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SymBio Pharmaceuticals
4582

Quarterly trends and results
Earnings (cumulative)

FY12/20

FY12/21

FY12/21(JPYmn)

Q1

Q1–Q2

Q1–Q3

Q1–Q4

Q1

Q1–Q2

Q1–Q3

Sales

551

1,361

2,333

2,987

1,420

3,147

5,553

YoY

-65.8%-32.1%

16.2%

5.3%

157.6%

131.3%

138.1%

Gross profit

128

330

611

867

1,010

2,275

4,046

YoY

-79.0%-37.7%

8.5%

0.2%

690.9%

589.5%

562.4%
72.9%

Gross profit margin

23.2%

24.2%

26.2%

29.0%

71.1%

72.3%

SG&A expenses

1,090

2,170

3,753

5,373

1,221

2,470

3,622

YoY

-9.6%

-14.7%

-8.4%

4.0%

12.0%

13.8%

-3.5%

SG&A ratio

197.6%

Operating profit

Q1–Q4% of Est.
60.7%

FY Est.
9,151
206.4%

159.5%

160.9%

179.9%

85.9%

78.5%

65.2%

-962

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

-211

-195

424

YoY

-

-

-

-

-

-

-

-

Operating profit margin

-

-

-

-

-

-

7.6%

14.9%

Recurring profit

31.2%

-991

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

-209

-204

414

YoY

-

-

-

-

-

-

-

-

Recurring profit margin

-

-

-

-

-

-

7.5%

14.8%

Net income

30.7%

1,361

-992

-1,885-2,694-4,090

-210

-206

YoY

-

-

-

-

-

-

-

-

Net margin

-

-

-

-

-

-

5.9%

12.6%

Quarterly

FY12/20

325(JPYmn)

Q1

Q2

Q3

Q4

Q1

Q2

Q3

551

809

972

654

1,420

1,726

2,406

YoY

-65.8%

105.7%--21.1%

157.6%

113.3%

147.6%

128

202

281

256

1,010

1,265

1,771

YoY

-79.0%-

738.4%-15.2%

690.9%

525.5%

530.6%

Gross profit margin

23.2%

39.1%

71.1%

73.3%

25.0%

28.9%

SG&A expenses

1,090

1,080

1,583

1,620

1,221

1,249

1,152

YoY

-9.6%

-19.4%

1.8%

51.8%

12.0%

15.6%

-27.2%

SG&A ratio

197.6%

133.5%

162.9%

247.5%

85.9%

72.4%

47.9%

Operating profit

-962

-878

-1,302-1,364

-211

16

619

YoY

-

-

-

-

-

-

-

Operating profit margin

-

-

-

-

-

0.9%

25.7%

Recurring profit

Q4

73.6%

-991

-892

-1,338-1,395

-209

YoY

-

-

-

-

-

-

-

Recurring profit margin

-

-

-

-

-

0.3%

25.7%

-992

-893

-809

-1,396

-210

4

530

YoY

-

-

-

-

-

-

-

Net margin

-

-

-

-

-

0.2%

22.0%

Net income

1,149

FY12/21

Sales
Gross profit

28.3%

1,350

5

618

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)(JPYmn)FY12/20
Q1

Q1–Q2

FY12/21
Q1–Q3

Q1–Q4

Q1

Q1–Q2

Q1–Q3

SG&A expenses

1,090

2,170

3,753

5,373

1,221

2,470

3,622

YoY

-9.6%

-14.7%

-8.4%

4.0%

12.0%

13.8%

-3.5%

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

438

834

1,745

2,267

473

912

1,286

-7.1%

-13.4%-11.5%

-7.2%

8.0%

9.4%

-26.3%

651

1,336

2,008

3,107

747

1,557

2,335

-11.1%-15.5%

-5.6%

14.0%

14.7%

16.6%

16.3%

Q2

Q3

Q4

Q1

Quarterly

FY12/20(JPYmn)Q1

FY12/21
Q2

Q3

SG&A expenses

1,090

1,080

1,583

1,620

1,221

1,249

1,152

YoY

-9.6%

-19.4%

1.8%

51.8%

12.0%

15.6%

-27.2%

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

Q1–Q4

438

396

911

522

473

439

374

-7.1%

-19.4%

-9.7%

11.0%

8.0%

11.0%

-59.0%

651

685

672

1,098

747

810

778

-11.1%-19.3%

23.2%

83.9%

14.7%

18.3%

15.7%

Q4

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

Cumulative Q3 FY12/21 results
Sales: JPY5.6bn (+138.1% YoY)
Operating profit: JPY424mn (loss of JPY3.1bn in cumulative Q3 FY12/20)
Recurring profit: JPY414mn (loss of JPY3.2bn in cumulative Q3 FY12/20)
Net income: JPY325mn (loss of JPY2.7bn in cumulative Q3 FY12/20)
Sales increased YoY in cumulative Q3 FY12/21, 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 late 2020, and constraints on sales activities due to tighter restrictions on facilities visits.
In Q3, sales of Treakisym® for the indication of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) accelerated.
This was partially because the backlog of delayed medical treatments cleared on COVID-19 measures, including vaccinations
for the elderly. Other factors included the March 2021 approval of BR-therapy and P-BR therapy to treat r/r DLBCL, andChugai Pharmaceutical's polatuzumab vedotin being added to the NHI drug list in May 2021.
Profits at the operating profit level down grew on reduced SG&A expenses and sales growth, and the company achieved
profitability in cumulative Q3. SG&A expenses decreased 3.5% YoY to JPY3.6bn and R&D expenses decreased 26.3% YoY to
JPY1.3bn. This included expenses for conducting clinical trials of intravenous formulations of Treakisym® and brincidofovir.
Excluding R&D expenses, SG&A expenses rose 16.3% YoY to JPY2.3bn. 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 tocover each region to establish a highly productive internal sales organization capable of making proposals that fit the needsof each region. With the termination of its alliance agreement with Eisai, in September 2020, the company concluded abasic 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 cumulative Q3, 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 (P-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 P-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 used in P-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.
On the quality control front, the company conducts secondary packaging and quality screening on imported batches of both
the FD and RTD formulations of TREAKISYM® to maintain stable quality.
On the supply front, the company is striving to replace the FD formulation of TREAKISYM® with RTD formulation in themarket, but the current conversion rate is behind plan. Due to the possibility of the FD formulation being out of stock,
SymBio began controlling shipments of FD from September 21, 2021. The company has secured sufficient quantities of the
RTD formulation to ensure stable supply.
Treakisym® (SyB L-0501[FD formulation]/SyB L-1701 [RTD formulation]/SyB L-1702 [RI administration]; genericname: 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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2

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 toprovide 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 chimericantigen receptor T-cell (CAR-T) therapy approved in Japan. Growing use of Treakisym® as a pretreatment agent inregenerative 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 P-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, thecompany applied for approval for partial revision to manufacturing and marketing authorization for Treakisym® in P-BR
therapy and obtained approval in March 2021. Polatuzumab vedotin was added to the NHI drug price list in May 2021, andnow Treakisym® may be used in P-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, so development of ahighly effective but safe new drug was sought after. Since BR therapy is already being used in the West to treat r/r DLBCL,
patient organizations and related academic societies petitioned MHLW so that it could be used in Japan as soon 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.
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 and Gunma University regarding efficacy of using the two compounds in combination or with existing drugs
and also explore new indications.

）

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

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3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 and on August 16, 2021, the investigational
drug was administered to the first patient enrolled (first patient in [FPI]) in the clinical trial.
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 organ transplants(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. Further, through joint research with the
National Cancer Centre Singapore and University of California San Francisco Brain Tumor Center, SymBio is investigating
new indications for BCV.

Overseas
The company’s US-based wholly-owned subsidiary SymBio Pharma USA, Inc. appointed Dr. Carolyn Yanavich as its Vice
President, and Head of Project Management and Clinical Operations on October 11, 2021, and launched full-scale
operations aimed at accelerating global development of antiviral drug brincidofovir toward commercialization.

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

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