Transcript Diapositive 1 - Sirona Biochem

Bio Europe, Paris
March 11, 2015
TM
TSX-V: SBM
Sirona’s Fluorination Chemistry Technology
The Solution to Unstable Carbohydrate Molecules
Carbohydrate
molecules are
unstable by
nature
Our technology
stabilizes
carbohydrate
molecules
Resulting in improved bioavailability and selectivity
that translates into better safety and efficacy
TSX-V: SBM
Current Collaborations & Pipeline
Cosmetic Products
Therapeutic Area
Compound
Partnering Status
Skin lightening
SBM-TFC-849
Valeant / Obagi
Skin lightening
SBM-TFC-1067
Ready for licensing
Anti-aging
SBM-TFC-837
Ready for licensing
Pharmaceutical Products
Therapeutic Area
Compound
Partnering Status
Diabetes
SBM-TFC-039
Partnered with Wanbang
Biopharma in China
Ready for licensing in ROW
Regenerative Medicine
SBM-TFC-837
Ready for licensing
Inflammatory Disease
In development
JV with Bloom Burton & Co
TSX-V: SBM
Skin Lightening Agent
SBM-TFC-1067
TM
TSX-V: SBM
Global Skin Lightening Market
25.0
$ billions
20.0
17.3
18.1
18.9
19.8
2016
13.2
4.5
0.4
2017
13.7
4.8
0.4
2018
14.1
5.2
0.5
15.0
10.0
5.0
0.0
Japan
Asia-Pacific
US, EU, ROW
TSX-V: SBM
2015
12.8
4.1
0.4
Safety of SBM-TFC-1067
In vitro stability: percentage of hydroquinone released
Hydroquinone Released (%)
140
128.6
120
Water RT 14 days
Bis Tris buffer RT 14 days
100
88.8
PBS RT 14 days
80
Ringer solution at pH 6.8 at RT 14 days
60
Ringer solution at pH 8.5 at 70°C 24H
Ringer solution at pH 5.5 at 70°C 24H
Fibroblasts RT 48H
Keratinocytes RT 48H
40
Human skin extract RT 48H
20
Synthetic perspiration RT 48H
11.8
4.2
0
Deoxyarbutin
SBM-TFC-1067
SBM-TFC-1067 is stable and extremely safe, with zero hydroquinone released in all tested conditions (chemical, biological)
TSX-V: SBM
Summary of Safety Evaluations
Genotoxicity Test
(SOS Chromotest)
Acute Toxicity Test
(on keratinocytes)
• No genotoxicity between concentrations of 0 to 0.25%
• MTT50: 66µg/ml
(on human reconstituted cornea)
• Low toxicity at a concentration of 0.14%
• No toxicity at a concentration of 0.01%
Phototoxicity Test
• No phototoxicity
Ocular Irritation Test
(on fibroblasts)
Skin Irritation Test
(on RHE)
Sensitization Test
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• No irritation at a concentration of 0.05%
• Non sensitizer (high flow, no haptenation, MTT75:
20µg/ml, no IL-18 induction)
• Irritant on keratinocytes
Transcutaneous Diffusion
SBM-TFC-1067
0.01%
20µg of compound at 100µg/mL (in 90% purified water/5% ethanol/ 5%
DMSO) was deposited on human skin (exchange surface: 2cm2)
Results
EPIDERMIS
DERMIS
Quantity TFC-1067 per
gram epidermis (ng/g)
SD (ng/g)
22278
1296
5142
831
Flux
SD
TFC-1067
0.12 µg/h/cm²
0.020
Deoxyarbutin
0.17 µg/h/cm²
0.041
SBM-TFC-1067 penetrates into the site of action (epidermis layer of the skin)
With a high flux capacity and excellent efficacy, very low concentrations could be used in
aqueous formulations
TSX-V: SBM
Efficacy of SBM-TFC-1067
Inhibition of Human Tyrosinase (300U/ml)
0.4
0.272 mM
IC50 (mM)
0.3
0.2
0.1
0.035 mM
0
SBM-TFC-1067
Deoxyarbutin
SBM-TFC-1067 has 8 times the efficacy of deoxyarbutin
TSX-V: SBM
Safety and Efficacy Summary
Safety
• Superior safety profile over deoxyarbutin
with zero hydroquinone released
• No genotoxicity (0-0.25%)
• Very minor ocular irritation at 0.14%
• No ocular irritation at 0.01%
• No skin irritation at 0.05%
• No sensitization
• No phototoxicity
TSX-V: SBM
Efficacy
• 8 times the efficacy of
deoxyarbutin
• High flux capacity to the site of
action in the epidermis
• Antioxidant properties
Glycoprotein Program
Anti-Aging and Regenerative Medicine
TM
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Natural Anti-Freeze Glycoproteins (AFGPs)
…enable survival under freezing temperatures
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Efficacy of SBM-TFC-837
Viability of fibroblasts under stressed conditions of
serum deprivation
Cell viability (%)
100
80
Stress
control
60
40
Stress +
TFC-837 at
5mg/ml
20
0
D0
D1
D2
D3
D4
D5
D6
D7
D10
D12
At the conclusion of a 12 day study, 100% of the unprotected cells were dead whereas 75% of the
glycoprotein-protected cells were fully viable.
SBM-TFC-837 protects fibroblasts from the stressed condition of serum deprivation
TSX-V: SBM
Sirona’s Glycoprotein program: Biomimicry
The potential opportunities are enormous
Sirona’s Glycoprotein
program
Adjuvants for biological
material preservation
Cosmetic Active
Ingredients
Anti-aging
Protection &
Regeneration
Stem cells
Healing, Wound care,
Tissues
Organs
Transplant
Islet cells
Skin explants,
RHE,
Hypothermic protection,
Platelets
Cornea
Sunscreen
Red blood
cells
Post-sunburn/
radiotherapy
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Cells
Adipocytes
Renal
Reperfusion
Living
organisms
Vaccines
SGLT2 Inhibitor Program
Type 2 diabetes
TM
TSX-V: SBM
Diabetes
2012 statistics from the International Diabetes Federation (www.idf.org)
More than 371 million people have diabetes.
By 2030, this will rise to 552 million.
In 2011, 4.8 million people died due to
diabetes and more than $471 billion US
was spent on related healthcare.
Global prevalence is drastically increasing.
TSX-V: SBM
SGLT2 Inhibitors
A New Class of Diabetes Drugs
The novel mechanism of action for SGLT2 inhibition is
blocking the re-uptake of glucose from the kidneys
and improving the obesity profile.
TSX-V: SBM
Global SGLT2 inhibitor Market
7,000
6,000
($ US million)
5,000
4,000
3,000
2,000
1,000
0
2013
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2014
2015
2016
2017
2018
2019
2020
SBM-TFC-039 Ongoing Development
Milestone
Status
Upfront payment
Complete
Preclinical Studies (first line tests)
• Urinary Glucose Excretion (UGE)
• Oral glucose tolerance test (OGTT)
• Pharmacokinetic study in rats
• Batch production of 80g of compound
• 14 day toxicology study with repeated administration
in Sprague Dawley (SD) rats
Complete (06/2014)
Complete (06/2014)
Complete (07/2014)
Complete (12/2014)
Complete (02/2015)
Milestone payment for completion of toxicology study
Expected in March 2015
Preclinical studies (second line tests)
Investigational New Drug (IND)
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SBM-TFC-039 14 Day Rat Toxicity Study
14 Days Repeated Oral Administration and Toxicokinetic observation
Days
0 1
2
3
4
Group
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5
6
7
8
Treatment
9
10 11 12 13
7 Days Recovery
14
1
2
Dose
(mg/kg/
day)
Animal Numbers & Sex
1
SBM-TFC-039
0
3M + 3F
2
SBM-TFC-039
100
3M + 3F
3
SBM-TFC-039
300
3M + 3F
4
SBM-TFC-039
800
3M + 3F
5
Canagliflozin
300
3M + 3F
3
4
5
6
7
Same schema for
toxicity and
toxicokinetic studies
Results of the 14 Day Toxicology Study
mg/kg/day
Maximum Tolerated Dose
900
800
700
600
500
400
300
200
100
0
SBM-TFC-039
Canagliflozin
• Efficacy study dosing: 3 mg/kg/day
• Pharmacokinetics study dosing: 10mg/kg/day PO and 1 mg/kg/ day IV
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Toxicity Study Results
Parameter
Results
Mortality
• No mortality in the groups treated with SBM-TFC-039
• 1 rat died in the Canagliflozin group
Clinical
Observation
• Soft stool observed in the 800 mg/kg/day and Canagliflozin groups
Weight
• No effects
Food intake
• No effects, except for a significant increase in the male 100 mg/kg/day group and Canagliflozin
group on day 9
Hematology
• Platelet counts significantly decreased in the 300 & 800 mg/kg/day groups and returned to
normal at the end of the recovery period
Biochemistry
• Alanine transaminase (ALT) increased significantly in the 300 mg/kg/day and Canagliflozin groups
• Total cholesterol increased significantly in the 800 mg/kg/ day and Canagliflozin groups
• Blood urea nitrogen (BUN) increased significantly in the 300, 800 mg/kg/ day and Canagliflozin
groups
• These indexes returned to normal at the end of the recovery period
Histopathology
Examination
• No visual abnormalities
• Renal weight / body weight increased significantly in the 100, 300, 800 mg/kg/day and
Canagliflozin groups
• Thymus weight / brain weight decreased significantly in the 300, 800 mg/kg/day and Canagliflozin
groups
• Target organ toxicity could be the liver, kidney and thymus
Coagulation
• No effects
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Toxicokinetic (TK) Study Results
Parameter
Results
AUC last
• No obvious gender difference after the last measurable exposure
• Repeated administration of the 100 and 300 mg/kg/day doses increased exposure 2 fold (from 2.1 to 4.2),
suggesting drug accumulation
• Repeated administration of the 800 mg/kg/day dose did not increase exposure significantly (0.7 to 0.8),
suggesting no drug accumulation
• Repeated administration of Canagliflozin did not increase exposure significantly, suggesting no drug
accumulation
TSX-V: SBM
Summary of Toxicity and TK Study Results
• The maximum tolerated dose (MTD) is more than
800 mg/kg/ day for SBM-TFC-039, significantly
greater than 300 mg/kg/day for Canagliflozin
• No obvious gender differences suggesting equal
exposure between the sexes
• Repeated administration of the 100 and 300
mg/kg/day doses increased exposure 2 fold (from
2.1 to 4.2), suggesting drug accumulation
• Repeated administration of the 800 mg/kg/day and
Canagliflozin doses did not increase exposure,
suggesting no drug accumulation
TSX-V: SBM
SBM-TFC-039 Summary
SBM-TFC-039 Reduced glycemia with a long duration of action
•
•
•
•
A highly selective and potent SGLT2 inhibitor
Triggered glycosuria in a dose-dependent manner
Glucosuria lasted 24 hours
Reduced blood glucose levels following glucose
challenge
• Reduced blood glucose level in obese diabetic rats
and normalized diabetes in a 28-day chronic study
• Well tolerated and orally bioavailable
TSX-V: SBM
Summary
• Sirona Biochem is a development stage
biotechnology company that is the leader
in commercializing carbohydrate chemistry
• The opportunity exists to:
o
License our glycoprotein for anti-aging and
regenerative medicine
o
License our SGLT2 inhibitor for type 2
diabetes / NASH
o
License our skin lightener
TSX-V: SBM
www.sironabiochem.com
TM
TSX-V: SBM