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SymBio Pharmaceuticals
4582

Symbio Pharmaceuticals Ltd. announces earnings results for 1H FY12/21; see the results section for details.

Earnings (cumulative)(JPYmn)FY12/20
Q1

Q1–Q2

FY12/21
Q1–Q3

Q1–Q4

Q1

Sales

551

1,361

2,333

2,987

1,420

YoY

-65.8%-32.1%

16.2%

5.3%

157.6%

128

330

611

867

1,010

YoY

-79.0%-37.7%

8.5%

0.2%

690.9%

Gross profit margin

23.2%

24.2%

26.2%

29.0%

71.1%

SG&A expenses

1,090

2,170

3,753

5,373

1,221

YoY

-9.6%

-14.7%

-8.4%

4.0%

12.0%

197.6%

Gross profit

SG&A ratio

Q1–Q2

FY12/21
Q1–Q3

Q1–Q4

% of Est.

FY Est.

15.5%

9,151
206.4%

159.5%

160.9%

179.9%

85.9%

-962

-1,840-3,142-4,506

-211

YoY

-

-

-

-

-

-

Operating profit margin

-

-

-

-

-

14.9%

Operating profit

Recurring profit

-

-991

-1,883-3,221-4,616

-209

YoY

-

-

-

-

-

-

Recurring profit margin

-

-

-

-

-

14.8%

Net income-992-1,885-2,694-4,090

-210

YoY

-

-

-

-

-

Net margin

-

-

-

-

-

Quarterly

-

1,361

-

FY12/21(JPYmn)

Q1

Q2

Q3

Q4

Q1

Sales

551

809

972

654

1,420

YoY

-65.8%

105.7%--21.1%

157.6%

128

202

281

256

1,010

YoY

-79.0%-

738.4%-15.2%

690.9%

39.1%

71.1%

Gross profit margin

23.2%

25.0%

28.9%

SG&A expenses

1,090

1,080

1,583

1,620

1,221

YoY

-9.6%

-19.4%

1.8%

51.8%

12.0%

197.6%

133.5%

162.9%

247.5%

85.9%

-962

-878

-1,302-1,364

-211

YoY

-

-

-

-

-

Operating profit margin

-

-

-

-

-

-991

-892

-1,338-1,395-209

SG&A ratio
Operating profit

Recurring profit
YoY-

Recurring profit margin

-

-

-

Q2

Q3

Q4

-

-

-

-

-

-

-992

-893

-809

-1,396

-210

YoY

-

-

-

-

-

Net margin

-

-

-

-

-

Net income

1,149
12.6%

FY12/20Gross profit

1,350

Source: Shared Research based on company data
Note: Figures may differ from company materials due to differences in rounding methods.
“-”denotes YoY change of over 1000%.

Breakdown of SG&A expenses
Earnings (cumulative)

FY12/20(JPYmn)Q1

FY12/21

Q1–Q2

Q1–Q3

Q1–Q4

Q1

SG&A expenses

1,090

2,170

3,753

5,373

1,221

YoY

-9.6%

-14.7%

-8.4%

4.0%

12.0%

R&D expenses
YoY
SG&A expenses excl. R&D
YoY

438

834

1,745

2,267

473

-7.1%

-13.4%-11.5%

-7.2%

8.0%

651

1,336

2,008

3,107

747

-11.1%-15.5%

-5.6%

14.0%

14.7%

Q2

Q3

Q4

Q1

Quarterly

FY12/20(JPYmn)

Q1
1,090

1,080

1,583

1,620

1,221

YoY

-9.6%

-19.4%

1.8%

51.8%

12.0%

YoY
SG&A expenses excl. R&D
YoY

Q1–Q3

Q1–Q4

Q3

Q4

FY12/21

SG&A expenses
R&D expenses

Q1–Q2

438

396

911

522

473

-7.1%

-19.4%

-9.7%

11.0%

8.0%

651

685

672

1,098

747

-11.1%-19.3%

23.2%

83.9%

14.7%

Q2

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

1H FY12/21 results
Sales: JPY3.1bn (+131.3% YoY)
Operating loss: JPY195mn (loss of JPY1.8bn in 1H FY12/20)
Recurring loss: JPY204mn (loss of JPY1.9bn in 1H FY12/20)
Net loss: JPY206mn (loss of JPY1.9bn in 1H FY12/20)
Sales increased YoY in 1H, largely due to the transfer of sales from Eisai Co., Ltd. to the company’s own sales force.
However, there were headwinds such as the clearance of market inventory of the FD formulation sold by Eisai prior to theswitch to the company’s own sales force in December 2020, delays in medical care due to the COVID-19 outbreak from late2020, and constraints on sales activities due to tighter restrictions on facilities visits.

From Q3 onward, the company says that it expects sales of drugs targeting relapsed or refractory diffuse large B-cell
lymphoma (r/r DLBCL) to accelerate. The backlog of delayed medical treatments should clear on measures to combat COVID19, such as coronavirus vaccinations for the elderly. Other factors include the March 2021 approval of BR-therapy and PolaBR therapy to treat r/r DLBCL, and Chugai Pharmaceutical's polatuzumab vedotin being added to the NHI drug list in May
2021.
Although SG&A expenses increased in 1H, losses at the operating profit/losses level down narrowed thanks to the effect ofsales growth, and the company recorded operating profit in Q2 (April–June 2021). SG&A expenses increased 13.8% YoY to
JPY2.5bn and R&D expenses increased 9.4% YoY to JPY912mn. This included expenses for conducting clinical trials of
intravenous formulations of Treakisym® and brincidofovir. Excluding R&D expenses, SG&A expenses rose 16.6% YoY to
JPY1.6bn. The switch to in-house sales drove up the cost of sales.

Domestic
Preparations for in-house sales organization begin
The business alliance agreement between SymBio and Eisai Co., Ltd. under which Eisai acts as a sales agent expired in
December 2020, and the company switched to in-house sales for domestic sales of Treakisym®.
The company has thus far deployed a nationwide network of marketing representatives as well as hematology experts to covereach region to establish a highly productive internal sales organization capable of making proposals that fit the needs ofeach region. With the termination of its alliance agreement with Eisai, in September 2020, the company concluded a basic
agreement with Suzuken Co., Ltd and Toho Pharmaceutical Co., Ltd for the procurement and sale of pharmaceuticals toachieve nationwide distribution. The company has established two distribution centers, one in Eastern Japan and the other inWestern Japan, under management by S.D. Collabo Co., Ltd.
During 1H, in January 2021, the company launched sales of the ready-to-dilute (RTD) formulation of Treakisym®, for which it
obtained manufacturing and marketing approval in September 2020.
On March 23, 2021, the company obtained approval of a partial change to the manufacturing and marketing authorization
for bendamustine-rituximab combination therapy (BR therapy) and bendamustine-rituximab-polatuzumab vedotin combination
therapy (Pola-BR therapy) to treat r/r DLBCL patients. This enabled conventional lyophilized (freeze-dried [FD]) powder
formulation of Treakisym® to be used in BR therapy right away. In April 2021, the company obtained approval of Treakisym®
ready-to-dilute (RTD) liquid formulation for use in BR therapy and Pola-BR therapy for the treatment of r/r DLBCL. In May
2021, Chugai Pharmaceutical's polatuzumab vedotin was added to the NHI drug price list, enabling Treakisym® to be usedin Pola-BR therapy.
Stable product supply
With the launch of sales of Treakisym® RTD formulation in January 2021, the company now markets both Treakisym® in both
RTD formulation and FD formulation.
SymBio imports FD formulation Treakisym® for injection from Astellas Deutschland (consolidated subsidiary of Astellas
Pharma) and Treakisym® RTD formulation from Eagle Pharmaceuticals Inc. In 1H, secondary packaging and quality tests wereapplied to imported batches, resulting in stable quality, and as of May 2021, inventories had maintained proper levels toenable stable product supply.
On the supply front, the company is aiming for 91% completion of the switchover from the FD formulation to the RTD
formulation of Treakisym®.
Treakisym® (SyB L-0501[FD formulation]/SyB L-1701 [RTD formulation]/SyB L-1702 [RI formulation]; generic name:bendamustine hydrochloride or bendamustine hydrochloride hydrate, product name: Treakisym®)
The anticancer agent Treakisym® is used to treat malignant lymphomas, indicated for untreated low-grade non-Hodgkin’s
lymphoma and mantle cell lymphoma (marketing approval obtained in December 2016), refractory or relapsed low-grade
NHL and MCL (October 2010), and chronic lymphocytic leukemia (August 2016).

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The combination therapy of Treakisym® and rituximab (BR therapy) was newly included in the Practical Guidelines for
Hematological Malignancies 2018 published by Japanese Society of Hematology as a standard treatment option, whichapplies to all of the approved indications. This has seen Treakisym® establish its position as a standard treatment for
lymphatic cancer.
Also, SymBio obtained approval for the partial revision to the marketing authorization of Treakisym® in July 2018. Treakisym®
can now be used in combination with new anti-CD20 antibodies and not just rituximab for the treatment of CD20-positive
follicular lymphoma, the most common histological type of low-grade NHL. This allows the company to provide patients a
new treatment option: combination therapy with obinutuzumab. In March 2019, SymBio obtained approval for the partial
revision to its application to use Treakisym® as a pretreatment agent in tumor-specific T cell infusion therapy. This allows
Treakisym® to be used as a pretreatment agent for Kymriah® intravenous infusion, which was the first chimeric antigen
receptor T-cell (CAR-T) therapy approved in Japan. Growing use of Treakisym® as a pretreatment agent in regenerative
medicine has solidified its positioning as standard therapy for malignant lymphomas.
In the phase III clinical study of Treakisym® administered in BR therapy targeting r/r DLBCL, the company filed for approval
for partial revision to manufacturing and marketing authorization in May 2020 and obtained that approval in March 2021. In
April 2021, it obtained approval for partial revision to manufacturing and marketing authorization of Treakisym® RTD liquid
formulation for use in BR and Pola-BR therapy as treatment for r/r DLBCL. The company has conducted a follow-up study withoverall survival as the primary endpoint, because evaluating the survival data (e.g., overall survival and progression-freesurvival) for Treakisym® administered in BR therapy is crucial for establishing Treakisym® as a treatment for DLBCL. It is now
making preparations to publicize the results of that study. Also, after Chugai Pharmaceutical Co., Ltd. applied for
manufacture and marketing approval for polatuzumab vedotin in combination with BR therapy to treat r/r DLBCL in June
2020, the company applied for approval for partial revision to manufacturing and marketing authorization for Treakisym® in
Pola-BR therapy and obtained approval in March 2021. Polatuzumab vedotin was added to the NHI drug price list in May
2021, and now Treakisym® may be used in Pola-BR therapy. Previously there were no effective treatments for the additional
indication of r/r DLBCL, which was usually treated by a combination of anticancer agents as salvage chemotherapy, sodevelopment of a highly effective but safe new drug was sought after. Since BR therapy is already being used in the West totreat r/r DLBCL, patient organizations and related academic societies petitioned MHLW so that it could be used in Japan assoon as possible.
The company concluded an exclusive licensing agreement in Japan with Eagle Pharmaceuticals (based in New Jersey, US) in
September 2017 for the RTD and rapid infusion (RI) formulations of Treakisym® (the RI formulation reduces administrationtime). Manufacturing and marketing approval of the RTD formulation was obtained in September 2020, and the company
launched it in January 2021. The company has concluded clinical trials to confirm safety of the RI formulation and applied forapproval in May 2021. Unlike the current FD formulation, the RTD formulation reduces the workload of medical
professionals, because it eliminates the need for troublesome manual dissolution. The RI formulation can be administered injust 10 minutes, versus 60 minutes for the current FD and RTD formulation. This reduces the burden on patients andhealthcare professionals, providing significant value added. Multiple patent protections in the form of a liquid productlicense will enable the extension of the product life of Treakisym® to 2031.
Rigosertib Sodium (SyB L-1101 [IV]/SyB C-1101 [oral]; anticancer agent; generic name: rigosertib Sodium)
Onconova Therapeutics, Inc., the licensor, conducted a global phase III trial (INSPIRE study) across more than 20 countries
addressing higher-risk myelodysplastic syndromes (higher-risk MDS) with overall survival as the primary endpoint. The target
is patients who do not respond to the current standard treatment with hypomethylating agents, relapse after treatment under
the current standard of care, or are intolerant to hypomethylating agents. In August 2020, Onconova announced acomparator trial to physicians’ choice of treatment failed to achieve the primary endpoint. The company leads clinical trials
conducted in Japan and is looking to apply the knowledge gleaned from additional analysis of the INSPIRE study to rigosertib
development going forward.
Regarding the oral formulation of rigosertib, Onconova completed a phase I/II clinical trial for the drug used in combination
with azacytidine, whose results suggested the efficacy and safety of the combination therapy. To verify the tolerability andsafety among Japanese patients, SymBio began a phase I clinical trial in Japan in June 2017 and completed patient enrollment
in June 2019.
The company said it would conduct joint research into Treakisym® and rigosertib with the University of Tokyo's Institute ofMedical Science regarding efficacy of using the two compounds in combination or with existing drugs and also explore new
indications.

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3）

Antiviral drug SyB V-1901 (generic name: brincidofovir

In September 2019, SymBio concluded an exclusive global license agreement with Chimerix Inc. (hereafter Chimerix) for
brincidofovir (SyB V-1901, hereafter BCV IV and BCV Oral), an antiviral drug in intravenous and oral forms). The company
acquired exclusive global rights to develop, manufacture, and market BCV for all diseases except smallpox.
The company has concluded that it would prioritize global development of BCV IV (mainly in Japan, the US, and Europe) totreat adenovirus (AdV) infections in patients receiving hematopoietic stem cell transplantation to address an unmet medical
need. In March 2021, the company submitted of an investigational new drug (IND) application to the Food and Drug
Administration (FDA) of the US with the goal of obtaining permission for the launch of a phase II clinical trial for a phase II
clinical trial of BCV IV as a treatment for adenovirus infections that primarily occur in children (although also in adults). In
April 2021, the company received granted fast track designation from the FDA.
Based on safety and efficacy data acquired from its study, the company plans to review the drug’s efficacy against dsDNA
viral infections in patients receiving hematopoietic stem cell transplantation and extend its target indications to include
multiviral infections. By exploring the potential for expanding target disease areas to viral infections related to organtransplants (including kidney transplants), the company aims to grow the market for and maximize the business value of BCV.
Clinical trials by Chimerix have demonstrated superior, broad-spectrum antivirus activity of BCV Oral against dsDNA viruses,
raising expectations for its potential as a safe and effective therapy to prevent and treat a range of viral infections in patients
receiving hematopoietic stem cell transplantation.

Chimerix announced in December 2020 that the FDA had accepted its new drug application (NDA) for BCV as a medical
defense against smallpox and that it had received FDA approval in June 2021.

Overseas
The company marketed SyB L-0501 in China and Hong Kong, and product sales were in line with the company’s plans.

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

Full-year company forecast
FY12/20(JPYmn)Sales

1H Act.
1,361

Gross profit

FY12/212H Act.
1,626

FY Act.
2,987

1H Act.
3,147

2H Est.
6,004

FY Est.
9,151

330

537

867

2,275

4,682

6,957

Gross profit margin
SG&A expenses

24.2%
2,170

33.0%
3,203

29.0%
5,373

72.3%
2,470

78.0%
3,126

76.0%
5,596

SG&A ratio

159.5%

197.0%

179.9%

78.5%

52.1%

61.2%

834

1,433

2,267

912

1,107

2,019

1,336
-1,8401,770-2,666

3,107-4,506

1,557
-195

2,020
1,556

3,577
1,361

R&D expenses
SG&A expenses excl. R&D
Operating profit
Operating profit margin

-

-

-

-

25.9%

14.9%

Recurring profit
Recurring profit margin-1,883--2,733--4,616
-

-204
-

1,554
25.9%

1,350
14.8%

Net income-1,885-2,205-4,090

-206

1,355

1,149

Net margin

-

-

-

-

22.6%

12.6%

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

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