ANALYST NET Company Report

SymBio Pharmaceuticals Ltd.
（4582 JASDAQ）

Report issued:19/Feb/2018

Pipeline value of JPY30 billion even after allowing for ongoing new drug search costs
A drug venture company seeking earnings without the risks of drug discovery
SymBio is not itself involved in the basic research and discovery of drugs. Rather, it is a biopharmaceuticals venture business which seeks to leverage its links with a network of drug
discovery companies worldwide to select and bring to market promising new drugs.
It has a niche strategy, seeking to maximize market share and revenues by focusing its
development efforts on drugs for relatively rare conditions in, for example, oncology,
hematology and pain management which, despite strong medical need, the major
pharmaceutical companies have mostly steered clear of.
Another element in its strategy is to minimize development risk by concentrating on
candidate drugs which have already demonstrated effectiveness and safety.
As a result, the first product developed by SymBio, Treakisym, took only five years fromlicensing-in to reach the approval and commercialization stage.

Expanding indications for its key product, and product life-cycle management
Treakisym was approved for the treatment of recurrent and refractory non-Hodgkin's
lymphoma and mantle cell lymphoma in 2010, and in 2016 for chronic lymphocytic
leukemia, untreated low-grade non-Hodgkin's lymphoma and mantle cell lymphoma. As aresult, sales in 2017, the seventh year since initial commercialisation, rose roughly 60% yearon-year and market size has expanded to JPY 7.6 billion (official drug price basis).
At present, development is underway with the aim of adding further indications, and patientsare being enrolled for Phase 3 clinical trials on relapsed /refractory medium and high-grademalignant non-Hodgkin's lymphoma (DLBCL).
In addition, lifecycle management by drug type modification is also underway. There is a riskof TREAKISYM® being exposed to competition from generics in 2020, 10 years after
approval, but the company intends to mitigate that risk by introducing an easy-to-administer
liquid formulation from Eagle Pharmaceuticals in the United States to replace the current
lyophilised preparation. Fair Research Inc. believes these measures could propel the
TREAKISYM® market to a peak value of around JPY20.4 billion.

Pipeline value at around JPY30 billion (pre-tax) after new drug search costs
Assuming the company builds its own sales structure, and after allowing for the ongoingcosts of searching for new drugs, we modelled the company’s pipeline value, together with
end-December 2017 cash on the balance sheet, at around JPY30.3 billion (before tax, using
a discount rate of 10%. (Also, using a discount rate of 8% yields a value of approximately
JPY36.6 billion).
Nevertheless, in the intervening three years before turning profitable in 2021, the company
will continue operating at a loss, and the end-December 2017 cash may not be sufficient tocover costs for that period. The proceeds from the exercise of stock acquisition rights could
help, as could payment of the company’s compensation claim (now in arbitration) relating to
the cancelled development of the IONSYS drug due to the circumstances of the licensor, but
it should be borne in mind that the company is planning to raise cash.

Executive Summary
Fair Research Inc.
Tsuyoshi Suzuki

Company outlook
Location

Minato-ku, TokyoCEO

Fuminori Yoshida

Establishment

March 2005

Capital10,392million

ListedOct. 2011

URL

www.
symbiopharma.com

SectorPharmaceuticals

Workforce

78 – consol. basis

Indicators as at 2018/2/16
Stock price20７

52 week closing high311

52 week closing low

200

Shares issued

54,049thou.

Trading unit

100 shares

Market cap

JPY11,188 mil.

Forecast dividend

0.0

EPS-forecast-56.55

Forecast PER

NA

Actual BPS

50.00

Actual PBR

4.14X

EPS, PER, BPS and PBR are on a total shares
outstanding basis, excl. treasury shares

Results

Sales
JPY mil.

2015/12 period actual
2016/12 period actual

EPS
JPY

Year-end share price
High
Low

YoY
％

Op. profits
JPY mil.

YoY％

Rec. profit
JPY mil.

YoY％

Net profit
JPY mil.

YoY
％

1,933

-1.1

-2,551NA-2,630NA-2,632

NA

-81.3

383

177

2,368

22.5

-2,127NA-2,316NA-2,313NA-58.82509

173

2017/12 period actual
2017/12 1H actual

3,444
1,786

45.4
47.5

-3,947-1,235NANA-3,976-1,268NANA-3,977-1,266NANA-79.78-26.09

311
311

200
200

2017/12 2H actual
2018/12 period
company forecast

1,658

43.2

-2,712NA-2,708NA-2,711NA-53.69

243

212

4,201

22.0

-2,981NA-3,044NA-3,056NA-56.55

1/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is basedon the information and materials that Fair Research judged reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
nhatsoever for any results including direct or indirect damage arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property right of this report belongs to Fair Research, and any copy, transmission or quote of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

Company outline – management philosophy＜Business Model＞

SymBio Pharmaceuticals Ltd. is regarded as a bio-venture but has the following
special characteristics:

Requiring neither labs nor
factories SymBio is apharmaceuticals venturewith none of the risks
assumed by drug discovery
firms, operating a niche
strategy focused on
maximizing profits.

1. Controls risk and maximises earnings with a “labless” and “fabless” strategy.
In terms of business model, the company does not itself conduct basic research on
new drugs. Rather, it seeks out and carefully investigates new drug candidates
developed by drug discovery ventures and pharmaceutical companies around theworld. A new drug selected as a result of this process is the subject of a licensing
agreement and, following development in Japan, is either licensed out to anothercompany for commercialization or commercialized by the company itself.
(Since the company itself conducts drug development in Japan it should berecognized as not simply a technology trader but as a bio-drug company).
2. Targets large market share and high earnings using a niche strategy.
The company focuses its development efforts on drugs for relatively rare conditionsin, for example, oncology, hematology and pain management which, despite strong
medical needs, the major pharmaceutical companies have mostly avoided. It seeks
to maximize market share and profits using this niche strategy.
3. Post-POC (proof of concept) strategy
In most cases proof of concept has already been established. By insisting on priorevidence of efficacy and safety in human subjects, the company reduces thedevelopment risks of new drug candidates.
This business model is one which seeks to control the risk inherent in drug discovery
and, at the same time, secure good returns from pharmaceuticals.
The success or failure of this business model is dependent on having a network of
drug discovery companies worldwide and a keenly discerning eye, as evidenced by
the company’s track record.

SymBio is one of those rarebio-ventures whose first
product on the market took
only five years fromadoption to approval.

Normally, it takes some 10-20 years to bring a drug from basic research to themarket. In terms of the probability of success, some estimates suggest that, counting
from the chemical compound stage, it is less than 1/30,000, and even from the POC
stage, around 7 to 8%. But SymBio managed to get its first product, Treakisym, fromadoption to manufacturing and commercial approval in around five years, and in thethree years following launch captured 57% of the market. In the eleven or so years
since founding, the company has screened 1,500 drug candidates, of which over 700
have been formally investigated in-house. And of these, five products have been
adopted and two are currently under development. Development of two others was
terminated, not for reasons of clinical trial failure, but because of circumstances on
the licensor’s part, and in the case of the third terminated candidate, changes in thelicensor’s business strategy led to changes in targeted indications and was
terminated when Phase 2 trials did not demonstrate superior therapeutic
performance (please refer to the Licensing and Development Timeline chart at theend of this report).

The determinants ofcommercial success areinteractions with a networkof drug discovery
companies and the ability todiscern and evaluate.

We believe this track record has been made possible by the expertise of thecompany’s staff and by the way the company is organized. SymBio has a workforceof 78, of whom around 40 are involved in research and development. The drug
search function is supported by a Scientific Advisory Board (SAB) of specialists(including Nobel Prize candidates) who review drug candidates (a list of Board
members is given below). Needless to say, the company’s founder and CEO,Fuminori Yoshida, is an important factor in terms of both his experience and his
personal network (please refer to his career history below).
2/18

This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

Members of the Scientific Advisory Board（SAB）
Chair: George Morstyn, M.D., Ph.D.
• Former Senior Vice-President of Development and CMO, Amgen Inc.
• Currently chief executive officer of G & R Morstyn Pty Ltd.,
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;
Tomomitsu Hotta, M.D.
• Honorary President, National Cancer Center• Honorary Director, NHO Nagoya Medical Center
Makoto Ogawa, M.D., Ph.D.
• Honorary President, Aichi Cancer Center
Tatsutoshi Nakahata, M.D., Ph.D.
• Adviser and Professor, Center for iPS Cell Research and Application (CiRA),
Head of Drug Discovery Technology Development Office• Kyoto University
Toshio Suda, M.D., Ph.D.
• Professor, International Research Center for Medical Sciences, Kumamoto University• Professor, Cancer Science Institute of Singapore, National University of Singapore
Tsutomu Takeuchi, M.D., Ph.D.
• President of Keio University Hospital
Shinji Nakao, M.D., Ph.D.
• Professor, Kanazawa University. Institute of Medical, Pharmaceutical and
Health Sciences, Faculty of Medicine, Department of Hematology / Respiratory Medicine• Executive Director of The Japanese Society of Hematology; Vice President of The JapaneseSociety of Hematopoietic Cell Transplantation; Councilor, The Japanese Society of Internal Medicine
Koichi Takahashi, MD• Assistant Professor, Department of Leukemia and Genomic Medicine, The University of Texas
MD Anderson Cancer Center

Source: SymBio HP

Fuminori Yoshida, CEO Biography1949 Born in Tokyo
Graduated from the Science Faculty1971 (majored in Chemistry) of Gakushuin
University
1973

Obtained master's degree from M.I.T(specialised in Life Sciences)
Studied Management and Medical Policy
Theory at Harvard University Graduate
School1975 Joined Mitsubishi Corporation
1977 Joined AHS Japan (currenty Baxter)
1980 Founded Japan Bio-Rad Laboratories
1991 Joined Japan Syntex (now Roche)
CEO Amgen Japan, Vice-President
Amgen Inc.
Founded SymBio Pharmaceuticals
2005
Limited
1993

Source: Fair Research Inc. using Securities Report filings and other information

3/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）<Main Pipeline Products>

Issue Date Feb.19 2018

As of Feb.2018, the company’s two mainstay pipelines are TREAKISYM® andrigorsertib.
Pipelines

Source: Company results meeting(1) TREAKISYM® (SyB L-0501, freeze-dried injected preparation/ SyB L-1701,
RTD preparation/ SyB L1702, RI preparation/ SyB-C-0501, oral preparation)
TREAKISYM® (generic name bendamustine) is a cancer drug developed in Germany

in 1971. Among malignant lymphomas it is used in the treatment of low risk nonHodgkin’s lymphoma and chronic lymphocytic leukemia.

Malignant lymphoma
Lymphoma is a hematologic malignancy caused by the cancerization oflymphocytes (a type of white blood cell providing immunity). This condition comesin two main forms, Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma(NHL). The majority of Japanese patients with malignant lymphoma (94%) have the
NHL form. NHL is divided into the three following types depending on the speed atwhich the disease progresses. The TREAKISYM® therapy is directed at NHL and ishighlighted in red.

4/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

Types of malignant lymphoma
Degree of Maligancy
Type(speed of progression)
Low-grade
Small lymphocytic
MALT(measured in years)
Follicular(grade 1-3a)
Marginall Zone B cell
Rinpa Plasma cell
Nodal marginal B cell
Medium grade(measured in months)

High grade(measured in weeks)

Plasma cell tumour
Mantle cell
Follicular (grade 3b)
Diffuse large cell typePrecursor B lymphoblastic
Burkitt's lymphoma

Source: “Treatment Guide” - Eisai and Symbio
TREAKISYM® went fromlicensing-in to approval in
only 5 years, and additional
indications are still being
pursued.
Having received initialapproval in 2010,
TREAKISYM® wasapproved for two additional
indications in 2016, leading
to further penetration of themarket.

In December 2005, SymBio acquired sole development and sales rights in Japan
from Astellas Pharma’s European subsidiary, Astellas Deutsche. Subsequently, in
October 2010, only five years after licensing-in, approval was granted for two
indications, recurrent refractory low-risk NHL, and mantle cell lymphoma (MCL).
Commercialization began in December of that year. Further, in August 2016,
approval was granted for the treatment of chronic lymphocytic leukemia (CLL) andin December of the same year, for untreated low risk NHL/MCL. By 2017, theseventh year of commercialization, domestic sales had expanded to JPY7.6 billion(official drug price basis). The level of market penetration (2017 average) is 58%
for recurrent/refractory low-risk NHL, but is still an estimated 35% for untreatedlow-risk NHL/MCL, for which approval was granted later, in 2016. Since for thelatter indication the superiority of B-R therapy, using a combination of rituximab
and TREAKISYM®, has been demonstrated against the current standard therapy (seethe note to CHOP-R therapy below) it is expected that further market penetration
can be achieved.
B-R Treatment Effectively against R-CHOP

Source: SymBio pharmaceuticals IR meeting
Note: CHOP-R therapy
Chemotherapy treatment combining the molecular target drug rituximab and the anticancer drugs
cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and the steroid drug
prednisolone.

5/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

An additional development in August 2008 was the licensing-out to Eisai of joint
development and sole sales rights in Japan for TREAKISYM®. The format is that
SymBio buys in TREAKISYM® from Astellas Deutsche and releases to Eisai, whichthen sells domestically. We estimate that Eisai covers half the development costs of
TREAKISYM®. The out-licensing contract with Eisai expires in 2020, and from 2021,
although no firm decision has yet been made, SymBio is considering setting up its
own in-house sales function.
At present, patient
enrolment is proceeding forPhase3 trials directed atrecurrent/refractory medium
and high-risk NHL.

As of February 2018, development continues with the company looking to further
expand the number of indications for TREAKISYM®. Looking particularly promising
is the targeting of recurrent/refractory medium/high risk NHL (below, r/rDLBCL).
The first patients for Phase 3 clinical tests were enrolled in January 2018. In addition,
there was an announcement that Phase I clinical trials using an oral preparation andtargeting progressive solid tumor subjects had begun.
Note: In Japan the most common form of medium-risk NHL is diffuse large B-cell lymphoma(DLBCL).

Progress is also being madein product life-cycle
management throughchanges in the drug
formulation.

A further important point to note is the issue of life cycle management throughchanges in drug formulation. In 2020 TREAKISYM® will be 10 years from receiving
drug approval, and from 2021 will face the risk of competition from generics. The
company plans to extend the product life span until 2031 by developing new
formulations. On September 21st in 2017, the company announced it was
introducing liquid ready-to-dilute (RTD) and rapid-infusion (RI) formulations fromthe US company, Eagle Pharmaceuticals Inc. to add to the existing freeze-dried (FD)formulation. The existing formulation does have the advantage of being storable atroom temperature, but prior to administration it takes time and effort to dissolve withsolvent and dilute with physiological saline. On the other hand, while the liquid
formulation needs to be refrigerated it can be administered simply by diluting withphysiological saline solution, thus shortening the dispensing work and reducing theburden on healthcare staff. The US company Teva Pharmaceutical Industries
launched an RTD formulation in 2014, and in January 2016 brought to market an RI
formulation (product name: BENDEKA®, licensed in from Eagle Pharmaceuticals)with a shorter administration time. In only two years, BENDEKA® has come toaccount for 97% of the TREAKISYM® market.
Comparison of FD, RTD and RI formulations

Source: SymBio IR materials

6/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
Introduction of liquid
formulations likely toextend product life cycle to2031

Issue Date Feb.19 2018

SymBio expects to commercialize an RTD formulation in 2021 without additional
trials because its function and method of administration are the same as for the FD
formulation. In the case of the RI formulation, the different concentration anddifferent administration time mean that safety tests and other procedures arenecessary. Nevertheless, due to results already obtained in the US,commercialization in Japan can probably be achieved in 2022-2023. These
formulations will extend the TREAKISYM® life-cycle to 2031.
As for drugs which could compete, it should be noted that in the area of NHL and
CLL the absence of drugs with a sufficient level of safety and effectiveness using
conventional chemotherapy alone has stimulated interest and there are now anumber of pipeline drugs in development. In August 2017 Chugai Pharmaceuticalapplied for approval for obinutuzumab, but since it is targeted at CD20 positive B
cell follicular lymphoma it is basically used in combination with TREAKISYM®, andwe therefore believe it will have no adverse impact on sales. In addition, the EZH2
inhibitor (Tazemetostat) licensed in by Eisai from Epizyme Inc. is still at the PhaseII level.
(2) Rigosertib (SyB L-1101: injected preparation; SyB C-1101 oral preparation)

Rigosertib is underdevelopment for injection
and oral preparations
mainly to treat
myelodysplastic syndrome(MDS).

SymBio is developing a cancer agent from the US company, Onconova
Therapeutics, mainly for the treatment of myelodysplastic syndromes (MDS). In
July 2011, when Onconova completed Phase 2 clinical trials, SymBio acquired soledevelopment and sales rights in Japan and Korea for injected and oral preparationsof this drug (estimated up-front lump sum payment of around JPY800 million).
The current development status is as follows:(a) Injected preparations
A joint international Phase 3 trial is underway for patients who do not benefit fromthe standard hypomethylating agent (=HMA) therapy (=HMA refractory), and forpost-treatment patients with relapsed high risk MDS. SymBio is responsible forPhase 3 in Japan.
High-risk MDS is identified as high risk by the International Prognostic Scoring
System, and is judged to be in the intermediate 2 risk category (the higher risk group)with a high risk of transition to leukemia. Currently the standard treatment is theadministration of azacitidine (trade name Vidaza®) and decitabine (trade nameDacogen), but some high risk MDS cases have shown a resistance to the standard
therapeutic drugs or have a relapse after treatment. Rigosertib is indicated for suchrecurrent and refractory MDS, and at present there are no competing approved
drugs. There is one competing candidate agent under development (Syros
Pharmaceuticals' SY-1425), which is still in Phase 2 trials.

The original developer,
Onconova, is continuinginternational joint Phase 3
trials using a revised trial
design.

Onconova completed Phase 3 (ONTIME) trials for recurrent and refractory high risk
MDS in February 2014. The test results showed no statistically significant differencein overall survival (OS) between the patient cohort treated with rigosertib and thecontrol (palliative care) cohort. However, in terms only of HMA refractory patientsand those whose disease advanced during pre-treatment, there was a significant
difference in OS between the cohort treated with rigosertib (7.9 months) and thecontrol cohort (4.1 months). Onconova then changed the test design to focus on thispart of the results and in August 2015 initiated global joint Phase 3 trials (INSPIRE)
targeting HMA refractory patients and high-risk MDS patients whose condition
recurred after treatment.

7/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

ONTIME trial results (left chart) and subpopulation results (right chartusing same cases as for INSPIRE trials)

Source: SymBio IR materials

SymBio is also participating
In June 2012, SymBio began Phase 1 trials targeting recurrent refractory high-riskin the joint international
MDS subjects. The trials were completed in October 2015. As a result of discussions
trials.
with Onconova and the relevant authorities, SymBio joined the international joint
Phase 3 trials (INSPIRE) conducted by Onconova from December 2015, becoming
As a result of the interim
responsible for the clinical trials in Japan. In January 2018, based on the interim
analysis in January 2018INSPIRE analysis, Onconova decided to continue the trial with an increased number
trials proceeded withof cases (from 225 to at least 360). In Japan, it was also decided to continue with anadditional cases. An
increased number of cases. Application and approval was therefore delayed for
application for approvalaround 1.5 years, until about 2021 for application and until around 2022 forwill be made in 2021 orapproval.
later.
Following completion oftests in Japan for the oral
preparation, SymBio plansto participate in theinternational joint Phase 3
trials currently being
planned by Onconova.

(b) Oral preparation
In Europe and America, Phase 1/2 trials of rigosertib (in combination withazacitidine) directed at high-risk MDS have already demonstrated safety andefficacy (see chart below). In Japan, SymBio in June 2017 began Phase 1
monotherapy trials targeting high-risk MDS to confirm the safety of higher doses,
and in October 2017 completed the first patient enrolments. After Phase 1 thecompany plans to start domestic trials in combination with azacitidine (productname: Vidaza®) and to participate in the international joint Phase 3 planned by
Onconova.
Phase 2 Responses to Combination Treatment

Source: Compiled by SymBio Pharmaceuticals from papers presented at
the 14th International MDS Symposium in 2017

8/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）<Revenue structure>

We estimate that
TREAKISYM® wholesale
price is about 50% of theofficial price, and the costof the medicine to SymBio
is about 66% of thewholesale price.

R&D costs associated withrecurrent search activities
came to JPY500 million,
and we estimate totalcompany administration
costs came to around
JPY1.4 billion.

Issue Date Feb.19 2018

SymBio’s sources of revenue consist of product sales and milestone payments. In
the year ending December 2008, it registered an operating profit after receiving alump sum contract payment from licensing out sole distribution rights for
TREAKISYM® in Japan to Eisai. In each subsequent year, however, it has registeredonly operating losses.
In the period ending December 2017 the company recorded sales of JPY3.44 billion,
mostly attributable to wholesaling TREAKISYM® to Eisai. The cost of goods (mostly
the value of supplies from Astellas Deutschland) was JPY2.41 billion for a grossprofit of JPY1.03 billion. SymBio’s wholesale price of TREAKISYM® to Eisai wasan estimated 50% of the official price, and SymBio’s acquisition cost of supplies
from Astellas Deutschland was around an estimated 66% of the wholesale price.
R&D costs came to JPY3.02 billion, of which we estimate JPY1.38 billion was
attributable to a contract lump sum (liquid formula licensing-in) paid to Eagle.
Breaking out the remaining JPY1.64 billion we get JPY300 million for
TREAKISYM®-related costs, rigosertib-related costs of JPY350 million, and around
JPY 400-500 million associated with the patient-controlled pain management drug
IONSYS® (development discontinued in November 2017. Refer to “Timeline”
section). We believe the residual JPY500-600 million or so is attributable to the
R&D costs of recurrent new drug candidate search activities.
Non-R&D SG&A came to JPY1.96 billion, of which sales costs came to around
JPY300 million and non-R&D general administration to JPY1.6-1.7 billion. This isa somewhat larger amount than normal because in 2017 there were costs associatedwith licensing in the new TREAKISYM® formulations, and legal and other costs
generated by IONSYS®. In a normal year, general administration expenses would
come in at around JPY1.4 billion.
As a result, the company recorded an operating profit loss of JPY3.9 billion.
SymBio Pharmaceuticals – Balance sheet and P&L

Source: compiled by Fair Research Inc. from Securities Report filings, etc.

9/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）< TREAKISYM® andrigosertib market size>

We model a market size of
JPY10.6 billion for thethree indications for which
TREAKISYM® approval has
been granted, and around
JPY9.8 billion forrecurrent/refractory
medium-high risk NHL(now in Phase 3).

Issue Date Feb.19 2018

We anticipate an enlarged market for TREAKISYM® due to rising market penetration
and an increase in the number of indications. Approvals have already been granted
for the following areas: 1. recurrent/refractory low-grade NHL/MCL; 2. chronic
lymphocytic leukemia (CLL); 3. 1st Line low-grade NHL/MCL. In area 1, sales havereached JPY4.72 billion but, as the number of patients is estimated at 9,336, we
think market saturation has already reached 58%. We anticipate sales in this segment
will be sustained by changes in formulation. For CLL and 1st Line low-grade
NHL/MCL, for which approval has only relatively recently been granted, sales of
the two together still stand at around the JPY2.68 billion level. The number ofsubject patients is estimated at 656 and 6967, respectively, with average market
penetration in 2017 standing at around 35%. However, we anticipate further
penetration is possible. If the CLL segment were to see a rise in penetration to 55%,
this would suggest a market size of JPY340 million. And if we assume that the
maximum market penetration for untreated intermediate grade NHL/MCL is 75%,
this would infer a market size of JPY5.57 billion.
Again, in the case of relapsed/refractory medium/high risk NHL (r/r DLBCL), now
in Phase 3, there are an estimated 18,000 plus patients, and assuming a market
penetration of 60%, we would posit a potential market size of JPY9.77 billion.
Sales for the above three approved indications total JPY10.63 billion. Adding insales of Phase 3 r/rDLBCL yields estimated potential total sales of JPY20.4 billion.
The market for TREAKISYM® (Number of patients)

Source: SymBio IR materials

We estimate the market sizeof injected rigosertib at
JPY4.6 billion, and thepotential market size fororal rigosertib at JPY11.6
billion.

Since the use of injected rigosertib on high-risk MDS patients is limited to MHA
refractory patients, there are an estimated 900 subjects. Using the Vidaza® drug
price for reference, we model an estimated market size of around JPY4.6 billion. As
for the oral preparation, we model the number of subject patients at 2300, assuming
it is that portion of the high-risk MDS patients who are not being treated with theinjected preparation, and thereby posit a market size for the oral preparation of
JPY11.6 billion. For the two preparations together, the total market size comes toaround JPY16 billion.

10/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）<Modelling the productpipeline value andcorporate value>

Issue Date Feb.19 2018

We now look at the corporate value of SymBio using a DCF model. This simulation
posits a product value for TREAKISYM® (assuming that indications are expanded to
r/rDBLCL, that formulation changes are made, and that the company will take overits own merchandising), and a product value for rigosertib (both the injected andoral formulations). From the sum of these two we deduct the DCF value of thecompany’s costs attributable to drug search activities and administration. We modela discount rate of 10% to reflect the fact that the company, while continuing tooperate at a loss, is a low risk lab-less and fab-less drug venture and does alreadyhave a product on the market.
<Assumptions made for TREAKISYM®>
Using the market size calculations described earlier we model peak sales being
attained in the fourth year after going to market and sales staying at that peak level
for the subsequent 3-4 years. We assume that the market will then decline at a rateof 5% per year before shrinking sharply (at an annualized 10%) from 2031 onwards.
We are assuming an 80% probability of success in relapsed/refractory intermediate
grade NHL (r/rDLBCL), now undergoing Phase 3 trials.
While we assume Eisai will provide the sales channel until 2020, sales will go inhouse from 2021. We are modelling the ratio of cost of goods to sales at 26% at thattime. In 2021 and after, supplies will have almost entirely switched to the liquid
formulation (either RTD or RI) and we are assuming royalty payments to Eagle
Pharmaceuticals as 22% of sales (estimated figure based on Eagle’s materials andelsewhere). In addition, the milestone payment at the launch of the RI formulation
should, we assume, be in the area of JPY700 million.

Assuming the company
switches to selfmerchandising in 2021 wemodel a discounted present
value for TREAKISYM®
(pre-tax) of JPY31.9 billion(discount rate 10%).

Development costs are not being shared evenly with Eisai but are assumed to be
entirely by SymBio. The assumptions we made are shown in the “Development
Costs” line in the chart. The costs associated with commercializing assume 40
medical representatives (MR) in 2020 and 50 from 2022 onwards. These and otherpromotional costs are as shown in the chart.
We therefore posit a value for TREAKISYM® of approximately JPY31.92 billion(before tax).
Modelling TREAKISYM® Value(JPY100mil)
2018

2019

2020

2021
RTD insertion

2022

2023

2024

2025

2026

2027

2028

2029

2030

RI insertion

Sales (official drug price basis)
Treakisym total

Sales

101.1

102.4

104.5

120.5

136.3

166.3

196.3

204.0

198.7

193.6

184.0

174.8

166.0

NHL/MCL r/r low-risk NHL/MCL

47.2

47.2

47.2

47.2

47.2

47.2

47.2

47.2

44.8

42.6

40.5

38.4

36.5

Chronic lymphocytic leukemia

3.0

3.2

3.3

3.3

3.4

3.4

3.4

3.4

3.2

3.1

2.9

2.8

2.6

Untreated low-risk NHL/MCL

50.9

52.0

54.0

55.0

55.7

55.7

55.7

55.7

52.9

50.3

47.8

45.4

43.1

15.0

30.0

60.0

90.0

97.7

97.7

97.7

92.8

88.2

83.8

117.5

130.3

154.3

178.3

184.5

179.1

174.1

165.4

157.1

149.3

45.5

47.0

45.7

44.4

42.2

40.1

38.1

39.2

40.6

39.4

38.3

36.4

34.6

32.8

r/r medium-high risk NHL (DLBCL)

0.0

0.0

0.0

Sales via Eisai (until 2020)

41.8

42.1

45.3

Switch to own-merchandising(Note: assuming r/r DLBCL success prob. 80%)

Bulk powder cost (+manuf. costs)

27.6

27.8

29.9

30.0

33.2

39.3

0.0

0.0

0.0

25.9

28.7

33.9

7.8

5.2

1.3

26%
7.0

Milestone payments to Eagle
Royalty payments to Eagle
22%
13.0

16.9

15.6

r/rDLBCL Ph3 ：Trial costs for 60 cases

6.0

7.0

6.0

RTD and RI trials application

3.0

5.0

5.0

5.0

3.0

Other direct costs

1.0

1.0

1.0

1.0

1.0

Development staff costs

3.0

3.9

3.6

1.8

1.2

0.3

7.0

10.0

11.0

12.0

14.0

15.0

15.0

15.0

15.0

15.0

15.0

15.0

15.0

Own MR costs

3.0

6.0

7.0

8.0

10.0

10.0

10.0

10.0

10.0

10.0

10.0

10.0

10.0

Other sales costs

4.0

4.0

4.0

4.0

4.0

5.0

5.0

5.0

5.0

5.0

5.0

5.0

5.0

-5.8

-12.6

-11.2

41.9

49.2

57.7

78.6

81.8

79.1

76.4

71.8

67.5

63.4

Development costs

Sales costs (incl. MR costs)

Profits
Disc. Rate

Discounted P.V.

10%

319.2

1.0

Source: Calculations by Fair Research Inc.

11/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

<Assumptions for rigosertib>
We model a 50%
probability of success forthe rigorsertib injected
formulation, and 30% for
the oral formulation, andposit a value of around
JPY9 billion (discount rate10%).

As described earlier, we assume peak sales four years after launch, a level whichshould be maintained for the subsequent 3-4 years. The market should then subside
at a rate of 5% annually until 2035 when it will begin shrinking sharply at 10% per
year. In terms of market launch, the timing has fallen behind schedule due to theresults of the interim INSPIRE analysis and the attendant additional indications. We
are now factoring in 2023 or thereabouts for the injected preparation and 2025 forthe oral preparation. Probability of success reflects the stage of the trial, with thePhase 3 injected preparation posited at 50% and the Phase 1 oral preparation at 30%.
Our simulation also posits payments for supplies of medicine from Onconova androyalties to Onconova coming in at 25% of sales. We assume milestone payments atlaunch of JPY500 million for the injected preparation and JPY1.5 billion for the oral
preparation. We have assumed development costs as shown in the Development
Costs line in the chart. Since the marketing channel and MR is the same as for
TREAKISYM® we have omitted sales costs. As a result, we model a value forrigosertib of JPY8.96 billion (pre-tax).
Modeling Rigosertib Value
Event

Sales

Injection (high-risk MDS)

Oral (high -isk MDS)

Injection (high-risk MDS)
30.3

2020

Intl. joint Ph3

2024

Approved

2025

0.0

11.3

File

0.0

12.1

33.8

2034

99.5

0.0

12.9

36.2

2033

33.7

45.0

0.0

13.6

2032

37.5

48.3

104.7

0.0

13.9

38.8

（JPY100mil)

39.4

51.8

110.2

0.0

14.2

40.9

2031

41.5

54.5

116.0

0.0

13.3

41.7

2030

43.7

55.6

116.0

0.0

12.5

42.5

2029

46.0

56.7

116.0

0.0

11.8

39.8

2028

46.0

53.0

100.0

8.0

37.5

2027

90.0

15.0

2026

46.0

50.0

3.8

2023

80.0

0.0

2022

40.0

47.0

2021

30.0

40.0

2019

20.0

32.0

2018

0.0

0.0

2.5

Approved

0.0

15.0

5.0

9.0
35.3

11.3

File

0.0

0.0

No. of patients

0.0

10.0

Intl. joint
Ph.3(+addit.cases)

0.0

0.0

Ph1

900

0.0

Combined with AZA

25%

0.0

0.0

5.2

0.0

0.0

3.0

0.0

0.0

6.5

1.0

0.0

0.0

4.0

1.2

0.0

0.0

7.8

1.0

-2.7

0.0

0.0

5.0

1.5

0.0

0.0

7.5

1.0

-6.5

0.0

0.0

5.0

1.8

2300

0.0

6.2

0.8

-7.8

With AZA

0.0

4.0

1.7

Oral (high-risk MDS)

4.9

0.8

-7.5

＜＝probability of success

Milestone paymnents

3.0

1.4

Injection 50%、Oral 30%

Total development costs

0.8

-6.2

Sales adj. for prob. of success

Trial costs

1.1

Bulk chem.+ manuf. cost + royalties

Other direct costs

-4.9

89.6

Disc. P.V.

Development staff costs

Profits

10%

Disc. rate

Source: Calculations by Fair Research Inc.

12/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

Further costs are generated annually by search and examination activities for new
drug candidates and by total company administration. Based on analysis of data inthe earnings structure section we model JPY500 million for R&D costs related toongoing exploration, and JPY1.4 billion for company administrative costs, for a totalof JPY1.9 billion.
On the basis of the above assumptions we calculate discounted present value,
yielding a present value for all-company costs of –JPY13.6 billion.
Looking next at the value (pre-tax) of the total SymBio pipeline, we take thepresent value of the company’s two main drugs, the present value of the totalcompany costs and the current cash on the balance sheet, arriving at a figure of
JPY30.3 billion. Using a discount rate of 8% yields a figure of 36.6 billion.
Modelling the value of SymBio’s product pipeline
Taking into accountrecurrent drug search costs,
all-company corporate
administration costs andcurrent cash on the balance
sheet, we model a pre-tax
value for SymBio of
JPY30.3 billion (discountrate 10%).

(JPY 100mil.)Discount

Total(before tax）

Rate

10%

8%

302.6

366.0

Treakisym

319.2

369.1

Rigosertib

89.6

113.9

Headquarter's costs-135.7-146.5

Cash

29.5

29.5

(Ref） Assuming eff.tax rate 31%
Disc.rate
Total (after tax）

10%
208.8

2018/2/16
Market cap

Disc. rate

8%
252.5
111.9

Source: Calculations by Fair Research Inc.

13/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

<Adherence to medium On February 8th 2018, SymBio announced its results for FY2017 andterm management plan simultaneously released its medium-term management plan. We provide the data
and balance sheet risk>
below.
SymBio Pharmaceuticals medium-term management plan
(JPY million)

Source: SymBio Pharmaceuticals

In the table below, we systematize the sales and earnings data for TREAKISYM® andrigosertib calculated in the previous pages. The data in the table conforms quite
closely to the data in the company’s medium-term management plan.
Long-term sales and profits trajectory(JPY100mil.)
2018

2019

2020

2021

2022

2023

2024

2025

2026

2027

2028

2029

2030

41.8

42.1

45.3

117.5

130.3

164.3

193.3

216.5

226.1

224.1

218.4

213.8

204.8

Treakisym

41.8

42.1

45.3

117.5

130.3

154.3

178.3

184.5

179.1

174.1

165.4

157.1

149.3

Rigosertib

0.0

0.0

0.0

0.0

0.0

10.0

15.0

32.0

47.0

50.0

53.0

56.7

55.6

-29.7

-25.2

-37.7

15.1

23.7

36.0

70.9

71.8

95.3

94.9

92.6

91.0

86.0

-11.2

41.9

49.2

57.7

78.6

81.8

79.1

76.4

71.8

67.5

63.4

Total sales

Op. profits

total
Treakisym-5.8

Rigosertib

-4.9

-6.2

-7.5

-7.8

-6.5

-2.7

11.3

9.0

35.3

37.5

39.8

42.5

41.7

Other costs

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

-19.0

Turns profitable

Source: Fair Research.Simulation; Sales figures take account of probability

The company is forecastinga return to operating profit
in 2021.

An important point to note is that both the company’s medium-term plan and oursimulation point to a return to operating profit in 2021. Even if the company defers
on bringing the marketing in-house from 2021, preferring the option of a tie-up withanother company, the terms of such a tie-up could contribute to an improvement in
profitability. This, together with milestone income on the back of the introductionof liquid formulations, means the company, in our view, would still turn profitablein 2021.

One other important point to note over the three-year period from 2018 to 2020
concerns the level of development costs. These will continue to be elevated in orderto fund an increase in the conditions for which TREAKISYM® is indicated, to fundthe development of an RI formulation and to fund additional cases in rigosertib
clinical trials. It will also be necessary to increase the number of MR’s. This makes
it likely that the company will continue to generate losses in excess of JPY3 billion
every year and could exhaust development funds. At the end of 2017 the company
held JPY2.95 billion in cash but over the next three years is expected to accumulate
net losses totaling in excess of JPY10.7 billion, leaving a shortfall of approximately
There is a possibility of a
JPY7.7 billion. However, the cash position recovered to the JPY3.6 billion level atcash shortfall in thethe end of January with the exercise of stock acquisition rights. This will help secureintervening three years prior the company’s needs for the current year 2018.
to returning to profit.
It is also possible that the shortfall will be attenuated by compensation from The
Medicines Company, the US firm which was the licensor for IONYS® until it
abruptly withdrew from the business, forcing SymBio to terminate the project andtriggering a demand for compensation of JPY9 billion via arbitration by the
14/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
The exercise of new stockacquisition rights and
IONSYS®-relatedcompensation may besufficient, but thepossibility of a cash callshould be borne in mind.

Issue Date Feb.19 2018

International Chamber of Commerce (see Timeline below). SymBio had alreadymade a JPY1 billion lump-sum contract payment to The Medicines Company andfrom 2016 to 2017 made annual payments of around JPY500 million for clinical
trials. Direct costs alone therefore had totaled at least JPY2 billion. Indirect costs
and future profits foregone makes up the remainder of SymBio’s claim. The
Medicines Company, however, does not agree with the claim. All things
considered, it is as well to assume that SymBio is planning to raise cash.

15/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
Time-Line (reference)Issue Date Feb.19 2018

SymBio was established in March 2005 by Fuminori Yoshida, who had previously
been Corporate Vice President of the US company Amgen Inc., and had also served
as President of Amgen Japan. Initial funding of JPY1 billion for the licensing-in anddevelopment of TREAKISYM® was provided by, among others, Daiichi
Pharmaceutical Co., Ltd.., (now known as Daiichi Sankyo Inc.), EPS Corporation,and SBI Holdings, Inc. In December 2005, SymBio signed a licensing agreementwith Astellas Pharma in Germany (now known as Astellas Deutsche) for the soledevelopment and sales rights of Treakisym in Japan. The development of
TREAKISYM® subsequently proceeded favourably and in August 2008 SymBio
licensed out the sales rights to Eisai Co., Ltd.
The company faced a shortage of funds for development following the “Lehman
Shock” of September 2008. The president, Fuminori Yoshida, visited more than 50
venture capital funds and other institutions around the world and SymBio overcame
its problems with an infusion of JPY1.5 billion from the bio-venture firm, Cephalon.
The two companies maintained good relations subsequently. Cephalon is now awholly-owned subsidiary of Teva Pharmaceutical Industries, having been bought
out in May 2011.
In October 2010, approval was given for the production and sale in Japan of
TREAKISYM® for relapsed/refractory low-risk NHL (see section on types ofmalignant lymphoma). The product was launched in December, making SymBio arare example in Japan of a bio-venture with an actual product in the market. The
company then listed on JASDAQ in October 2011.
While sales of TREAKISYM® continued to steadily grow, the company won approval
to expand its application to chronic lymphoma leukemia in August 2016, and tountreated patients with low-grade NHL in December. Phase 3 Clinical trials are also
underway with a view to expanding the indications to recurrent refractory high-riskNHL. At the same time, the company is working on product lifecycle management
via drug formulation changes, and has signed a Japan development andcommercialization rights agreement with the US company Eagle Pharmaceuticals
Inc. covering easy-to-use liquid formulations (RTD and RI formulations).
The company’s second promising candidate drug after TREAKISYM® is rigosertib,
which the company licensed in from the US company Onconova Therapeutics inJuly 2011. SymBio participated in Phase 3 international joint trials from December
2015 and continues to pursue development. As of January 2018, Phase 3 interim
analysis has been released and tests are being continued on additional cases (refer tothe earlier pipeline discussion).
In October 2015, SymBio contracted to license in from the US company, The
Medicines Company, the patient-controlled pain management drug, IONSYS®
(lump sum contract payment JPY1 billion). Phase 3 trials began in Japan in June
2016 but in May 2017 the licensor abruptly announced it was withdrawing. Patient
enrolment was therefore halted and in November 2017 the agreement was
terminated. The company has applied for arbitration claiming compensation of
approximately JPY9 billion.
(Refer to “Licensing-in and development timeline” at the end of this report)

16/18
This report is prepared by Fair Research Inc. (Fair Research) for the purpose of providing information to investors, and not for solicitation of securities trading. Although this is based on
information and materials that Fair Research judges reliable, there is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Fair Research shall not take any responsibility
whatsoever for any results including direct or indirect damages arising from the use of, or reliance to, this report. Investors should take their own responsibility for securities and other transactions. The
intellectual property rights of this report belong to Fair Research, and any copy, transmission or quotation of any contents without permission is legally prohibited.

Issue Date Feb.19 2018
SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Dec.2005

March.
2006

Licensing-in and development timeline

Approved for chronic
lymohoma leukemia

r/r medium to high-risk NHL

Start of patient enrollment for Phase 3

Phase 3 trials start for r/r medium-highrisk NHL

Phase 2 starts

Phase 1 starts(Medium/high risk NHL)

L-0501, C-0501,L-1701,L-1702)

1st in-licensed product
Treakisym （SyB
Licensing contract with
Astellas Pharma (nowAstellas Deutsche)(Low-risk NHL)
Phase 1 starts

Phase 1 completed
Phase 1 starts

Sept. 2007
Dec.
Grants Eisai joint
development and sales

Applic.to use on r/r low-risk
NHL and mantle cell

Phase 2 completed

Aug. 2008
OctoberMar. 2009
OctoberApproved for use on r/r low-Mar. 2010
October

1st Line patients Phase 2
startsrisk NHL and mantle cell
Sales start in Japan

Nov. 2011

Chronic lymphoma

DecemberMay 2013

Aug, 2016

leukemia Phase 2 starts

Decemberand RI formulations inJapan

Pharma forcommercialisation of RTD

Contracts with Eagle

Approval for additional
indication - 1st Line

Aug. 2017

SeptemberJan. 2018

Start of Phase 1 trials of oral
formulation for solid cancers

Source: compiled by Fair Research Inc. from multible materials

5th in-licensed product

SyB 0702(Developed in-house)

Inhibitor

IONSYS (patient-controlled pain management)

Started development at thecompound stage. Terminatedbefore Phase 1.

establishmnet of POC, because
NEDO funding was obtained.

for Gleevec-resistant leukemia
cells. This was before theAcquired exclusive rights
worldwide for SyB 0702, effective

HSP32

4th in-licensed product

Licensing-in agreement with The
Medicines Company（SyB P-1501)

Rigosertib（SyB L-1101 injection

Licensing-in agreement withand C-1101 oral）

SyB 1001

After being bought by Teva,

rights from Cephalon Inc.
subsid. Anesta

Licensed in Japan joint dev.

For systemic lupus erythematosus

3rd in-licensed productAntiemetic

June 2010

Oct. 2011

Onconova Therapeutics

SymBio starts Phase 1 trials for r/r
MDS

Oct. 2015

Phase 3 starts

Licensor withdraws, patient
enrollment terminatedJune 2016

May 2017

Licensing agreement cancelled,arbitration petitioned

NovemberAug. 2007

SyB D-0701

Licensing-in from
AbeillePhase 1 starts
Phase 1 completed

Phase 2 starts

dev. rights were ceded to
ImmuPharma so dev. halted

June 2012

additional cases

INSPIRE interim data leads toHigh-risk MDS SymBio Phase I (oralmonotherapy)

trialsSymbio joins global Phase 3 INSPIRE

r/r MDS

SymBio completes Phase 1 trials fortrialsOnconova starts Phase 3 INSPIRE

trialsOnconova completes Phase 3 ONTIME

Aug. 2015

Feb. 2014

July 2011

2nd in-licensed productMar. 2007
October
July 2008

Dec.2010

Dec. 2013

Development stopped
due to change inlicensor strategy.
Target changed but
effectivenes notdemonstrated

Oct. 2015

Dec .2015

June
2017

Jan. 2018

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SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Issue Date Feb.19 2018

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