ANALYST NET Company Report

SymBio Pharmaceuticals Ltd.
Issued June 1, 2021

（4582 JASDAQ）

New Direction for SymBio - Building on Success
From drug discovery venture to global specialty pharma
SymBio Pharmaceuticals Ltd. does not undertake research in new drugs. Rather, it
relies on a worldwide network of drug discovery companies and its own expertiseto adopt and develop promising new drugs. It occupies a niche, seeking to maximise
market share and earnings by focusing on areas of medical need in rare diseases(particularly hematopoietic tumours) unmet by the drug majors. Most of the drugcandidates it takes on already have a proven record of efficacy and safety, whichmakes them a low-risk development proposition. The company’s first drug was
Treakisym®, which was approved and launched five years after being adopted by
the company and was accorded standard treatment status in 2018. With thecompletion of its switch to in-house sales in 2020 it became a pharmaceuticals
company specialising in hematology. In September 2019, the company acquired thesole global license (development, manufacturing and sale) for brincidofovir, its third
product, thereby laying the groundwork for its evolution into a licensor with a global
reach embracing firstly Asia and extending to the US.
Beginnings of the company’s second stage of development

Basic Report (revised)
Fair Research Inc.
Tsuyoshi Suzuki

Company Outline
LocationTokyo

President

Fuminori Yoshida

EstablishedMarch 2005

Capital

JPY17,070mil

ListedOct. 2011

With the approval in March 2021of Treakisym®, the company’s main product, forthe treatment of r/r DLBCL, the market size almost doubled. Further, sales of the
RTD liquid formulation began in early 2021, and an application for a rapid infusion(RI) formulation was completed in May of the same year. Through changes informulation the company prolonged patent life and significantly increased
profitability, securing its first profitable year in 2021. Looking ahead, the company
plans to team up with academia in the development of new therapies using novel
Treakisym® and brincidofovir mechanisms. The company also plans to expedite
the global development of brincidofovir to treat viral infections following
hematopoietic stem cell (HSC) transplantations. In fact, in February 2021 thecompany submitted an IND to the FDA for Phase 2 trials relating to adenovirus
infections after HSC transplantations. Fast track status was acquired for trials onchildren. Further, the company is now also planning to develop in Japan a treatment
for viral hemorrhagic cystitis following HSC transplantations. In this way, SymBio
intends to use a certain percentage (15-20%) of operating revenues fromTreakisym® to fund a second stage in global development to maximise the value of
its product pipelines.
Will maintain earnings growth momentum and then evaluate development

URL

www.
symbiopharma.com

Industry

Pharmaceuticals

Employees

127 (unconsol.)

Until Treakisym® reaches its sales peak it is likely to exhibit strong profit growth
momentum, reflecting a high profit margin. While the imminent acceleration of
brincidofovir development may deplete some of the momentum it seems more thanlikely that earnings will continue to grow until around 2026-2027. Treakisym®
sales will then reach their peak and a pause in earnings growth will set in. However,the development of brincidofovir and of Treakisym® to treat solid cancers will bythen be almost ready to produce future expansion. EPS growth may come to a halt,
giving way to a phase of earnings multiple expansion.

Key Indicators as of May 31 2021

Share price

1,889

52-week high1,889

52-week low
Sharesoutstanding
Trading unit

337
38,414,806

Market cap

JPY72,950 mil

Est. dividend

0.0

Forecast EPS

JPY30.1

Forecast PER

63.11X

Actual BPS

JPY100.64

Actual PBR

18.87X

100 shares

Note: EPS, PER, BPS and PBR based onshares outstanding, excl. treasury shares

Net Income YoY
JPYmil％EPS
JPY

Share Price (JPY)
High
Low

Results

Revenues
JPYmilYoY％

Op. Income
JPYmilYoY％R.P.
JPYmilYoY％

2016/12 Actual

2,368

22.5

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

NA

-58.8

509

170

2017/12 Actual

3,444

45.4

-3,947NA-3,976NA-3,977

NA

-79.7

335

196

2018/12 Actual

3,835

11.4

-2,656NA-2,748NA-2,752NA-165.5289

115

2019/12 Actual

2,837

-26.0

-4,301NA-4,376NA-4,376

NA-189.0275

150

2020/12 Actual

2,987

5.3

-4,506NA-4,615NA-4,090NA-124.1653

243

2021/12 Forecast

9,151

206.4

1,361

NA

1,350

NA

1,149

NA

30.1

1/28
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
whatsoever 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）

Issued June 1 2021

Company Outline and Philosophy
SymBio Pharmaceuticals Ltd. is a global specialty pharma with a focus on rare
conditions with high medical need but paid little attention by the major
pharmaceutical companies in the area of cancer and hematology. Its involvement
The company is engaged in extends from clinical trials, rather than the high-risk area of drug discovery, throughdrug discovery without the to sales activity. The company’s business model has three characteristics:
risks
presented
bylaboratories
ormanufacturing.
It
has ① Post-POC strategy
The company does not itself undertake drug discovery research but investigates
evolvedfromacandidates developed by drug discovery ventures and pharmaceuticals
pharmaceuticalventurecompanies around the world. Usually, proof of concept has already been
operating a niche strategy inestablished. By insisting on prior evidence of efficacy and safety in humansearch of high returns to a
subjects the company reduces the development risks of new drug candidates.
global specialist pharma.
Business Model② SymBio is a specialty pharma operating a high return, high market share niche
strategy.
The company focuses its efforts on drugs for relatively rare indications in, forexample, cancer and hematology, where the need is high, but where the major
pharmaceuticals companies are relatively unrepresented. Using this niche
strategy, the company seeks high market share and high returns. Until 2020, The
company’s business model involved entering into licensing agreements
covering new drug candidates it has selected, developing them in Japan and thenlicensing out to other pharmaceuticals companies. However, it has now set up
its own sales function in Japan and has established itself as a pharma
specialising in hematology.
③ Evolving into a global licensor
Further, in September 2019, SymBio acquired exclusive rights (development,
production and sales) to brincidofovir, a product with global applications.
SymBio has thus evolved from a company seeking licenses in Japan to one
providing licenses around the world, firstly in Asia, including China, and also
the US and Europe.

The key to returns is thecompany’s network of drug
discovery companies and its
own expertise
SymBio is an unusual bioventure in that its first
product on the market took
only five years frominception to regulatory
approval

The success or failure of this business model is dependent on the company’s
network of pharma-collaborators around the world and the company’s own
expertise. Hence, the company’s track record. Normally, it takes some 10-20 years
to bring a drug from basic research to the market. In terms of the probability ofsuccess, some estimates suggest that, counting from the chemical compound stage,
it is less than 1/30,000, and even from the POC stage, only around 7-8%. But
SymBio managed to get its first product, Treakisym®, from adoption in 2005 to
manufacturing and sales approval in 2010, a period of only five years. In July 2018
Treakisym® achieved recognition as a standard therapy in the area of malignant
lymphomas. In the fifteen years since the company was founded, six products havebeen licensed in, and so far three of them are actually under development or at theplanning stage.

We believe this track record has been made possible by the expertise of thecompany’s staff and by the way the company is organised. SymBio has a staff of155, of whom 55 are involved in R&D (as of end of 2020). The drug search function
is supported by a Scientific Advisory Board (SAB) of experts (including Nobel Prize
Its network and expertise are candidates). Needless to say, a major role has been played by the company founderenhanced by an outstanding and CEO, Fuminori Yoshida, who developed the network and contributes his
expertise.
workforce

2/28
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
whatsoever 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）

Issued June 1 2021

Main events
2005/3

SymBio established2005/12Acquires from Astellas in Germany the exclusive rights in Japan for the development and sale of bendamustine

2008/8Concludes with Eisai an agreement on the sale in Japan of freeze-dried bendamustine

2010/10

Acquires approval for manufacture and sale of Treakisym® (freeze-dried bendamustine) in Japan

2010/12Starts sales of Treakisym®

2011/7

Concludes rigosertib licensing agreement with US company Onconova Therapeutics Inc.

2011/10

Listed on JASDAQ

2015/8Onconova re-designs rigosertib tests and starts joint international Phase 3 (INSPIRE ) trials

2015/10The Medicines Company in the US acquires sole development and sales rights in Japan for IONYS® post
operative self-administered pain management medicine

2016/5

Treakisym® approved for additional indication in Japan - chronic lymphocytic leukemia

2016/8

Approval given for expanded indications in Japan for low-malignity non-Hodgkin's lymphoma and mantle cell
lymphoma2017/9Acquires from US company Eagle Pharmaceuticals the sole rights in Japan to develop and sell bendamustine
liquid formulation (RTD and RI preparations)

2017/10

Petition seeking arbitration for damages due to non-performance of The Medicines Company's agreement on
license for IONSYS®

2017/11IONSYS® agreement cancelled

2018/7

Approval of Treakisym® and Gazaiba® combined treatment for follicular lymphoma (CD positive)

2018/7

Treakisym® listed for the first time in the Hematopoietic Tumor Clinical Practice Guidelines (2018 Edition) as afront-line treatment for malignant lumphomas

2019/3Treakisym® approved as pre-treatment for Kymriah CAR-T treatment of r/r acute lymphocytic leukemia

2019/9Acquires sole global license for development, manufacture and sale of the anti-viral agent BCV from the US
company, Chimerix (excludes smallpox)

2020/8Top-line results of internatonal joint Phase 3 (INDPIRE) trials on rigosertib show no significant difference fromphysician-chosen treatment

2020/9Approval given for the Treakisym® RTD formulation on existing indications

2020/9IONSYS® arbitration handed down: SymBio to receive half the costs of arbitration-related costs

2020/12

SymBio takes over sales of Treakisym®

2021/1Enters agreement with the Institute of Medical Science, Tokyo University on joint research into discovering new
indications for which bendamustine and rigosertib night be indicated2021/3Phase 2 trials start in the US to test BCV targeting adenovirus infections following HSC transplants

2021/3

Combined Treakisym® and Rituxan® therapy approved for treatment of r/r DLBCL

2021/3

Combination of Treakisym® Rituxan® and Polivy® approved

2021/4Treatisym RTD liquid formulation approved for r/r DLBCL treatment

2021/4Development of BCV targeting adenovirus infections in children given fast track examination status

2021/5

Application submitted for approval of Treakisym® RI formulation

Source: Compiled by Fair Research Inc. using securities reports and other sources

3/28
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
whatsoever 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）
Main product pipelines

Issued June 1 2021

As of May 2021, the company’s main product pipelines consist of Treakisym®,
rigosertib and, since its introduction in September 2019, brincidofovir.
1. Treakisym® (SyB L-0501 (freeze-dried injection formulation)/SyB L1701 (RTD liquid formulation)/SyB L-1702 (RI liquid formulation)

Treakisym® (generic name: bendamustine) is a cancer drug developed in Germany
in 1971. It is used to treat malignant lymphomas, particularly the less malignant nonHodgkin’s lymphoma and chronic lymphocytic leukemia.
Reference: malignant lymphomas
Lymphoma is a blood disease caused by the cancerisation of immunity cells called
lymphocytes (a type of leukocyte). There are two major types: Hodgkin’s lymphoma(HL) and non-Hodgkin’s lymphoma (NHL). 94% of malignant lymphomas in Japan are
NHL, which can be classified into the following three types depending on speed of
disease progression (the NHL’s for which Treakisym® is indicated are highlighted in
red).

Types of malignant melanoma

Source: Eisai and SymBio’s “Treatment Guide”

4/28
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
whatsoever 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）

Issued June 1 2021

(1) Progressive expansion of authorised indications
Treakisym was approved
within a mere five years of
In December 2005, SymBio acquired exclusive development and sales rights tolicensing-in,
following
Treakisym® in Japan from the Astellas Pharmaceuticals European subsidiary (nowwhich there was an
named Astellas Deutschland GmbH). It began clinical trials and, within a mere 5
expansion of indications
years, in October 2010, it received approval for two indications, low malignancy
recurrent/refractory NHL and mantle cell lymphoma (below, MCL) and, in
After its initial authorisation December, commenced sales. Further approvals were received in August 2016 forin 2010 Telmelysin® was chronic lymphocytic leukemia (below, CLL), and in December for untreated lowauthorised for two further malignancy NHL/MCL. Finally, in July 2018, with respect to all approved
indications in 2016, with a indications, Treakisym® was newly listed in the Guidelines for Clinical Practice inconsequent increase in Hematopoietic Tumours for 2018 (edited by the Japanese Society of Hematology)
market penetration
as a standard treatment option.
Treakisym has been used asa standard treatment since
July 2018

Behind this was the demonstration of the superiority of the B-R therapy combining
Treakisym® (generic name: bendamustine) and rituximab over the conventional
standard CHOP-R therapy (see comparison of the two therapies in the chart below).
Comparative tests of CHOP-R and B-R therapies

Source: SymBio company briefing materials showing superior results of B-R therapy

Market penetration proceeds
well until 2018

Note: CHOP-R therapy
Chemotherapy combining the molecular targeted drug rituximab with the cancer
drugs cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and thesteroid prednisolone.

Once it had established itself as a standard therapy Treakisym® carved out a risingmarket share, from an average annual level of 35% in 2017 to a level of 56% at theend of September 2018. It thus easily surpassed the erstwhile standard R-CHOP
therapy, and in 2018, its 8th year, it chalked up domestic sales of JPY8.5 billion(regulated drug price basis).
After a short-tem period ofstagnationsales
are There was subsequently a temporary period of stagnating sales (in 2020 domestic
expected to bounce back sales totaled JPY8.1 billion on a regulated drug price basis) due to quality control
with the extension of problems at a supplier and swings in inventories as a result of the company’s switch
approved indications to r/r to in-house merchandising. However, this has been offset by a further expansion in
authorised indications and the number of patients is expected to double. More
DLBCL
5/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

precisely, in March 2021 authorisation was received for the treatment ofrelapsed/refractory large B-cell lymphoma (r/r DLBCL) using the B-R therapy andthe B-R + Polivy® therapy. We expect sales for the expanded indication to become
more apparent in the second half. We estimate 2021 domestic sales at around JPY11.3
billion rising to a possible JPY15-17 billon eventually (see Treakisym® market size
below).
Note: In Japan, the most common form of medium-malignancy NHL is the r/r DLBCL

Reference
Results of the Phase 3 trials of the B-R therapy targeting r/r DLBCL wereannounced at the European Hematology Association conference in June 2020.
The overall response rate (ORR) reported was a high 76.3%, and the complete
response rate (CR) was 47.4%. An important finding was the efficacy in elderly
patients (age 65 and over) for whom HSC transplantation was not the standard
therapy. In addition, it was reported that the complete response for non-GCB
DLBCL’s, which have a poor prognosis, was 39%. The release of data on the main
endpoint, overall survival, is expected in the first half of 2021.

Results of Phase 3 trials of the B-R therapy targeting r/r DLBCL(n)

ORR(%)

38

76.3

47.4

28.9

～64 years old

7

85.7

71.4

14.3

65～74 years old

20

75.0

45.0

30.00

75～ years old

11

72.7

36.4

36.3

All patients

CR(%)

PR(%)

Response rate by age

Source: SymBio company briefing materials
About 73% of DLBCL patients are 65 years or over. They have traditionally beenoffered a multi-drug therapy but the side effects caused by taking a combination ofmultiple anticancer drugs has been a problem. Patient groups and academics havealso petitioned for the early use of the B-R therapy.

(2) Increase in combination therapies
Treakisym® is estblishing Treakisym® is gradually becoming a crucial component in the area of treatments foritself as crucial in blood blood cancers. In the field of hematological cancers targeted by Treakisym®, various
cancer therapies
new therapies have emerged in recent years (see below), but in each case,
Treakisym® is used in combination with new drugs. We provide below a few
examples:A
numberofnewcombination therapies tosupplememt the B-R therapy
is on the way①

In July 2018, a combination of the anti-CD20 antibody obinutuzumab(commercial name: Gazyva) and Treakisym® was approved for thetreatment of CD20 positive follicular lymphoma, thereby providing a new
therapeutic option.

Note: follicular lymphomas account for around 80% of low-malignity nonHodgkin’s lymphomas② The CAR-T therapy (drug name: Kymriah) developed by Novartis is awell-known ground-breaking therapy for leukemia and other
6/28
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
whatsoever 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）

Issued June 1 2021

hematopoietic tumours. In March 2019, it was also approved in Japan forrelapsed / refractory acute lymphocytic leukemia (ALL) and DLBCL.
Treakisym® has been approved for use as a concomitant drug in CAR-T
therapy pre-treatment, rather than as a CAR-T therapy competitor.
③ In June 2019, the FDA announced the expedited approval of a three-drugtherapy for the treatment of surgery ineligible relapsed or refractory
diffuse large B-cell lymphoma (r/r DLBCL). This therapy consists of the
B-R therapy of bendamustine (Treakisym®) + rituximab (Rituxan®)
together with the anti-CD79 antibody drug-conjugate polatuzumab
vedotin (product name: Polivy®, developed by Genentech and Roche). In
Japan, an application for approval of the combined B-R and Polivy®
therapy was submitted by Chugai in July 2020 and approved in March
2021. While the amount of Treakisym® required for the B-R therapy alone
is 120mg per dose, for the three-drug therapy it is 90mg. However, we
think the decision on whether to select the B-R therapy or the P-BR
therapy will be made by doctors on the basis of the patient’s condition andgenotype, so neither will become dominant.
④ According to SymBio, a large number of new therapies for blood cancers
combining other drugs, particularly immune checkpoint inhibitors, with
the B-R therapy (B-R +X), are being developed in the US and Europe,
As can be seen from the above, the B-R therapy has already become a crucialcomponent in the area of hematopoietic tumours, and since new add-on therapies arebeing developed it is unlikely to be challenged by other treatments.
Note: The B-R therapy results (response rates, progression free survival of 69.5
months) produce very high readings, such that new drug candidates are unlikely, as
single agent therapies, to do meaningfully better.

(3) Life-cycle management using formulation changes
Progress is also being madein life-cycle management
through
formulation
changes

Sales
of
the
RTD
formulation
began
inJanuary 2021, and approval
for expanded indications
was received in March

Until December 2020 the Treakisym® sold was the freeze-dried (FD) formulation
manufactured by Astellas Deutschland GmbH. In 2020, 10 years had passed since
Treakisym® was approved and from 2021 there is a risk of competition fromgenerics. Preparations have therefore been made to extend the product’s life to 2031
by means of new formulations.
As a first step, on 21st September 2017, SymBio announced it was licensing in readyto-dilute (RTD) and rapid infusion (RI) formulations from the US company, Eagle
Pharmaceuticals Inc. While the FD formulation has the advantage of roomtemperature storage it is time consuming and troublesome because of the need todissolve in a solvent and to dilute in physiological saline prior to administration. In
the case of a liquid formulation, while refrigerated storage is necessary, the burden
on medical staff is reduced because it only requires dilution in physiological saline.
The switch to a liquid formulation should also mean an appreciable reduction in
cost.
The company came to an understanding with the Pharmaceuticals and Medical
Devices Agency (PMDA) that, since efficacy and method of administration was thesame as for the FD formulation, no additional tests would be required andpharmacological stability data alone would suffice for approval application
purposes. It then submitted an application in September 2019, received approval in
September 2020 for the treatment of existing approved indications, and launched in
the market on January 12, 2021. The RTD formulation was also approved for the
additional r/r DLBCL indication in April 2021. Liquid formulations accounted for
20% of SymBio’s output in the first quarter of 2021 but should reach 91% by theend of the year.
7/28

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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

Comparison of the FD, RTD and RI formulations

Source: SymBio results meeting materials
Reference: Having launched a freeze-dried formulation in 2014, the US
company, Teva Pharmaceuticals Industries, in January 2016 launched an
RI preparation (product name: Bendeka®, licensed in from Eagle
Pharmaceuticals) which is more easily administered). In only two years
Bendeka® accounted for 97% of the Treakisym® market.

Has reached the application
stage for the RI liquid Since the RI liquid preparation has a different concentration and administration time,
a number of clinical tests to confirm safety and investigate pharmacokinetics were
formulation
undertaken before submitting an application in May 2021. With its 10-minuteadministration time and low salt content it is regarded as particularly suitable for theWith the introduction of many elderly patients with malignant lymphomas. Regulatory approval and market
liquid formulations the launch is expected for the second half of 2022. With the introduction of liquid
product’s life cycle is formulations the product’s life cycle will be extended until the end of 2031.
extended to 2031
(4) Search for new modes of action

Moving on to developmentof novel therapies outside
the area of hematologicalcancers by focusing on
novel
Treakisym®
mechanisms

The extension of indications to r/r DLBCL marks the completion of Treakisym
development on malignant lymphomas. However, separate research has pointed tothe existence of novel Treakisym® mechanisms (STAT3 inhibition, LUBAC
inhibition). SymBio’s policy is to expand its corporate value through joint researchwith academia, and by locking in on medical targets that make full use of AI,
promoting research on the possibility of developing therapies for other cancer types,
such as solid tumours, and the development of new therapies in combination withother drugs. By further developing Treakisym® it aims to make SymBio a global
company.
The direction of further Treakisym® development
Bendamustine◆B+R+（X)
Alkylating agent◆STAT3 inhibitor

Purine derivative◆LUBAC inhibitor

1960~1999

2000~2025

In E. Germany two scientists first synthesiseStandard combination therapy withrituxan for relapsed/refractory lowgrade NHL, MCL and CLL

Alkylating agent and purine deivative together
are anti-cancer agent

Further research results suggest
new modes of action (STAT3
inhibition, LUBAC inhibition)

Widely used for breast cancer, bladder cancer,
small cell lung cancer, NHL, , multiple
myeloma, etc.

Approval expected for r/r DLBCL
indication

WHAT's NEXT?

2026~
Joint research with academia
AI harnessed in search for new
disease targets
Patent strategy for new therapies
Global development

Source: SymBio company briefing materials(the r/r DLBCL indication in the centre panel received approval in March 2021)

8/28
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
whatsoever 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）

Issued June 1 2021

2. Rigosertib (SyB l-1101 injection formula; SyB C-1101 oral
formula)Rigosertib is a cancer drug indicated mainly for myelodysplastic syndromes (MDS)
developed by Onconova Therapeutics Inc. in the US. After Onconova completed
Phase 2 clinical trials in July 2011, SymBio acquired sole development and sales
rights for injectable and oral formulations in Japan and South Korea (the one-off
contract payment is estimated at around JPY800 million).
(1) Development timeline
SymBio was responsible for the Japanese part of the joint international Phase 3
clinical trials targeting high-malignity MDS patients who had not responded to thestandard treatment using hypomethylating agent (HMA) or who had experienced arecurrence after treatment.

Rigosertib
was
being
developed as an injection
and oral formula mainly fortreating
myelodysplastic
syndrome

Onconova Therapeutics completed Phase 3 (ONTIME) trials targeting
relapsed/refractory high-risk MDS in February 2014. The results of these trials
showed no statistically significant difference in overall survival (OS) between thecohort receiving rigosertib and the control group (palliative care). However, there
was a significant difference to overall survival when limited to patients who wereresistant to the HMA standard treatment or whose condition had deteriorated during
prior treatment. The OS for the patient cohort receiving rigosertib was 7.9 months
versus 4.1 months for the control group. On the basis of these partial results
Onconova revised the trial design and from August 2015 proceeded withinternational collaborative Phase III clinical trials (INSPIRE trials) targeting highrisk MDS patients who were unresponsive to HMA or had a relapse after treatment.
SymBio was responsible for the Japan segment of the Phase 3 trials.
Reference: The International Prognostic Scoring System classifies high-risk MDS
into higher risk and medium risk, with the latter subdivided into two risk levels, thehigher of which denotes a likelihood of transitioning to leukemia. Currently, thestandard treatment is administration of azacitidine (trade name Vidaza) anddecitabine (trade name Docagen), but some high-risk MDS occurrences are resistantto the standard treatment or relapse after treatment. Rigosertib is indicated for such
relapsed or refractory high-risk MDS, and there are at present no competing
approved drugs,

However, unforeseen difficulties became apparent in the development of the highrisk MDS injection formulation. On 24th August 2020, Onconova released the topline results of the INSPIRE trials, the primary endpoint of which was overall
survival (OS). Unfortunately, the results showed no significant difference in OS
between injection rigosertib (6.4 months) and physician’s choice of treatment (6.3
months) (The P value was 0.33).
Onconova conducted joint international Phase 3 trials of the oral formulation
targeting untreated high-risk MDS, whose results suggested efficacy and safety(SymBio in 2019 completed tests confirming safety and tolerability).
9/28
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
whatsoever 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）

Issued June 1 2021

(2) Onconova’s development strategy
Elsewhere, Onconova is pursuing development which stresses rigosertib acting as a
RAS mimicking molecule. On June 22, 2020, Onconova began patient registrations
for an investigator-led study (Phase 1 / 2a) of the effect on KRAS (G12D)-positive
advanced non-small cell lung cancer of a therapy combining immune checkpoint
inhibitor nivolumab (Opdivo®) and rigosertib (orally administered). Further, on
April 22, 2021, Onconova announced it had begun patient registrations for Phase 2
investigator-led tests of rigosertib (injection formula) as a treatment for locallyadvanced / metastatic squamous cell carcinoma related to recessive malnutritiontype epidermolysis bullosa.
Reference: Rigosertib as a RAS mimicking moleculeNo significant difference
observed in Phase 3 joint
international trials

It has been established that rigosertib acts as a RAS mimetic molecule. It is thoughtthat rigosertib competitively inhibits the activated RAS from binding to signaling
molecules (in the figure below these are RAF, and additionally PLK, RAL, and PI3K).
In so doing it is thought to block the RAS-RAF-MAPK signaling pathway, suppressing
RAS-generated carcinogenesis.

Rigosertib’s mode of action

Onconova
beginningdevelopment focused on
RAS mimicking molecule
effectSource: Cell Magazine, 165 (3).643, April 21, 2016, quoted in SymBio’s company
briefing materials

In addition, it is thought that KRAS, a type of RAS, has a significant effect on thecancer micro-environment. That is, the activation of KRAS leads to enhancement ofa type-II macrophage (M2) and MDSC, which suppresses immunity, and further
enhancement of IL-6, which suppresses T cells and the like. KRAS inhibitors arethus thought to have a synergistic effect, altering the cancer immune environment
and enhancing the effectiveness of immune checkpoint inhibitors.

10/28This 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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

KRAS signals and the cancer micro-environment

Source: Onconova Therapeutics. “Key Opinion Leader Meeting”, February 7, 2019(3) SymBio’s development strategy
SymBio will search for synergistic effects from different mechanisms of action andtarget new illnesses. To do this it will use additional analysis of the INSPIRE tests,
joint research with the Institute of Medical Science of the University of Tokyo(contract concluded in January 2021), combined with analysis and hypothesis
verification using artificial intelligence. It has been suggested that rigosertib has an
inhibitory effect on microtubule polymerization (destabilizing microtubules) inaddition to its action as a RAS mimetic molecule, in addition that the effects of
SymBio could be ready with Treakisym® and azacitidine may be enhanced by rigosertib. The company therefore
a revamped development intends to explore the possibility of oral combination therapies with existing drugs,
policy within 2021
including Treakisym® The company will also apparently use AI analysis techniques
to identify potential new diseases to target and, within the year, will draw up arevamped rigosertib development plan.
SymBio is exploring thepossibility of a therapy
combining oral rigosertib
and another drug

Rigosertib and Treakisym® (bendamustine) combination possible●STAT3 inhibition

Expected results＝＞ Suppression of proliferationand drug resistance●BENDA+RIGO combination therapy●LUBAC inhibition＝＞ Inhibits activation of NF-k β● Combining with other agents to create new therapies●RAS inhibition● Provides pathway to complementary relationships●Destabilizing microtubules● New insights into full cancer therapies● Non-cancer therapies

Source: SymBio company briefing materials

11/28
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
whatsoever 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）
3.
BCV is anantiviral drug

Issued June 1 2021

Brincidofovir （SyB V-1901）

advanced Brincidofovir is a highly active multiviral infection drug developed by the US
company, Chimerix Inc.

The company acquired
exclusive global rights for
all indications excluding
smallpox

On October 1, 2019 SymBio announced it had acquired from the US company,
Chimerix Inc., exclusive global rights (development, manufacturing andmerchandising) to brincidofovir (BCV) for all indications except smallpox, making
BCV the company’s third strategic product after Treakisym® and rigosertib.
SymBio had until now been an acquirer of licenses from overseas for mainly
domestic development but this acquisition allows it to evolve into a provider of
product licenses globally.
Reference: Why Chimerix retains all rights pertaining to smallpox
The US Biomedical Advanced Research and Development Authority (BARDA) has
provided Chimerix with more than USD100 million to develop BCV as one element
in countering bio-terror. The FDA has accorded BCV fast-track and orphan drug
status, and Chimerix’s application in December 2020 for approval of BCV targetingsmallpox is expected to complete examination procedures on 7th July 2021.

(1) Brincidofovir characteristics
Compared to other anti-viral drugs such as cidofovir (CDV) and foscarnet (FOS),BCV is highly active and effective against multiple infectious diseases.
Brincidofovir (BCV) is highly active across a broad spectrum

Comparedtootherantivirals, BCV is highly
active and is effective acrossa broad spectrum

Source: Chimerix Inc.
Note: EC50 (the concentration at which a drug or antibody shows a 50% maximum
response from the lowest value) indicates that the lower the number, the higher theactivity. In the above chart, EC50 is color-coded depending on the level. Green has
high activity and red has low activity. The left-most BCV column is green for various
viruses = has a broad spectrum

12/28This 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
whatsoever 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）

Issued June 1 2021

Reference: cidofovir (CDV)
Was approved by the FDA in 1996 for the treatment of cytomegalovirus retinitis in
AIDS patients. CDV is a cytosine nucleotide analog which inhibits the replication of
DNA viruses such as adenovirus, papillomavirus, and polyomavirus as well as theherpesvirus family. CDV is also effective against ganciclovir (GCV) resistance (UL97
gene mutation) and is thought to be of utility when foscarnet (FOS) cannot be
administered due to the development of GCV resistance. It is not approved in Japan.

As can be discerned from the previous figure, cidofovir (CVD) has a similar levelof activity across as broad a spectrum as BCV. However, while CVD is nephrotoxic
and difficult to use, BCV has low toxicity and is very safe despite being highly
active.

Additionally, highly stable
and low nephrotoxicity(2) BCV mode of action
Brincidofovir (BCV) has a structure in which a fatty chain (hexadecyloxypropyl: HDP)
is bonded to cidofovir (CDV) and is rapidly taken into a lipid bilayer membrane andefficiently translocated into cells. The compound whose fatty chain is cleaved bymetabolism by intracellular phospholipase and the generated activated form (CDV-PP:
CDV diphosphate) is retained in the cell for a long time, resulting in a dramatic
improvement in antiviral activity. In addition, because HDP binding does not cause
accumulation of renal tubular epithelial cells by the OAT-1 transporter and the low levelof CDV released into the blood, nephrotoxicity, a fundamental problem of CDV, isreduced. (Because CDV does not have a fatty chain, the rate of incorporation into cells
is low, and a high concentration is required to enhance the effect, with nephrotoxicity
the likely outcome.)

Source: SymBio IR materials

The target indications areviral infections resulting
from the transplantation ofhamatopoietic stem cells,and viral infections causedby organ transplantations.
The former would be given
priority in light of thecompany’s ambition of
becomingaspecialist
pharma in the area ofhematology(3) Indications
In general, in the case of hematopoietic stem cell (HSC) transplantations and organtransplantations（ZOT）, irradiation and immuno-suppressants are used to suppress
rejection, thus rendering the patient vulnerable to infection. It used to be that CDV,FOS or some other anti-viral drug was used to offset this, but with the risk of causing
a nephrotoxic side-effect. Hence, the importance of BCV, which has low
nephrotoxicity, to SymBio's goal of becoming a specialty pharmaceuticals company
in the region of hematology.
SymBio was planning to use BCV to treat viral infections after HSC
transplantations, an area with poor prognosis, high lethality, and strong unmet
medical needs. After a meeting of the company’s Global Advisory Board in February
13/28

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
whatsoever 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）

Issued June 1 2021

2020 it was decided that that the first development target would be adenovirus
infections contracted after HSC transplantation, and that tests on children would be
The company would make agiven particular priority. Since Chimerix data had already confirmed safety, the first
start
with
adenovirus
step would be Phase 2 dosing tests, after which, when trials on children had begun,
infections following HSC
adult dosing tests would start.
transplantations,
withinwhich it would prioritisechildren.
It is estimated that worldwide there are some 78,000 HSC transplantations a year, of
which around 43,000 are autologous, and therefore less subject to rejection. There
are some 35,000 allogeneic transplants in which immunoreactions need to becontrolled to suppress rejection, and which are highly vulnerable to viral infection.
These are on the rise.
BCV lifecycle management

Source: SymBio Pharmaceuticals results meeti
ng material, February 2019
Reference: hematopoietic stem cell transplantation

In March 2021 The
company submitted an IND
application to the FDA for
Phase 2 study of adenovirus
infections
following
hematopoietic stem celltransplantation to the FDA
and secured fast track status
for paediatric therapies.

Transplantation of bone marrow, which contains hematopoietic stem cells, is carriedout to effect a complete cure of blood diseases (notably leukemia and other bloodcancers) which are not easily cured by cancer drug treatments (chemotherapy) orradiation therapy alone. Bone marrow transplantation includes autologous bonemarrow transplantation using a relative’s bone marrow, and allogeneic bone marrowtransplantation using the bone marrow of another person with the same leukocyte
type. The latter is growing in frequency.

On 10th March 2021, SymBio submitted an application to the FDA to carry out Phase
2 trials on BCV to support an Investigational New Drug (Registration No:
NCT04706923.) targeting adenovirus infections following HSC transplantations.
Subsequently, on April 26, the FDA accorded fast-track status to development
programs directed at adenovirus infections in children. If all proceeds smoothly, it
is expected that the first patients will be registered in the second half of 2021. The
first step is to conduct a staggered escalation of dose size to confirm safety andtolerability in trials of four groups of six patients each, ending in the second half of2022. The plan is then to proceed to Phase 3 (several hundred cases) in 2023, and to
The company is planning to file an NDA in 2026 prior to market launch in 2027 or after.
begin developing a drug forthe treatment of viral In Japan, the plan is to simultaneously develop a therapy for viral hemorrhagic cystitis(vHC) after hematopoietic stem cell transplantation. Phase 1 clinical trials in Japan
hemorrhagic cystitis.
should start in 2021. Additionally, Chimerix has recommenced development of an
improved version of the oral preparation it had previously suspended. Reference: Viral
hemorrhagic cystitis (extracted from SymBio IR materials)

14/28This 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
whatsoever 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）

Issued June 1 2021

Among the viral infections that frequently occur after HSC transplantations,
adenovirus infections that cause hemorrhagic cystitis are generally intractable, andcause severely irritating symptoms such as frequent urination, abdominal pain, anddysuria, with dissemination and death when severe. Cases have been reported inwhich the adenovirus is transferred to the kidney and causes renal failure, resulting
in death. It is particularly likely to occur with unrelated donors and umbilical cord
blood transplants, which are frequently carried out in Japan, and are often extremely
intractable due to the time required for reconstitution of the immune system. It issaid to occur at a frequency of 8.6% to 24% in allogeneic transplants.
Reference: HHV-6 encephalitis (extracted from SymBio IR release)
HHV-6 (human herpesvirus 6) is the sixth human herpesvirus to be discovered. In
allogeneic hematopoietic stem cell transplantations, reactivation of HHV-6 occurs in
30-70% of patients, causing HHV-6 encephalitis. Most HHV-6 encephalitis cases
develop at 2-6 weeks, with the most frequent occurring at 3 weeks after
transplantation. The three major symptoms are memory impairment, impaired
consciousness and, in 30-70% of cases, convulsions. In a typical case, symptoms
gradually progress from memory impairment to impaired consciousness andconvulsions. In the case of rapid progression, the neurological symptoms worsen
every hour, and there are many cases where respiratory control is required for
repeated convulsions and respiratory depression. In HHV-6 encephalitis cases earlyintervention is extremely important because a rapid deterioration in the patient’s
condition early on is common. Clinical guidelines* stipulate the first-line drug isfoscarnet (FOS) or ganciclovir (GCV), and the second-line drug is cidofovir (CDV).
CDV is considered a second-line choice because of its strong nephrotoxicity and thepoor migration of the drug into the cerebrospinal fluid (CSF). However, no studies
have been conducted to date on the clinical effects of these drugs, although effects
have been confirmed in vitro on HHV-6 encephalitis cases.
*Guidelines for hematopoietic cell transplantation: prevention and treatment ofviral infection HHV-6 (Japan Society for Hematopoietic Cell Transplantation,
February 2018)

The company will need topartner up with a pharma in
the US or Europe in order todevelop a therapy for viral
infections
after
organ
transplants

The company is also planning to expand the scope of development beyond viral
infections after HSC transplantation to viral infections from organ transplantation.
Unlike Japan, organ transplants are quite frequently carried out in Europe and the
US. For instance, looking at kidney transplants, in Japan there are 1,600 per year,
compared with 20,000 in the five biggest countries of Europe, and the same numberin the US. Of these, it is estimated that about one-third are infected with the BK
virus or CMV (cytomegalovirus). While the number of cases does not exceed 560
or so in Japan, the total for the US and the five biggest countries of Europe isprobably around 15,000. Since organ transplants are not part of the area SymBio
specialises in, and there are not so many cases in Japan, SymBio will probably tie
up with an overseas pharmaceuticals company to promote sales following organtransplants.
Number of organ transplants (ZOT)

Source: SymBio results meeting materials

15/28
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
whatsoever 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）

Issued June 1 2021

Thought is also being given The company is also looking beyond antiviral agents used during surgery toto ophthalmological and ophthalmological (eye drops) and dermatological (ointment) formulations. In thesedermatological applications areas, anti-bacterial agents are mainstream but antiviral agents barely exist, and it isinferred there is a pronounced medical need. In addition, since cidofovir has beenshown to exhibit antitumor action in brain tumours (GBM), BCV may also be
indicated for GBM as a safer drug. BCV will thus become a drug with a protracted
life cycle.

16/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
Start-up of the company’s in-house sales
Approximately
400
hematology
departments
nationwide are divided into
6 blocks, and sales arepromotedby62
professionals.

There are an estimated 4,000 or so physicians in Japan specialising in hematology,
and around 1,200 hospitals with hematology departments. SymBio sees itself
covering around 400, or one-third, of the key facilities and will target around 1,200
physicians. Leading up to the launch of its in-house sales structure in 2021 it has
been recruiting professional staff since 2018, with a view to having a total of 57 such
staff serving six blocs nationwide.
The company successfully completed its recruitment on schedule in June 2020. It
now has a sales group of 62 individuals, including 51 Medical Representatives
highly qualified in the area of hematology, six RSM’s (Regional Sales Managers),
four HE’s (Hematology Experts), and one person (KAM) coordinating the Key
Opinion Leaders (KOL’s). SymBio believes this is an extremely strong network,
particularly because the KAM and HE’s work so closely with the KOL’s. Even in
the context of the current coronavirus pandemic, appointments can be made andconsultations held online between the highly qualified staff and KOL’s. The size ofthe sales group compares favourably with other companies considering they are
restricted to one area in oncology (Eisai has a staff of 150 MR’s covering three
oncology areas).
The in-house sales structure at SymBio

The distribution network, Source: SymBio company briefing materials
logistics centre and coremanagement system are also
up and runningOn 7th September 2020, SymBio announced it was starting work to take over sales
from Eisai. The tie-up with Eisai was terminated on 9th December 2020, following
which the company’s in-house sales force was activated. In addition, the company
concluded basic agreements to transact with Suzuken and Toho Pharmaceutical witha view to using them as general agencies for the conduct of transactions. With theestablishment of two logistic centres, one for East Japan and one for West, its
logistics network was completed. The set-up of an ERP system controlling internal
communications and the upgrading of the IT system were completed in the second
quarter of 2020.

17/28
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
whatsoever 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）
Potential market size forkey products

Issued June 1 2021

Potential market size for key products
1. Potential market size for Treakisym®

The company sees the three
indications
for
which
Treakisym® had received
approval as of 2020
achieving sales of JPY8.7
billionWe see the market for Treakisym® growing, particularly on the back of the
expansion in indications in 2021. Indications for which approvals had already been
given and products launched as of 2020 are: ① Recurrent/refractory low
malignancy NHL/MCL ②Chronic lymphocytic leukemia (CLL), and ③Untreated
low malignancy NHL/MCL. Since the very first indication was approved in 2010
Treakisym® has already achieved a high degree of market penetration, which islikely to be maintained by new formulations. SymBio is targeting sales in 2021 of
JPY4.1 billion (regulated drug price basis). Treakisym® was approved forindications ② and ③ above in 2016, so has already achieved market penetration.
SymBio is assuming a target for annual sales in 2021 of JPY4.6 billion forindications ②and③ combined, and is likely to sustain that sales level.
Increase in patients due to additional approvals for Treakisym®

Source: SymBio company briefing materials

Themarketforrecurrent/refractory
medium/high malignancy
NHL, for which approval
was given in 2021, isestimated at JPY6-8 billion

Looking ahead, the biggest driver of market growth is going to be in the area ofrecurrent/refractory medium/high malignancy NHL (r/r DLBCL), for whichapproval was given in March 2021. It is estimated that there are in excess of 18,000
patients in this area. Assuming a market penetration of 40-50% we infer this area
would have a market value of JPY6-8 billion. SymBio will start sales in the second
quarter of 2021 and is assuming a target of JPY2.6 billion (regulated drug pricebasis) in the whole of that first year. Sales are expected to peak (at JPY6-8 billion)
in 2024-2025.
Total sales for the three previously approved indications are expected to be JPY8.7
billion yen, and with the additional approval for r/r DLBCL in March 2021, sales
are expected to be JPY15-17 billion.
2. Potential market size for brincidofovir

The size of the market fortreating viral infections
following HSC transplants

Here, we consider the implications for SymBio’s own development policy of themarket size of BCV in the area of viral infections after HSC transplantations.
There are an estimated 78,000 hematopoietic stem cell transplants carried out
worldwide every year, and the autologous kind, which are less vulnerable to
18/28

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
whatsoever 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）

Issued June 1 2021

rejection, total some 43,000. Allogeneic transplants (from someone other than thepatient), which total around 35,000 a year, require the use of immuno-suppressantsto inhibit rejection, and carry a high risk of viral infection.
SymBio expects that 50-60% of allogeneic transplants will be in Europe and theUnited States, and about 70% will be in Japan. This means 2,600 cases annually inJapan, and some 14,000 cases annually in the US and the five main countries in
Europe. Outside of the main industrialised countries the population-adjusted rate ofsuch transplants is only around 1/20th that of the industrialised regions but is boundto increase in the future.
No. of HSC transplants worldwide

Source: SymBio company briefing materials

The market for HSC
transplants is valued at JPY8
billion in Japan and JPY42
billion in Europe+US. The
Asia (incl. China) market
potential is also substantial

If we assume, in the light of the cost of other antiviral drugs, that the drug cost percase is JPY3 million, the market size for treating viral infections after HSC
transplantations would work out at JPY8 billion in Japan and an estimated JPY42
billion in the US and the five major European countries. The number of HSC
transplantations in Asia is growing in number and, assuming that the populationadjusted number of cases is equivalent to that of Japan, the potential size of theChinese market (approximately 1.4 billion people) could be in excess of JPY 83
billion. However, it is less than half when considering only the coastal areas where
the medical environment is well-established.

19/28
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
whatsoever 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）

Issued June 1 2021

Pipeline value simulation
Our calculation is based on a We here estimate the value of the Treakisym® pipeline using the DCF method. The
number of assumptions
discount rate is set at 8% (previously 10%), given that while SymBio operates at aloss it is a low risk pharmaceuticals venture which does not use laboratories or
manufacturing facilities, and is on the verge of profitability. Additionally, theapplication for the IND Phase 2 for brincidofovir has only just been submitted, andThe 8% discount rate our assumptions are quite challenging. We also take into account whole company
reflects the company’s costs in calculating enterprise value.
proximity to profitability
1. Treakisym® assumptions
In line with our earlier comments, we assume that peak sales will occur in the fourthyear after market launch and will maintain at that level for the next 3-4 years, before
shrinking at 5% per year and, from 2031, shrinking rapidly at 10% per year. Further,
The assumtions we are
we set the probability of success in clinical trials directed at r/r medium/highmaking for our Treakisym®
malignity NHL (r/r DLBCL) at 100%, reflecting the established position of
calculations are roughly in
Treakisym® as a standard therapy in the area of hematopoietic tumours.
line with those for our
previous simulation
From 2021 sales will be handled in-house and will in the same year be switchedalmost entirely to the liquid formulations (RTD and RI). Liquid formulations will
Changes have been madehave, we assume, a cost advantage over the conventional formulations. After
only to milestone payments
switching, we assume the cost rate, including the payment of royalties to Eagle,
should be in the area of 20-25%. Milestones will be payable on the achievement of
JPY10 billion in sales and with the successful launch of the RI formulation. We
anticipate payments of JPY550 million in each of 2022 and 2023.
All development costs (excluding milestone payments) are to be borne by SymBio
itself but, since these extend only to the development of the RI formulation, should
be in the area of JPY400-600 million.
Assuming a 62-person Sales expenses, based on the 62-person salesforce discussed earlier, will amount tosalesforce, annual sales around JPY2 billion per year.
expenses will come to JPY2
billionReference: Brincidofovir assumptions

Estimates for brincidofovir arecomplicated by the number of
uncertainties. The calculation
therefore targets only HSC
transplantations
We have posited a market sizeof JPY8 billion for Japan and
JPY42 billion for the US andEuropeBig expansion in develoment
costs since previous estimate

Making estimates concerning brincidofovir are complicated by the number of uncertainties. We
therefore restrict the extent of our calculations to five viral infections after HSC transplantations.
The markets targeted by our assumptions are Japan, the US and Europe. We assume a Japanesemarket value of JPY8 billion and an overseas market value of JPY42 billion (the market sizes arehigher than in our previous estimates because we use more viral infection indications).
In terms of schedule, we assume development will start with adenovirus infections after HSC
transplantation in the US, that Phase 2 will continue until 2022 and Phase 3 (400 subjects) from2023 to 2026. We further assume an NDA application will be submitted in 2025 and market launch
will occur in 2027. We believe that development of therapies targeting vHC, which have been
given precedence in Japan, will be switched to global development in Europe and the UnitedStates. We further assume that the development of other therapies (for vHC, HHV-6, BKV and
EKV) will take place sequentially after the adenovirus therapy with delays of 2 years each. The
development costs for each indication will differ depending on the number of cases but for thesake of simplifying the calculation we are assuming such costs at JPY8 billion each.

Launch assumed to take place in2027 or after

Under the terms of the licensing-in, SymBio is to pay Chimerix a total of JPY180 million inmilestones (including the licensing-in payment of JPY5 million), and royalties at a fixed ratio ofsales. The company has disclosed that the royalties percentage rate will be a two-digit sum, andfor the purposes of our simulation we assume it is 12%.

Quite challenging assumptions

SymBio itself could handle the development of overseas sales but we are assuming sales rights
will be licensed out. In that case, we are assuming a gross profit margin of 50% for SymBio. We
are positing milestone income linked to a licensing-out totaling JPY42 billion at peak sales. Since

20/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
for milestones and gross profit

POC on human subjects has been established we are assuming an 80% probability of success.

The company has annually recurring administration costs and R&D spending tofind and study new drug candidates. We posit R&D expenditure directed at thelatter at JPY600 million, and all-company administrative costs at JPY1.6 billion,
We are positing all-company for a relatively high total of JPY2.2 billion.
costs(including
basic
research spending) at around
2. Simulation results
an annual JPY2.2 billion
The table below shows the results of our discounted present value calculation using
the tentative suppositions given above. The value of Treakisym® comes in at
JPY62.8 billion before tax, assuming a discount rate of 8%. For reference,brincidofovir for viral infections after HSC transplantations is valued at JPY33.3
billion before tax, which would bring the total to JPY96.1 billion. While we have
Treakisym® has a pipeline
excluded this from the present exercise, if we add the value of brincidofovir forvalue of JPY62.8 billion.
organ transplants, Treakisym® for new indications, and rigosertib, the total pipeline
Adding in the values ofvalue could be in excess of JPY100 billion.
brincidofovir and rigosertib
the company’s total pipeline
value could exceed JPY100
Estimates of SymBio pipeline value (pre-tax)
billion(JPY100mil）
Success Prob.

Treakisym®

Disc. Rate 10%

Disc. Rate 8%

100%

570

628

80%

220

333

Sub Total

790

961

All company costs

-220

-275

570

686

Brincidifovor (HSCT only)

Total
Source: Calculated by Fair Research Inc.

Note: No direct comparison can be made between pipeline value and market value;
rigosertib pipeline value has not been included in the above

21/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
Trend in revenues and medium-term company plan

SymBio’s revenues come from the sale of products and from rights income. It turnedin an operating profit in the December/2008 period after receiving a lump-sum
contract fee from Eisai for sole sales rights to Treakisym® in Japan, but thenrecorded operating losses in every subsequent period. In 2021, however, profitability
is expected to return along with double-digit operating profits thereafter.
1. Results in 2020
Sales were lacklustre in2020 mainly because of a
product quality problem andan inventories adjustment
due to the switch in sales
channels

Sales in the December 2020 period totaled JPY2,987 million, most of which
consisted of wholesale deliveries of Treakisym® to Eisai. Sales had temporarily
fallen off because of quality problems in and after the Spring of 2019 with the freezedried Treakisym® formulation, and because of inventory adjustments madenecessary by the switch in sales channels. However, more robust quality testing wasintroduced and this led to a recovery in the second half of 2020. For the defective
products, JPY69 million yen was recorded as an inventory valuation loss in cost of
sales (the 2019 inventory valuation loss was JPY187 million).

Excluding the payment ofa milestone, savings weremade on R&D. However,extra costs incurred onprovision of in-house sales
structure

R&D disbursements in 2020 came to JPY2,261 million, down from JPY2,442
million in 2019. The 2020 figure includes the JPY500 million milestone payable on
the approval of the RTD formulation. Allowing for that, the decrease was reallyabout JPY700 million. We assume that the increase in costs associated with theestablishment of the sales structure led to enhanced efficiency in R&D activities.

Operating loss of JPY4.5
billion in 2020

SG&A expenditures other than R&D in 2020 rose JPY400 million from the previous
year to JPY3,107 million. This was probably because of an acceleration in spendingon the new sales structure. As a result, operating losses increased to JPY4.5billion
in 2020.
Trends in P&L and balance sheet(JPY mil.)
2014/122015/122016/122017/122018/122019/122020/12

Sales
Product sales
Licensing

1,955
1,940
15

1,933
1,933
0

2,368
2,137
231

3,444
3,444
0

3,835
3,809
25

2,838
2,811
27

2,987
2,977
10

Cost of goods sold

1,428

1,483

1,737

2,413

2,662

1,973

2,120

SG&A
of which, R&D
Excl R&D

1,830
774
1,056

3,135
2,035
1,100

3,031
1,667
1,364

4,978
3,017
1,961

3,828
1,832
1,996

5,166
2,442
2,724

5,373
2,266
3,107

Op. profits-1,303-2,552-2,127-3,947-2,656-4,302-4,506

Rec. Profits-1,110-2,630-2,317-3,976-2,748-4,377-4,615Pre-tax profits-1,112-2,628-2,309-3,974-2,748-4,372-4,086

Net profits-1,116-2,632-2,313-3,978-2,752-4,376-4,090Liquid assetsof which, cash etc.
Fixed assets
Liquid liabs
Fixed liabs
of which, corp bonds
Net assets
Shareholders equityof which, optioms

7,290
5,692
164
488
2
0
6,964
6,763
200

4,827
4,261
158
551
2
0
4,432
4,132
300

6,685
5,719
193
942
451
450
5,485
5,054
431

4,037
2,947
216
1,011
1
0
3,239
2,702
537

6,038
4,821
200
1,336
1
0
4,901
4,372
530

4,887
3,910
386
872
1
0
4,400
3,779
620

5,815
3,848
459
1,615
2
0
4,657
4,037
620

Income from options
issued/exrcised

54

0

687

1,178

4,301

3,771

4,244

Income from CB's issued

500

0

3,000

0

0

0

(Reference)0
Switch to inhouse sales

Event

IONSYS
expenses,etc.

Treakisym
liquidformulacosts

BCVlicensing in
Preparationof In-house
sales

Milestone
payment for
RTD approval
Received thesettlement
regarding
IONSYS

Source: Fair Research Inc. using securities report filings

22/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
2.
First-quarter
sales
maintained a recovery track,
although not yet at cruising
speed. The annual sales goalis attainable

2021 first quarter results

Sales in the first quarter of 2021 came in at JPY1.42 billion yen, 157.6% of the same
period of the previous year. This was mainly due to the correction in the sales pricelevel (see note below) reflecting the start of the in-house sales system on December
10, 2020. We infer around JPY1.6 billion when translated to regulated drug priceterms. Because of a number of one-off factors, such as the existence in the market
of inventories (around JPY400 million) preceding the in-house sales system, and theeffects of COVID-19, sales in the first quarter did not reach cruising speed (that is,
JPY2.1-2.2 billion). However, these factors will abate from the second quarter,
allowing plenty of room to meet the sales target in 2021 for indications (excluding
r/r DLCBL) of JPY8.7 billion on a regulated drug price basis (around JPY7.0 billion
in terms of SymBio shipments).

At the same time, because of changes in the cost structure due to the introduction of
Sharp increase in grossin-house sales, the cost of sales ratio fell to 28.9% (same period of the previous year
profitdue
torapid
was 76.8%) and gross profit rose sharply on a YoY same-period basis from JPY 882
improvementin
cost
million to JPY1,009 million.
structure
There was an increase of JPY131 million in SG&A expenditures. This was due to
expenditure of JPY473 million for BCV and RI formulation clinical development(up 8.0% from the first quarter of the previous year) and the increase in cost of sales
Sharp cut in opperating loss associated with the switch to an in-house sales structure. As a result, first quarter
operating profits were in the red to the tune of JPY210 million. This represents a
Profitability on a monthly JPY751 million cut in the loss compared to the first quarter of the previous year. It
basis possible in the second may be possible to reach profitability on a monthly basis during the second quarterin light of the switch to the RTD formulation and the expansion in indications to r/rquarter
DLBCL.
Q1 2021 results(JPY100 mil）
Q1/2020
Sales

Q1/20215.51

2021 Target

14.20(COGS basis:
JPY1.6 bn)

COGS

91.51
(COGS
basis:11.3 bn

4.23

4.10

21.94

76.8%

28.9%

24.0%

Gross profit

1.27

10.09

69.57

SG&A

10.89

12.20

55.96

4.38

4.73

20.19

-9.61

-2.10

13.61

COGS rateof which, R&D

Op. profit(of which, excl.
r/r DLBCL
JPY8.7)

For QTR
JPY2.1-2.2
bil

Source: Collated from securities report filings
Note: We believe that the wholesale price for Treakisym® sold by SymBio to Eisai
was 50% of the regulated price, and that the price paid by SymBio to Astellas was
66% of. the wholesale price. With the switch to in-house sales, wholesale prices toEisai are replaced by wholesale prices to the recipient medical facility, and Astellas
will be replaced by Eagle as a supplier of the RTD and RI formulations. Since it will
be easier to handle these formulations, distribution costs will be reduced. Thesechanges mean the cost structure will change significantly.

23/28
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
whatsoever 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）

Issued June 1 2021

3. Outlook for 2021
Sales in 2021 are expected to see a marked change in level. This will be driven by
the start of in-house sales on December 10, 2020, and additionally by the expansionof indications to r/r DLBCL approved in March. SymBio has set a target of JPY9,151
million for sales in 2021 (figure released in the medium-term management plan ofFebruary 2021; on the basis of regulated drug prices: JPY11.3 billion). The grossprofit will improve significantly due to the rise in the sales price level accompanying
the activation of the in-house sales system, and the switch to the RTD formulation.
Big change in profit Thus, while the rate of gross profits in 2021 was only 29.0%, in 2021 it should be
structure, with gross profit closer to 76.0%. Gross profit should therefore rise significantly to JPY6,957 million
rate surging to 76%(in 2020, JPY866 million).
Sales are expected to jumpin 2021 to the JPY9 billion
level due to the switch to inhouse sales and the launch of
liquid formulations

R&D
spending
will
fluctuate due to one-off
factors such as lump sum
payments for licensing-in
contracts, or milestone
payments. Excluding those,
product development is on a
growth trend

SG&A expenditure is expected to total JPY5,596 million, some JPY221 million
higher than the previous year. Within this, R&D in 2021 is forecast to come in at
JPY2.01 billion, a decline of JPY251 million. However, the 2021 forecast includes
a milestone payment of some JPY500 million related to approval of the RTD
formulation. Without this, the figure for 2021 R&D expenditure would be higher.
The company plans to increase this by pressing forward with the development BCV.
It plans to lift SG&A apart from R&D expenditures from JPY3,107 million in 2020
to JPY3,577 million in 2021 with spending on its in-house sales structure.

With the major increase in gross profit and a relatively small increase in SG&A it isvery likely the company will turn profitable (operating profit of JPY1,361 million)
Increasein
non-R&D
in 2021.
SG&A due to spending on
the in-house sales structure

4. Medium-term management plan (2021-2023) and beyond
We can infer from the highrate of marginal profit of theliquidTreakisym®
formulations,thatthegrowth in profits generated
by expanded inidications
and higher sales could be
sharp,
but
milestone
payments and BCV’s global
development will restrain
operating profit to the 1520% range

In its medium-term management plan SymBio sees the effect of an expansion ofTreakisym® indications filtering through to results. Revenues should rise 20% to
JPY10,985 million in 2022 and a further 12.5% to JPY12,369 million in 2023.
The management plan posits operating profit of JPY1,738 million in 2022, rising to
JPY2,099 million in 2023. We can infer from the high rate of marginal profit (about80%) of the new Treakisym® formulations, based on the sales growth noted in themedium-term management plan, that operating profits could be higher than theplanned value. However, in 2022 and 2023 operating income is expected to settle atthe value noted in the medium-term management plan (operating income margin of
15-20%) due to the occurrence of milestone payments to Eagle (about JPY550
million yen each year) and the full-scale development of BCV.

From 2024, SymBio will accelerate development to expand the viruses targeted by
Earnings growth momentum
should be maintained for the BCV, and also expects to undertake research and development of Treakisym® totarget solid cancers. Given this, until around 2026 we expect Treakisym® sales
time being
expansion to continue but at a slightly reduced pace.
Even if Treakisym reaches
peak sales and earnings
growth plateau’s, thedevelopment of BCV andothers will be evaluated fortheir growth potential

Further, even after Treakisym® reaches peak sales, and if R&D spending as apercentage of sales proceeds at 25% or so, until the time of patent expiry in 2031
Treakisym® will continue to be SymBio’s cash cow, able to provide returns of 1520% on an ongoing basis. During this period, even if profit growth reaches alanding, it is expected that the progress in development of BCV and Treakisym®
will become the source of future growth in enterprise value.

24/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）

SymBio Pharmaceuticals 2021 company plan and medium-term company plan
(JPYmil）

2020(actual）

Sales

2021

2,987

9,151

866

6,957

GP margin ratio

29.0%

76.0%

SG&A

5,373

5,596

2,266

2,019

-4,506Gross profitof which, R&D
Operating profit
OP margin ratio

2022

2023

(forecast） （med. term plan） （med.term plan）

10,985

12,369

1,361

1,738

2,099

14.9%

15.8%

17.0%

Recurring Profit-4,615

1,350

1,727

2,088

Net profit-4,090

1,149

1,470

1,778

Source: Compiled by Fair Research Inc. from SymBio’s medium-term management
plan and securities report filings
Reference: Committed credit line agreement (upper limit JPY3 billion), December 2020

End to reliance solely onequity finance for funds

The company has usually relied on equity finance via the exercise of new shareoptions to raise funds for operations. However, with the prospect of turning profitablein December 2020 it concluded committed credit line agreements with two banks(upper limit JPY3 billion). It seems that in the future the company will cover its
working capital needs with bank loans. However, if the development of several Phase
3 BCV indications occur at the same time it may be necessary to raise funds
externally, including via equity.

25/28
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
whatsoever 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.

Issued June 1 2021

SymBio Pharmaceuticals Ltd. （4582 JASDAQ）
Conclusions

In 2020, SymBio set up is own sales structure and acquired brincidofovir, thereby
establishing the foundations for its growth as a specialist pharma in the area ofhematology with ownership of global licensing.
The period up to 2020 was
for laying the foundationsof a specialty pharmacompany
The year 2021 is the second
stage: Takeoff

The addition of r/r DLBCL to approved indications for Treakisym®, SymBio’s key
product, and changes in formulation secured the company’s path to profitability in
2021. Looking ahead, SymBio will seek to maintain an operating profit margin in
the upper 10% level. At the same time it will use profits from Treakisym® as thefunding source to maximise the business value of its pipelines by developing
therapies using novel mechanisms of Treakisym® and rigosertib. The company will
also promote the global development of brincidofovir (BCV) in the field of viral
infections after hematopoietic stem cell transplantations. The Treakisym® pipeline
on its own has a value of JPY62.8 billion. We infer that adding in the other productpipelines would produce a total value in excess of JPY100 billion. In the context ofits profitability the company now has no need to rely purely on equity as a source offunding.
2021 will thus be the year that SymBio takes off as a global specialty pharma.

The second stage of development (2021-2025)
2021～2025
Maximise value of current
products/prospective pipelines

Enterprise Value = EPS ×

Pipeline Value
2021~

Treakisym®
Extend indications
Switch to RTD
Switch to RI
Combine with new compounds

Rigosertib
Combination therapy with
Treakisym® and/or others
New disease targets

Treakisym® - New modes of action
and new disease targets
License in new pipelines
BCV - global business expansion

Sustained sales andprofit expansion

Pipelines' underlying
enterprise value

BCV - global business expansion
Applied research with academia

BCV

New insights from AI discoveries

Recycling profits into maximising enterprise value

Source: SymBio company briefing materials

26/28
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
whatsoever 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）

Issued June 1 2021

Fair Research Inc.
BIZ SMART 1-3-21 Shinkawa, Kayabacho, Chuo-ku
Tokyo 104-0033 Japan
Tel. 03-6403-9217
E-mail: info@fair-research-inst.jp

27/28This 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
whatsoever 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）

Issued June 1 2021

Disclaimer□ This report is prepared by Fair Research Inc. ("Fair Research") for the purpose of providing information toinvestors for fees under a contract with the covered company, and not for solicitation of securities trading.

□ Although, in preparing the report, Fair Research has obtained information through interviews with the covered
company, assumptions and views set forth in the report are not of the said company but are in principle based on
analysis and evaluation by Fair Research.

□ Although the report is written based on the information and materials that Fair Research judges reliable, there
is no guarantee of accuracy, credibility, completeness, suitability and timeliness. Also, views and forecasts set forthin the report represent judgment by Fair Research at the time of issue of the report and may be changed without
notice.

□ Fair Research shall not take any responsibility whatsoever for any results including direct or indirect damages
arising from the use of, or reliance on, this report. Investors should take full responsibility for securities and othertransactions.

□ 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
About “ANALYST NET”

□ ANALYST NET is the name of report services issued and distributed by Toward the Infinite World, Inc.
(hereinafter "TIW"). TIW serves as a delivery platform for providing information and a secretariat function.

□ Reports issued in the "ANALYST NET" brand name are intended to provide introductions to and descriptions ofindustries and companies by the different approach from the existing analyst reports, and mainly prepared byanalysts outside of "TIW" and business partners (hereinafter "authors").

□ TIW shall not review nor approve contents of the reports in principle (provided, however, that only in the case ofclear mistakes or inadequate expressions, they are pointed to authors).

□ TIW may directly or indirectly receive fees from the company covered by the report in compensation for planningand proposal for issuing the report and provision of the delivery platform function.

□ Authors may directly or indirectly receive fees from the covered company other than for preparation of the report.
Authors are also likely to hold securities issued by the covered company. TIW shall not manage these in principle,
nor take responsibility. Please review separate disclaimer by authors.

□ The report is prepared only for the purpose of providing information relevant to the investment decisions,andis not intended for solicitation of securities and other transactions. Investors should make final decision on securities
and other transactions in their own judgment and responsibilities.

□ Although, in preparing the report, authors have obtained information through interviews with the covered
company, assumptions and views set forth in the report are not of the said company but are in principle based on
analysis and evaluation by authors.

□ Although the report is written based on the information and materials that authors judged reliable, there is no
guarantee of accuracy, credibility, completeness, suitability and timeliness. Also, views and forecasts set forth in thereport represent judgment by authors at the time of issue of the report, and may be changed without notice.

□ TIW and authors shall take no responsibility for direct, indirect, incidental or special damage that may be incurredby investors as a result of reliance on the information or analysis set forth in the report.

□ The copyright of the report belongs to TIW or authors in principle. With respect to the information provided in thereport, copy, sale, indication, delivery, publication, amendment, dissemination or commercial use of such information
without approval of TIW are against the law.

□ "ANALYST NET" is a registered trademark owned by TIW.

28/28
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
whatsoever 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.