NTP-2014 has shown strong efficacy across multiple models

Report
2010 ASENT Conference
March 2010
Highlights
• A novel mechanism of action and a new class of therapy in a
large marketplace where existing mechanisms leave substantial
unmet need
• Multiple positive, predictive and highly significant efficacy
studies in neuropathic pain, nociceptive pain and epilepsy
• Strong safety pharmacology profile and GLP toxicology results
• Experienced drug development team
• Strong IP position, including 2 issued and 28 filed patents
covering novel mechanisms and composition of matter
• Target IND filing 2Q10 for lead compound, NTP-2014
1
Mechanism of Action
Demonstrated molecular site of action, cellular activity, in vivo efficacy
• Novel mechanism of action
– Enhances inhibition via a specific and unique action that is
unlike that of any marketed product
• Highly specific activity generates strong efficacy without generating
typical CNS side effects, such as sedation
– Enables a greatly expanded and IP-rich pipeline using SAR via
recombinant receptor technology and rapid screening via in
vitro electrophysiology
• NTP’s molecules are new chemical entities (NCEs)
– Novel composition of matter intellectual property
2
Epilepsy Efficacy Data
NTP-2014 has shown strong efficacy across multiple models
• MES (Maximum ElectroShock) – Acute seizure model
– Showed complete protection for the duration of the study (four hours)
– No adverse events observed
• 6 Hz Psychomotor Seizure – Refractory epilepsy model (CPS)
– Eliminated seizures in a “therapy resistant” epilepsy model where multiple
blockbuster products have shown no efficacy
– No adverse events observed
• MTLE (Mesial Temporal Lobe Epilepsy) – Refractory epilepsy model (CPS)
– Showed near complete suppression of discharges, controlling seizures better than
all other AEDs tested, including four blockbuster therapies
– No adverse events observed
CPS – Complex Partial Seizures
3
Epilepsy Efficacy – Temporal Lobe Epilepsy Model
NTP-2014 is more potent than existing therapies
* p < 0.05 versus control
10 mice per treatment group
Number of discharges not shown
Comparators not run concurrently; historical data
100
80
60
*
*
40
20
Control
Cumulative Duration of Hippocampal
Discharges from 0-60 Minutes Post-dose(s)
120
*
693
100
*
*
1,386 2,772
200
400
106
25
212
50
423
100
6
1
314
50
628
100
119
50
50
umol/kg
mg/kg
0
Avg daily human mg/kg:
VPA
60
CBZ
20
PGB
6
2014
NTP-2014 showed near complete suppression of discharges and controlled
seizures better than four blockbuster therapies:
Depakote (valproic acid)
Tegretol (carbamazepine)
Lamictal (lamotrigine)
Lyrica (pregabalin)
CONFIDENTIAL
4
Neuropathic & Nociceptive Pain Efficacy Data
NTP-2014 has shown strong efficacy across multiple models
•
•
•
•
Formalin Paw – Neuropathic & Nociceptive Pain
–
Late Phase: Showed near 100% pain reduction; results superior to gabapentin
–
Early Phase: Demonstrated pain reduction, where gabapentin is ineffective
–
No adverse effects reported
Chemotherapy Induced Peripheral Neuropathy – Neuropathic Pain
–
Demonstrated 100% reversal of pain
–
No significant adverse effects observed
Chung – Neuropathic Pain
–
Exhibited rapid and significant reduction in pain
–
No significant adverse effects observed
Tail Flick – Nociceptive Pain
–
Showed rapid and dramatic reduction in pain; similar to the effect of high dose morphine
–
Onset of pain relief occurs within ten minutes of oral dose and extends for a long duration
–
No significant adverse effects observed with 2014; significant adverse effects with morphine
5
Neuropathic Pain Efficacy – Chemo-induced PN
NTP-2014 demonstrated the maximum pain relief possible in this model
Grams of Force
Nine rats per treatment group
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
-
584 umol/kg
100 mg/kg
179 umol/kg
75 mg/kg
Baseline
(PreTaxol)
PreTreatment
Pain Level
NTP-2014
PreTreatment
Pain Level
GBP
In a Taxol-induced model of neuropathy, NTP-2014 completely reversed
chemotherapy-induced pain at a lower equimolar dose than gabapentin.
CONFIDENTIAL
6
Oral Nociceptive Efficacy – Tail Flick
NTP-2014 showed extremely robust efficacy after oral administration
100
8-10 mice per treatment group
90
80
% Response
70
60
500 mg/kg PO
50
300 mg/kg PO
40
100 mg/kg PO
30
20
10
0
10
20
30
45
60
90
120
150
180
Time (minutes)
When administered orally, NTP-2014 exhibits a highly significant reduction in
pain. Further, such protection occurs within ten minutes of dosing and extends
for a longer duration than after IP administration. This creates an exciting
opportunity for a highly effective, fast acting, non-opiate therapy for acute pain.
CONFIDENTIAL
7
Development Timeline
NTP plans to initiate human clinical trials in 2Q10
Form / CMC
(2014)
IND Creation
(2014)
Phase IIa - Neuropathic Pain
(2014)
Ph I SD
(2014)
Ph I MD
(2014)
Phase IIa - Acute Nociceptive Pain
(2014)
Early Signal
(2014)
Phase IIa – Epilepsy
(2014)
Platform Development
Efficacy, PK, Toxicology, Form / CMC
(2nd Compound)
IND Creation
(2nd Cmpnd)
Dec 2009
Dec 2010
Dec 2011
Ph I SD
(2nd Cmp)
Ph I MD
(2nd Cmpnd)
Dec 2012
NTP’s development plan will reduce risk and be highly capital
efficient through use of multiple Phase IIa proof-of-concept
studies.
8

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