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TM

TSX-V: SBM

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TSX-V: SBM

FSE: ZSB

Introduction and History

• Sirona Biochem was founded in 2009

• TFChem was acquired in 2011

Sirona Biochem (Parent Company)Vancouver, BC, Canada

TFChem (Wholly Owned Subsidiary)Cosmetic Valley, France

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Sirona’s Fluorination Chemistry Technology The Solution to Unstable Carbohydrate Molecules

Resulting in improved bioavailability and selectivity that translates into better safety and efficacy

Carbohydrate

molecules are

unstable by

nature

Our technology

stabilizes

carbohydrate

molecules

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Current Collaborations & Pipeline

Cosmetic Products

Therapeutic Area Compound Partnering Status

Skin lightening SBM-TFC-849 Valeant Pharmaceuticals

Skin lightening SBM-TFC-1067 Ready for licensing

Anti-aging SBM-TFC-837 Ready for licensing

Therapeutic Area Compound Partnering Status

Diabetes SBM-TFC-039 Partnered with Fosun Pharma in ChinaReady for licensing in ROW

Regenerative Medicine SBM-TFC-1165 Ready for licensing

Inflammatory Disease In development JV with Bloom Burton & Co

Pharmaceutical Products

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Skin Lightening Agent

SBM-TFC-1067

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The Problem

• Deoxyarbutin is a tyrosinase inhibitor that prevents melanin formation• Deoxyarbutin is unstable and is broken down in the body, releasing hydroquinone,

a known carcinogen• Hydroquinone is banned in the EU and restricted in USA• The problem is to develop the safest and most effective skin lightener in the world

Deoxyarbutin and arbutin are commonly used skin-lightening agents that have safety risks associated with their use

O O OH+

Hydroquinonetoxic

O HO

OH

breaks down into

Deoxyarbutin

OH

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SBM-TFC-1067

Superior safety and 8 times the efficacy of deoxyarbutin.

• Our goal was to develop a safer and more effective compound than Deoxyarbutin

• We have successfully developed a stabilized Deoxyarbutin, with zero hydroquinone released, thus eliminating potential adverse events

Sirona Biochem ’s Solution

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Global Skin Lightening Market

2015 2016 2017 2018

Japan 12.8 13.2 13.7 14.1

Asia-Pacific 4.1 4.5 4.8 5.2

US, EU, ROW 0.4 0.4 0.4 0.5

0.0

5.0

10.0

15.0

20.0

25.0

$ b

illio

ns

19.8

17.318.1 18.9

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Safety of SBM-TFC-1067

0

20

40

60

80

100

120

140

4.211.8

88.8

128.6

Hyd

roq

uin

on

e R

ele

ase

d (

%)

Deoxyarbutin SBM-TFC-1067

In vitro stability: percentage of hydroquinone released

Water RT 14 days

Bis Tris buffer RT 14 days

PBS RT 14 days

Ringer solution at pH 6.8 at RT 14 days

Ringer solution at pH 5.5 at 70°C 24H

Ringer solution at pH 8.5 at 70°C 24H

Fibroblasts RT 48H

Keratinocytes RT 48H

Human skin extract RT 48H

Synthetic perspiration RT 48H

SBM-TFC-1067 is stable and extremely safe, with zero hydroquinone released in all tested conditions (chemical, biological)

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Summary of Safety Evaluations

Genotoxicity Test(SOS Chromotest) • No genotoxicity between concentrations of 0 to 0.25%

Acute Toxicity Test(on keratinocytes) • MTT50: 66µg/ml

Ocular Irritation Test(on human reconstituted cornea)

• Low toxicity at a concentration of 0.14%• No toxicity at a concentration of 0.01%

Phototoxicity Test(on fibroblasts)

• No phototoxicity

Skin Irritation Test(on RHE)

• No irritation at a concentration of 0.05%

Sensitization Test• Non sensitizer (high flow, no haptenation, MTT75:

20µg/ml, no IL-18 induction)• Irritant on keratinocytes

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20µg of compound at 100µg/mL (in 90% purified water/5% ethanol/ 5% DMSO) was deposited on human skin (exchange surface: 2cm2)

ResultsQuantity TFC-1067 per gram epidermis (ng/g)

SD (ng/g)

EPIDERMIS22278 1296

DERMIS 5142 831

With a high flux capacity and excellent efficacy, very low concentrations could be used in aqueous formulations

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)

SBM-TFC-1067 0.01%

Transcutaneous Diffusion

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Efficacy of SBM-TFC-1067

0

0.1

0.2

0.3

0.4

SBM-TFC-1067 Deoxyarbutin

0.035 mM

0.272 mM

IC5

0 (

mM

)

Inhibition of Human Tyrosinase (300U/ml)

SBM-TFC-1067 has 8 times the efficacy of deoxyarbutin

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Safety and Efficacy Summary

EfficacySafety

• Superior safety profile over deoxyarbutinwith 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

• 8 times the efficacy ofdeoxyarbutin

• High flux capacity to the site of action in the epidermis

• Antioxidant properties

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Synthesis of SBM-TFC-1067 and Patents

• The synthesis of SBM-TFC-1067 is a three

step process

• Scale-up and manufacturing would be

straightforward

• Patent: PCT application on 04/03/2015:

PCT/FR2015/050530

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TM

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Glycoprotein Program Anti-Aging and Regenerative Medicine

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Natural Anti-Freeze Glycoproteins (AFGPs)

…enable survival under freezing temperatures

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Data Illustrating Protection of Oocytes and Platelets From Cold Temperatures

Incubation of oocytes at 4°C during 24h

G.L.Fletcher; S.V.Goddard; Y.Wu; CHEMTECH 1999, 30(6), 17-28.

Naturally Occurring Antifreeze Glycoprotein

Protects Cells From Stressed Environment

Platelets preserved (not activated) at 4°C

F. Tablin; A. E. Olivier; N.J. Walker; L.M. Crowe; J.H. Crowe; J.

Cell. Physiol. 1996, 168, 305-313.

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Exciting Data Generated From First Generation of

Synthetic Antifreeze Glycoproteins

Etablissement Français du Sang, Strasbourg, Pr. J.P. Cazenave

Note: Unprotected platelets remain viable for

approximately 3-5 days

21 Day Study of Glycoprotein Protection Against Platelet Aggregation at 3 Temperatures.

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Data Continued - Skin Fibroblast Temperature Studies

ProteoCell biotechnologies, Canada, Dr. S. Hussein

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Data Continued - Skin Fibroblast Oxidative Stress Studies

ProteoCell biotechnologies, Canada, Dr. S. Hussein

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Data Continued - Stem Cell Preservation Studies

Johnson and Johnson, United States, S. Nelson

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Data Continued - β-Islet Cell Preservation Studies

Alberta University , Canada, Dr. Rajotte

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The Second Generation of Antifreeze Glycoproteins

We have successfully stabilized three patented antifreeze glycoproteins.

The first generation of these synthetic

antifreeze glycoproteins were very

effective at preserving cells against

stressed environments but they were

unstable and could not be used for

human applications…

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0

20

40

60

80

100

D0 D1 D2 D3 D4 D5 D6 D7 D10 D12

Cell v

iab

ilit

y (

%)

Viability of fibroblasts under stressed conditions of serum deprivation

Stresscontrol

Stress +TFC-837 at5mg/ml

At the conclusion of a 12 day study, 100% of the unprotected cells were dead whereas 75% of theglycoprotein-protected cells were fully viable.

Efficacy of SBM-TFC-837

SBM-TFC-837 protects fibroblasts from the stressed condition of serum deprivation

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Efficacy of SBM-TFC-837

0

20

40

60

80

100

120

no irradiation irradiation control irradiation + TFC-837 # TM0021-F4

(5 mg/mL)

irradiation + TFC-837 # TM0021-F4

(10mg/mL)

irradiation + TFC-837 # TM0021-F4

(15 mg/mL)

irradiation + TFC-1165 # TM0025

(5 mg/mL)

irradiation + TFC-1165 # TM0025

(10 mg/mL)

irradiation + TFC-1165 # TM0025

(15 mg/mL)

Fib

rob

last

Via

bili

ty (

%)

1H

3H

24H

Viability of fibroblasts after UVA irradiation (11J/cm2)

SBM-TFC-837 protects fibroblasts from the stressed condition of UV irradiation

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Sirona’s Glycoprotein program: Biomimicry

The potential opportunities are enormous

Sirona’s Glycoproteinprogram

Cosmetic Active Ingredients

Anti-agingProtection & Regeneration

Healing, Wound care,

Hypothermic protection,

Sunscreen

Post-sunburn/ radiotherapy

Adjuvants for biologicalmaterial preservation

Cells

Stem cells

Islet cells

Platelets

Red bloodcells

Adipocytes

Tissues

Skin explants, RHE,

Cornea

Organs

Transplant

RenalReperfusion

Living organisms

Vaccines

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Ongoing Development

• Evaluation in other stressed conditions

• Gene and protein expression

• Mechanism of action

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Synthesis and Patents

• Family of compounds with one

carbohydrate mimic and 1 to 3 amino

acids

• Patent: priority application of EP on

17/03/2014: EP 14305374.2; application of

PCT on 17/03/2015: PCT/EP2015/055577

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TM

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SGLT2 Inhibitor ProgramType 2 diabetes

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Diabetes2012 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.

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Market Segmentation

Total Type 2 Diabetes Therapeutics Market

Insulins Non-Insulin Therapeutics

Human Insulin Modern Insulin Standard of Care (SOC) Add-on to SOC

Biguinides

Sulfonylureas

Meglitinides

Glitazones

Incretins

SGLT2* Inhibitors

*Sodium-glucose co-transporter 2

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Emerging MarketsIndia & China Outpacing the USA

By 2030, experts predict that Type 2 Diabetes will grow by:US 25%, India 66%, and China 44%

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SGLT2 InhibitorsA 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.

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Global SGLT2 inhibitor Market

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

2013 2014 2015 2016 2017 2018 2019 2020

$U

S m

illio

ns

Forxiga

Invokana

Lusefi

Suglat

Ertugliflozin

Farxiga

Jardiance

Invokana

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Competitive Lifecycle

2013 2017 2021 2025 2029 2033

New Product/ Indications Existing Competition

Canagliflozin (J & J, Mitsubishi Tanabe)

Dapagliflozin (AZ, Ono)

Empagliflozin (BI, Eli Lilly)

Ipragliflozin (Astellas)

Ertugliflozin (Pfizer)

Luseogliflozin (Taisho)

Tofogliflozin (Chugai, Sanofi, Kowa)

SBM-TFC-039 (Sirona, Fosun)

CPL-200-075 (Celon)

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SGLT2 Inhibitor ProgramSirona’s preclinical program for type 2 diabetes

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Head-to-head trial

• Six hours after administration, SBM-TFC-039 reduced blood glucose by 44% compared to 26% for Canagliflozin

• SBM-TFC-039 (1 mg/kg) proved to be more efficacious than Canagliflozin

0 2 4 6 80

5

10

15

20

25

Control Lean

Control Diabetic

SBM-TFC-039 1 mg/kg

Canagliflozin 1 mg/kg

Hrs

[Blo

od G

luco

se]

(mm

ol/L)

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SBM-TFC-039 Preclinical Study Results

0 4 8 12 16 20 240

5

10

15

20

25

Control Diabetic

1 mg/kg SBM-TFC-039

Control Lean

Time (hr)

[Blo

od G

luco

se]

(mm

ol/L)

• In an acute dosing study, SBM-TFC-039 reduced the blood glucose levels in diabetic rats to the level of lean rats within 6 hours.

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SBM-TFC-039 Preclinical Study Results

• In a 28-day chronic dosing study, SBM-TFC-039 reduced blood glucose levels by 71% in ZDF rats (fed state) compared to non-treated rats.

Day 0 Day 7 Day 14 Day 21 Day 280

10

20

30

Control Lean

Control Diabetic

1 mg/kg SBM-TFC-039

[Blo

od G

luco

se]

(mm

ol/L)

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SBM-TFC-039 Preclinical Study Results

• When challenged with glucose SBM-TFC-039 reduced blood glucose excursion by 89% in diabetic rats.

0 30 60 90 1200

5

10

15

20

25

Control Diabetic

1 mg/kg SBM-TFC-039

Control Lean

Time (min)

[Blo

od G

luco

se]

(mm

ol/L)

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• SBM-TFC-039 triggered glucose excretion in a dose dependent manner

Con

trol

1mg/

kg

3m

g/kg

10m

g/kg

0

200

400

600

800

1000

UG

E (

mg/2

4hr/

100g b

ody w

eig

ht)

SBM-TFC-039 Preclinical Study Results

• SBM-TFC-039 was well tolerated

Primate Study

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SBM-TFC-039 Specifications

Test concentration

(M)

Solubility(µM)

1st 2nd Mean

Flags

Aqueous solubility (PBS, pH 7.4)

SBM-TFC-039 2.0E-04 249.93 248.10 200 ADJ

Test concentration

(M)

Weighted Average

of Three Replicates

Partition Coefficient (logD, n-octanol/PBS, pH 7.4)

SBM-TFC-039 1.0E-04 2.68

ADJ Adjusted. When the observed mean of solubility is greater than 200µM, the mean value is adjusted to the maximum assay concentration which is 200µM

• Synthesis in 11 steps / performed at a lab level / max 7.5g with 2.4%overall yield. Scale-up and optimization yet to be performed.

• Solubility

• Partition coefficient

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Intellectual Property – SGLT Inhibitor

• European patent protecting structure, process and use filed May 2011

• Expansion through PCT process May 2012

• National phase in all major markets in 2013

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SBM-TFC-039 Development Status

Study Description Status

Multi-gram synthesis Complete

Efficacy in mice Complete

Tolerability in rodents (MTD in mice, CVS and CNS safety pharmacology)

Complete

Pharmacokinetics in rats Complete

Metabolic profiling in rats (in vitro and in vivo) Complete

Efficacy in normal and diabetic rats Complete

Ancillary pharmacology (ADME-Tox, in vitro metabolism and pharmacology)

Complete

In vitro selectivity (SGLT2 vs. SGLT1) Complete

Efficacy in normal monkeys Complete

Pharmacokinetics in monkeys Complete

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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

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TM

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SGLT2 Inhibitor ProgramFosun Pharma’s preclinical program for type 2 diabetes

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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

Group Treatment 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

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7Days

14 Days Repeated Oral Administration and Toxicokinetic observation 7 Days Recovery

Same schema for toxicity and toxicokinetic studies

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Results of the 14 Day Toxicology Study

0

100

200

300

400

500

600

700

800

900

SBM-TFC-039 Canagliflozin

mg

/kg/

day

Maximum Tolerated Dose

• Efficacy study dosing: 3 mg/kg/day• Pharmacokinetics study dosing: 10mg/kg/day PO and 1 mg/kg/ day IV

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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

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TM

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www.sironabiochem.com