1. No category

April 2015
Forward Looking Statements
This presentation contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. Such
statements include, but are not limited to, statements about the future
expectations, plans and prospects of the development of Islet Sciences
Inc.’ s products. These forward-looking statements about future
expectations, plans and prospects of the development of the Company's
products are subject to a number of risks, uncertainties and assumptions,
including those identified under “Risk Factors” in the Company’s most
recently filed Annual Report on Form 10-K, Quarterly Report on Form 10Q and in other filings the Company periodically makes with the SEC.
Actual results may differ materially from those contemplated by these
forward-looking statements. The Company does not undertake to update
any of these forward-looking statements to reflect a change in its views or
events or circumstances that occur after the date of this presentation.
CONFIDENTIAL
2
Corporate Snapshot
Biotech company developing new medicines and technologies for the
treatment of metabolic disease
Treatment
De-risked Late-Stage Pipeline in High-Value
Indications – NASH/NAFLD & T2DM
Best-in-Class SGLT2 Inhibitor
Metabolic
Disease
Small Molecule Immune/Inflammatory
Modulators
Novel Beta-Cell Loss Diagnostic
Early
Diagnosis
Strong Intellectual Property
CONFIDENTIAL
3
Development Pipeline
Therapeutic
Product Candidates
Lead
Preclinical
Phase 1
Phase 2a Phase 2b Phase 3
T2DM
Remo Biphasic
Status / Anticipated Milestones
- Two pha s e 2b s tudi es compl eted
- 2b s tudy for T2DM i ni tia ted
- i ni tia tion of 2b s tudy for NASH 2H 2015
NASH
- Precl i ni ca l pa cka ge compl ete
Territory Rights
Gl oba l outs i de of
Ja pa n, Korea ,
Ta i wa n, Chi na ,
La tin Ameri ca
T1DM
ISLT-2669
Inflammation
ISLT-P
T1DM
- Fi rs t s peci es s a fety/effi ca cy s tudy compl eted
- Precl i ni ca l devel opment ongoi ng
- T2DM, NASH, Immune di s orders
- Fi rs t s peci es s a fety/effi ca cy s tudy compl eted.
- Status under revi ew
- Precl i ni ca l ongoi ng
IL-12 Inhibitor Library
Diagnostic
Product Candidates
Discovery
Validation
CLIA/510k Approval
Launch
T1DM
ISLT-B dx
T2DM
Completed
Status / Anticipated Milestones
- As s a y devel opment compl eted
- T1DM CLIA va l i da tion a nd l a unch pl a nni ng
- T2DM va l i da tion pl a nni ng
ISLT/Gl oba l
ISLT/Gl oba l
ISLT/Gl oba l
Territory Rights
ISLT Wol dwi de
Planned
CONFIDENTIAL
4
High-Need Target Indications:
Diabetes
>50% of Americans will have diabetes or be prediabetic by 2022
$5.7 billion3
Addressable U.S. Market
Today1
Addressable U.S. market
20222
86M
110M
29M
55M
$0 in 2013
1 Source: National Diabetes Statistics Report, 2014
ADA website
Source: American Diabetes Association, 2011 National Diabetes Fact Sheet, Jan. 26, 2011
3 Datamonitor Healthcare
2
CONFIDENTIAL
5
High-Need Target Indications:
NASH/NAFLD
≥ 30% of U.S. population has nonalcoholic fatty liver disease (NAFLD)
> 12% of U.S. population have more serious Non-alcoholic Steatohepatitis (NASH)
$35+ billion4
Currently there are no approved therapies for NASH
Addressable U.S. Market
Today1
Addressable U.S. market
20252
102M
93M
25M
29M
$600MM in 20103
1 Chalasani et
al. AASLD Practice Guidelines. 2012
J and Torok N. NASH and the metabolic syndrome. 2008
3,4 Deutche Bank
2Jiang
CONFIDENTIAL
6
Remogliflozin Etabonate
Selective once-daily SGLT2 inhibitor with best-in-class potential
Type 2 Diabetes – Phase 2b




Best-in-class lowering of HbA1c, plasma glucose, and weight
Low incidence of GFI
No increase in LDLc
No dose adjustment expected for patients with renal impairment
NASH/NAFLD – Phase 2b





Clinical evidence: robust increases in insulin sensitivity and reductions in ALT/AST
Preclinical results: dose-dependent decrease in liver triglycerides, weight and ALT/AST
Reduction in pro-inflammatory cytokines
Significant anti-oxidant activity
Plan to initiate phase 2b for NASH in 2015
>20 clinical trials completed and >800
subjects have received remogliflozin
etabonate with no drug-related SAEs:
CONFIDENTIAL
Phase 1
Phase 2a
Phase 2b
17
3
2
7
Remogliflozin
Only Differentiated SGLT2 Inhibitor
SGLT2 is a well validated target for type 2 diabetes
 Three approved drugs in United States
 Little positive differentiation (share same basic chemical structure)
 Current class profile: Moderately efficacious, increases in LDLc, increases in GFI, dose
adjustment required with CKD
Remogliflozin
Dapagliflozin
(Farxiga)
Canagliflozin
(Invokana)
Empagliflozin
(Jardiance)
Ertugliflozin
Company
Islet/BHV
AZN
JNJ
LLY
PFE/MRK
Stage
Phase 2b
Approved
Approved
Approved
Phase 3
O-aryl glucoside
C-aryl glucoside
C-aryl glucoside
C-aryl glucoside
C-aryl glucoside
Chemistry
Nighttime SGLT2 inhibition can lead to:
 Increases in LDL Cholesterol (LDLc)
 Increased genital fungal infections (GFI)
 Nocturia / polyuria
 Changes in bone metabolism
Remogliflozin’s shorter half-life + Biphasic formulation enables overnight
drug-holiday and best in class once-daily target product profile
CONFIDENTIAL
8
Remogliflozin
Competitive Landscape Diabetes
Biphasic
Remogliflozin
+
HbA1c Lowering
Weight Loss
Renal Impairment
Nighttime Inhibition
Genital Fungal Infections
Change in LDLc
Cardiovascular Risk
Anti-oxidant/NASH
=
+
+
+
+
+
+
+
Dapagliflozin
Canagliflozin
Empagliflozin
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
Superior
CONFIDENTIAL
Class Comparative
Inferior
9
Remogliflozin
HbA1c Reduction
-2
0
4
8
12
0.4
0.2
Observed BID reductions
in HbA1c:
0
-0.2
1% - 1.4%
-0.4
-0.6
-0.8
-1
Placebo
Remo 100mg
-1.2
Difference between BID and QD attributable to PK and effect
on evening post prandial glucose
-2
0
4
8
12
0.4
0.2
0
Observed QD reductions
in HbA1c:
0.5% - 0.8%
-0.2
-0.4
-0.6
-0.8
CONFIDENTIAL
-1
Placebo
Remo 250mg
10
Remogliflozin
Weight Loss
-2
0
2
4
8
12
1.5
1
0.5
Observed BID reductions
in weight:
0
-0.5
1.8% - 4.0%
-1
-1.5
-2
-2.5
Placebo
Remo 100mg
-3
Difference between BID and QD attributable to PK and effect
on evening post prandial glucose
-2
0
2
4
8
12
1
0.5
0
-0.5
Observed QD reductions
in weight:
1.5% - 2.5%
-1
-1.5
-2
-2.5
Placebo
Remo 250mg
-3
CONFIDENTIAL
-3.5
11
Remogliflozin
Differentiation: Genital Fungal Infections
 Literature indicates excess bladder volume and hyperglycemia responsible for GFI
 By correlation, overnight SGLT2 inhibition leads to elevated urine glucose and increased
bladder volume
 Daytime not a concern due to regular urination (pressure relief) and fluid intake (UGE dilution)
 Risk factors that combine to create increased GFI incidence are high UGE (>80 g/24 hr) and
hemoconcentration (as indicated by elevated hematocrit)
Remo QD
Remo BID
Dapagliflozin
(Farxiga)
Canagliflozin
(Invokana)
Empagliflozin
(Jardiance)
Ertugliflozin
GFI (%)
1.9
2.8
8.4
11.4
6.4
NA
Nighttime
inhibition
No
Yes
Yes
Yes
Yes
Yes
0.5 - 0.8
1.0 – 1.4
0.7 - 0.9
0.7 - 0.9
0.4 – 0.6
0.6 – 0.8
HbA1c
Lowering (%)
Difference attributable to nighttime inhibition of SGLT2
CONFIDENTIAL
12
Remogliflozin
Differentiation: LDL Cholesterol
Empagliflozin
Canagliflozin
 Drug On-Board overnight correlates with
increases in LDLc
Dapagliflozin
Remogliflozin BID
 Drug Off-Board overnight correlates with
no increase in LDLc
Remogliflozin QD
10 mg
25 mg
4.6%
6.5%
100mg
300mg
4.5%
8.0%
2.5mg
5mg
10mg
5.0%
3.1%
9.5%
50mg
100mg
250mg
500mg
1000mg
6.5%
4.9%
13.2%
11.9%
9.3%
100mg
250mg
500mg
1000mg
-8.9%
-1.5%
3.7%
-0.1%
Type 2 diabetics commonly show an elevation in plasma triglycerides (with little or no change in
LDLc and HDLc concentrations) as reflected by either increased total triglycerides or VLDL
concentrations
TG/VLDL are mobilized for energy during low glucose periods (e.g. sleep)
With glucose elimination (e.g. with SGLT2 inhibition during sleep) greater amounts of TG/VLDL are
mobilized.
This leads to small increases of LDLc concentration as VLDL transitions to LDLc
CONFIDENTIAL
13
Remogliflozin
Differentiation: Renal Impairment
Accumulation
D UGE
Remogliflozin
Mild
Moderate
+10%
+10%
0%
0%
Dapagliflozin
Mild
Moderate
+39%
+100%
-42%
-80%
Canagliflozin
Mild
Moderate
+15%
+29%
-13%
-33%
Empagliflozin
Mild
Moderate
+18%
+20%
NA
>44% of diabetics over 20 y/o
>61% of diabetics over 65 y/o
have impaired renal function
 Diabetics are at increased risk of
developing chronic kidney disease
 Renal Impairment: kidneys are damaged with reduced filtration rates
 Can cause waste to build up, leading to cardiovascular disease, anemia, and bone disease
Remogliflozin not expected to require dose adjustment
in patients with mild to moderate renal impairment
CONFIDENTIAL
14
Remogliflozin
Rationale for Biphasic Formulation
• Best-in-class side effect profile (QD) due to absence of during sleep period
• Best-in-class efficacy (BID) due to increased effect on evening post-prandial glucose
Combined single dose of instant release and delayed release provide
exposure during the day/evening but not during the overnight period, thereby
combining the positive effects of QD and BID dosing in single formulation.
Remo
UGE Amount
CONFIDENTIAL
Wake
Sleep
Dinner
Lunch
Breakfast
Delayed Release
Wake
Sleep
Dinner
Lunch
Breakfast
Instant Release
15
Remogliflozin
Biphasic Achieves Ideal PK/PD Profile
Results of randomized, crossover study in healthy volunteers
• Formulation was well-tolerated with few AEs and no significant safety signals
• UGE extended well into dinner, but not substantially during sleep
Median Plasma Concentration vs. Time
Median UGE vs. Time
CONFIDENTIAL
16
Remogliflozin
Progression of NASH
Obesity
Insulin Resistance
Normal
Inflammation
Oxidative Stress
NAFLD
NASH
Fibrosis
Cirrhosis/HCC
CONFIDENTIAL
17
Remogliflozin
NASH/NAFLD
Remogliflozin effectively addresses major pathological events leading to NASH in
one molecule:
Obesity
Insulin Resistance
Oxidative Stress
Inflammation
 Reduces oxidative stress
 Unique intrinsic anti-oxidant activity
20.0
250
16.0
200
Trolox umol/g
Serum TBARS (nmol/ml)
18.0
14.0
12.0
10.0
8.0
Canagliflozin
150
Dapagliflozin
100
Remogliflozin
6.0
4.0
50
2.0
0.0
0
Normal
Untreated
Remo 0.1%
Remo 0.3%
SGLT2 Inhibitor
NAFLD
CONFIDENTIAL
18
Remogliflozin
NASH/NAFLD
Remogliflozin effectively addresses major pathological events leading to NASH in
one molecule:
Obesity
Insulin Resistance
Oxidative Stress
Inflammation
Significant Improvement in Postprandial Glucose Disposal
Week 12
Baseline
CONFIDENTIAL
19
Remogliflozin
NASH/NAFLD
Remogliflozin effectively addresses major pathological events leading to NASH in
one molecule:
Obesity
Insulin Resistance
Oxidative Stress
Inflammation
HOMA Insulin Sensitivity (%)
HOMA β-Cell Function (%)
Δ (%) vs. Placebo
(95% CI)
Δ (%) vs. Placebo
(95% CI)
2.7 (-15.3, 24.6)
26.2 (6.3, 49.8))
Remo 100 mg BID
22.9 (1.4, 48.9)
20.8 (1.9, 43.3)
Remo 250 mg BID
19.1 (-2.0, 44.7)
29.4 (8.9, 53.8))
Remo 500 mg BID
25.5 (3.8, 51.6)
36.8 (15.6, 61.9)
Remo 1000 mg BID
28.3 (5.7, 55.5)
46.3 (23.3, 73.6))
Pioglitazone 30 mg
9.5 (-9.7, 32.7)
41.6 (19.5, 67.9)
Remo 50 mg BID
Treatment Ratio (%)
Treatment Ratio (%)
Significant Increases in Insulin Sensitivity and Beta Cell Function
Remogliflozin
NASH/NAFLD
Remogliflozin effectively addresses major pathological events leading to NASH in
one molecule:
Obesity
Insulin Resistance
Oxidative Stress
Inflammation
 Improved Liver Function
 Reduced Inflammation in the Liver
140
120
% Control
100
80
60
MCP-1
40
20
0
Normal Untreated
Remo
0.1%
Remo
0.3%
NAFLD
ALT Reduction
CONFIDENTIAL
21
IL-12 Antagonists
Immune/Inflammation Modulating Drugs
Protects against Beta Cell Death
•
•
•
•
•
•
First-in-class series of compounds
Antagonists of IL-12 targeting STAT4
pathway.
Immune- and inflammation modulating.
Preserves insulin producing beta cell
function by preventing cytokine-induced
destruction.
Displays anti-fibrotic activity in rodent model
of NASH.
Current lead candidate ISLT-2669
demonstrates longer half-life and superior
oral bioavailability.
CONFIDENTIAL
Reduces Fibrosis in NASH
22