addex pharmaceuticals investor presentation september 2010
TRANSCRIPT
Addex Pharmaceuticals
Investor PresentationSeptember 2010
Disclaimer
These materials do not constitute or form part, or all, of any offer or invitation to sell or issue, neither in the United States of America nor elsewhere, or any solicitation of any offer to purchase or subscribe for, any securities, nor shall part, or all, of these materials or their distribution form the basis of, or be relied on in connection with, any contract or investment decision in relation to any securities.
These materials contain forward-looking statements based on the currently held beliefs and assumptions of the management of Addex Pharmaceuticals Ltd, which are expressed in good faith and, in their opinion, reasonable. Forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause the actual results, financial condition, performance, or achievements of Addex Pharmaceuticals Ltd, or industry results, to differ materially from the results, financial condition, performance or achievements expressed or implied by such forward-looking statements. Given these risks, uncertainties and other factors, recipients of this document are cautioned not to place undue reliance on these forward-looking statements. Addex Pharmaceuticals Ltd disclaims any obligation to update these forward-looking statements to reflect future events or developments.
These materials are strictly confidential and must not be disclosed or distributed to third parties.
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•Goal: allosteric modulators for human health
•Focus: CNS, metabolic disorders, inflammation
•Proprietary allosteric modulator discovery platform
•15 discovery/development programs
• Pharma validation– Partners: Johnson & Johnson and Merck & Co., Inc.
– Investors: SR-One (GSK) and Roche Venture Fund
•138 staff / founded 2002 in Geneva, Switzerland
The Company
4
Financials• Cash for operations through end of 2011
CHF56.7 (US$54/€42) million in cash as of June 30
• Market cap (6 Sep): CHF52m (€40m / US$51m)
• SIX Swiss Exchange: ADXN (ISIN:CH0029850754)
• 5,871,242 shares outstanding as of June 30, 2010
• Five analysts covering:
Piper Jaffray Sam Fazeli & Michael AitkenheadJefferies Peter Welford & Philippa GardnerHelvea Olav Zilian Bank Vontobel Andrew C. Weiss & Silvia SchanzBank am Bellevue Bob Pooler
Partner Phase IIPreclinical Phase I MilestoneLead
OptimizationHit-to-Lead
Assay Development &
Screening
Molecule / Mechanism
PIPELINE
Merck & Co., Inc.
Ortho-McNeil-Janssen
ADX68692FSHR NAM
ADX63365mGluR5 PAM
ADX71943GABA-B PAM
ADX71149mGluR2 PAM
Start Ph IIa1Q11
Start Ph II 4Q10
Start Ph IIa 1Q11
Ortho-McNeil-JanssenStart Ph IIa
1Q11
ADX48621mGluR5 NAM
NAM = negative allosteric modulator (an inhibitor) ‡ and undisclosed additional indications PAM = positive allosteric modulator (an activator) *
Ortho-McNeil-Janssen Pharmaceuticals, Inc., a Johnson & Johnson subsidiary
Parkinson’s Disease Levodopa Induced Dyskinesia (PD-LID)
Dystonia
Schizophrenia
Anxiety
Osteoarthritic Pain
Schizophrenia ‡
Endometriosis / Benign Prostatic Hyperplasia
funded & developed by OMJPI*
funded & developed by OMJPI*
funded & developed by Merck
Start Ph I2011
Partner Phase IIPreclinical Phase I MilestoneLead
OptimizationHit-to-Lead
Assay Development &
Screening
Molecule / Mechanism
DISCOVERY PROGRAMS
NAM = negative allosteric modulator (an inhibitor) ‡ and undisclosed additional indications PAM = positive allosteric modulator (an activator)
Inflammation
CNS
Metabolic Disorders
Merck & Co., Inc.
Alzheimer’s / Depression
Parkinson’s Disease ‡
DepressionPost Traumatic Stress Disorder
Sleep Disorders
Type II Diabetes
Type II Diabetes
Rheumatoid Arthritis, Psoriasis,
Alzheimer’s, Multiple Sclerosis
Psoriasis, Osteoarthritis
Gout, Type II Diabetes
funded by MerckmGluR4 PAM
GIPR PAM
TNFR1 NAM (CD120a)
GLP1 PAM
Orexin 2R NAM
mGluR7 NAM
mGluR2 NAM
A2A PAM
IL1R1 NAM (CD121a)
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Partnered Programs
8
Agreement• With Ortho-McNeil-Janssen Pharmaceuticals, Inc. (OMJPI)
– Utilize Addex platform to identify & develop orally available mGluR2 PAM for schizophrenia, anxiety and undisclosed indications• OMJPI funds collaboration on discovery & lead optimization• OMJPI funds & performs preclinical and clinical development
– Addex sits on oversight committees
ADX71149
Terms
• €3 million upfront
• Research funding to Addex during discovery collaboration (2005-2007)
• €112 in potential milestones upon completion of clinical and regulatory milestones
• Low double-digit royalties
9
Progress to Date
• Collaboration generated clinical candidates
– €4.2 million in R&D funding between 2005-2007
• Comprehensive Ph I program started in June 2009
– €1 million milestone paid upon initiation of Phase I
– More than 5 Phase I trials in healthy volunteers• SAD, MAD
• Food & gender
• Ketamine challenge (schizophrenia model)
• Anxiety challenge
• Phase II program scheduled to start in 1Q11
– schizophrenia
– anxiety
– potentially other indicationsNote
mGluR2 activation is clinically validated in anxiety & schizophrenia
ADX71149
* Nature Medicine 2007: http://bit.ly/bbnsyQ
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ADX63365
Agreement
• Merck & Co., Inc. licensed Addex mGluR5 PAMs in 2008
• mGluR5 PAM expected to be highly differentiated– Merck already had demonstrated mGluR5 PAM have efficacy in
animal models of schizophrenia
– Preclinical data show efficacy for cognitive deficit (& psychosis)
– Despite efficacy of marketed drugs many schizophrenia patients remain unable to learn new skills to support themselves
– FDA has recognized cognitive deficit as an unmet medical need in schizophrenia
• Merck is responsible for development of ADX63365 & backups
Terms
• $22 million upfront
• $680 million in milestones
• Undisclosed royalties
11
Progress
• Deal signed (Dec 07)
• 1st Preclinical milestone (Feb 08)– $250,000
• 2nd preclinical milestone (Jul 09)– $500,000
– Orally available mGluR4 PAM showed efficacy in model of PD
• Collaboration extended (Dec 09)– Merck commits $1.8 million in research funding
– Going forward all costs transferred to Merck
Agreement
• Discover and develop metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAM) with Merck & Co., Inc.
• The deal includes mGluR4 PAM leads already discovered by Addex
• Merck is responsible for preclinical and clinical development
• Addex will sit on oversight committees Terms
• $3 million upfront
• $167.5 million in potential milestones
• Annual tech access fee $250,000
• Research funding 2009/2010
• Undisclosed royalties
• Option to co-promote in EU
mGluR4 PAM
12
Platform Revenues
Partner Product Indication(s)Status
at signingStatus April
30, 2010Upfront
Cash
Milestones or R&D funding
received
Total Potential
Milestones
Ortho-McNeil-Janssen
Pharmaceuticals, Inc.mGluR2 PAM
ADX71149 Anxiety &
schizophreniaHit-to-Lead
(Dec 2004)Phase I €3 million €5.2 million €112 million
Merck & Co., Inc. mGluR4 PAMParkinson’s
diseaseHit-to-Lead
(Dec 2007)
preclinical efficacy in PD model
$3 million $2.5 million $167.5 million
Merck & Co., Inc.mGluR5 PAM
ADX63365 schizophrenia
Clinical Candidate
(Jan 2008)
not disclosed
$22 million n.a. $680 million
Proprietary Platform Revenues
• Addex has received partnering revenue every year since 2004
• Cash inflows generated to date: CHF43 million
• All three partnerships are fully funded by our partners
• Potential for up to about $1 billion in milestones plus royalties
* and undisclosed indications
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Wholly Owned Programs
14
ADX48621 Overview• Phase I completed
– Three studies: SAD, MAD, gender & food effects– 110 patients treated to date, including older volunteers– Safety & tolerability justify further clinical study– Ph II to start in 4Q10 for PD-LID and 1Q11 for dystonia
• Differentiated– Only product shown to reduce dystonia in MPTP model– Chemical series unrelated to other mGluR5 NAM
Unique metabolic profile
– NCE patents valid through 2025 in most territories – Unrelated series of backup molecules in clinical candidate
selection
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•ADX48621 effects in HIC model suggestIt should be tested further as a potential drug for PD It has potential to be a dopamine sparing agent
ADX48621 efficacy in HIC model• Haloperidol induced catalepsy (HIC) is a preclinical model of PD
ADX48621 dose-dependently reversed HIC in 3 independent experimentsMTEP mGluR5 antagonist is well documented to work in the HIC model
0
10
20
30
40
50
60
70
80
90
Vehicle ADX48621, 1mg/kg
ADX48621, 3mg/kg
ADX48621, 10mg/kg
ADX48621, 30mg/kg
MTEP, 30mg/kg
Late
ncy
(sec)
1st experiment2nd experiment3rd experiment
***
*********
****
***
**
***
+ 1 mg/kg haloperidol
**p<0.01, ***p<0.001 versus vehicle group
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MPTP model of PD-LID
What is the MPTP Model?
• MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
– Neurotoxin destroys dopaminergic neurons
– Symptoms similar to PD, treatable with levodopa
• MPTP monkeys develop levodopa induced dyskinesia (LID), including both chorea (trembling) and dystonia (cramping) seen in humans
• MPTP PD-LID model is predictive of efficacy in humans
– KOLs consider it among the most translational models in the CNS space
– AFQ056 (mGluR5/Novartis) showed efficacy in MPTP PD-LID model
– AFQ056 showed efficacy in Phase IIa PD-LID trial
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• ADX48621 or vehicle administered 30 min prior to levodopa
• Behavioral assessment began upon levodopa administration – trained observers performed video review
– dyskinesia & PD disability scoring (10 min every 30 min for 2hrs)
lower scores (left axis) indicate fewer symptoms/disabilitydyskinesia symptoms are side effects from levodopadisability is a measure of Parkinson’s disease severity
ADX48621 MPTP Study Design
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ADX48621 reduced dyskinesia without compromising levodopa efficacy
0
5
10
15
L-DOPA (100%)
vehicle
ADX48621 (mg/kg)
3 10 30
*
dysk
ines
ia (
0-2
hr)
ADX48621 dose-dependently reduced dyskinesia
(chorea + dystonia)
Dyskinesia
ADX48621 efficacy in MPTP model
ADX48621 does not reduce levodopa efficacy
Disability
+ levodopa
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ADX48621 is the first drug-candidate known to have efficacy on dystonia
0
5
10
15
L-DOPA (100%)
vehicle
ADX48621 (mg/kg)
3 10 30
*
dys
ton
ia (
0-2
hr)
Dystonia
Dystonia = sustained muscle contractions (e.g. cramps)
0
5
10
15
L-DOPA (100%)
vehicle
ADX48621 (mg/kg)
3 10 30
**
chor
ea (
0-2
hr)
Chorea
Chorea = involuntary
movements (e.g. trembling)
ADX48621 efficacy in MPTP model
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ADX48621Commercial Potential
• Levodopa induced dyskinesia (LID) and dystonia are unmet medical needs– Most Parkinson’s disease (PD) patients develop LID– There are no drugs specifically approved for PD-LID – PD represents a growing unmet medical need – Dystonia is poorly addressed by existing drugs– Dystonia market could be significant
• Occurrs in multiple conditions • Occurrs as a side effect of drugs
– PD-LID/dystonia is a faster path to market than PD
• Addex can retain co-promotion rights– PD, PD-LID & dystonia are treated by specialists– geographic split possible– mGluR4 PAM & mGluR2 NAM represent potential additions to future
neurodegenerative disease franchise
21
ADX71943
• ADX71943 is a gamma-aminobutyric acid subtype B (GABAB)receptor PAM
–Clinically/commercially validated mechanismgeneric GABAB agonist, baclofen, is marketed
other orthosteric GABAB agonists are clinically validated
–ADX71943 is differentiatedADX71943 is the only allosteric modulator of GABAB in development
Demonstrated analgesic effects in three preclinical pain models Potential for chronic pain (e.g. osteoarthritis) and other indications
• Phase I to start in 2011
• ADX71943 is available for partnering
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Phase I
Dose-dependent reduction in nocifensive behaviour.
Statistically significant from the dose of 3 mg/kg.
Phase II
Dose-dependent reduction in nocifensive behaviour.
Statistically significant from between the doses of 3 and 10 mg/kg.
*p<0.05, **p<0.01, ***p<0.001 vs. ADX71943 vehicle ++p<0.01, +++:p<0.001 vs baclofen vehicle
0
20
40
60
80
100
ADX71943vehicle
0.3 1 3 10 30 100 Baclofen,6 mg/kg
Noc
ifen
sive
beh
avio
ur (
s)
.
1st experiment2nd experiment3rd experiment
PHASE I
* *
+++
*****
*
***
ADX71943 (mg/kg)
***
Baclofen,vehicle
ADX71943 significantly reduces nocifensive behaviour in the formalin test in mice after single oral administration
0
20
40
60
80
100
120
140
160
180
200
vehicle 0.3 1 3 10 30 100 Baclofen,6 mg/kg
Noc
ifen
sive
beh
avio
ur (
s)
.
1st experiment
2nd experiment
3rd experiment
PHASE II
***
***
++
***
***
**
ADX71943 (mg/kg)
Baclofen,vehicle
ADX71943
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ADX71943 significantly attenuates CFA-induced mechanical hyperalgesia after single oral administration
• Single oral of administration ADX71943 caused a dose-dependent increase of the withdrawal threshold in CFA-inflamed rats.
• The effect was statistically significant from the dose of 10 mg/kg.
non-CFA CFA 1 hr 2 hr0
5
10
15
20
25
***
**
Time post-dose (hr)
With
dra
wal
Th
resh
old
Vehicle1 mg/kg ADX-719433 mg/kg ADX-7194310 mg/kg ADX-7194330 mg/kg ADX-7194330 mg/kg Naproxen
24
ADX71943 significantly reduces nocifensive behaviour in the writhing test in mice after single oral administration
• ADX71943 caused a dose-dependent reduction of acetic acid-induced writhing in mice.
• The effect was statistically significant from the dose of 3 mg/kg.
*p<0.05, **p<0.01, ***p<0.001 vs. JQ-02 vehicle; +++p<0.001 vs. 1%CMC vehicle
Experiment 1
Experiment 2
Experiment 3
Experiment 4
ADX71943 (mg/kg)
0
2
4
6
8
10
12
14
16
18
20
22
Baclofenvehicle
ADX71943vehicle
0.3 1 3 10 30 100 3 mg/kg
Nu
mb
er
of
wri
the
s
+++
*********
***
*
** ***
*
Baclofen
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ADX71943 demonstrates antihyperalgesic effects in the MIA model of OA in rats
0
50
100
150
200
250
300
350
Pre-MIA Post-MIA Day 1 Day 8
With
draw
al th
resh
old
(g)
Max
imum
resp
onse
bew
teen
1 a
nd 2
hr
Vehicle 1 mg/kg ADX71943 3 mg/kg ADX7194310 mg/kg ADX71943 30 mg/kg ADX71943 Celecoxib (30 mg/kg)
* ***
***
*****
Pre-treatment Treatment
Day post-MIA -1 14 14 21
###p<0.001 vs. Pre-MIA baseline; paired t-test, n=10 animals per group. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle;one-way ANOVA with Dunn's multiple comparison n=10 per group.
###
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Mechanical allodynia in the MIA model of OA in rats
• The effects of ADX71943 and celecoxib in the von Frey test did not reach statistical significance
##
Vehicle 1 mg/kg ADX71943 3 mg/kg ADX71943
10 mg/kg ADX71943 30 mg/kg ADX71943 Celecoxib (30 mg/kg)
0.0
2.5
5.0
7.5
10.0
12.5
15.0
Pre-MIA Pre-drug Day 1 Day 8
Max
imu
m P
aw W
ith
dra
wal
Th
resh
old
(g
)
Days post-MIA -1 14 14 21
Pre-treatment Treatment
##p<0.01 vs. Pre-MIA; paired t-test, 9≤n≤10 animals per group
27
ADX68692
Roles of FSH/LH
Females
• FSH involved in folliculogenesis– maturation of follicles
– estrogen production
• LH triggers ovulation, progesterone
Males
• FSH supports spermatogenesis
• LH stimulates testosterone production
Status
• ADX68692 is a follicle stimulating hormone receptor (FSHR) NAM
• Orally available non-steroidal molecule with drug-like characteristics
• In late preclinical development
• ADX68692 is available for partneringPreclinical Data & Potential Indications
• Statistically significant reduction in testosterone & prostate weight Benign prostatic hyperplasia (BPH)
• Statistically significant reduction in estradiol Endometriosis
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Control group
02468
1012141618
-14 -11 -8 -5 -2 2 5 8 11 14 17 20 23 26 29
Day of treatment
ADX68692: 20 mg/kg/day
02468
1012141618
-14 -11 -8 -5 -2 2 5 8 11 14 17 20 23 26 29
Day of treatment
In vivo target related efficacy in female rats: 4 week treatment
– Treatment with ADX68692 at pharmacological and multiple of pharmacological doses for 4 weeks was well tolerated
– Treatment for 4 weeks with ADX68692 reduced the number of female rats in the estrus/proestrus phase (ovulatory phase), and increased the number of female rats in the diestrus phase, indicating disruption of menstrual cycle.
– Eventually at the highest dose, animals were found in persistent diestrus
– Histopathological examination showed follicular atresia which is the consequence of the FSH function blockade (blockade of ovulation)
– Estradiol levels were lowered, even in the proestrus phase
SynchronisationTreatment start
To
tal n
um
ber
of
anim
als
in P
roes
tru
s/E
stru
s st
age
29
In vivo target related efficacy in female rats: 4 week treatment
Effect on Estrous cycle duration
0
2
4
6
8
10
12
14
16
18
20
Number of Estrous cycles during treatment duration Mean duration of Estrous cycle (days)
0 mg/kg/day 2x10 mg/kg/day 2x30 mg/kg/day 2x100 mg/kg/day 2x300 mg/kg/day
***
***
***
***
POC that ADX68692 disrupts the estrous cycle and increases its mean duration, eventually leading to complete blockade at high dose.
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In vivo target related efficacy in male rats: 4 weeks treatment
Circulating testosterone levels were significantly lowered at the lowest and intermediate dose.Relative weight changes were observed for prostate (). These changes were dose dependent and became statistically significant at the highest dose
Group 1 (0 mg/kg/day) Group 2 (2 x 10 mg/kg/day)
Group 3 (2 x 30 mg/kg/day) Group 4 (2 x 100 mg/kg/day)
0.0
5.0
10.0
15.0
20.0
25.0
After 3-week treatment with ADX68692
Tes
tost
ero
ne
(nn
mo
l/L)
******
0.0
0.1
0.2
0.3
0.4
0.5
Prostate: relative weight (g)
*
31
GLP-1 PAM project
• To develop a small molecule GLP-1 PAM for the
treatment of Type II Diabetes– Orally available
– Should increase insulin secretion and decrease blood glucose
– No or reduced nausea/vomiting compared to competition
– Should preferably induce weight loss
– Could be used in combination with other therapies
32
Oral GLP1R PAM in db/db mouse model
• Leptin receptor–deficient db/db knockout mice are considered an established model – develop human Type II diabetes mellitus – hypertension and obesity – disrupted circadian blood pressure (BP) rhythm
• We orally administered to db/db mice– ADX91886 GLP1R PAM – Januvia sitagliptin DPP IV inhibitor– or vehicle
• 15 min later 2 g/kg glucose is given orally• Blood glucose + insulin levels were measured 10 ; 20 ; 30 ;
60 ; 90 min after glucose administration
33
Plasma glucose
15 30 45 60 75 90
0
10
20
30
40
50
C: Sitagliptin 10 mg/kg poB: ADX91886 (220 mg/kg po)
A: Vehicle po
B
*****
******
***
**
**
Time (min)
Pla
sma
glu
cose
(mM
)
Plasma insulin
15 30 45 60 75 90
0
5
10
15
20
25
30
C: Sitagliptin 10 mg/kg po
B: ADX91886 (220 mg/kg po)
A: Vehicle po
B
** ** **
***
***
*** ***
Time (min)
Pla
sma
insu
lin(n
g/m
l)
Oral GPL1R PAM compared to
sitagliptin in db/db mice
Glucose AUCB (0-90 min)
A B C0
5
10
15
20
25
30
A: Vehicle po
B: ADX91886 (220 mg/kg po)
C: Sitagliptin 10 mg/kg po
***
*
Glu
cose
AU
CB
(mM
.hr)
34
mGluR2 NAM
• Data from Addex and others show that mGluR2 inhibition can reverse cognitive deficit – in models of cognitive deficit– in physiologically relevant models of AD– mechanism may be complementary to marketed
drugs
• Published data suggest that mGluR2 inhibition may reduce generation of beta-amyloid*– mGluR2 NAM may also be disease modifying
*The Journal of Neuroscience, March 17, 2010; 30(11):3870-3875
35
Familiar object
Novel object
ADX92639 (mg/kg, p.o.)
120
sham β- Amyloid*
0
30
60
90
t1 t2 t1 t2 t1 t2 t1 t2
Veh 10 30 Donepezil
ADX92639 (mg/kg, p.o.)
Lin
e c
ros
se
s
Locomotor activity during the test
veh 10 30 Donepezil
18
0
3
6
9
12
15 *** *** ***
Exploration of novel vs familiar objects
veh veh veh veh 0
3
6
9
12
15
18
Exp
lora
tio
n t
ime
(se
c)
***
sham β-Amyloid*
• ADX92639 reverses cognitive impairment induced by intracebroventricular (icv) β-amyloid in
the rat NOR test after oral administration:
– Full and donepezil-like reversal of the memory deficit at 30 mg/kg
– No effect on locomotor activity observed during the test
ADX92639 is effective against icv β amyloid-induced deficit in NOR in the rat
*Single administration into the lateral ventricle of 8 μl solutionFinal concentration of amyloid = 2 mg/ml
(1 mg/kg, ip) (1 mg/kg, ip)
36
Allosteric ModulatorDiscovery & Optimization
37
Allosteric Modulation
Because they bind a different site on the receptor, allosteric modulators do not turn receptors on or off the way the body’s natural activators and most drugs do. Instead, they act more like a dimmer switch, offering control over the ease & intensity of (de-)activation while allowing the body to retain its natural control over initiating receptor activation via the active site (e.g. the on/off switch).
38
Allosteric Advantages
• Greater specificity than orthosteric molecules – e.g. mGluRs
• Can target receptors considered “intractable” or only tractable by biologics, peptides or proteins
– e.g. GLP-1
• Non-competitive mechanism–Un-exploited intellectual property–Less dose related toxicity
•Acts like a dimmer not “on/off” switch–Body maintains control of receptor activation cycle
Natural ligand
Time
PAM + natural ligand
NAM + natural ligand
Bio
log
ical
res
po
nse
Allostery preserves natural rhythm
Time
Natural ligand
Agonist
Antagonist
Bio
log
ical
res
po
nse
Orthosterics are steady state
39
Serendipity has yielded some marketed allosteric modulators. Most recent examples include:
• Sensipar/Mimpra cinacalcet (Amgen) – Positive allosteric modulator (PAM) of calcium sensing receptor– Approved 2004– treats secondary hyperparathyroidism
• Selzentry/Celsentri maraviroc (Pfizer) – Negative allosteric modulator (NAM) of CCR5– Approved 2007– Treats CCR5-tropic HIV-1
Allosteric Modulators 101
40
• Allosteric modulators are hard to find– Industrial tools for orthosteric drugs are not appropriate – Pharma has been focused on tools for finding orthosteric drugs– Why didn’t pharma industrialize allosteric drug discovery?
• Upfront investment to build allosteric drug discovery platform was high
• Time to value creation was long & uncertain
• Addex is industrializing allosteric modulation discovery– Proprietary assays
• High throughput screening & optimization tools (384 well plates & robotics)
• Direct detection systems – proximal to target – continuous real-time observation– works for molecules (i.e. allosteric modulators) that do not activate target receptor
– Allostery biased library of over 70,000 compounds
The Addex raison d'être
41
Proprietary Screening AssaysG-Protein Coupled Receptors
• Phoenyx– a cAMP dynamic non stop assay
• FBBA (GLP1R, mGluR7)– Fluorescence-Based Binding Assay – Measures bi-molecular interactions
• Proxylite (GLP1R, GIP)– Proximal & dynamic assays for functional measurements of
all types of GPCRs
42
• APRA (TNFR1)–Accessory Protein Relocalization Assays
• ADX-tags series 1 (IL1R) –Proximal & dynamic assays for functional measurements –Measures activation-dependent association or dissociation of
binding partners
• ADX-tags series 2 (TNFR1, IL1R)–measures conformational changes that lead to activation signal–measures multimerization changes that lead to activation signal
Proprietary Screening Assaystype 1 single-pass transmembrane proteins
43
Allostery Biased Library in-silico analysis
Addex library and marketed drugs share the same physicochemical property space BUT Addex library occupies a unique structural space
Addex library and marketed drugs share the same physicochemical property space BUT Addex library occupies a unique structural space
Physicochemical Comparison Structural Comparison
Addex CompoundsMarketed Drugs
Addex CompoundsMarketed Drugs
44
Platform Validation
• Addex identified selective orally available small molecules for– Challenging GPCRs (mGluRs, GABA-B & A2A)– Peptide receptors (GLP1R, GIPR)– Cytokine receptors (TNFR1 & IL1R1)
• The proof is in the pudding – Merck & Co., Inc. licensed mGluR4 PAM & mGluR5 PAM– Johnson & Johnson licensed mGluR2 PAM
45
Summary
• 15 Programs for High Value Targets/Indications–Highly differentiated allosteric mechanism
–Low target related risk (i.e. mostly clinically validated targets)
• Allosteric Modulator Platform–Proprietary tools + tailored library
–Platform + multi-disciplinary approach are scalable
• 3 Validating Partnerships (MRK/J&J)
• Top Tier Investors
• Cash to end of 2011
46
Management & Boards
Vincent Mutel, Chief Executive Officer Tim Dyer, Chief Financial Officer Charlotte Keywood, Chief Medical Officer Sonia Poli, Head of Non-Clinical Development Laurent Galibert, Head of Inflammation & Metabolic Disorders
Board of Directors
André J. Mueller, Chairman
Vincent Mutel, Vice Chairman & CEO of Addex
Andrew Galazka, SVP Scientific Affairs, Merck-Serono
Ray Hill, former Head of EU Licensing, Merck & Co., Inc.
Vincent Lawton, former MD of Merck Sharp & Dohme U.K.
Beat E. Lüthi, CEO of CTC Analytics
Antoine Papiernik, Sofinnova Partners
Scientific Advisory Board
George F. Koob, Ph.D., Chairman
Bernhard Bettler, Ph.D.
Arthur Christopoulos, Ph.D.
Patrick M. Sexton, Ph.D.
Mark A. Geyer, Ph.D.
Barbara J. Mason, Ph.D.
Jean-Philippe Rocher, Head of Core Chemistry Robert Lütjens, Head of Core Biology Tatiana Carteret, Head of Human Resources
Chris Maggos, Investor Relations & Communications
Executive Management
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allosteric modulators for human health