COMPANY RESEARCH AND ANALYSIS REPORT

SymBio Pharmaceuticals Limited
4582
Tokyo Stock Exchange Growth Market

23-Jan.-2023
FISCO Ltd. Analyst

Yuzuru SatoFISCO Ltd.
https://www.fisco.co.jp

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/■ Index■Summary---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 01
1. Overview of the 3Q FY12/22 results. . ...........................................................................................................

01

2. Trends in the development pipeline. . ............................................................................................................

01

3. Outlook.................................................. ......................................................................................................

02■Company profile---------------------------------------------------------------------------------------------------------------------------------------------------------- 03■Trends in the development pipeline--------------------------------------------------------------------------------------------------------- 06
1. TREAKISYM® (generic name: bendamustine hydrochloride). ......................................................................

06

2. Brincidofovir (BCV) (intravenous formulation/oral formulation). ....................................................................

10

3. Rigosertib (intravenous formulation/oral formulation). ..................................................................................

16■Results trends--------------------------------------------------------------------------------------------------------------------------------------------------------------- 17
1. Summary of 3Q FY12/22 results..................................................................................................................

17

2. Financial condition................................. ......................................................................................................

19■Outlook-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 20
1. Outlook for FY12/22. . ............................. ......................................................................................................

20

2. Long-Term Strategy............................... ......................................................................................................

21

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/■ SummarySignificant increases in sales and profits expected in FY12/22 andBCV to see even higher growth potential with an expanded field ofdevelopment
SymBio Pharmaceuticals Limited <4582> (hereafter, also “the Company”) is a bio-venture progressing developmentsfrom the clinical trial stage, targeting indications for oncology, hematology, and rare diseases for which there arefew patients but medical needs are high. Through a “no lab or fab” strategy, the Company is pursuing efficientbusiness management. The pipeline includes TREAKISYM®, which has already been commercialized as a treatment
for malignant lymphoma, along with the antiviral drug brincidofovir (BCV) in-licensed from Chimerix Inc. <CMRX>(hereafter, Chimerix) (U.S.) and rigosertib, which it in-licensed from Onconova Therapeutics, Inc. <ONTX> (hereafter,
Onconova) (U.S.). With the start of operations of a subsidiary to lead its global development strategy in the U.S.,
the Company began reporting consolidated financial results from FY12/22. The Company has transitioned to theTokyo Stock Exchange Growth Market in connection with the market restructuring of the Tokyo Stock Exchange
in April 2022.
1. Overview of the 3Q FY12/22 results
In the 3Q FY12/22 (January to September 2022) results, the Company posted significant increases in sales andprofits. Consolidated net sales increased 32.5% to ¥7,355mn, in comparison to the non-consolidated result for thesame period of the previous fiscal year, and operating profit was up 274.5% to ¥1,588mn on the same basis. The
main reason for the increase in net sales was that in March 2021, the Company expanded the indication areas for
TREAKISYM® by obtaining approval for the manufacturing and marketing authorization, allowing the product tobe used in the bendamustine-rituximab (BR) therapy and in the polatuzumab vedotin plus bendamustine-rituximab(P+BR) therapy to treat recurrent/refractory diffuse large B-cell lymphoma (hereafter, r/r DLBCL). The Company
booked ¥550mn in sales milestone payments, and R&D expenses rose ¥277mn. However, the Company madeprogress in switching to the RTD formulation (liquid type) from FD formulation (lyophilized powder intravenous type),causing the gross profit margin to improve, and progress was also made on curtailing SG&A expenses. As a result,the operating profit margin rose significantly, from 7.6% in the same period of the previous fiscal year to 21.6%.
One company began selling a generic version of TREAKISYM®, but it appears that the effect on the Company was
negligible.
2. Trends in the development pipeline
In February 2022, the Company received marketing approval for TREAKISYM® Liquid Formulation Rapid Infusion(RI) administration (which reduces the infusion time from the original 60 minutes to 10 minutes). The Company has
been working to switch from the RTD formulation to RI administration and expects that the switch will be almost
fully completed sometime around March 2023. The Company is also advancing joint research with academia to
explore the possibility of expanding to new applications through combination therapy with rigosertib. In February
2022 four pharmaceutical companies announced that they had received manufacturing and marketing approval for
generic versions of RTD formulation products. In November 2022, two of those companies announced that they had
also received authorization for RI administration. TOWA PHARMACEUTICAL CO., LTD. <4553> launched sales inJune 2022, while Pfizer Japan Inc. did so in December 2022. Together with U.S. company Eagle Pharmaceuticals,Inc. <EGRX> (“Eagle”), the license holder, on December 16, 2022 the Company filed a patent infringement lawsuit
against TOWA PHARMACEUTICAL CO., LTD., which had launched advance sales. On December 26, 2022, it also
filed a patent infringement lawsuit against Pfizer Japan Inc., which had also launched advance sales.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Summary

As for BCV (intravenous formulation), the Company’s primary focus of current development, the Company isexpanding joint research with major overseas academic institutions. This research has been possible because BCV
is characterized by highly effective antiviral activity against a wide range of DNA viruses. At this time, the possibilities
for development are growing for treatments for conditions with high unmet medical needs such as intractable cranial
nerve disease and cancer. In terms of the status of development, the Company is conducting a phase II global joint
clinical trial indicated for adenovirus (AdV) infections that develop after hematopoietic stem cell transplantation. Also,in December 2022, the Company started a phase II global joint clinical trial indicated for BK virus (BKV) infections
after kidney transplantation. The prospect of launching clinical trials for EB virus (EBV) positive lymphoma in 2023
has emerged as a result of various joint research studies conducted with major overseas academic institutions.
Apart from this, progress is being made on non-clinical studies indicated for conditions such as glioblastoma andmultiple sclerosis. If the Company succeeds at development in these areas, future trends will be given attention all
the more because the market value of BCV may surpass ¥100.0bn.
3. Outlook
In FY12/22 results, the Company is forecasting increases in sales and profits based on increased sales of
TREAKISYM®, with net sales increasing 21.1% year-on-year (YoY) to ¥10,003mn, and operating profit increasing
96.9% to ¥2,000mn. The increase in net sales will largely result from the full-year contribution from net sales of
TREAKISYM® for r/r DLBCL and growth in market share. In FY12/23, the major risk factors will be the drug priceof TREAKISYM® and sales trends for generic drugs. The Company foresees an increase in the number of potential
patients and higher demand from the penetration of BR therapy and P-BR therapy. However, partly because theprice of generic drugs was set at approximately 43% of the price of the brand-name drug, the Company’s net sales
may decrease depending on future trends.
Key Points
TREAKISYM® achieved growth through expanded indications to r/r DLBCL and increased market share, but
trends in generic drugs emerged as risk factors• The growth potential for BCV has increased significantly as the possibilities for development have expanded
to conditions such as malignant lymphoma, brain tumors, and multiple sclerosis, in addition to viral infectious
diseases• For its FY12/22 results, the Company expects continued increases in sales and profits due to growth in
TREAKISYM®, and it aims to remain profitable in FY12/23•

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Summary

Results trends
Net sales（left）

Operating profit (loss) （right）（¥mn）
15,000

（¥mn）
4,000
2,000

12,000

2,000

1,016

9,000
6,000

0
-2,656

3,000

3,835

-2,000-4,301-4,506

2,837

2,987

FY12/19

FY12/20

8,256

10,003-4,0000-6,000FY12/18

FY12/21

FY12/22 E

Note: Figures for FY12/21 and prior fiscal years represent non-consolidated results.
Source: Prepared by FISCO from the Company’s financial results■ Company profile
A bio-venture that conducts developments from the clinical trial
stage, targeting the fields of oncology, hematology, and rarediseases
SymBio Pharmaceuticals is a bio-venture founded by the current Representative Director and President Chief
Executive Officer Fuminori Yoshida in March 2005. For its business strategy, its basic policy is to conduct development and provision of new drugs for underserved therapeutic areas in which development has not been progressed
due to the small numbers of patients. One of its features is a business model that aims to achieve highly efficientand rapid drug discovery within the areas targeting oncology, hematology, and rare diseases, which are fields withhigh medical needs, by in-licensing development candidates for which POC* for humans has been obtained, andconducting development from the clinical trial stage.
*	POC (proof of concept): when the usefulness and efficacy of a new drug candidate compound is recognized following its
administration to animals or humans during research and development.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Company profile

The first development candidate to be in-licensed was the anticancer agent bendamustine hydrochloride (hereafter,
bendamustine hydrochloride; product name in Japan: TREAKISYM®) indicated for malignant lymphoma that wasdeveloped by Astellas Pharma GmbH (Germany), for which the Company concluded an exclusive development andmarketing rights agreement for Japan in December 2005. With the development code SyB L-0501 (FD formulation),
the Company began the phase I clinical trial in 2006 for indications for recurrent/refractory low-grade non-Hodgkin’s
lymphoma (NHL) and mantle cell lymphoma (MCL), and in 2010, it acquired manufacturing and marketing approval.
It progressed licensing activities during this time, and in 2007, it expanded the target areas for the exclusive
development and marketing rights in China, South Korea, Taiwan, and Singapore. Then with Eisai Co., Ltd. <4523>
it concluded licensing agreements for Japan in 2008 and for South Korea and Singapore in 2009. The domestic
licensing agreement with Eisai Co., Ltd. was terminated on the deadline of December 9, 2020, and the Company
transitioned to its own sales system. In addition, the Company terminated the marketing agreements for Asia during
FY12/21.
The Company launched TREAKISYM® in the Japanese market in December 2010, and since then, the Company
has progressed its development to expand its indications. It has made efforts to increase the number of patientsfor which TREAKISYM® is indicated. In 2016, the Company acquired marketing approval for chronic lymphocytic
leukemia (CLL) and untreated (first line of treatment) low-grade NHL/MCL, and then in March 2021, it acquired
approval for r/r DLBCL. In 2017, it concluded an exclusive development and marketing rights agreement for Japan
with Eagle Pharmaceuticals, Inc. <EGRX> (U.S.) for the TREAKISYM® liquid type RTD formulation/RI administration(development codes: SyB L-1701/SyB L-1702)*. The Company obtained marketing authorization for the RTD
formulation in September 2020, and has been working to switch from the FD formulation to the RTD formulation
since 2021. Following the receipt of authorization for RI administration in February 2022, the Company is presently
in the process of switching to RI administration.
*	The FD formulation, which the Company has purchased from Astellas Pharma up to the present time, has to be dissolved at
a medical site at the time of use (which requires about 3 hours, including the adjustment time). But this work is not requiredwith the liquid formulation, so it has the advantage of greatly reducing the burden placed on medical practitioners. Also, theonly difference between the RTD formulation and the RI administration is the volume of diluted physiological saline, which isdiluted to 250ml in the RTD formulation and to 50ml in the RI administration. Therefore, for the intravenous injection time,
the RTD formulation takes the same time as the FD formulation, which is 60 minutes, but the RI administration reduces
this to only 10 minutes, greatly reducing the burden on the patient.

Also, as the second in-licensed product, the Company concluded an exclusive development and marketing rights
agreement in 2011 for Japan and South Korea with Onconova for rigosertib (development codes: SyB L-1101(intravenous formulation) / SyB C-1101 (oral formulation)) as a development candidate indicated for myelodysplastic
syndrome (MDS)*. Moreover, in September 2019, it concluded an exclusive global development, manufacturing,marketing, and licensing agreement with Chimerix for BCV for all viral diseases excluding smallpox. The featuresof BCV are that compared to cidofovir (CDV; unapproved in Japan), it has high antiviral efficacy and safety and iseffective against a wide range of DNA viruses, and will become a mainstay drug for the Company.
*	M DS is a disease in which the patient cannot produce normal blood cells due to abnormalities in the hematopoietic
stem cells in their bone marrow, causing a decrease in normal blood cells and symptoms such as anemia, infection, andhemorrhage. It is also an intractable disease that is highly likely to transition to acute myeloid leukemia, and frequently
occurs in the elderly.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Company profile

History
Date
March 2005
December 2005

Summary
Established SymBio Pharmaceuticals Limited at Minato-ku, Tokyo
Concluded a license agreement with Astellas Pharma GmbH (Germany) to acquire exclusive development and marketing rights inJapan for anti-cancer agent Bendamustine Hydrochloride

March 2006

Obtained manufacturer’s license (packaging, labeling and storage) from Tokyo Metropolitan Government

March 2007

Concluded a license agreement with Astellas Deutschland GmbH (Germany) to acquire development and marketing rights in
China, Taiwan, South Korea and Singapore for anti-cancer agent SyB L-0501

August 2008

Concluded a license agreement with Eisai Co., Ltd. to grant co-development and marketing rights in Japan for anti-cancer agent
SyB L-0501

March 2009

Concluded sublicense agreement with Cephalon, Inc. (U.S.) to grant development and marketing rights in China for anti-cancer
agent SyB L-0501

May 2009

Concluded a license agreement with Eisai to grant co-development and marketing rights in South Korea and Singapore for
anticancer agent SyB L-0501

September 2010

Launched SYMBENDA® (generic name: bendamustine hydrochloride) in Singapore for the treatment of low-grade non-Hodgkin’s
lymphoma and chronic lymphocytic leukemia

October 2010

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan (launched
in December 2010)

July 2011

Concluded a license agreement with Onconova Therapeutics, Inc. for anti-cancer agents SyB L-1101/SyB C-1101

October 2011

Launched SYMBENDA® (generic name: bendamustine hydrochloride) in South Korea for the treatment of chronic lymphocytic
leukemia and multiple myeloma

October 2011

Listed on Osaka Securities Exchange JASDAQ Growth Market

February 2012

Launched INNOMUSTINE® in Taiwan for the treatment of low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia

October 2015

Concluded a licensing agreement with The Medicines Company (U.S.) to acquire exclusive development and marketing rights inJapan for post-operative, self-administered pain-management medication, SyB P-1501 (the agreement ended in November 2017)

May 2016

Established SymBio Pharma USA, Inc. at Menlo Park, California, USA

August 2016

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan for the
additional indication of chronic lymphocytic leukemia

December 2016

Acquired manufacturing and marketing approval of anti-cancer agent for malignant lymphoma TREAKISYM® in Japan for the
additional indication of first-line treatment of low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma

September 2017Concluded a license agreement with Eagle Pharmaceuticals, Inc. to acquire development and marketing rights in Japan forbendamustine liquid formulations (RTD formulation and RI administration) *RTD: Ready-to-dilute, RI: Rapid Infusion

October 2017

Filed for arbitration for damages against The Medicines Company (U.S.) due to the non-fulfillment of the licensing agreement

July 2018

TREAKISYM® was newly listed as the standard treatment for malignant lymphoma in the 2018 edition of the Japan Society of
Hematology’s Guidelines for the Treatment of Hematopoietic Tumors,

September 2019Concluded an exclusive global license agreement with Chimerix Inc. (U.S.) concerning the rights to develop, manufacture, andcommercialize the antiviral drug, brincidofovir (excluding smallpox)

September 2020

In the final arbitration ruling for the claim for damages filed against The Medicines Company (U.S.) due to the non-fulfillment of
a licensing agreement, the Company will receive from the Medicines Company 50% of its expenses relating to the arbitration
proceedings, including attorneys’ fees.

December 2020

Start of own sales of TREAKISYM®

January 2021

Concluded a joint research agreement with The Institute of Medical Science, The University of Tokyo to search for new indications
for bendamustine and rigosertib

March 2021

Submitted an IND application to the FDA in the U.S. for a global joint clinical trial indicated for adenovirus infections (in infants)
after hematopoietic stem cell transplantation

March 2021

Acquired marketing approval for a TREAKISYM® and rituximab combination therapy (BR therapy) and TREAKISYM®, rituximab,
and polatuzumab vedotin combination therapy (P-BR therapy) indicated for r/r DLBCL

April 2021

Obtained marketing approval of the RTD formulation of TREAKISYM® for its use in BR and P+BR therapy for the treatment of r/r
DLBCL

August 2021

Reached First Patient In (FPI) in a phase II global joint clinical trial of BCV indicated for adenovirus infections after hematopoietic
stem cell transplantation

February 2022

Obtained approval for a partial change to the manufacturing and marketing approval for the RI administration of TREAKISYM®

June 2022

Submitted a clinical trial plan notification to the PDMA for a phase II global joint clinical trial of BCV indicated for patients with BKV
infection after kidney transplantation (also submitted to the TGA of Australia in August 2022)

Source: Prepared by FISCO from the Company’s securities report and website

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/■ Trends in the development pipeline
TREAKISYM® achieved growth through expanded indications to
r/r DLBCL and increased market share, but trends in generic drugs
emerged as risk factors
1. TREAKISYM® (generic name: bendamustine hydrochloride)
TREAKISYM® is an anticancer agent for malignant lymphoma. Malignant lymphoma is a disease in which lymphocytes, which are a type of white blood cell, undergo canceration (tumorification) and lumps (masses) can grow inlymph nodes distributed throughout the body and organs other than lymph nodes (such as the stomach, intestines,
thyroid, spinal cord, lung, liver, skin, and eyes). It is the most frequent disease among blood cancers, with patients inJapan surpassing 30,000 annually, and the number of patients requiring treatment is predicted to increase gradually
going forward as the elderly population grows. Malignant lymphoma is mainly divided into Hodgkin’s lymphoma (HL)and non-Hodgkin’s lymphoma (NHL), with about 90% of cases in Japan being NHL. It is classified into low-grade,medium-grade, and high-grade according to the progression rate of the symptoms, and there are various diseasetypes.
Types of non-Hodgkin’s lymphoma
Type according to grade

Non-Hodgkin’s lymphoma type (disease type)Low grade: Indolent lymphoma(progresses yearly)

Follicular lymphoma (grade 1, 2), MALT lymphoma, lymphoplasmacytic lymphoma
Mycosis fungoides, Sezary syndrome, chronic lymphocytic leukemia / small lymphocytic lymphoma, etc.

Medium grade: Aggressive lymphoma(progresses monthly)

Follicular lymphoma (grade 3), mantle cell lymphoma, diffuse large B-cell lymphoma
Peripheral T cell lymphoma, extranodal NK / T cell lymphoma, adult T cell leukemia / lymphoma (chronictype), etc.

High grade: Highly aggressive lymphoma Burkitt’s lymphoma, acute lymphocytic leukemia / lymphoblastic lymphoma(progresses weekly)
Adult T-cell leukemia / lymphoma (acute type, lymphoma type), etc.
Source: Prepared by FISCO from National Cancer Center Japan materials

Estimated number of malignant lymphoma patients(Number ofpeople)140,000

119,390

112,410120,000
99,7900-14 years

100,000
80,00060,00045,49037,32015-44 years

30,73045-54 years
34,04030,54055-64 years

31,71065-74 years

40,000

0

9,920
8,550
2015-19

21,02020,03019,42020,00011,670
8,760

630

590

2020-24

12,0908,520

75 years or
older
560

2025-29

Note: Number of patients who required treatment during these periods
Source: Estimations by the Company based on cancer information service data from the National Cancer Center Japan

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline(1) Expansion of indications
As its sales strategy for TREAKISYM®, the Company has been working to sequentially expand its indications. It
acquired marketing approval for recurrent/refractory low-grade non-Hodgkin’s lymphoma (NHL) and mantle cell
lymphoma (MCL) in October 2010, chronic lymphocytic leukemia (CLL) in August 2016 and untreated (first line oftreatment) low-grade NHL/MCL in December 2016. Also, in July 2018, TREAKISYM® and rituximab combination
therapy (BR therapy) was newly listed in the Japan Society of Hematology’s Guidelines for the Treatment of
Hematopoietic Tumors, and it has come to be recommended as the standard treatment option for all indications
for which it has been approved. So TREAKISYM® has come to be positioned as the standard treatment for
malignant lymphoma in both name and reality.
Other than the above, for CD20-positive follicular lymphoma (FL), which is a typical type of low-grade NHL, theCompany acquired approval in July 2018 for partial changes relating to combination use with a new anti-CD20
antibody formulation, in addition to rituximab, and combination therapy with obinutuzumab* 1 was added as atherapy option. Furthermore, in March 2019, it acquired approval for partial changes relating to pre-treatment
with tumor-specific T-cell infusion therapy* 2, and for the first time in Japan, TREAKISYM® can be used as a
pre-treatment for the CAR T-cell therapy*3 Kymriah® intravenous drip*4.
*1	Obinutuzumab (GAZYVA®; sold by Chugai Pharmaceutical Co., Ltd. <4519>): similar to rituximab, which is recommended
in the treatment guidelines domestically and overseas as a therapeutic drug for NHL, it is a glycosylated modified type II
anti-CD20 monoclonal antibody that binds to CD20, a protein that expresses on B cells other than stem cells and plasma
cells, and it directly attacks and destroys the B cells it targets together with the body’s immune system.
*2	Tumor-specific T-cell infusion therapy: a therapy administered to patients after artificially applying and multiplying cancer
specificity outside the body to the cancer patient’s own T cells (a type of lymphocyte).
*3	CAR T-cell therapy (chimeric antigen receptor T-cell therapy): among tumor-specific T-cell infusion therapies, this is atherapy to introduce, amplify, and infuse into the gene-coding T cells the chimeric antigen receptors (CAR) that combine
the antigen-binding site of the antibody that recognizes the membrane antigen on the tumor cell and the T-cell receptor’s
intracellular domain.
*4	Kymriah® intravenous drip (generic name: tisagenlecleucel): sold by Novartis Pharma KK as the first CAR-T therapy
approved in Japan. In March 2019, it acquired manufacturing and marketing approval indicated for recurrent/refractory
CD19-positive B cell acute lymphoblastic leukemia (B-ALL) and recurrent/refractory CD19 positive DLBCL.

Then in March 2021, it announced the acquisition of marketing approval for r/r DLBCL *1. In addition to the
combination therapy (BR therapy) with rituximab developed by the Company, the combination therapy with
polatuzumab vedotin (P-BR therapy)*2 developed by Chugai Pharmaceutical Co., Ltd. <4519> was also approved.
Through these marketing approvals, the number of patients TREAKISYM® is indicated for has greatly expanded(actual sales started from 2Q FY12/21).
*1	The standard treatment for untreated DLBCL is to provide a combination therapy of rituximab and chemotherapy, but
recurrence is seen in approximately 40% of patients. Also, autologous stem cell transplantation (ASCT) is recommended
as one treatment for r/r DLBCL, but for approximately half of patients, the relief chemotherapy provided prior to ASCT
is not successful and ASCT cannot be provided. Moreover, there are many patients for whom ASCT is not suitable as atreatment, such as due to their age or complications, and it has yet to be established as the standard treatment.
*2	Polatuzumab vedotin: an anti-CD79b antibody drug compound developed by Roche <ROG>using the antibody drug
conjugate technologies of Seattle Genetics Inc. (U.S.), in which humanized anti-CD79b monoclonal antibodies and tubulin
polymerization inhibitors are combined with a linker. CD79b proteins are expressed specifically on many B cells, and thisis a promising target in terms of developing new therapies. It is considered that polatuzumab vedotin binds with CD79b
while suppressing the effects on normal cells and destroys B cells through the delivered chemotherapy agent.

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07 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Details of malignant lymphomas

Source: Reprinted from the business plan and items relating to growth potential

The results of the phase III clinical trial for BR combination therapy indicated for r/r DLBCL announced by theCompany were excellent, with a complete response rate of 47.4% and an overall response rate of 76.3%. In
particular, it seems that medical specialists were surprised by the level of the complete response rate for persons
aged 76 years and older, which was 36.4%. There was no effective treatment for r/r DLBCL until now, and amulti-drug combination therapy that combines multiple anticancer agents (3 to 6 types) was administered as relief
chemotherapy. However, it had strong side effects and little effectiveness. For these reasons, it is highly likely thatthe use of BR therapy and P-BR therapy, which have few side effects and high effectiveness, will spread as thestandard therapies and sales of TREAKISYM® are forecast to further increase due to an increase in the numberof patients and growth in market share. The choice of whether to use BR therapy or P-BR therapy depends onthe doctor’s decision, based on factors such as the patient’s symptoms and gene type*.
*	In BR therapy, TREAKISYM® 120mg/m2 (body surface area) is administered once a day for 2 consecutive days, and thennot administered for 19 days. This constitutes one cycle, and it is administered for a maximum of six cycles while observing
the patient’s condition. In P-BR therapy, the dosage is 90mg/m2.

(2) RTD formulation /RI administration
Sales of the RTD formulation, which is the TREAKISYM® liquid type, began in January 2021, and the full switchfrom the FD formulation was completed in December of the same year. The switching rate has advanced instages, increasing from approximately 20% in March 2021 to slightly less than 50% by June, and increasing toslightly less than 60% as of September. This was mainly because sales were started initially for existing indications
except for r/r DLBCL, but it acquired marketing approval for r/r DLBCL in April 2021, so it can now be sold forall existing indications.
The Company also received marketing approval for RI administration in February 2022. As of the end of September
2022, it had confirmed that more than 94% of the medical institutions with which it conducts business intend toswitch to RI administration, and expects that the switch will be almost fully completed sometime around March
2023. RI administration reduces the infusion time from the original 60 minutes to 10 minutes, thereby making it
possible to significantly reduce the burden on healthcare professionals and patients. In particular, outpatients canbe treated in a shorter time period, providing them with a major advantage. Therefore, at FISCO we believe that
there is a high likelihood that the use of RI administration will spread even more at medical facilities conducting
multi-drug combination therapy, leading to growth in market share.

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08 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Sales progress of TREAKISYM®
Drug

Indication

SyB L-0501(FD lyophilized powder formulation)

r/r low-grade NHL/MCL
CLLFirst-line low-grade NHL/MCL
r/r DLBCL

Marketing approval in October 2010
Marketing approval in August 2016
Marketing approval in December 2016
Marketing approval in March 2021

Progress

SyB L-1701(RTD liquid formulation)

Already approved indications

Marketing approval in September 2020
(Marketing approval for relapsed and refractory DLBCL in April 2021)

SyB L-1702(RI liquid formulation)

Already approved indications

Marketing approval in February 2022

Source: Prepared by FISCO from the Company’s results briefing materials and website(3) Impact of generic drugs
In February 2022, it was announced that four companies (TOWA PHARMACEUTICAL CO., LTD. <4553>, Pfizer
Japan Inc., Meiji Seika Pharma Co., Ltd., and KOA ISEI CO., LTD.) had received marketing approval for genericdrugs using the RTD formulation of the brand-name drug. Of these companies, TOWA PHARMACEUTICAL
CO., LTD. and Pfizer Japan Inc. have announced that they received marketing approval for RI administration in
November 2022. There are three indications, which are low-grade NHL/MCL, recurrent/refractory DLBCL, andpre-treatment with tumor-specific T-cell infusion therapy. This means that with the exception of CLL, the genericdrugs will cover all of the indications of the brand-name drug. Following on from the launch of sales by TOWA
PHARMACEUTICAL CO., LTD. in June 2022, Pfizer Japan Inc. launched sales in December 2022. Althoughgeneric drugs had almost no impact on the Company’s sales through 1H FY12/22, there could be an impact in the
future because the drug price of the generic drugs is set at a low level of approximately 43% of the brand-namedrug and Pfizer Japan Inc. has launched sales. Eagle, which is the original developer of the brand-name drug,holds a formulation patent and several use patents related to the RTD formulation and RI administration. The
Company, which holds exclusivity rights for these patents domestically, had sent a written notification to the four
companies regarding its concerns over potential patent infringement. On December 16, 2022, the Company filed
a lawsuit against TOWA PHARMACEUTICAL CO., LTD., which had begun advance sales, in the Tokyo District
Court, on the grounds that it had infringed upon the relevant patents. Specifically, the Company is claiming an
injunction against the manufacture and sale of the generic drugs and compensation for damages based on patent
infringement. Thereafter, the Company also filed a similar lawsuit against Pfizer Japan Inc. on December 26, 2022.
The formulation patent for RTD formulation determines the density of components (bendamustine, glycol, andantioxidants) and the component ratio, among other things. Although the components of the generic drugs madeby the four companies differ from what is listed in the patent, it is not necessarily the case that this difference alone
clears them of patent infringement, and it appears that judgement will be made based on a comprehensive view
including use patents. In fact, in the U.S., Mylan <MYL> and three other companies had tried to sell generic drugs
for RTD formulation, but at a trial held in August 2021, the court ruled in favor of Eagle and declared that its patent
was valid until 2031. However, it cannot be denied that a different ruling may possibly be made in Japan, so theCompany must be mindful of business risks. Although RTD formulation/RI administration are products subject
to price maintenance premiums*, and the prices are being maintained, if sales of generic drugs are launched, it
is possible that they will no longer be applicable starting from FY2023, the next drug price revision year, and thatthe price of the drugs will be reduced.
*	Price maintenance premiums (premium to promote the development of new drugs and eliminate off-label use) are premiums
applied to new drugs that meet certain criteria during the period of drug price revisions. This is a system in which drug
prices are maintained or made difficult to lower until the patents expire in an aim to promote the creation of innovative new
drugs and the development of unauthorized or off-label drugs.

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09 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline(4) Future development plans
For TREAKISYM®, the Company is advancing joint research with academia to search for new indications, andits policy is to work to further increase business value. Specifically, in January 2021 it concluded a joint research
agreement with The Institute of Medical Science, The University of Tokyo, and they are conducting research into
new treatments through possible developments not only for blood cancer, but also for solid cancers and othertypes of cancer, and also through combinations with other drugs, while utilizing AI technologies. In addition, in
August of the same year it concluded a joint research agreement with Kyoto University, and they are progressing
research into its inhibitory effect on LUBAC, which it has been suggested is involved in refractory activated B
cell type (ABC) DLBCL. Furthermore, the Company started an investigator-led phase II clinical trial indicated forautologous hematopoietic stem cell transplantation in patients with r/r DLBCL through BR therapy at Saitama
Medical University in January 2022.

The growth potential for BCV has increased significantly as thepossibilities for development have expanded to conditions suchas malignant lymphoma, brain tumors, and multiple sclerosis, inaddition to viral infectious diseases
2. Brincidofovir (BCV) (intravenous formulation/oral formulation)(1) Overview and licensing agreement
BCV’s features are that it can provide a higher antiviral activity and efficacy than cidofovir (CDV), which is known
as a treatment of cytomegalovirus (CMV) retinitis, and that it exhibits antiviral activity against a wide range of DNA
viruses. Moreover, academic research has uncovered that BCV has high anti-cancer activity, and it is gaining
attention as a development candidate to enhance a niche area with high unmet medical needs where treatments
have not yet been established.
Comparison of antiviral activity (EC50)
BCV

CDV

Maribavir

Letermovir

Ganciclovir

Foscarnet

Acyclovir

ADV

Virus

0.02

1.3

-

>10

4.5-33Inactive

>100

BKV

0.13

115

-

-

>200

Inactive

>200

EBV

0.03

65.6

0.63

>10

0.9

<500

6.2

CMV

0.001

0.4

0.31

0.005

3.8

50-800>200

Note: E
 C50 (the concentration at which a drug or antibody shows a 50% maximum response from the lowest value) indicates that the lower thevalue, the higher the activity. BCV possesses high antiviral activity for all viruses.
Source: Prepared by FISCO from the Company’s results briefing materials

BCV has a structure that conjugates a lipid chain into CDV, which allows for more efficient uptake of BCV into
cells than CDV alone. Once inside target cells, the lipid chain is cleaved, releasing CDV, which is then converted
to its active form of cidofovir diphosphate (CDV-PP), which fulfills the role of inhibiting viral DNA replication. Dataobtained from in vivo tests and other studies shows that BCV has a much higher antiviral replication effect than
CDV and other antiviral drugs through these action mechanisms. In terms of the safety profile, CDV has risks
for side effects such as strong nephrotoxicity, including renal dysfunction caused by the accumulation of CDV in
renal tubular epithelial cells. However, because the lipid conjugation of BCV brings no accumulation of CDV in
renal tubular epithelial cells, BCV has the outstanding feature of reducing the risk of nephrotoxicity associatedwith CDV. CDV has been granted fast-track designation by the FDA for the prevention of cytomegalovirus andthe treatment of adenovirus, while in Europe, the EMA has granted orphan drug designation for the same viruses.

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10 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

How BCV works

Source: Reprinted from the Company’s website

Chimerix had been developing an oral formulation of BCV, but it discontinued development because it did not
obtain statistically significant results in the phase III clinical trials, and as there were some side effects, including
diarrhea. Subsequently, Chimerix was looking for a partner to whom it could out-license BCV to concentrate
its management resources in the anticancer agent field, and in September 2019, the Company and Chimerix
concluded a licensing agreement for the global manufacture, marketing and development (excluding smallpox) of
BCV. The key point for the Company’s decision to in-license BCV was that it has excellent safety and functionality(high antiviral activity against a wide range of viruses), and it judged that its development was highly likely to be a
success. Also, its target diseases are “rare diseases,” and “niche areas with high unmet medical needs,” are not
only consistent with the Company’s development targets, but are also the same blood disease areas targeted by
TREAKISYM®, so it judged that synergies for sales would be easier to obtain.
In terms of the reason why Chimerix failed to develop an oral formulation, the Company thinks that as the drug
absorption rate from the digestive organs was low, it was necessary to administer a large dosage. The Company
believes that an intravenous formulation could have the same effect as an oral formulation at just 10% of thedosage, so it thinks there is a lower risk of side effects and a higher probability of success. The agreement covers
not only an intravenous formulation, but also an oral formulation, allowing for the possibility of developing theoral formulation in the future. Of the viral infectious diseases, the reason why smallpox alone is excluded fromthe agreement is that the U.S. government needs to maintain its ability to manufacture and stockpile a smallpox
treatment independently within the country as a measure to counter bioterrorism*.
*	In June 2021, Chimerix announced that the U.S. FDA approved its New Drug Application (NDA) for BCV Oral as a medical
countermeasure for smallpox.

This licensing agreement is noted for being a global licensing agreement and for covering manufacturing rights. The
use of a licensing agreement covering manufacturing rights stems from a TREAKISYM® quality defect issue that
occurred in 2019. The Company understands that controlling manufacturing rights on its own and constructing
systems to limit business risks to the best of its ability benefit all stakeholders, including patients, and is criticalin order to aim for growth as a global specialty pharmaceutical company. The Company has already found a
manufacturing contractor, and when the chances for launching the product become clear, the Company intends
to transfer the technology and outsource manufacturing to the contractor.

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11 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Target indications of these developments include viral infections after hematopoietic stem cell transplantation ororgan transplantation, and based on university research findings, the Company indicates its intention to advancedevelopment of EBV* positive lymphoma, glioblastoma stemming from CMV infection, and multiple sclerosis,
an intractable disease which has been revealed to largely be caused by EBV. In October 2021, the Company
commenced operations of SymBio Pharma USA, which will serve as an integrated development base in the U.S.
(the company was established in 2016, but had been in a dormant state). The Company hired a talented individualwith the expertise and experience to smoothly advance clinical trials on a global scale as the vice president. It
plans to double its workforce in 2023 from roughly 10 (including 5 full-time employees) as of September 2022
and to enhance its development systems.
*	EBV is a type of herpes virus. EBV is known for infecting roughly 50% of five-year olds and nearly 95% of adults. In infancy
or early childhood, nearly all EBV infections are asymptomatic. EBV infections can cause transitory symptoms such as
fever, sore throat, and swollen lymph nodes beginning in adolescence. EBV typically infects B lymphocytes and lies hidden
within the cell, inactive, but becomes active due to some sort of environmental change. It has been found that EBV is linked
to the onset of certain cancers, including some lymphomas and nasopharyngeal cancer.

Furthermore, in relation to the BCV licensing agreement, the Company paid a lump-sum contract payment of $5
million USD (approx. ¥540mn) to Chimerix, the original developer, in FY12/19. According to the agreement, as a
future milestone, the Company will pay a maximum of $180 million USD (approx. ¥19.4bn) as a two-digit royalty
payment corresponding to net sales of goods.
(2) Development plansa) Adenovirus infections after hematopoietic stem cell transplantation
For the initial development target of BCV (formulation), the Company initiated a phase II global joint clinical trial inAugust 2021 indicated for infants (but including adults) with adenovirus infections after hematopoietic stem celltransplantation (scheduled number of patients: 24 cases) in the US. Adenovirus is a naturally existing virus thatcauses infectious diseases such as pharyngitis, tonsilitis, conjunctivitis, gastroenteritis, and hemorrhagic cystitis
through the infection of areas including the respiratory organs, eyes, intestines, and urinary organs. Althoughcases of able-bodied individuals developing serious complications after being infected are rare, there is a highrisk of serious complications when patients’ immunity is lowered after hematopoietic stem cell transplantation,and there are still no treatments, so there is a strong desire for the development of treatments or preventative
drugs. Every year, there are 35,000 cases of hematopoietic stem cell transplantation around the world, among
which there are approximately 2,000 patients infected with adenovirus (Source: Bone Marrow Transplantation
2016, Bone Marrow Transplantation 2019).
In the phase II clinical trial, drug dosage is divided into four groups, and aspects such as safety, tolerability, andefficacy are evaluated and the recommended dosage for the next trial is determined. As of November 2022, thetrial has advanced to Group III, with the trial expected to be completed sometime around spring 2023. If the trial
progresses smoothly, it is predicted that the Company could start talks with the FDA in the second half of 2023 andenter phase III clinical trials in 2024. Furthermore, if the results of the phase II clinical trial confirm a high efficacy,
it is also possible that the Company will conclude a partner agreement and advance to the phase III clinical trial.

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12 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipelineb) BK virus (BKV) infections after kidney transplantation
As the second pipeline, the Company has started phase II global joint clinical trials indicated for BKV* infections
after kidney transplantation. On December 13, 2022, the Company began dosing its first patient in Australia, withplans to advance the trial in Australia, Japan, and South Korea. The planned number of cases is 36. The trial will
confirm safety, tolerability, and efficacy (changes in BKV levels in blood plasma after administration), as well as
determine the suggested dosage for the next trial. The trial period is scheduled to last approximately two years.
*	BKV is a DNA virus that belongs to the polyomavirus family. For BKV, nearly 100% of even able-bodied individuals are
infected during infancy, and although there are no notable symptoms as long as the individual is in healthy condition, in astate where immunity is lowered after organ or bone marrow transplantation, the virus becomes active, causing illnesses
such as hemorrhagic cystitis and interstitial nephritis. Furthermore, if symptoms worsen, there are even cases in which
failure of the newly transplanted kidney occurs and the organ is lost.

Kidney transplantation is the only definitive treatment for end-stage renal disease. It is FISCO’s view that the
number of patients worldwide who require transplantation surgery is approximately 100,000. Because immunity
is lowered following kidney transplantation, cases of infection are frequent; the incidence rate is less than 15% for
BKV, less than 20% for CMV, and less than 10% for the varicella-zoster virus. There are 8,000 patients with BKV
infections every year (Source: International Report on Organ Donation and Transplantation Activities Executive
Summary 2019, April 2021 & Transplantation 2012). Currently, immunosuppressive drugs and CMV anti-infective
agents are prescribed as symptomatic therapy, but the results are limited, so BKV infection is a disease with a highlevel of unmet medical needs for which treatment has yet to be established. For this reason, the early developmentof an effective therapeutic medicine is desired.
Potential needs for kidney and liver transplantation(Unit: people)
U.S.

EU

Kidney transplantation

39,51528,053

Liver transplantation

13,07010,754Japan

Other countries

Total

1,827

30,702100,097395

11,56535,784

Source: Prepared by FISCO from the Company’s results briefing materials

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13 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipelinec) EB virus (EBV) positive lymphoma
As the third BCV pipeline, clinical trials for EBV positive lymphoma are increasingly anticipated to begin in 2023.
This is because animal testing conducted by the National Cancer Center Singapore (NCCS), with whom theCompany concluded a joint research agreement in September 2021, has confirmed clear anti-tumor activity
against EBV positive NK/T-cell lymphoma*1. The principal investigator of the study announced the study’s findings
at the American Society of Hematology (ASH) Annual Meeting held in December 2022. In NK/T-cell lymphoma, a
rapidly progressing form of lymphoma, for which no effective treatment is currently available, the study confirmed
for the first time that BCV suppressed the expression of MYC*2, an oncogene that contributes to tumor malignancy,
and the expression of a dominant gene cluster, and that BCV induced immunogenic cell death which is known
to activate cancer immunity. In addition, BCV showed clear tumor growth inhibitory effect in a mouse modelin which the tumor was transplanted. The principal investigator of the study said: “In this joint research, theanti-tumor activity of BCV against NK/T-cell lymphoma was newly confirmed. BCV has the potential to become anew therapeutic agent in the field of oncology, including lymphoma.” This joint research suggests the possibility of
expanding the areas targeted for BCV development. Malignant lymphoma is also a TREAKISYM® target disease.
Therefore, if the Company succeeds in developing BCV, synergies can be expected, bringing even greater attention
to future development trends.
*1	N K/T-cell lymphoma is a type of malignant lymphoma that originates from NK or T cells. NK/T-cell lymphomas areclassified as low-grade (progressing yearly), intermediate-grade (progressing monthly), or high-grade (progressing weekly).
They mainly present in the perinasal space or on the skin. This disease is characterized by its relatively high prevalencein Southeast Asia, including China.
*2	MYC, also known as c-Myc, is one of the oldest oncogenes, and abnormalities of this family of genes have been found ina wide range of cancer types, including translocations, mutations, and amplifications in hematopoietic tumors. It functions
as a nuclear transcriptional regulator and is known to be a very important factor that controls the balance of proliferationand differentiation of hematopoietic cells by regulating the expression of dominant genes.

d) CMV infection in brain tumors (GBM)
The Company has announced that a non-clinical study has been conducted since September 2021 to investigate
anti-tumor efficacy against brain tumors at the Brain Tumor Center within the Department of Neurological Surgery
at the University of California, San Francisco in the U.S. Additionally, in March 2022, the Company also announced
the initiation of a non-clinical study to investigate anti-tumor efficacy against brain tumors associated with CMV
infections in collaboration with Brown University in the U.S.
There are approximately 30,000* incident cases of GBM (glioblastoma), which has a particularly high degree ofmalignancy among brain tumors, and CMV infections are discovered in nearly half of those cases. The reactivationof CMV causes inflammation in cells, and creates a hypoxic state, thereby increasing the VEGF which is a
growth factor related to the formation of new blood vessels, and it has been indicated that this may accelerate
the multiplication of cancer cells. The standard treatments for GBM are surgical operations, radiation therapy,
and chemotherapy, but the average life expectancy is between 15 to 20 months, and the survival rate after five
years is extremely low at under 5%, so it is becoming a field where there is a strong desire for the developmentof effective treatments. Although there are many GBM treatments in development, there are none which target
both CMV and brain tumors, so if BCV is proven to be effective, it is predicted that its market value will increase
further. The Company is examining the results of the two non-clinical studies under way at U.S. universities andworking to determine whether or not it will progress to clinical trials.
*	Company estimates based on GlobalData: Forecast of incident cases of GBM in US, 5EU, China and Japan (2027).

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14 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipelinee) Multiple sclerosis
Research in recent years has found that EBV is involved in the cause behind the onset of multiple sclerosis, anintractable disease. Developing BCV as a treatment for this disease is now emerging as a possibility. Multiple
sclerosis is one type of neurological disease that causes functional impairments in areas such as the brain, spinal
cord, and optic nerve due to inflammation of the central nervous system or optic nerve for some reason or another.
As resurgence and remission occur over and over in repeated cycles, vision, limb functions, and cognitive abilities
will decline if symptoms develop further. There are many patients in North America and Europe, with approximately
3 million people around the world and approximately 18,000 in Japan.
Multiple items are being sold as treatments, with some predicting that the scope of overall sales of these treatments will grow from $24.0bn in 2021 to a scale of more than $30.0bn in 2027. However, because the cause of
onset is unclear, there are only symptomatic treatments to prevent remission and hold back the progression of
the disease, and root treatments have not yet been developed. For this reason, even now many companies areadvancing development.
Against this backdrop, in August 2022, the Company entered into a collaboration agreement with the National
Institute of Neurological Disorders and Stroke (“NINDS”), part of the National Institutes of Health (NIH) in the U.S.,
for the transfer of materials related to BCV. The purpose of the agreement is to conduct non-clinical studies toevaluate the potential antiviral activity of BCV against EBV, eyeing future development activities in the multiple
sclerosis area. The studies will investigate how the progression of the disease changes by suppressing the activityof EBV with BCV. If positive results are obtained, it is highly likely that the Company will move forward with clinical
trials. Given the large size of the market, BCV is expected to garner even greater interest.
f) Polyomavirus infection
In November 2022, the Company entered into a Material Transfer Agreement (MTA) for BCV materials with Penn
State College of Medicine and started a non-clinical study to evaluate the efficacy of BCV in a mouse model ofpolyomavirus infection*. Polyomaviruses are known to cause serious diseases through their infection. As existing
antiviral drugs show little efficacy, the development of an effective treatment is eagerly awaited, and future trends
will be watched all the more closely.
*	Normally, polyomavirus infections such as BKV and JCV are asymptomatic. However, when the body’s immune system issignificantly compromised for some reason, these viruses are reactivated and manifest as severe infections in the infected
tissues (primarily in the genitourinary system, central nervous system, and hematopoietic cells).

g) Cranial nerve diseases
In December 2022, the Company announced that it has entered into a Sponsored Research Agreement (SRA)
with Tufts University in the U.S. to conduct a non-clinical study that will evaluate the efficacy of BCV in a herpes
simplex virus (HSV) infection model. Some DNA viruses such as HSV are directed against cranial nerve tissues andare known to cause serious diseases in various cranial nerve areas due to infection caused by their reactivation.
This research will test the potential utility of BCV against HSV infection and reactivation using human-induced
neural stem cells in a three-dimensional bioengineered brain model. The goal of this study is to pave the way forthe development of new treatment methods for cranial nerve diseases such as Alzheimer’s disease, for which notreatment method has been established yet. BCV may be able to suppress the onset and progression of these
diseases by directly inhibiting the causative virus, so progress on future development is anticipated.

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15 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

Status of progress on brincidofovir (BCV) developmentDrug
SyB V-1901(Intravenous
formulation)

Indication

Progress

Adenovirus infections in patientswith immunodeficiency, including
immunodeficiency after hematopoietic stem
cell transplantation (children and adults)

Phase II global joint clinical trial being conducted (U.S. and UK)

BKV infection after kidney transplantation

Phase II global joint clinical trial being conducted (Japan, Australia, South Korea)

EBV positive lymphoma

Pre-clinical study being conducted in collaboration with National Cancer Center
Singapore (NCCS)

GBM from CMV infections

Pre-clinical study being conducted in collaboration with Brown University in the U.S.

Multiple sclerosis

Pre-clinical study being conducted at NIH in the U.S.

Polyomavirus infection

Pre-clinical study being conducted at Penn State College of Medicine in the U.S.

Cranial nerve diseases

Non-clinical study being conducted at Tufts University in the U.S.

Source: Prepared by FISCO from the Company’s results briefing materials and news releaseh) Underlying market value of BCV
In terms of antiviral treatments, maribavir (LIVTENCITY) from Takeda Pharmaceutical Company Limited <4502>
received U.S. marketing approval in November 2021 as a treatment for refractory or resistant CMV infection* afterorgan or hematopoietic stem-cell transplantation. According to estimates by Takeda Pharmaceutical Company
Limited, every year approximately 200,000 adults around the world undergo transplantation surgery, and it isunderstood that roughly 25% of these people face the risk of CMV infection. With the number of indicated patients,
including those with first-line CMV infections after hematopoietic stem-cell transplantation, at 25,000, Takeda
Pharmaceutical Company Limited projects net sales to reach between $700 and 800mn USD during the peakof maribavir. The number of patients indicated for BCV, which this company develops, is approximately 40,000
when including patients with brain tumors from CMV infections, and if patients with multiple sclerosis, cranial
nerve diseases such as Alzheimer’s disease, EBV positive lymphoma, and GBM (glioblastoma) are also included,
BCV could grow into a blockbuster drug with a potential market value far surpassing $1.0bn, so future trends
will be watched closely.
*	Four types of antiviral treatments (ganciclovir, valganciclovir, foscarnet, and cidofovir) are indicated for refractory or resistant
CMV infections

Due to its potent antiviral action against a wide range of DNA viruses, BCV has attracted the attention of leading
overseas academic institutions. In response to this high degree of interest, the Company has signed various joint
research and material transfer agreements with these institutions beginning in 2021. This shows that on the R&D
front, the Company has taken full advantage of its adoption of an external resource-based “no lab” strategy. It
is anticipated that the Company will expand its development areas by continuing to foster joint research withacademia.

Exploring the possibilities of developing rigosertib throughcombinations with other drugs, including TREAKISYM®
3. Rigosertib (intravenous formulation/oral formulation)
Rigosertib is an anticancer agent candidate that has unique multi-kinase inhibitory action (which causes cancer cells
to die by inhibiting the multiple kinases involved in cancer cell proliferation, invasion, and metastasis). Its licensor,
Onconova, has conducted the phase III global joint clinical trials (INSPIRE trial) for myelodysplastic syndrome(MDS). In August 2020, it was announced that the primary endpoint had not been achieved in comparison to thedoctor-selected therapy.

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16 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Trends in the development pipeline

The Company is responsible for clinical development in Japan, and its policy is to search for new disease targets,
including from the findings obtained from the INSPIRE trial’s additional analysis. Specifically, through the joint
research agreements concluded with the Institute of Medical Science, The University of Tokyo, and Gunma University,
they are creating new treatments through combination therapies for bendamustine and rigosertib and their combined
use with other existing drugs, and searching for new disease targets, including in treatment areas other than the
oncology area, while utilizing AI technologies. There do not appear to be any major developments on this front at
this time.

■ Results trends
In the 3Q FY12/22 results, sales and profits increased significantly
through the increase in sales of TREAKISYM®
1. Summary of 3Q FY12/22 results
In the 3Q FY12/22 consolidated results, sales and profits increased significantly. Net sales increased 32.5% YoY to¥7,355mn, operating profit rose 274.5% to ¥1,588mn, ordinary profit increased 344.8% to ¥1,843mn, and profit
attributable to owners of parent rose 378.9% to ¥1,555mn.
3Q FY12/22 results (cumulative)(¥mn)
3Q FY12/21 (cumulative)
Results(non-consolidated)

3Q FY12/22 (cumulative)

vs. net sales

Results(consolidated)

vs. net sales

YoY change

YoY % change

Net sales

5,553

-

7,355

-

1,802

32.5%

Gross profit

4,045

72.9%

5,466

74.3%

1,420

35.1%

SG&A expenses

3,621

65.2%

3,877

52.7%

256

7.1%

R&D expenses

1,286

23.2%

1,563

21.3%

277

21.6%

Other SG&A expenses

2,335

42.1%

2,314

31.5%

-21

-0.9%

Operating profit

424

7.6%

1,588

21.6%

1,164

274.5%

Ordinary profit

414

7.5%

1,843

25.1%

1,428

344.8%

Extraordinary profit

0

-

106

-

106

-

Profit attributable toowners of parent

324

5.9%

1,555

21.2%

1,230

378.9%

Source: Prepared by FISCO from the Company’s financial results

The main reason for the increase in net sales was steady growth in the market share of TREAKISYM®, due partly tothe approval of RI administration, which dramatically reduces the burden on patients and healthcare professionals, inaddition to penetration of BR therapy and P-BR therapy for TREAKISYM®. The launch of sales of a generic productby one company seems to have had only a negligible impact.

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COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Results trends

The gross profit margin rose from 72.9% in the same period in the previous fiscal year to 74.3%. The Company
recorded a sales milestone of ¥550mn under cost of sales in 3Q FY12/22. Excluding this impact, the gross profit
margin would have been 81.8%, an increase of 8.9 percentage points. This increase was mainly due to the full switchfrom the FD formulation to the RTD formulation. In terms of the exchange rate, although the yen weakened rapidly invalue, the impact was negligible because the Company had entered into foreign exchange forward contracts at justunder ¥120 per U.S. dollar. Moreover, the TREAKISYM® sales milestone has concluded with the latest payment,
and no further milestone payments will be incurred in the future.
Among SG&A expenses, R&D expenses increased 21.6% YoY to ¥1,563mn. The main reasons for this increase wereincreases in clinical trial expenses and joint research expenses related to BCV, along with costs at the Company’s
U.S. subsidiary. Other SG&A expenses decreased slightly by 0.9% to ¥2,314mn. The main reasons for this decrease
were that sales activities for TREAKISYM® were shifted mainly online due to the spread of COVID-19, allowing theCompany to reduce the number of CMRs (contract MRs) and that the Company worked to curtail other expenses.
Non-operating income (expenses) improved ¥264mn YoY mainly owing to the recording of foreign exchange gainsof ¥345mn in connection with the weaker yen.
Looking at how results trended on a quarterly basis, the Company recorded an increase in sales but a decrease inprofits. In 3Q FY12/22, net sales rose 3.1% YoY to ¥2,481mn, while operating profit decreased by 65.1% to ¥216mn.
Excluding the impact of the sales milestone, operating profit was firm, increasing 23.8% to ¥766mn.

Quarterly result trends
Net sales（¥mn）

Operating profit (loss)

4,000

3,500
2,703

3,000
2,406

2,500

2,557

2,481

2,647

1,726

2,000
1,500

2,315

1,420

1,000

619

500

863
591

509
216

15

411

0
-500

-210
1Q

2Q

3Q

4Q

FY12/21

1Q

2Q

3Q

4Q

FY12/22

Source: Prepared by FISCO from the Company’s financial results

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18 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

Results trends

Cash on hand increased as the Company entered a monetization
phase
2. Financial condition
As of the end of 3Q FY12/22, total assets were up ¥2,165mn compared to the end of the previous fiscal period to¥10,618mn. Looking at the main change factors, in current assets, there were increases of ¥2,272mn in cash anddeposits and ¥52mn in inventories. In non-current assets, there were decreases of ¥10mn in property, plant andequipment and ¥27mn in intangible assets in step with the recording of depreciation and amortization. In addition,deferred tax assets decreased ¥143mn.
Total liabilities were up ¥56mn compared to the end of the previous fiscal period to ¥1,763mn. The main change
factors were an increase of ¥752mn in accounts payable-other, while there was no more provision for productchangeover of ¥186mn, and a decrease in income taxes and consumption taxes payable. Moreover, net assets
increased ¥2,108mn to ¥8,854mn. Retained earnings increased ¥1,464mn due to the recording of profit attributableto owners of parent. In addition, there were increases of ¥379mn both in share capital and capital surplus following
the issuance of new shares and the 58th stock acquisition rights through a third-party allotment (CVI Investments,Inc.) conducted in June 2022. As a result, the equity ratio rose 5.9 percentage points, from 73.7% to 79.6%.
The exercise price of the stock acquisition rights is fixed at ¥785 and the number of dilutive shares is 2 million shares.
The Company will allocate most of the ¥662mn procured through the issuance of new shares and the ¥1,568mn
scheduled to be procured through the exercise of stock acquisition rights to development funds for BCV. It alsoplans to allocate some of the funds to new in-licensing and investment funds for M&As and other opportunities.
Apart from this, at the end of March 2022, the Company renewed its syndicated loan (commitment line) agreementwith three banks. The upper limit has been set at ¥3,150mn with the commitment period set to last until April 4,2024. If there is a sudden need for funds, the Company’s policy is to address the situation, even through borrowing
from financial institutions.
Balance sheet and management indicator(¥mn)
FY12/19

FY12/20

FY12/213Q FY12/22

Change

4,887

5,815

6,747

9,095

2,348

3,910

3,848

3,860

6,133

2,272

386

459

1,705

1,522

-183

Total assets

5,273

6,274

8,452

10,6182,165

Total liabilities

873

1,617

1,707

1,763

56

-

-

-

-

-

4,400

4,657

6,745

8,854

2,108

71.7%

64.3%

73.7%

79.6%

5.9pt

Current assets(Cash and deposits)
Non-current assets(Interest-bearing debt)
Net assets
Management indicator
Equity ratio

Note: Figures for FY12/21 and prior fiscal years are non-consolidated.
Source: Prepared by FISCO from the Company’s financial results

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19 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/■ Outlook
For its FY12/22 results, the Company expects continued increases
in sales and profits due to growth in TREAKISYM®, and it aims toremain profitable in FY12/23
1. Outlook for FY12/22
For FY12/22 results, the Company has upwardly revised its forecasts announced in August 2022 at each profit
level. The Company’s forecast now calls for net sales to increase 21.1% YoY to ¥10,003mn, operating profit toincrease 96.9% to ¥2,000mn, ordinary profit to increase 129.7% to ¥2,300mn, and profit attributable to ownersof parent to decrease 18.8% to ¥1,650mn. The main reason for the increased forecast for operating profit isgreater-than-anticipated progress on the streamlining of SG&A expenses. The forecast for ordinary profit wasincreased mainly because of the recording of foreign exchange gains.
Outlook for FY12/22(¥mn)
FY12/21
Results(non-consolidated)

FY12/22 (consolidated)
vs. net sales

Company
forecast

Revisedforecast

vs. net sales

Change% change
21.1%

Net sales

8,256

-

10,003

10,003-

1,746

Operating profit

1,016

12.3%

1,770

2,000

20.0%

983

96.9%

Ordinary profit

1,001

12.1%

1,750

2,300

23.0%

1,298

129.7%

Profit

2,032

24.6%

1,480

1,650

16.5%

-382

-18.8%

Note: The Company forecasts for FY12/22 were announced in August 2022. The revised forecasts are based on figures announced in November 2022
Source: Prepared by FISCO from the Company’s financial results

Net sales are expected to increase for three consecutive fiscal periods and reach an all-time high, as TREAKISYM®
sales are continuing to perform firmly in 4Q FY12/22. The expected increase in sales is mainly supported by growth insales of products for r/r DLBCL. Although monitoring net sales by target field is challenging, the Company estimatesthat sales of products for r/r DLBCL will be around ¥4.0bn in FY12/22, which is nearly double the level of sales in
the previous fiscal year, given that sales began in earnest in 3Q FY12/21. Solid sales are also anticipated in othertarget fields. It appears that the impact of generic drugs has been limited.
The gross profit margin is forecast to rise from 70.2% in the previous period to around 76% (around 82% whenexcluding the impact of the sales milestone), because the switch to RTD formulation/RI administration has been
fully completed since the beginning of the period. The exchange rate has been trending at around ¥140 per U.S.
dollar, moving toward a weakened yen since the formulation of the plan when it was ¥110 per U.S. dollar. However,purchases from Eagle for the fiscal year under review have been hedged with the Company’s U.S. dollar-denominated financial assets on hand and foreign exchange forward contracts (at just under ¥120 per U.S. dollar), so
profits will largely be unaffected. For FY12/23, the Company has entered into foreign exchange forward contracts
at just under ¥130 per U.S. dollar for the anticipated purchases. Purchase costs for TREAKISYM® and overseas
development expenses for BCV are affected by foreign exchange rate movements. The Company estimates that an
exchange rate movement of ¥1 per U.S. dollar will impact operating profit by approximately ¥20mn for the full year.

We encourage readers to review our complete legal statement on “Disclaimer” page.

20 21

COMPANY RESEARCH AND ANALYSIS REPORTFISCO Ltd.
https://www.fisco.co.jp

SymBio Pharmaceuticals Limited

23-Jan.-2023

4582 Tokyo Stock Exchange Growth Market

https://www.symbiopharma.com/ir_e/

OutlookAmong SG&A expenses, the Company projects R&D expenses to increase ¥764mn YoY to ¥2,500mn. The main
factors behind this increase include expenses for BCV clinical trials in addition to the recording of expenses for theoperation of its U.S. subsidiary that will serve as an integrated development base, and an increase in expenses forjoint research with academia. The Company projects that other SG&A expenses will remain at around ¥3,100mn,
mostly the same level as in the previous fiscal year. As a result of the streamlining of sales, the number of CMR
personnel has decreased and will absorb other increases in expenses. The Company is forecasting a decreasein profit attributable to owners of parent because of a snapback decline from deferred tax assets recorded in theprevious fiscal year.
The Company is currently formulating its results forecasts for FY12/23, and it aims to ensure positive operating profit.
Generic drugs and drug price trends will be risk factors for net sales. However, the number of indicated patientshas been increasing and product value has been rising as RI administration dramatically reduces the burden on
healthcare professionals and patients. Considering these factors, the Company’s market share in current target
areas, which has remained at just under 50%, is expected to increase. Due in part to these positive factors, it isdifficult to forecast the trend in net sales at this time.
Meanwhile, the Company anticipates an increase in expenses of just over ¥1.0bn to roughly ¥3.6bn. While there
will be no more ¥550mn sales milestone, the increase in expenses is due in part to an increase in expenses for
BCV clinical trials under R&D expenses, as well as plans to increase personnel at the subsidiary in the U.S. that willserve as its integrated development base. If a development project for AdV infection after hematopoietic stem celltransplantation enters phase III clinical trials within 2023, the Company will incur a development milestone paymentof ¥550mn. Based on current progress, it is highly likely that this payment will be pushed back to 2024. In other
SG&A expenses, the Company plans to continue to curtail these expenses in FY12/23.

Advance development of BCV and aim for growth as a global
specialty pharmaceutical company
2. Long-Term Strategy
In the long term, the Company is forming a policy to aim for growth as a global specialty pharmaceutical company.
Specifically, in addition to initiatives aimed at expanded sales of TREAKISYM®, the Company’s strategy involves
establishing POC in multiple niche areas with high unmet medical needs through BCV, and expanding its overseas
business while considering entering partnership agreements. As for BCV, in order to carry out a stable supply ofhigh-quality products, the Company plans to maximize profit by conducting in-house manufacturing (manufacturingconsignment) and also uncover fundamental business values contained by each pipeline while advancing joint
research with academia and others, and bridging that to maximization of business values, while simultaneously
working on enhancing pipelines by in-licensing new development candidates.
The Company has set “Local & Global” and “50 and 50 in 30” as the management keywords. These keywords signify
taking a dramatic leap forward as a global pharmaceutical company by successfully guiding the development of BCV
with the aim of increasing the percentage of total sales from overseas sales to 50% by 2030. At FISCO, we expectthat the Company’s corporate value will substantially improve if it succeeds at developing BCV as a treatment forviral infection after hematopoietic stem-cell transplantation or organ transplantation, and as a treatment for brain
tumors or multiple sclerosis caused by viruses, and are focused on future development trends.

We encourage readers to review our complete legal statement on “Disclaimer” page.

21 21

Disclaimer
FISCO Ltd. (“FISCO”) offer stock price and index information for use under the approval of theTokyo Stock Exchange, the Osaka Stock Exchange and Nikkei Inc.
This report is provided solely for the purpose of offering information, and is not a solicitationof investment nor any other act or action.
FISCO prepared and published this report based on information which it considered reliable;
however, FISCO does not warrant the accuracy, completeness, fitness nor reliability of thecontents of this report or the said information.
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mentioned in this report may increase or decrease in value or lose their value due to influence
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This report has been prepared at the request of the company subject hereto based on theprovision of information by such company through telephone interviews and the like. However,
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◾ For inquiry, please contact: ◾

FISCO Ltd.
5-13-3 Minami Aoyama, Minato-ku, Tokyo, Japan 107-0062
Phone: 03-5774-2443 (IR Consulting Business Division)
Email: support@fisco.co.jp