Download Innovative Anti-Inflammatory-Based Treatments for Diabetes and

Innovative Anti-Inflammatory-Based
Treatments for Diabetes and
cardiovascular Diseases
Jürgen Langhärig, Ph.D., MBA
Vice President Business Development
Bio€quity Presentation, May 11, 2016
Non-Confidential Presentation, May 2016
Disclaimer
Except for the historical information presented herein, matters discussed in this
presentation are forward-looking statements that are subject to certain risks and
uncertainties that could cause actual results to differ materially from any future
results, performance or achievements expressed or implied by such statements, e.g.
unforeseen exchange rate and interest rate fluctuations, delayed or unsuccessful
development projects.
Statements that are not historical facts, including statements preceded by, followed
by, or that include the words “believes”; “anticipates”; “plans”; “expects”;
“estimates”; or similar statements are forward-looking statements. Serodus is not
under an obligation to up-date statements regarding the future following the
publication of this release; nor to confirm such statements in relation to actual
results, unless this is required by law.
Non-Confidential Presentation, May 2016
2
What Makes us Different?
• Advancing novel anti-inflammatory treatments of diabetes and
cardiovascular diseases. We treat the root cause.
First-in-class candidates halt the progression of diabetic nephropathy
and type 2 diabetes
Significant market opportunities for diabetes assets
• Capital-efficient public company with an agile operational
model and extensive IP protection
• Strong team with proven track record in developing products
to the market and in deal making
Stock exchange OSE: SER
Non-Confidential Presentation, May 2016
3
Proven Leadership in Drug Development &
Licensing
> 5 commercialized pharmaceuticals | > 10 licensing agreement with big pharma
Eva Steiness, Prof, MD, D.M.Sc.
Chief Executive Officer
Tore Kvam, M.Sc., MBA, CEFA
Chief Finance Officer
Jürgen Langhärig, Ph.D., MBA
VP Business Development
Nikolai C. Brun, MD, Ph.D.
VP Drug Development
Torben Skarsfeldt, M.Sc., D.Sc.
VP Project Director
Trygve Gulbrandsen, M.Sc., D.Sc.
VP Project Director
Non-Confidential Presentation, May 2016
4
Status & Catalysts for Novel Anti-Inflammatory
Pipeline
DIABETES
CARDIOVASCULAR
Lead Candidates:
R&D
Pre-Clinical
Phase 1
Phase 2a
Stop progression
of diabetic
SER150: Diabetic Nephropathy
nephropathy
SER140:
Type 2 Diabetes
Reduces infarct
size
SER130: Myocardial
Infarction
Improves
pulmonary
function
Fragile X
Syndrome
Preclinical
Halt and revert
progression of
diabetes
Results:
2017
Phase 2b
Results:
2016
Results:
2018
Results:
2018
Results:
2018
SER100: Pulmonary Hypertension
(Orphan Indication)
Phase 1
Results:
2018
Reduces systolic
SER100: Therapy-Resistant Systolic Hypertension
blood pressure
Non-Confidential Presentation, May 2016
5
Diabetes: An Inflammatory Disease of Pandemic
Proportions and with Severe Complications
Comorbidities of Diabetes
• Diabetes is a rapidly
growing disease that
progresses relentlessly
• WHO: 422M diabetics
worldwide in 2014
• The costs associated with
diabetes are enormous –
$250B in US
SER150
Diabetic Retinopathy
Diabetic Nephropathy
Diabetic Neuropathy
• No cure is available
Non-Confidential Presentation, May 2016
Stroke
Heart Disease
SER140
Peripheral
Vascular Disease
6
Serodus Diabetes Candidates Address Large Patient
Populations at Critical Points of Diabetes Progression
120
Appearance of
microalbuminuria
Kidney function rate (Glomerular filtration rate
ml/min/1.73 M2 BSA)
Diabetes
onset
100
80
Diabetes
diagnosis
60
ESRD
40
20
SER140 patient population and
SER150 patient population
SER140 patient
population
SER140 patient population
0
0
5
10
15
20
25
30
Years from diabetes onset
Seaquest – J Clin Endocrinol Metab, July 2010, 95(7):3103–3110 (modified from).
Non-Confidential Presentation, May 2016
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SER150: Phase 2 Candidate to Stop the
Progression of Diabetic Nephropathy
Non-Confidential Presentation, May 2016
8
SER150: Halt the Progression of Diabetic Nephropathy
and Loss of Renal Function in Type 2 Diabetes
Mode of Action
API
Administration
Dual Thromboxane A2 (TXA2) receptor antagonist and Thromboxane
synthase inhibitor
New chemical entity (small molecule)
Oral – Capsule
IP
In-licensed from Evolva, Switzerland; composition-of-matter patent
supported by complementary cloud of patents
CMC
Scalable route of manufacturing established for drug substance and
drug product
Program
Status/Next
Milestone
• Phase 2a ongoing in Type 2 Diabetes patients with Diabetic Nephropathy
in Germany
• Next Milestone: Cohort 2 enrolment
• Phase 2a to be completed by Mid-2016
Non-Confidential Presentation, May 2016
9
SER150 Mode of Action: Breaking the Vicious
Cycle
3
IL-1β
2
Receptor activation leads to
further platelet activation in
Kidneys and further local
production of TXA2
1
2
Resting Platelet
SER150 inhibits
TXA2 production
1
3
4
SER150 blocks
the receptor
4
TXA2 binds to
TX receptor
Resting platelets are activated
by the IL-1β
Thromboxane is produced by
activated platelets aggregated
locally in the diabetic kidney
Thromboxane in turn activates
more resting platelets
converting them into activated
platelets
SER150 inhibits thromboxane
production and blocks the
receptor
Activated Platelet
TXA2: Thromboxane
Non-Confidential Presentation, May 2016
10
mg/hour
Clinical Pharmacology: SER150 Reduces ExerciseInduced Urinary Albumin Levels in T2D Patients
6
5
Placebo
4
SER150
In diabetic patients,
high protein
excretion is seen
during exercise
After treatment
with SER150, a drop
in exercise-induced
proteinuria was
seen
3
2
1
0
Baseline
First post-stress
Baseline
Day -1
Day 15
First post-stress
Day 29
Stress test at 90% of maximal heart rate for 5 minutes followed by rest and micturation to measure induced albuminuria.
Source: Internal Report.
Non-Confidential Presentation, May 2016
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SER150: Status & Phase 2a Study Design
Status
• Recruitment ongoing at 10 sites in Germany: Cohort 1 completed dosing
• Study enrolment expected to be completed by mid-2016
• Identification of potential partners has been initiated
Primary Endpoint
• Safety
Secondary Parameters
• Effect on urinary thromboxane excretion
• Effect on urinary albumin excretion
Study Design
Randomised, double blind, placebo-controlled, dose-escalation study
Non-Confidential Presentation, May 2016
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SER140: Halt the Progression of Type 2 Diabetes
Non-Confidential Presentation, May 2016
13
Inflammation Drives Type 2 Diabetes
Hyperglycemia
Dyslipidemia
Pro-inflammatory mediators
(over expression of IL-1β)
Auto inflammatory syndrome
Inflammation due to
impaired uptake in
peripheral tissue
ß-Cell dysfunction
and apoptosis
Insulin secretion
T2D
Mechanism for the induction
of T2D mellitus:
• Hyperglycemia and
Dyslipemia activates
proinflammatory mediators
• These mediators may:
Insulin resistance
Source: Modified after Akash et al, 2012.
Non-Confidential Presentation, May 2016
• Cause Insulin resistance
and inflammation
• Suppress the insulin
secretion in pancreatic
islets
14
SER140: Halt the Progression of Type 2 Diabetes
and Restore Diabetic Control
Mode of Action IL-1β receptor antagonist
API
A novel peptide derived from human IL-1β
Administration Repeated short-term courses of subcutaneous (SC) injection
IP
Composition of matter patent
CMC
Solid Phase Peptide Synthesis
• Reduces inflammatory processes in animal models
Program Status • Significantly prevents/delays development of diabetes in
a relevant test model
Non-Confidential Presentation, May 2016
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SER140 Restores Inflammation Imbalance in
Diabetes
How SER140 works:
Diabetic Imbalance
Inflammation
Induction
Inflammation
Normal
No IL-1
balance
• Is a selective and competitive
IL-1β receptor antagonist
Inhibition of
inflammation
SER140 Restores the Balance
• Reduces inflammatory processes
in animal models
Inflammation
Normal
IL-1β
SER140
• Inhibits IL-1β-induced TNFα
secretion and NF-KB protects
pancreatic beta-cells from
IL-1β-induced apoptosis
• Significantly halts development
of diabetes in a relevant test
model
IL-1 balance
Non-Confidential Presentation, May 2016
16
SER140 Significantly Delays Onset of Diabetes
in NOD Mice
Development of Diabetes
• Proportion of mice (%)
having normal glucose
levels
100
90
Normoglycaemic mice (%)
80
• SER140 significantly delays
onset of diabetes in NOD
mice
70
60
50
40
30
SER140 10mg/kg, SC, QD
Vehicle, SC, QD
20
10
0
0
1
2
Source: Cucak et al, 2016.
3
4
5
6
7
8
Weeks
Non-Confidential Presentation, May 2016
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Risk-Reducing Cardiovascular Disease Candidates
Non-Confidential Presentation, May 2016
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Inflammation-Focused Cardiovascular Disease
Candidates
SER100 for Pulmonary
Hypertension
SER100 for TherapyResistant Systolic
Hypertension
SER130 for Acute
Myocardial Infarction
Target
Indication
Patients with WHO Group I and IV pulmonary
hypertension with standard medical treatment
who are admitted to hospital because of acute
worsening of condition
For patients with elevated systolic
blood pressure in treatment with at
least three anti-hypertensives
Reduction of inflammation and
infarct size
Mode of Action
Opioid receptor like-1 (ORL-1) agonist
Opioid receptor like-1 (ORL-1) agonist
Interleukin-4 (IL-4) agonist
API
Novel 12-amino acid peptide
12-amino acid peptide
A novel peptide derived from
human IL-4
Administration
Intravenous infusion; oral administration to be
developed
Target: non-injectable
Intravenous infusion
IP
Composition of matter patent; PCT patent to be
filed
Composition of matter patent
Composition of matter patent
CMC
Solid Phase Peptide Synthesis
Status
Orphan Drug Application (FDA) by 1.H. 2016
Next Milestone: Initiate Phase 2a
Synthetized by Solid Phase
chemistry
Phase 2a finalized, positive results
available in ISH
Next milestone: oral feasibility study
to be initiated after deciding on
preferred technology
Non-Confidential Presentation, May 2016
Pre-clinical program finalized
Next milestone:
Initiate Phase 1/2a
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Why is Serodus an Attractive Investment
Opportunity?
Advancing novel
anti-inflammatory
treatments for
diabetes &
cardiovascular
disease
Strong team track
record in
drug development
& out-licensing
Non-Confidential Presentation, May 2016
Capital-efficient,
agile business
model &
extensive IP
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