Download darinaparsin (organic arsenic)

A Pioneer in Neuromodulation with Kinetic Oscillations
Novel Treatment for
Peripheral T Cell Lymphoma (PTCL)
Opportunity to License in USA and Europe
Prepared by
The Sage Group
June 2016
1
Executive Summary
and
Corporate Overview
Executive Summary
• Solasia Pharma K. K. (“Solasia” or the “Company”; www.solasia.co.jp) is a privately owned
company based in Japan. It is headquartered in Tokyo, with a subsidiary in Shanghai and
offices in Beijing. Solasia has a strong and experienced management team from Amgen,
Searle, Roche, Takeda and Sosei. The Company has received over US$80M in funding.
• Solasia is a specialty pharmaceutical company established to develop and commercialize
innovative oncology therapies and supportive care products in Japan and Asian countries.
• Solasia targets the world’s largest oncology market in China and Japan, and has in-licensed
three western oncology compounds acquired for their focus on Asian markets. These include
Darinaparsin (SP-02) from Ziopharm Oncology, for which Solasia received worldwide rights.
• Darinaparsin has already been licensed for Japan and Asia to Meiji Seika. The Company is
working with Sage Group to license Darinaparsin in USA and EU.
• Darinaparsin is an water soluble organic arsenic derivative which has been shown to be safe
and efficacious in treatment of Peripheral T Cell Lymphoma, where there is a market due to
unmet clinical need. The Company has Orphan Drug designation in USA and EU.
• Solasia owns global rights to Darinaparsin, and because it is focused on Asian markets, it
would like to identify and negotiate one or more relationships in USA and Europe to market
the product also in those territories.
3
Solasia Corporate Profile
Established
2007
Headquarter ： Tokyo, Japan
Subsidiary ： Solasia Medical Information Consulting (Shanghai) Co. Ltd.
China Offices ： Shanghai & Beijing
Number of Employees 17
Office
Management
President, Representative Director
Chief Financial Officer
SVP, Product Development Head
VP, Business Development Head
VP, Business Development
General Manager in China
Board of Directors
Yasuhiro Abe (Itochu), Bard Geesaman (MPM), Norikazu Eiki (formerly Bayer), Masahiro
Michisuji (formerly Novartis), Stanley Lau (formerly Baxter), Yoshihiro Arai, Toshio Miyashita
Shareholders
Investment,
MPM Capital, Itochu, Meiji Seika Pharma, Lee‘s Pharma, Mitsubishi UFJ Capital, Shinsei
Mitsui Sumitomo Marine Capital, SMBC Capital, Nihon Venture Capital, Golden Asia Fund,
Kyowa Hakko Kirin, Sansei Capital, Mitsubishi Trust Bank
Raised capital
Approx. USD 80 million
4
Yoshihiro Arai (formerly Amgen, Searle)
Toshio Miyashita (formerly Sosei, Arakis, Hibiki Partners)
Shigeru Sakamaki (formerly Amgen, Takeda Bio)
Koji Shinozaki (formerly Itochu, MPM Capital)
Takashi Ono (Concurrently with Itochu, formerly Sosei)
Vivian Zhang (formerly Roche China)
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Darinaparsin Clinical and Marketing Plan
Preclinical
SP-02 darinaparsin
Peripheral T-Cell
Lymphoma
Originator ：
ZIOPHARM Oncology
Solasia’s Territory :
W-W
Clinical Study
Phase 1
Phase 2
NDA
Approval
Launch
Partner
Phase 3
Japan commercial right：
Meiji Seika Pharma
Japan, Korea, Taiwan, Hong
Kong（Solasia）
*
US（Solasia）
*: Pivotal study for NDA
5
Background to Darinaparsin (SP-02)
Background to SP-02 Darinaparsin - Organic Arsenic
Apoptosis Inducer
 Effective & well tolerated organic arsenic apoptosis inducer
mediated by damage to mitochondria
 Initial indication: peripheral T-cell lymphoma (PTCL)
 Solasia territory: Worldwide
 Complete & partial responses seen in PTCL patients in US
Phase 2 trial
 Phase 1 studies completion in Japan and Korea
 Complete & partial responses seen in PTCL patients in Phase
1 trials
 Good safety profile compared to competitors (FOLOTYNmucositis, ISTODAX: less hematologic toxicity)
 Partnering sales & marketing in Japan with Meiji Seika
 Pan-Asian (Japan, Korea, Taiwan and Hong Kong) pivotal
study initiated in 1Q 2016
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Darinaparsin (Product Code: SP-02L)
• Organic arsenic is characterized by its antitumor activity.
– Has similar structure to one of the intermediates of
the arsenic detoxification pathway, and is expected
to has lower toxicity than inorganic arsenic
– Chemical Name and Structure
• C12H22AsN3O6S
• Molecular Weight : 411.31
– Formulation: a sterile lyophilized powder for injection
• Mechanism of Action
– Disruption of mitochondrial functions
– Increase in reactive oxygen species
(ROS) production
• induction of apoptosis
• Arrest of cell cycle at G2/M phase
• Potent antiangiogenesis activity
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Mechanism of Action Unique Compared to Inorganic Arsenic
DARINAPARSIN (ORGANIC ARSENIC)
INORGANIC ARSENIC
• Cytotoxicity via two pathways: i) increase in
reactive oxygen species (ROS); ii) direct
disruption of mitochondrial function, stimulating
release of cytochrome C, thereby activating
caspase-9 & caspase-3
• Cytotoxicity not susceptible to known resistance
mechanisms (PML/RAR-a, BCL-2)
• Cell death via apoptosis & cell cycle arrest (G2/M)
• Cytotoxicity via caspase-8
• Cytotoxicity minimized by both functional
PML/RAR-a & BCL-2
• Cell death via apoptosis & cell cycle arrest
(G1)
Mitochondria
INORGANIC
ARSENIC
Mitochondria
DARINAPARSIN
Cytochrome C
Cytochrome C
ROS
BID
NADPHoxidase
BCL-2
Death
Receptor
Caspase-8
Caspase-3
CELL
DEATH
Caspase-9
Caspase-3
9
CELL
DEATH
Caspase-9
Overview of Non Clinical Studies
Overview of PreClinical studies (in vitro pharmacology)
Study
Summary result
Induce Apoptosis and Inhibit Cell Growth
of Leukemia Cell Lines
U266, KMS11, and MM.1s lines were 1- to 3-fold less sensitive to
darinaparsin than to ATO
Apoptosis Induction by Darinaparsin
Compared to ATO
Electron microscopy of NB4 cells incubated with darinaparsin
revealed time-dependent mitochondrial atrophy, mitochondrial
matrix condensation, and apoptosis.
Induction of Cell Cycle Arrest in G2/M
G2/M arrest was confirmed by assessing BrdU incorporation into
HL60 cells after 24-hour treatment of darinaparsin
Bcl-2 Down-regulation Appears not
Required for Darinaparsin-induced
Apoptosis
Bcl-2 protein down-regulation does not appear to be an obligate
feature of darinaparsin’s apoptotic mechanism of cytotoxicity
Increase in Intracellular Production of
Reactive Oxygen Species (ROS)
Studies in the HL60 leukemic cell line show that darinaparsin
treatment results in a prominent early burst in H2O2 production
followed by a sustained increase in superoxide production
NCI human cancer cell line panel screens
Active against cell lines derived from leukemia, non–small-cell
lung (NSCL), colon, brain, melanoma, ovarian, kidney, prostate,
and breast cancers over a wide range of concentrations
Antiangiogenic Activity
Incubation of HUVEC on extracellular matrix stimulates the
attachment, growth, and differentiation of endothelial cells,
resulting in the assembly of tube-like structures.
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Overview of PreClinical studies (in vivo pharmacology)
Study
Summary result
Multiple Myeloma Xenografts in Mice
In a xenograft of multiple myeloma LAGl-1 cells isolated from a
bortezomib-resistant subject, darinaparsin inhibited not only tumor
growth but also the synthesis of human IgG antibodies by these cancer
cells
Activity against Murine Renal Tumors in Mice
Darinaparsin inhibits the growth of in vivo-passaged, subcutaneously (SC)
implanted RENCA murine renal tumors in CD2F1 mice
Activity against Solid Tumors (Hollow Fiber
Assay)
A standard panel of 12 tumor cell lines was used to assess darinaparsin
activity in a hollow fiber assay. Darinaparsin exhibited modest
subcutaneous and IP activity
Increase in Survival with Darinaparsin
Administered (IP or Oral) in Mice Implanted
with P388 Leukemia
Intravenous administration of 200 mg/kg darinaparsin for 9 consecutive
days inhibited growth of established RENCA tumors
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Overview of Darinaparsin
Clinical Studies
Overview of Clinical Trials
IV
Study No.
Target
Primary Objective
# Subjects
Status
SGL1001
1
R/R Hematologic Malignancies
(AML: 10, CLL: 1)
Tolerability
11
Completed
SGL1002
1
Advanced Solid Tumors
(Colorectal: 15 and others)
Tolerability
40
Completed
SGL2001
1/2
R/R Multiple Myeloma
Ph-1: Tolerability
Ph-2: Efficacy (ORR)
Ph-1: 17
Ph-2: 14
Completed
SGL2001b
2
R/R Multiple Myeloma
Efficacy (ORR)
14
Completed
SGL2003
2
R/R Hematologic Malignancies
(Lymphoma: 29 and others)
Efficacy (ORR)
50
Completed
SGL2005
2
Advanced Hepatocellular Carcinoma
Efficacy (ORR, PFS)
15
Completed
SP-02L01
1
R/R PTCL
Tolerability
17
Completed
SP-02L02
2
R/R PTCL
Efficacy (ORR)
65
Ongoing
SP-02L03
1
R/R PTCL
Tolerability
6
Completed
Study No.
Oral
Phase
Phase
Target
Primary Objective
SGC1001
1
Advanced Solid Tumors and Lymphomas
Tolerability (2 days weekly)
22
Completed
SGC1002
1
Advanced Solid Tumors and Lymphomas
Tolerability (3 days weekly)
20
Completed
SGC1004
1
Advanced Solid Tumors
Tolerability (21 days monthly)
10
Completed
14
# Subjects
Status
Solasia’s Approach to Treatment of
PTCL with Darinaparsin
Darinaparsin Positioning in PTCL Treatment Algorithm
Potential as the drug approved in ASIA for relapsed/refractory PTCL
Combination
Chemotherapy
(e.g., CHOP)
Responder
FRONTLINE
Refractory
Relapsed
DARINAPARSIN
16
SALVAGE
Solasia Phase 1 Study with
Darinaparsin – Japan & Korea
Darinaparsin Phase 1 Study : Study Outline
• Target Indications: Relapsed or Refractory PTCL
– PTCL, not otherwise specified (PTCL-NOS)
– Angioimmunoblastic T-cell Lymphoma (AITL)
– Anaplastic Large Cell Lymphoma (ALCL) ALK-positive/negative
• Study Objectives
– To evaluate the safety, tolerability, efficacy and pharmacokinetics (PK) profile of
SP-02L monotherapy, respectively in Japanese and Korean patients, with relapsed or
refractory peripheral T-cell lymphoma (PTCL)
• Endpoints
– Primary：
• Incidence of dose-limiting toxicity (DLT) and adverse events
• Change in QTcF (ΔQTcF) from time-matched baseline
– Secondary：
• Tumor response (by revised Cheson’s Criteria) in subjects who completed at least
2 cycles of treatment
• Plasma concentration-time profile and PK parameters
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Darinaparsin Phase 1 Study : Study Design / Dosage
• Study Design: Multi-center, open-label, non-randomized study
Enrollment
Screening
Informed
Consent
Up to 4 Cycles
• Intravenous infusion over 1
hour
• Assessment of DLT in Cycle 1
• Evaluation of Tumor Response
at the end of Cycle 2 and 4
Responders were
allowed to continue
treatment beyond
Cycle 4
Follow Up
< Planned Dose Cohort / Dosing Schedule >
Japan
Korea
Dose Cohort
Dosing Schedule
1
-
200 mg/m2
4-week cycle
5-consecutive day administration followed by 23-day rest
2
1
300 mg/m2 4-week cycle
5-consecutive day administration followed by 23-day rest
3
2
300 mg/m2 3-week cycle
5-consecutive day administration followed by 16-day rest
19
Japan/Korea Ph1 Studies: Summary
• Darinaparsin is a novel “organic arsenic derivative” that has
antitumor activity.
• Darinaparsin was well tolerated at all doses and dosing schedules.
Liver function disorder (Grade 3) in 1 Japanese subject in the cohort
of 300 mg/m2 3-week cycle was determined as DLT.
• Darinaparsin demonstrated its potential antitumor efficacy (1CR,
3PRs out of 14 evaluable subjects).
• The results of two phase 1 studies suggested that 300 mg/m2/day
for 5-consecutive days every 3 weeks would be the most suitable
dosing schedule in an Asian phase 2 study of darinaparsin in patients
with relapsed or refractory PTCL.
20
Solasia Phase 2 Study with
Darinaparsin
Darinaparsin Asian Phase 2 Study: Study Outline
• Target Indications: Relapsed or Refractory PTCL
– PTCL, not otherwise specified (PTCL-NOS)
– Angioimmunoblastic T-cell Lymphoma (AITL)
– Anaplastic Large Cell Lymphoma (ALCL) ALK-positive/negative
• Study Objectives
– Primary：To evaluate the efficacy of SP-02L monotherapy in patients with relapsed
or refractory PTCL
– Secondary：
• To assess the safety of SP-02L monotherapy in patients with relapsed or
refractory PTCL
• To evaluate the pharmacokinetic (PK) profile of SP-02L at multiple doses in
selected sites in each country
• Endpoints
– Primary：Tumor response (best overall response) based on the International
Working Group Response Criteria for Malignant Lymphoma revised in 2007 (Cheson
2007)
– Secondary：Progression-free survival (PFS), overall survival (OS), time to response
(TTR), duration of response (DOR), occurrence of adverse events (AEs), SP-02L plasma
concentration-time profile, PK parameters, and urinary excretion rates
22
US Phase 2 Study (SGL2003) Results - Efficacy
50 patients were enrolled

(incl. 29 patients with Lymphomas, 21 others): 22 NHL, 7 Hodgkin’s
Lymphoma

(incl. 21 patients with AML and others)
22 NHL patients (8 DLBCL, 7 PTCL, FL 4, MCL 2, Others 1)
Efficacy (Physician Assessments):

2/7 responders (1 CR, 1 CRu) in 7 PTCL patients (RR=28.5%)

2/8 responders (2 PRs) in 8 DLBCL patients (RR=25%)
Peter J. Hosein, Izidore S. Lossos et al. A multicenter phase II study of darinaparsin in relapsed or refractory
Hodgkin’s and non-Hodgkin’s lymphoma; American Journal of Hematology 2011, 87; 111–114
23
Solasia Intellectual Property
Overview of Darinaparsin Patent Estate
Patent Family
Expiration Date
Description of Subject Matter
UTEX 001
Jan-7-2023
Composition of Matter and Methods of Treatment
S-Dimethylarsino-Thiosuccinic Acid, S-DimethylarsinoThiobenzoic Acid, S-(Dimethylarsino) Glutathione as
Treatments for Cancer
Worldwide Status
Granted cases in AU, EP, JP, and US
Pending cases in HK and JP
UTEX 002
Jul-15-2025
Darinaparsin Crystalline Forms and Analogs, and Related
Granted cases in JP, KR, and US
Methods of Treatment
Pending cases in JP
Compounds and Methods for the Treatment of Cancer
ZIPH 001
Jul-28-2026
Darinaparsin Crystalline Forms and Methods of Treatment Granted cases in AU, BE, CH, DE, EP, GI, FR, GB,
Compounds and Methods for the Treatment of Cancer IE, IT, JP, NL, ES, SE, and US
UTEX 004
Jan-16-2027
ZIPH 026
Aug-14-2029
Extended Middle Arsenicals and Methods of Synthesis
Compounds and Methods for the Treatment of Cancer
Methods of Treatment (Lymphoma)
Granted cases in JP and RU
Organoarsenic Compounds and Methods for the Treatment Pending cases in US, CN, EP, GC, HK, IN, JP, KR,
of Cancer
MX, and SG
ZIPH 015
Dec-12-2028
Methods of Synthesis
Compounds and Methods for the Treatment of Cancer
ZIPH 002
Sep-28-2027
Methods of Treatment (Angiogenesis)
Methods for Controlling Angiogenesis in Animals
ZIPH 029
Dec-5-2034
Granted cases in AU, CA, CH, CN, DE, EP, FR, GB,
IE, HK, JP, KR, NL, SG, and US
Pending cases in AU, CN, HK, and IL
Granted case in JP
Pending cases in CN, HK, JP, and SG
Granted case in US
Darinaparsin Crystalline Forms and Methods of Treatment
Pending cases in CN, JP, KR, US, and TW
Compounds and Methods for the Treatment of Cancer
25
Solasia Publications
on Darinaparsin
American Society for Hematology 2015
27
27
T Cell Lymphoma Forum 2015
28
Solasia CMC
Solasia CMC and COGS
• Solasia has a well defined manufacturing process for Darinaparsin
and a strong supply chain
• Manufacturing and batch scale up in kg quantities has been
performed successfully.
• COGS is low enough to make the program economically feasible.
30
Orphan Drug Designation
Solasia Has Orphan Drug Designation in US and EU
32
Solasia Press
Solasia Announces Meiji Seika Alliance in Japan
34
Contact Details
Solasia has appointed The Sage Group to manage its licensing
program for Darinaparsin. Please direct all enquiries to:
US Corporate Office
EU Corporate Office
Wayne Pambianchi
The Sage Group Inc.
1802 Route 31 North
#381 Clinton
New Jersey 08809 USA
Phone: +1 908 2319644
Cell: + 1 908 2306170
Fax: +1 908 2319692
[email protected]
Dr. Bill Mason
Sage Healthcare Ltd.
The Old Black Barns
Lord’s Lane, Ousden
Newmarket, Suffolk CB8 8TX
UK
Phone: +44 1638 508779
Mob: +44 7785 950134
[email protected]
Corporate Website
http://www.sagehealthcare.com
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