1. Eribis Pharmaceuticals AB
Novel Treatment of
Acute Myocardial Infarction (AMI)
CONFIDENTIAL 1

2. Eribis presentation
 The Company
 The indication – background & market
 EP94
 Pre-clinical Development
 General Properties
 Clinical Development
 Intellectual Property
 Q & A session
CONFIDENTIAL 2

3. The Company
CONFIDENTIAL 3

4. The Company
Eribis Pharmaceuticals AB is a Uppsala-based biotech company founded
in 2006, with the aim to develop new therapies for cardiovascular
disease.
CONFIDENTIAL 4

5. Management
 Herman Krapf, Chief Executive Officer
 Erik Bissessar, Chief Business Officer and Medical Scientific
Liason
 Peter Båvenholm, MD, Ph.D., Ass. Prof. Internal Medicine,
Chief Medical Officer
 Fredrik Röök, Business Development
 Stefan Persson, Ph.D., Pharmacology and Toxicology
 Claes Lundberg, Ph.D., Project Management
CONFIDENTIAL 5

6. Scientific Advisory Board
 Gerhard Wikström, MD, Ph.D., Ass Prof Cardiology, Uppsala
University Hospital
 Lars Grip, MD, Ph.D., Professor in Cardiology, Sahlgrenska
University Hospital
 John Pernow, MD, Ph.D., Prof in Cardiology, Karolinska
University Hospital
 Garrett Gross, Ph.D.,Professor of Pharmacology, Medical
College of Wisconsin
 Dan Atar, MD, Ph.D., Professor in Cardiology, Division of
Cardiology, Oslo University Hospital Aker
CONFIDENTIAL 6

7. Acute Myocardial Infarction (AMI)
background and market
CONFIDENTIAL 7

8. Cardiovascular disease (CVD)
the major health problem
 CVD include;
 acute coronary syndromes (ACS)
 stroke
 periphereal arterial disease (PAD)
 Burden of CVD is increasing in parallel with increase in life
expectancy
 Acute Myocardial Infarction (AMI) is the number one cause
of death in the Western world
 mortality rates near 10%
 first cause of chronic heart failure
CONFIDENTIAL 8

9. Acute coronary syndrome (ACS)
Acute coronary syndrome (ACS) is comprises three diseases
involving the coronary arteries: ST elevation myocardial infarction
(STEMI), non ST elevation myocardial infarction (non-STEMI) and
unstable angina.
While ACS mortality declined in the last four decades in the USA as life
expectancy increased, the decline largely represents the postponement
of ACS deaths until older age.
Thus, the burden of ACS is increasing in parallel with the increase in life
expectancy.
CONFIDENTIAL 9

10. Reperfusion therapy
Primary Treatment O ptions for AMI
Coronary Artery By-pass
Graft (CABG)
Percutaneous Coronary
Intervention (PCI)
 Across the seven major markets in 2006 the number of
cardiovascular procedures, including CABG and PCI were
estimated at 7.0m
 Incidence rates for PCI amounts to 3.7m (nonSTEMI + STEMI)
10

11. Large unmet need
Acute Coronary Syndrome
- the major markets
The American Heart Association (AHA) estimates that
there were 1.2 million cases of ACS in 2007 in the US.
This number includes both patients experiencing their first
event as well as patients with relapses.
Patients’ experiencing their first event is around 700,000;
STEMI and NSTEMI accounting for 85% of these events.
This incidence is similar to that in the five major markets in
Europe.
The total number of ACS cases in the US and the five
major EU markets is therefore estimated at around
2.5 – 3.0 million annually.
CONFIDENTIAL 11

12. Metabolic and biochemic changes
caused by reperfusion
Reperfusion injury (RI) limits the beneficial effects of revascularisation
Studies in different species suggest that 20-70% of myocardial damage may come from RI
(Gomes L 2007, Penna C 2008, Zhao ZQ, 2006)
RI leads to functional and structural myocardial damage
–generation of ROS
–a fast restoration of pH
–intracellular calcium overload
–mitochondrial dysfunction
–Apoptosis
(Yellon DM, 2007)
Cardioprotective strategies to minimize RI represents an
unmet medical need
CONFIDENTIAL 12

13. Principles of ischemic pre- and
postconditioning
Brief episodes of coronary artery occlusion are applied either before (preconditioning) or
immediately after (postconditioning) the prolonged ischemic insult
CONFIDENTIAL
Ref; Zhao ZQ et al., Am J Physiol Heart Circ Physiol, 2003;285:579-88 13

14. EP94
Cardioprotection in acute myocardial
infarction (AMI)
CONFIDENTIAL 14

15. EP94 – First in class drug
 Novel pharmacological cardioprotective intervention
 Tetrapeptide (stabilized)
 Injectable, small volume
 Microgram dosage
 Cardioprotective effects in rodent and non-rodent animal
models
 Low COGS (solid phase peptide synthesis)
 Patent protected
CONFIDENTIAL 15

16. Tentative molecular signaling pathways
involved in cardioprotection
CONFIDENTIAL 16

17. Mode of Action
 Acute Myocardial Infarction induces an ischemia/reperfusion-induced
tissue damage
 It is anticipated that EP94’s mode of action reduces the
ischemia/reperfusion damage through
 opoid receptors
 KATP channels
 iNOS
CONFIDENTIAL 17

18. Preclinical results
CONFIDENTIAL 18

19. Key studies presented:
• Rodent dose finding study
• Pig study, closed chest, iv.
• Pig study, open chest, infusion
• Pig study, closed chest, dose finding, iv.
• Pig study, closed chest, high-dose range finding, iv.
• Rodent study, dose finding, m.o.a. study
CONFIDENTIAL 19

20. EP94 shows a dose dependent reduction of myocardial
infarction size in rats
25 min occlusion = Vehicle administration
-5 0 25 = EP94 administration
Vehicle
EP94 (0.01 µg/kg x 1)
EP94 (0.1 µg/kg x 1)
Post-surgery 2 hrs reperfusion
stabilization EP94 (1 µg/kg x 1)
phase EP94 (5 µg/kg x 1)
EP94 (10 µg/kg x 1)
60
50
40
* * *
IS/AAR (%)
30 *
Pre-conditioning 20
10
N=12 N=6 N=12 N=12 N=12 N=9
0
le k g) /kg) / k g) /kg) /kg )
V ehic (0.01 ug/ .1 ug P94 (1 ug P94 (5 ug 94 (10 ug
EP9 4 EP 94 (0 E E EP
CONFIDENTIAL Study number 64-06 20

21. EP94 i.v. administered early or late during ischaemia in a
closed chest MI pig model reduces myocardial infarction size
significantly
40 min occlusion = Vehicle administration
60 min 5 12 19 26 33 40 = EP94 administration
Vehicle
Post-surgery
EP94 (1 µg/kg x 4) – Early intervention
stabilization
4 hrs reperfusion
phase
EP94 (1 µg/kg x 3) – Late intervention
EP94 (0.2 µg/kg x 3) – Late intervention
Closed chest pig MI/reperfusion model
80
70 **
60 *
IS/AAR (%)
50
40
30
Early Late Late
20
10
N =7 N =4 N =6 N =6
0
hic
le
x 4) x 3) x 3)
Ve / kg /kg / kg
ug ug ug
(1 (1 (0.
2
94 94 94
EP EP EP
Mean ± SEM
CONFIDENTIAL Study Report 09-01, Karlsson et al., Eur J Pharmacol 2011:651 pp146-151 21

22. Intracoronary infusion of EP94 in pigs reduces
myocardial infarction size significantly
30’ 5’
60 min 40 min occlusion Infusion
Post-surgery Vehicle
stabilization 4 hrs reperfusion
phase EP94 (0.2 µg/min, 15 min)
100 Open chest pig MI/reperfusion model
90
80
**
% of area at risk
70
60
50
40
30
20
10
N=5 N=5
0
Mean ± SEM Vehicle EP94
CONFIDENTIAL 22
Study Report 08-02, Karlsson et al., Eur J Pharmacol 2011:651 pp146-151

23. EP94 appears to reduce myocardial infarction
size dose-dependently
40 min occlusion = Vehicle administration
60 min 26 33 40 = EP94 administration
Vehicle
Post-surgery
EP94 (1 µg/kg x 3)
stabilization
4 hrs reperfusion
phase
EP94 (5 µg/kg x 3)
EP94 (25 µg/kg x 3)
Closed chest pig MI/reperfusion model
70
60
50
IS/AAR (%)
40
30
20
10
N=6 N=6 N=6 N=6
0
Vehicle 1 ug/kg 5 ug/kg 25 ug/kg
Mean ± SEM
CONFIDENTIAL Study Report 11-02 23

24. Ongoing studies
- preliminary results
CONFIDENTIAL 24

25. Dose range finding study in a closed chest pig
model
40 min occlusion = Vehicle administration
= EP94 administration
60 min 0 26 33 40
Vehicle
EP94 (1 µg/kg x 3)
Post-surgery EP94 (25 µg/kg x 3)
stabilization 4 hrs reperfusion
phase EP94 (125 µg/kg x 3)
OPTIONAL: EP94 (625 µg/kg x 3)
N = 12/group
CONFIDENTIAL Study protocol 2011-01 25

26. Results of the dose finding study is a…
CONFIDENTIAL 26

27. Rat acute myocardial infarction model – a combined dose
response and mode of action study
25 min occlusion = Vehicle administration
-10 0 5 10 = EP94 administration
Vehicle
EP94 (0.5 µg/kg x 2)
Post-surgery EP94 (1.0 µg/kg x 2)
stabilization 2 hrs reperfusion
phase EP94 (2.5 µg/kg x 2)
EP94 (5.0 µg/kg x 2)
EP94 (10 µg/kg x 2)
1) Opioid antagonists i.v. 2) KATP channel antagonists i.v. 3) iNOS inhibitor i.v.
a) Naltrindole (delta) – 5 mg/kg a) HMR1098 (sarc KATP blocker) – 6 mg/kg a) 1400W
b) Nor-BNI (kappa) – 0.3 mg/kg b) 5-HD (mito KATP blocker) – 10 mg/kg
c) CTOP (mu) – 0.1 mg/kg b) 1400W + EP94
d) HMR1098 + EP94
d) Naltrindole + EP94 e) 5-HD + EP94
e) Nor-BNI + EP94
f) CTOP + EP94
CONFIDENTIAL Study protocol 2010-01 27

28. Rat acute myocardial infarction model – a combined dose
response and mode of action study - cont´ d
Bell-shaped dose-response relationship in rat confirms
previous results in rats
70,00
60,00
**
50,00
*** ***
IS/AAR (%)
40,00
30,00
20,00
10,00
N=9 N=8 N = 10 N = 10 N=8 N=9 N=8
0,00
Vehicle 0.1 0.5 1.0 2.5 5.0 10.0
EP94 (ug/kg, i.v.)
Mean ± SEM
*** p < 0.001 vs vehicle
** p < 0.01 vs vehicle
CONFIDENTIAL 28

29. Rat acute myocardial infarction model – a combined dose
response and mode of action study - cont´ d
Blocking of mu-opioid receptors abolish the cardioprotective effects of
EP94
70,00
60,00
** **
50,00 ***
IS/AAR (%)
40,00
30,00
20,00
10,00
0,00 N=9 N=9 N=9 N=9 N = 10 N=9 N=9 N=9
) ) ) ) 4 4
c le kg kg kg kg P9 94 P9
hi g/ g/ g/ g/ E EP E
Ve m m m u + + I+
(5
(0
.1 0.
3 (1 NT O
P
BN
NT I( 94 CT r-
O
P N EP no
CT r-B
No
NT = naltrindole = selective delta-antagonist Mean ± SEM
CTOP = selective mu-antagonist *** p < 0.001 vs vehicle
Nor-BNI = selective kappa-antagonist ** p < 0.01 vs vehicle
CONFIDENTIAL 29

30. Rat acute myocardial infarction model – a combined dose
response and mode of action study - cont´ d
Effects of selective KATP ion channel antagonists
70,00
60,00
50,00
***
IS/AAR (%)
40,00
30,00
20,00
10,00
N=9 N = 10 N=9 N=9 N=9 N=9
0,00
le kg
) g) 4 g) 94
hi
c
g/ g/
k P9 g/
k
E EP
Ve (1
u m + 0
m +
(6 98
94 98 10
(1 HD
HD 5-
EP 10 R
5-
R HM
HM
Mean ± SEM
HMR 1098 = sarcolemmal KATP channel antagonist *** p < 0.001 vs vehicle
5-HD = mitochondrial KATP channel antagonist
CONFIDENTIAL 30

31. Rat acute myocardial infarction model – a combined dose
response and mode of action study - cont´ d
Effects of iNOS inhibition on EP94-induced cardioprotection
70,00
60,00
50,00 *** ***
IS/AAR (%)
40,00
30,00
20,00
10,00
0,00
c le 24- h u te e) e)
Vehi - ) - Ac (ac ut (ac ut
ipx 2) /kg iv EP94 4 00W
ug/ kg mg e) + )+1
EP9 4
(1 (0. 1 (ac ut (24- h
14 00W 14 00W E P9 4
Mean ± SEM
n = 9/group
1400W = iNOS inhibitor *** p < 0.001 vs vehicle
CONFIDENTIAL 31

32. Conclusions
• EP94 is effective in two different pig ischemia/reperfusion
models (open vs closed chest)
• EP94 produces a significant reduction of infarct size in pigs
already at 1 µg/kg
• The cardioprotective effect of EP94 seems to be dose-
dependent in pigs
• EP94 reduces the infarct size dose-dependently during both
pre- and post-conditioning in rats
• EP94 acts predominantly through mu-receptors in rats
CONFIDENTIAL 32

33. General properties,
Toxicology and Safety
Pharmacology
CONFIDENTIAL 33

34. EP 94 – General properties
 Tetrapeptide
 Manufactured by solid phase peptide synthesis
 Lyophilized powder
 Solubility: Good solubility in water
 Stability of drug substance:
 Stable at +4°C for more than 2 years
 Stability of drug product:
 Stable at -18°C, +4°C and 25°C for more than 6 months in saline
CONFIDENTIAL 34

35. Toxicology & Safety
 Single dose tox. study in rats and pigs
 Repeat dose tox. study, 14 days, in rats and pigs
 Safety Pharmacology
 Genotoxicity
 Pharmacokinetics and ADME
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36. Clinical Development
CONFIDENTIAL 36

37. Key factors for success with EP94 in a
clinical development programme
 Selection of patient population
 STEMI patients
 An adequate risk stratification algoritm
 Selection of primary endpoint
 Optimal method used to detect infarct size reduction
CONFIDENTIAL 37

38. Clinical development of EP 94
Phase I study
 Study Objective: Dose-escalation study to evaluated
the safety, and tolerability in healthy individuals
 Design: single-center, double-blind
 Estimated number of healthy volunteers: 40
 Primary outcome measures: tolerability, safety, PK
and hemodynamic parameters
CONFIDENTIAL 38

39. Clinical development of EP 94
Phase II, proof-of-concept study
 Study Objective: Dose-escalation study to investigate the cardioprotective
effect of ERIBIS Peptide 94 given as an adjunct to percutaneous coronary
intervention (PCI) in subjects with an acute STEMI
 Design: randomized, placebo-controlled, double-blind and multicenter
 Estimated number of patients: 350-400
 Primary outcome measure:
 To demonstrate a dose-dependent positive trend for myocardial salvage
and myocardial salvage index using a modified single contrast enhanced
steady-state free precession (SSFP) cine cardiovascular magnetic
resonance (CMR) examination performed one week after the acute event
CONFIDENTIAL 39

40. Clinical development of EP 94
Phase II, proof-of-concept study
 Secondary outcome measure:
 ST-resolution on 12 lead ECG 90 minutes after PCI
 Tropinin, CK-MB 3 to 6 hrs, 6 to 12 hrs, 18 to 24 hrs and 36 hrs after
randomization (Peak and AUC)
 To determine Left Ventricular Ejection Fraction (LVEF) and Wall Motion
Score Index (WMSI) 6 weeks and 6 months after PCI
 Myocardial salvage index 6 months after PCI
 Incidence of cardiac death and total mortality, stroke, new-onset heart
failure, and re-hospitalization for any congestive heart failure 6 month
follow-up visit
CONFIDENTIAL 40

41. Intellectual Property
CONFIDENTIAL 41

42. Intelectual Property
The IPR comprises patent protection for:
 Chemical structure of peptides and peptide-based compounds
 Clinical Utility
 Pharmaceutical Composition
 PCT application was filed in August 2007
 Regional and National patent applications submitted early
2009 in EU, USA, Canada, Australia, India, China and Japan.
 EU patent grant subject for approval, EPO decision to grant
obtained Feb 2011
CONFIDENTIAL 42

43. Summary
 First in class
 Significant cardioprotective effect
 Clear unmet medical need & large
market size
 New therapeutic principle
 Significant preclinical results
- good clinical prognosis
CONFIDENTIAL 43

44. Q & A answers
1. Does the peptide pass the blood brain barrier?
2. Does the NO-group give rise to worries in relation to
toxicology?
3. Does the NO-group give rise to worries in relation to
Carcinogenicity?
4. Are other receptors hit by this peptide?
CONFIDENTIAL 44

45. NO-study
EP94 has been evaluated with and without NO and acylation in response
to the EU patent office’s questions regarding Eribis application. To
show that the specific groups at position 2, acylation, and pos 4, NO-
group, are both necessary to have the cardioprotective effect shown
with EP94.
5 different peptides were compared with EP94 in this pre-conditioning
study.
•without NO-group of the 4th amino acid
•without acylation of 2nd amino acid
•without both acylation and NO-group
•with Asp instead of acylation on 2nd amino acid
•with Arg-Asp instead of acylation on 2nd amino acid
EP94 does not exert a significant level of cardioprotective activity without
these specific groups in the second and fourth position on EP94.
CONFIDENTIAL 45

46. Do you have rodent data?
How does EP94 and morphine perform together in the
models?
Any efficacy measures/differentiation from morphine/other
opioids.
Answer:
Eribis has performed a series of studies on rodents that
answer these questions.
This data will be available when Zealand performs a DD.
There is too much data to discuss during this initial
meeting.
CONFIDENTIAL 46

47. Morphine cont’
Morphine is regularly used as pre-medications in the pig studies. EP94
exerts its cardioprotective properties despite approx 13-333-fold higher
morphine doses in pigs. However, morphine has not regularly been
used as pre-medication in the explorative rat efficacy (cardioprotection)
studies conducted in Moscow.
MI patients are usually treated with morphine in the emergency room to
reduce pain and anxiety. Thus, one exploratory study in rats has been
conducted to address the possibility of an interaction between EP94
and morphine. This study did not reveal any synergistic, additive or
antagonistic effects of morphine on EP94-induced cardioprotection.
Consequently, EP94 has been used in combination with morphine in
the pig studies to mimic the clinical situation as closely as possible. The
pigs are routinely premedicated with 0.5 mg/kg/hr of morphine.
CONFIDENTIAL 47

48. How is the peptide cleared?
Answer:
It is anticipated that EP94 is degraded by various endo-
and exo-peptidases in the blood stream. The
degradation products are believed to be excreted in the
urine or partly utilized by the body. This will be verified
by dedicated ADME studies in the near future.
CONFIDENTIAL 48

49. Have you tried the peptide, but without the NO-group, in your
models?
Data from Rodents (cardio protective effect with EP94 (with and
without NO) - Y see study 257/10
es
How does nitroglycerin perform in your models?
- Not evaluated
How does nitroglycerin and morphine perform together in the
models? (against EP94)
- Not evaluated
Models where EP94 does not work (MOA)?
- EP94 has been shown to be cardioprotective in all models tested so
far, i.e. 2 different species and in total 5 different models.
CONFIDENTIAL 49

50. Any cellular assays (all in vitro receptor data (cell lines over-
expression the receptors) and work performed on primary
cells and specific cell lines that express the receptors).
Receptor binding to the human opioid receptors (µ,
δ, κ) expressed on CHO and HEK-293 cells.
- Study available during the DD process.
CONFIDENTIAL 50

51. Speculations on down stream target?
To investigate a possible downstream pathway which
may be mediating the beneficial effect of EP94 we
administered either the sarcolemmal KATP channel
antagonist, HMR 1098, or the mitochondrial KATP
channel antagonist, 5-HD, to rats prior to EP94
administration.
Both antagonists completely abolished the
cardioprotective effect of EP94 which suggests an
important role for the KATP channel as a key mediator
in the pathway by which EP94 reduces infarct size
similar to that seen with a number of other
cardioprotective agents as well as ischemic
preconditioning and postconditioning.
CONFIDENTIAL 51

52. Are the coronary arteries also affected?
Potential effects on coronary arteries have not been
investigated.
CONFIDENTIAL 52

53. Speculations on general cardiovascular
safety of EP94.
• EP94 does not affect blood pressure or heart rate in
anaesthesized animals (rats and pigs) at doses levels
ranging from 20 – 75 µg/kg (cf. pharmacological efficacy
studies)
• EP94 does not have significant effects on blood pressure in
and only a minor and late effect on heart rate in consious
rats at doses of 5-10 mg/kg (ESR08-006).
• The very low doses needed for pharmacological efficacy and
the short t1/2 (approx 40 min) is anticipated to reduce
cardiovascular safety risks to a minimum.
CONFIDENTIAL 53

54. " In-vivo SAR" (opioid component vs. the nitric oxide effects).
Unknown
Toxicology: Metabolism/metabolites and their distribution.
No evaluation of metabolites has been performed. It is anticipated that the bond
between amino acid 2 and 3 is susceptible to proteolytic cleavage and that the
major metabolites will contain 2 amino acids each.
ADME will be performed in the near future.
CONFIDENTIAL 54

55. A list of all published patent applications and
patents and their status.
PCT application PD53743CA00 - Novel Enkephalin
Analogues - Eribis Pharmaceuticals AB
EU pat appl. No 07 794 118.5
A “Decision to Grant” will be announced in Q2-2011
Eribis Pharmaceuticals AB owns the IP rights
CONFIDENTIAL 55

56. FTO analysis of key IP
FTO analysis has not been performed, however
patentability has been evaluated by third party
patent attorneys.
- statements are in the handouts.
CONFIDENTIAL 56

57. Thank you for listening!
Contact;
Herman Krapf, CEO
herman.krapf@ eribispharma.se
Erik Bissessar Founder & Chief Business Officer
erik.bissessar@ eribispharma.se
CONFIDENTIAL 57

58. Back-up bilder
CONFIDENTIAL 58

59. Chemistry Manufacturing
Control (CMC)
CONFIDENTIAL 59

60. EP 94 – General properties
 Tetrapeptide
 Manufactured by solid phase peptide synthesis
 Lyophilized powder
 Solubility: Good solubility in water
 Stability of drug substance:
 Stable at +4°C for more than 2 years
 Stability of drug product:
 Stable at -18°C, +4°C and 25°C for more than 6 months in saline
CONFIDENTIAL 60

61. Specification
Test Method Specifications
Appearance Visual observation Off-white to yellow powder
Mass spectral analysis EP 2.2.43; ESI M = 571.2 +/- 1.0
Amino acid analysis Pre-column derivatisation Gly:1; Tyr:1; Dab:1;
with OPA/Fmoc-Cl Phe (pNO2).1
EPA 2.2.56
RP-HPLC EP 2.2.29 Purity > 98.0% (area%)
Related Impurities by EP 2.2.29 Sum impurities < 2%
RP-HPLC
Water content Karl Fischer, EP2.5.12 To be reported
Acetate HPLC with UV detection To be reported
Residual TFA HPLC with UV detection < 0.1% (tentative)
CONFIDENTIAL 61

62. Specification cont’d
Test Method Specifications
Residual organic GC <USP 467> Individual according to ICH
solvents Q3
Bioburden EP 2.6.12 Aerobic bacteria < 10 CFU/0.1g
Anerobic bacteria < 10 CFU/0.1g
<USP 61> Yeasts and moulds < 10 CFU/0.1g
Bacterial endotoxins EP 2.6.14 <USP < 5 EU/mg (tentative)
85>
Net peptide content Pre-column To be reported
(NPC) derivatisation
by AAA with OPA/Fmoc-
Cl
EPA 2.2.56
Mass balance Calculation To be reported
NPC+acetate+w
ater
CONFIDENTIAL 62

63. EP 94
 Manufactured by Polypeptide
 Part no: SP080384
 Storage temp: 4°C
Lot no HPLC analysis Date
CF 07314 97.7% 26.3.2008
CF 07314 95,8% 11.2.2010
CONFIDENTIAL 63

64. EP 94
 Manufactured by Polypeptide
 Part no: SP080384B
 Storage temp: 4°C
Lot no HPLC analysis Date
MZ77114 98.9% 07.05.2009
CONFIDENTIAL 64

65. Drug Product
Stability of EP 94 in Saline
Stability (non- ICH) of EP94, 0.1mg/mL in 9 mg/mL NaCl
(preserved with NaN3 1mg/mL)
Temp Time 0 14 days 2.5 mo 4.5 mo 6 mo
-18°C 96.5 96.5 96.6 96.5
4°C 96.5* 96.5 96.6 96.4 96.2
Ambient 96.6 96.6 96.0 95.5
* Area %
CONFIDENTIAL 65

66. CMC - T do list
o
 Drug Substance
 Analytical development
 Specification
 Stability ICH
 Manufacturing
 Drug Product
 Analytical development
 Preformulation
 Interaction with packaging mtr
 Stability ICH
 Manufacturing for tox and clinical
 Regulatory
 IND/CTA chapter
CONFIDENTIAL 66

67. Refererences
1. Thom T, Haase N, et al. Writing Group Members. Heart Disease and Stroke
Statistics--2006 Update. Circulation; A Report From the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee; January 11, 2006; 2006.
CIRCULATIONAHA.105.171600.
2. Bishop E. Heart disease may actually be rising; researchers claim deaths are now
being delayed to a later age group. Wall Street Journal. 1996 November 13, 1996;
pB3(W) pB6(E) col 1 (11 col in)
3. Gerber Y, Jacobsen SJ, Killian J, Weston S, Roger VL. Impact of Participation Bias in a
Population-Based Study of Myocardial Infarction in Olmsted County, Minnesota, 2002
to 2004. Circulation. 2006;13:e827.
4. Eribis Peptide 94 Reduces Infarct Size in Rat Hearts Via Activation of Centrally
Located μ Opioid Receptors. J Cardiovasc Pharmacol. 2011 Nov 29 Gross GJ, Hsu A,
Nithipatikom K, Bobrova I, Bissessar E.
5. Dose-dependent cardioprotection of enkephalin analogue Eribis peptide 94 and cardiac
expression of opioid receptors in a porcine model of ischaemia and reperfusion.
Eur J Pharmacol. 2012 Jan 15;674(2-3):378-83 Karlsson LO, Bergh N, Li L,
Bissessar E, Bobrova I, Gross GJ, Akyürek LM, Grip L.
6. Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine
models for myocardial ischaemia and reperfusion. Eur J Pharmacol. 2011 Jan
25;651(1-3):146-51 Karlsson LO, Grip L, Bissessar E, Bobrova I, Gustafsson T,
Kavianipour M, Odenstedt J, Wikström G, Gonon AT.
CONFIDENTIAL 67