23
205
0
2
2
0
207
4,060
3,378
3,348
-2,666
0
4,054

1
124
0
52
178
0
2
2
0
180
4,083
3,711
3,681
-3,309
0
4,083

309
278
0
59
646
0
5
5
0
651
6,606
6,025
5,995
-5,413
0
6,606

330
196
0
73
599
0
4
4
0
602
4,873
6,025
5,995
-7,146
27
4,900

0
207
0
44
251
0
3
3
0
254
7,336
8,059
8,029
-8,752
97
7,433

306
143
0
39
488
0
2
2
0
490
6,764
8,331
8,301
-9,868
200
6,964

320
184
0
47
551
0
2
2
0
552
4,132
8,331
8,301
-12,500
300
4,432

322
553
0
68
942
0
451
451
0
1,394
5,054
9,948
9,918
-14,813431
5,485

Working capital
Total interest-bearing debt
Net debt

00-3,90250-2,31461
0-4,559-17
0-4,540125
0-6,163212
0-5,692114
0-4,261438
0-5,719Balance 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

Source: Shared Research based on company data.
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. In FY12/16, thecompany booked corporate bonds totaling JPY450mn under fixed liabilities. This is the unexercised portion of its third unsecured
bonds with convertible bond type stock acquisition rights (issued in April 2016, total value: JPY3.0bn, no interest on bonds).

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

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

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

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

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

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

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

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

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

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

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

4
-3
-217

7
-14
5
-655

8
-12
56
-2,1659-3-78-1,6508
142-1,73913-109
86-1,29824-24-98-2,53426-28
324-2,640Cash and cash equivalents (year-end)

4,121

3,916

6,311

4,240

5,294

5,092

4,261

5,719

Source: Shared Research based on company data.
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
Purchases of tangible fixed assets and intangible assets are limited as SymBio outsources manufacturing, clinical development,
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 the redemptionof securities.

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

Change in shares Total sharesissuedissuedChange 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 (pricedetermined by 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 (pricedetermined by 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

Source: Shared Research based on company data.

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

After its establishment, SymBio obtained financing totaling JPY1bn from Daiichi Pharmaceutical Co., Ltd. (now Daiichi Sankyo,
Inc.; TSE1: 4568), Medical & Biological Laboratories Co., Ltd. (JASDAQ: 4557), EPS Corporation (TSE1: 4282), and SBI Holdings,
Inc. (TSE1: 8473). The company used the cash raised to in-license its first drug candidate, bendamustine hydrochloride, from
Astellas Pharma GmbH in December 2005 with the exclusive right to develop and commercialize the drug in Japan.
After the global financial crisis of September 2008, the company experienced a shortage of capital as Treakisym was advancing in
the clinic. Mr. Yoshida visited at least 50 venture capital firms in Japan and elsewhere in December 2008, eventually raising
JPY1.5bn in capital from Cephalon, Inc. (acquired by Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) in October 2011).
SymBio obtained Japanese marketing and manufacture approval for Treakisym in October 2010 and began domestic sales in
December of that year.
As of February 2017, Treakisym for relapsed or refractory low-grade NHL and MCL is the company’s mainstay product. Clinical
trials are also under way toward attaining domestic approval for additional Treakisym indications, anti-cancer drug rigosertib for
myelodysplastic syndromes, and SyB P-1501, a patient-controlled analgesia for pain management.

March 2005

SymBio Pharmaceuticals Limited established with JPY30mn in capital.

December 2005

License Agreement finalized with Astellas Pharma GmbH for SyB L-0501 (bendamustine) development andcommercialization rights in Japan.

March 2006
March 2007
March 2007
August 2008
March 2009
May 2009
September 2010

Manufacturer's License (packaging, labeling and storage) obtained from Tokyo Metropolitan Government (License#13AZ200010).
Abeille Pharmaceuticals licensed SyB D-0701 (granisetron patch) to SymBio Pharmaceuticals for development &commercialization in Japan, China (HK), Taiwan, Korea and Singapore.
License Agreement finalized with Astellas Deutschland GmbH for SyB L-0501 (bendamustine) development &commercialization rights in China (HK), Taiwan, Korea and Singapore.
License Agreement finalized with Eisai Co., Ltd. for co-development and commercialization rights of SyB L-0501(bendamustine) in Japan.
SymBio Pharmaceuticals concluded Sublicense Agreement with Cephalon, Inc. for development and commercializationrights of bendamustine hydrochloride in China (HK).
License Agreement finalized with Eisai Co., Ltd. for co-development and commercialization rights of SyB L-0501(bendamustine) in Korea and Singapore.
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

Ⅲ stage multi-kinase inhibitor for Myelodysplastic Syndromes).

Onconova and SymBio Pharmaceuticals completed License Agreement for SyB L-1101/SyB C-1101 (rigosertib, a Phase

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October 2011

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

October 2011

Listed on Osaka Securities Exchange JASDAQ Growth Market.

February 2012

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

October 2015
August 2016
December 2016

Obtained exclusive development and marketing rights to Ionsys (patient-controlled analgesia system) in Japan from The
Medicines Company (US).
Received approval for Chronic Lymphocytic Leukemia to be added as indication for TREAKISYM®.
Announced approval of the anti-cancer drug TREAKISYM® for the additional indication of first-line treatment of low-grade
non-Hodgkin's lymphoma and mantle cell lymphoma.

News and topics
June 2017
On June 30, 2017, the company announced that it has initiated in Japan a phase I clinical trial of single-agent oral rigosertib in
higher-risk myelodysplastic syndromes (MDS).
The company initiated the phase I clinical trial since Onconova Therapeutics, Inc., the licensor for oral rigosertib, resumed the
supply of clinical trial materials after completing a change of manufacturing sites.
The purpose of the Japanese phase I study is to confirm the safety of high-dose oral rigosertib, which was added to the ongoingoverseas phase II study by Onconova in untreated or relapsed/refractory patients with higher-risk MDS. After demonstrating thesafety of high-dose oral rigosertib, SymBio intends to immediately recommence an oral rigosertib/azacitidine combination trial in
Japan, and participate in the global phase III study in untreated higher-risk MDS patients that Onconova is planning. In initiating
the subject phase I study, SymBio has terminated the phase I combination study for oral rigosertib/azacitidine.
The enrollment of patients is currently underway in the global phase III clinical trial for the intravenous version of rigosertib in
relapsed/refractory patients with higher-risk MDS, which SymBio has been taking part in.
The initiation of this phase I study will not impact the company’s FY12/17 forecasts.

On June 5, 2017, the company announced a US SEC filing (Form 8-K) by The Medicines Company as the licensor of thepatient-controlled pain management drug SyB P-1501.
On May 11, 2017, the company announced it has suspended further registration of new patients in a domestic phase III clinical
trial of SyB P-1501 indicated for the short-term management of acute post-operative pain during hospitalization. In relation to this,the Medicines Company, the licensor of this product, filed a Form 8-K with the US Securities and Exchange Commission on June 2,
2017.
The Form 8-K states that The Medicines Company commenced implementation of a workforce reduction on June 1, 2017 inconnection with the discontinuation and market withdrawal of IONSYS® (US product name of SyB P-1501) in the US and thecessation of related commercialization activities, while the New Drug Application for IONSYS® is to remain open until December
31, 2017.
SymBio will discuss with The Medicines Company the effects of the 8-K filing on the clinical trial plan of SyB P-1501 and plans tomake timely disclosures accordingly.

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May 2017
On May 11, 2017, the company announced that it has suspend further patient enrollment for the phase III trial of SyB P-1501(patient-controlled analgesia for pain management).
SymBio decided to suspend further registration of new patients in a domestic phase III trial of SyB P-1501 indicated for the
short-term management of acute post-operative pain during hospitalization.
In a quarterly report submitted to the US Securities and Exchange Commission (SEC) in May 2017, The Medicines Company, thelicensor of SyB P-1501, stated that it was considering a business alliance or company split for the SyB P-1501 business and that it
may suspend commercialization of the agent unless an acceptable agreement is concluded by Q2 FY12/17 (April–June 2017).
SymBio started the domestic phase III trial of SyB P-1501 in June 2016, enrolled the first patient in November, and has madeprogress with case accumulation. However, on April 21, 2017, The Medicines Company notified the company of its intentions as
outlined in the quarterly report. SymBio, which is committed to the primacy of patient welfare, interrupted patient enrollment on
the same day given concerns about the continuity of The Medicines Company’s SyB P-1501 business. Accordingly, SymBio
notified medical institutions participating in the study and the Pharmaceuticals and Medical Devices Agency (PMDA) that it
would suspend further patient enrollment.
SymBio will not register new patients in the trial until The Medicines Company makes a further announcement about thecommercialization of SyB P-1501. The company intends to disclose without delay any impact on the implementation plan of thetrial if an announcement is made.

February 2017
On February 24, 2017, the company announced a notice concerning the appointment of a representative director.
At a Board of Directors’ meeting held on the same day, the company decided to formally propose the approval of theappointment of a new representative director at its ordinary general meeting of shareholders to be held on March 29, 2017, andat a Board of Directors’ meeting to be held immediately following the shareholders meeting.
Change of positions
Name

New position

Current position

Kazuo Asakawa

Representative Director, Executive Vice President,
COO, and Head of the Japan Business Unit

Corporate Officer, Executive Vice President, COO,
and Head of the Japan Business Unit

January 2017
On January 31, 2017, the company announced the sales launch in Japan of the anti-cancer drug TREAKISYM® Intravenous
Infusion 25 mg.
The company, through Eisai Co., Ltd. (Eisai), launched sales in Japan on January 31, 2017 of TREAKISYM® Intravenous Infusion 25
mg, a standard low-dose product (non-proprietary name: bendamustine hydrochloride) for the treatment of low-grade B-cell
non-Hodgkin’s lymphoma and mantle cell lymphoma, and chronic lymphocytic leukemia. Based on a license agreement between
the company and Eisai, Eisai will be exclusively in charge of marketing the drug.

December 2016
On December 19, 2016, the company announced approval of the anti-cancer drug TREAKISYM® for the additional indication of
first-line treatment of low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma.
SymBio obtained approval for the additional indication of first-line treatment of this disease after filing a new drug application on
previously untreated patients in December 2015, based on the results of a domestic Phase 2 clinical trial and the outcome of an
overseas Phase 3 clinical trial. The company made no changes to its forecast of FY12/16 earnings based on this approval for
manufacturing and marketing of the drug.

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On December 9, 2016, Shared Research updated the report following interviews with the company.
On December 6, 2016, the company announced that Onconova presented Phase 2 clinical trial data on oral rigosertib at the2016 American Society of Hematology (ASH).
SymBio began handling the anticancer drug rigosertib in July 2011. Onconova Therapeutics, Inc., the drug’s licensor, presented
Phase 2 clinical trial data on oral rigosertib for patients with higher-risk myelodysplastic syndromes (MDS) at the 58th American
Society of Hematology (ASH) Annual Meeting in San Diego, California. The meeting lasted from December 3 to 6.
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.
The international joint Phase 3 clinical trial is currently underway for patients with relapsed or refractory higher-risk MDS.
Onconova is also making efforts toward finalizing the design for a pivotal Phase 3 oral rigosertib/azacitidine combination trial forhigher-risk MDS patients.

November 2016
On November 10, 2016, the Ministry of Health, Labour and Welfare announced it will host a meeting of the Drug Section Twoof the Pharmaceutical Affairs and Food Sanitation Council on November 24, 2016. One topic at the meeting will be on setting there-examination period and on whether to allow partial modifications to the approved manufacturing and marketing of drug
products TREAKISYM® Intravenous Infusion 25 mg and 100 mg.
As was announced in December 2015, the company applied for approval of the anti-cancer drug TREAKISYM® for additional
expected indications of mantle cell lymphoma and low-grade malignant non-Hodgkin's lymphoma for first-line treatment.

September 2016
On September 28, 2016, the company announced that anti-cancer drug TREAKISYM® Intravenous Infusion 100 mg received
approval for manufacturing and marketing in Japan.
The company received approval to manufacture and market TREAKISYM® Intravenous Infusion 25 mg, a standard low-dose
product of the anti-cancer drug TREAKISYM® (non-proprietary name: bendamustine hydrochloride) in Japan. It received approval
to manufacture and market TREAKISYM® Intravenous Infusion 100 mg for the indication of recurrent/refractory low-grademalignant non-Hodgkin's lymphoma and mantle cell lymphoma in October 2010, which has been marketed through Eisai Co.,
Ltd. since December 2010. Also, the additional indication of chronic lymphocytic leukemia was granted in August 2016.
There are no changes in the earnings forecasts for FY12/16 based on this approval.

August 2016
On August 26, 2016, the company announced that it had obtained the approval for additional indications of anti-cancer drug
Treakisym in chronic lymphocytic leukemia (CLL).
SymBio had applied for approval for the additional indication in response to a request from the Ministry of Health, Labour andWelfare for its development as one of the “unapproved or off-labeled drugs with high medical needs.” The company had alreadyreceived approval in October 2010 for manufacturing and marketing of Treakisym for the indication of relapsed or refractory
low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma (MCL). Treakisym, marketed by Eisai Co., Ltd. (Eisai) since

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December 2010, has obtained about 60% market share for the indication of relapsed or refractory low-grade NHL and MCL,
according to the company’s estimation. The company expects Treakisym to be a new treatment option for many CLL patients.
The company also applied for approval for additional indications of Treakisym in first-line treatment for low-grade NHL and MCL
in December 2015, and the application is currently being reviewed. Further, the company has completed phase II clinical trial for
relapsed or refractory Diffuse large B-cell lymphoma (DLBCL, or aggressive NHL). The company looks to expand the indication ofTreakisym and pursue the full range of its use, aiming to maximize the value of the product.
There are no changes in the earnings forecasts for FY12/16 based on this additional approval.

July 2016
On July 11, 2016, the company announced the achievement of a sales milestone in Taiwan for the anti-cancer drug
bendamustine and the receipt of a milestone payment.
InnoPharmax has exclusive development and marketing rights for bendamustine in Taiwan, and sells bendamustine under thebrand name Innomustine (Japanese brand name: Treakisym Injection). Since the launch of the product in 2012, total net sales
have exceeded EUR2.4mn, which will result in a milestone payment from InnoPharmax to SymBio. In October 2011, the Taiwan
Food and Drug Administration granted InnoPharmax manufacturing and marketing authorization for bendamustine for theindication of low-grade malignant non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. InnoPharmax has been selling
the product in Taiwan since February 2012.
This will have no impact on SymBio’s earnings forecast for FY12/16.

June 2016
On June 13, 2016, the company announced the start of phase III clinical trials for the patient-controlled analgesia, SyB P-1501.
The company started phase III clinical trials for SyB P-1501—a patient controlled analgesia for the short-term management of
acute postoperative pain during hospitalization.
The company obtained exclusive development and commercialization rights for the drug in Japan from the Medicines Company
in October 2015. The product, launched in the US, was approved by the US Food and Drug Administration (FDA) in April 2015,
and also approved by the European Medicines Agency (EMA) in November 2015.
SymBio will proceed with phase III clinical trials, and hopes to obtain manufacturing and marketing approval for the drug in Japan
in 2019.

April 2016
On April 6, 2016, the company announced the issue of a third series unsecured convertible bonds with subscription rights to
new shares, and series 39 subscription rights to new shares by third-party allotment.
The company expects to receive total funds of about JPY3.9bn, net of expenses. The company plans to use the funds for expenses
related to the development of new drug candidates between April 2016 and December 2018. As of April 6, 2016, SymBio was
negotiating license agreements for several new drug candidates with client companies. The amount of funding required is basedon costs to acquire rights to new drug candidates or to acquire companies with new drug candidates, as well as estimateddevelopments costs, primarily those required to conduct clinical trials upon acquiring companies with new drug candidates or
acquiring rights to new drug candidates.

Overview of the offering
Third series of unsecured convertible bonds with subscription rights to new shares▷ Payment date:

April 22, 2016

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Research Coverage Report by Shared Research Inc. | www.sharedresearch.jp▷ Number of stock subscription rights:

40 units▷ Issue price of stock subscription rights:

Gratis▷ Issue price of bonds:▷ Number of potential shares:

JPY75mn (JPY100 per JPY100 par value)

14,218,000▷ Total funding amount:

JPY3.0bn▷ Subscription and allocation method:

Issued to Whiz Healthcare Japan 2.0 Investment Limited Partnership via third-party▷ Conversion price:

JPY211

allotment.

Series 39 subscription rights to new shares▷ Allotment date:

April 22, 2016

▷ Number of stock subscription rights:

104 units▷ Number of potential shares:

4,472,000▷ Issue price:▷ Total funding amount:

JPY10mn (JPY94,000 per unit)

JPY953mn(JPY10mn from the issue of subscription rights to new shares; JPY944mn from theexercise of subscription rights)▷ Exercise price:▷ Subscription and allocation method:

JPY211
Issued to Whiz Healthcare Japan 2.0 Investment Limited Partnership via third-party
allotment.

February 2016
On February 8, 2016, the company announced that it had signed an agreement with Teikyo Heisei University to jointly researchand develop an innovative anti-cancer drug which uses the TTR1 nano-agonist molecule¹.
Based on the agreement, the company will provide resources to implement preclinical and IND-enabling studies in collaboration
with Teikyo Heisei University. SymBio also acquired the right to enter into an exclusive license agreement with Teikyo Heisei
University to globally develop and commercialize this innovative drug globally.
The team led by Dr. Isao Ishida, Professor of the Faculty of Pharmaceutical Sciences, Teikyo Heisei University, discovered an
antibody that acts against TRAIL-R1, which is an expression on the surface of cancer cells or cancer stem cells, and modified it toimpart more efficient anti-cancer activity (TTR1 nano-agonist). A drug delivery technique using an expression system in
Bifidobacterium² was developed that enables the TTR1 nano-agonist to act selectively on hypoxic cancer tissue. The anti-cancer
activity and safety of this new anti-cancer drug has been confirmed in animal models.
The impact of this agreement has been factored into the company’s FY03/16 forecast that will be released when it announces
FY12/15 results (February 10, 2016) and so will not have a significant impact on its FY12/16 earnings.
TTR1 nano-agonist¹: Member of the tumor necrosis factor (TNF) family that exerts its apoptotic activity in human cells when it trimerizes by binding
to its transmembrane receptors, TRAIL-R1 and TRAIL-R2. It is difficult to form a trimeric structure using conventional anti-TRAIL-R1antibodies, and thus
apoptosis-inducing ability is typically weak. Camelids (e.g. camels, alpacas, llamas) produce functional antibodies devoid of light chains of which thesingle N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments (VHHs or sdAb) have several advantages forbiotechnological applications: they are well expressed in microorganisms, have a high stability and solubility, and can penetrate tissues relatively easily.
Trivalent anti-TRAIL-R1 single-domain antibodies (TTR1: an abbreviation for Trivalent anti-TRAIL-R1) used in our collaboration have agonistic activities
and induce apoptosis, thus we call them TTR1 nano-agonist(s).
Bifidobacterium²: Genus of Gram-positive bacteria, and are one of the major genera of bacteria that make up the colon flora in mammals, withprobiotic activity limited to anaerobic environments. Bifidobacterium strains are important probiotics and widely used in the food industry (e.g.

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yogurt). As many types of cancer (specifically solid tumors such as pancreatic cancer) grow in a hypoxic environment, intravenously administered
Bifidobacterium expressing the TTR1 nano-agonist molecule will selectively live in cancer tissue and effectively kill cancer cells via TTR1 nano-agonist
molecule expression.

On February 4, 2016, the company made an announcement concerning its application for approval of bendamustinehydrochloride in Europe.
SymBio Pharmaceuticals had applied for approval of manufacturing and marketing of its anticancer agent Treakisym (genericname: bendamustine hydrochloride) in Europe for the treatment of first-line low-grade non-Hodgkin’s lymphoma (NHL) andmantle cell lymphoma (MCL). It received notice from Astellas Pharma GmbH (a European subsidiary of Astellas Pharma Inc.) on
February 2, 2016 that its application had been withdrawn on January 27, 2016.
The company is continuing with the regulatory approval process to receive approval for Treakisym domestically for the treatmentof first-line low-grade NHL and MCL. The company does not expect this event to affect its earnings forecasts.

December 2015
On December 28, 2015, the company announced the start of global phase III clinical trials for IV rigosertib to treat relapsed or
refractory higher-risk myelodysplastic syndromes.
SymBio Pharmaceuticals started global phase III clinical trials in Japan for the IV formulation of rigosertib to treat relapsed or
refractory higher-risk myelodysplastic syndromes. While SymBio will conduct the trials in Japan, its US partner Onconova
Therapeutics will conduct the trial in the US and Europe. The company does not expect the start of clinical trials to affect its
FY12/15 earnings forecasts.

On December 24, 2015, the company announced that it had applied for additional indications of anti-cancer drug Treakisym in
CLL, as well as in first-line low-grade NHL and MCL. It also applied for approval for domestic manufacturing and marketing of
small dose formulations of Treakisym.

Application for additional indication of Treakisym in CLL
On October 27, 2010, the company obtained approval for domestic manufacturing and marketing of the anti-cancer drug
Treakisym (generic: bendamustine) for treating relapsed or refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell
lymphoma (MCL). It has applied for an additional indication, the treatment chronic lymphocytic leukemia (CLL). This drug has
already been approved for the treatment of CLL in Europe and the US. It was designated as an orphan drug (drug for thetreatment of rare diseases) to treat CLL in June 2012. In response to a request from the Evaluation Committee on Unapproved or
Off-Labeled Drugs with High Medical Need for its development, SymBio has applied for approval for the additional indication.

Application for additional indication of Treakisym as first-line treatment of low-grade NHL and MCL
The company applied for approval to add an indication of Treakisym as the first-line treatment of low-grade non-Hodgkin’s
lymphoma (NHL) and mantle cell lymphoma (MCL).

Application for approval to manufacture and market Treakisym in small dose formulations in Japan
Considering the appropriate dosage for clinical use, the company has applied for approval to manufacture and market anti-cancer
drug Treakisym in a 25mg vial.
The company does not expect these applications to impact its FY12/15 earnings.

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On December 7, 2015, the company announced that it has started phase I clinical trials for the use of oral anticancer agent
rigosertib in combination with azacitidine for the treatment of higher-risk myelodysplastic syndrome (MDS).
The company has started phase I clinical trials in Japan for the use of the oral anticancer agent rigosertib in combination withazacitidine (Vidaza®, sold in Japan by Nippon Shinyaku Co., Ltd.) for treatment of higher-risk MDS.
The company already completed phase I clinical trials on the monotherapy use of rigosertib in June 2015. Once the combination
clinical trials are complete, the company will consider participating in an international joint study for the drug planned by its
licenser, Onconova Therapeutics Inc. Onconova Therapeutics has already completed patient enrollment for phase I/II clinical trials
of oral rigosertib for the same indication, and was planning to announce results at the American Society of Hematology meetingthat started on December 5, 2015. The start of the new clinical study will have no impact on the company’s FY12/15 earnings
forecasts.

November 2015
On November 24, 2015, the company announced the approval of IONSYS® (fentanyl iontophoretic transdermal system) in
Europe.
The company announced that The Medicines Company (MEDCO), with which it concluded a license agreement for IONSYS® on
October 2, 2015, received marketing authorization from the European Commission for IONSYS® to treat postoperative pain in
hospitalized patients on November 20, 2015.
IONSYS® was approved by the US Food and Drug Administration (FDA) on April 4, 2015, and was already being sold in the US.
The company was preparing for early phase III clinical trials in Japan.

October 2015
On October 30, the company announced that it had completed phase I clinical trials to use anticancer agent rigosertib(intravenous form) for myelodysplastic syndrome (MDS).
The company plans to participate in global phase III clinical trials already being conducted by US-based Onconova Therapeutics,
Inc. (Nasdaq: ONTX) for higher-risk MDS patients whose condition had deteriorated or those who had not responded to previous
treatment using hypomethylating agents (HMAs). It intends to begin trials with Japanese patients in 2015, and is targeting
simultaneous approval in Japan, the US and Europe. SymBio does not expect completion of the phase I trial to impact its FY12/15
earnings.

On October 19, 2015, the company announced the completion of a phase II clinical trial for Treakisym in patients with chronic
lymphocytic leukemia (CLL).
The company completed a domestic phase II clinical trial of anti-cancer drug Treakisym (generic: bendamustine hydrochloride)for patients with CLL, which it had been conducting in partnership with Eisai Co. Ltd. (TSE1: 4523). This drug has been approved
for the treatment of CLL in Europe and the US. In Japan, this drug was designated as an orphan drug for the CLL indication in June
2012, and the Evaluation Committee on Unapproved or Off-Labeled Drugs with High Medical Needs has submitted adevelopment request to the company. Going forward, SymBio plans to submit an application for manufacturing and marketing
approval in Japan in Q1 FY2016 using data from phase III clinical trials conducted overseas. The company does not expect
completion of the phase II trial to impact its FY12/15 earnings.

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Major shareholders
Amount Held

Top Shareholders
Fuminori Yoshida

6.7%

Cephalon, Inc.

5.6%

SBI Securities Co., Ltd

4.1%

Japan Securities Finance Co., Ltd.

1.8%

Eisai Co., Ltd.

1.8%

Nomura Securities Co., Ltd.

1.5%

Waseda No. 1 Investment LLP

1.5%

Daiwa Securities Co., Ltd.

1.5%

Matsui Securities Co., Ltd.

1.4%

Rakuten Securities, Inc.

0.9%

Source: Shared Research based on company data.
As of December 31, 2016
Ratio of shares held calculated after subtracting treasury shares from shares outstanding

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 77 employees as of December 31, 2016.

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.

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

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

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.

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Fentanyl
A synthetic opioid painkiller used for anesthesia, cancer, and post-operative pain management. It is widely used by Japanesehospitals, and subject to strict control under the Narcotics and Psychotropics Control Act because it is a narcotic.

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

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

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

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

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

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

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

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

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

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

Patient-Controlled Analgesia (PCA)
A pain management method in which patients control the timing of analgesic drug administration.

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

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

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

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

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

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

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

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

SymBio Pharmaceuticals Limited

Minato-ku, Tokyo, JAPAN
105-0001

Phone

Listed on+81-3-5472-1125

TSE JASDAQ GrowthEstablishedExchange listing

March 25, 2005

October 20, 2011

WebsiteFiscal year-end

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

December

IR contact

IR web

Tsutomu Abe

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

IR mail

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

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