2010 ASENT ConferenceMarch 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

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Mechanism of Action

• 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

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Demonstrated molecular site of action, cellular activity, in vivo efficacy

Epilepsy Efficacy Data

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• 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

NTP-2014 has shown strong efficacy across multiple models

CPS – Complex Partial Seizures

Cont

rol

100 200 400 25 50 100 1 50 100 500

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Cum

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ve D

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)

VPA CBZ PGBAvg daily human mg/kg: 60 20 6

mg/kg693 1,386 2,772 106 212 423 6 314 628 umol/kg

2014

* *

*

*

*11950

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NTP-2014 is more potent than existing therapies

CONFIDENTIAL

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)

Epilepsy Efficacy – Temporal Lobe Epilepsy Model

* p < 0.05 versus control10 mice per treatment group

Number of discharges not shownComparators not run concurrently; historical data

Neuropathic & Nociceptive Pain Efficacy Data

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• 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

NTP-2014 has shown strong efficacy across multiple models

Neuropathic Pain Efficacy – Chemo-induced PN

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NTP-2014 demonstrated the maximum pain relief possible in this model

In a Taxol-induced model of neuropathy, NTP-2014 completely reversed chemotherapy-induced pain at a lower equimolar dose than gabapentin.

CONFIDENTIAL

Nine rats per treatment group

-1 2 3 4 5 6 7 8 9

10 11 12 13 14 15 16 17

Baseline (PreTaxol)

PreTreatment Pain Level

NTP-2014 PreTreatment Pain Level

GBP

Gra

ms

of F

orce

179 umol/kg75 mg/kg

584 umol/kg100 mg/kg

Oral Nociceptive Efficacy – Tail Flick

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NTP-2014 showed extremely robust efficacy after oral administration

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

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10 20 30 45 60 90 120 150 180

% R

espo

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Time (minutes)

500 mg/kg PO

300 mg/kg PO

100 mg/kg PO

8-10 mice per treatment group

Development Timeline

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IND Creation(2014)

Ph I SD(2014)

Ph I MD(2014)

Phase IIa - Neuropathic Pain(2014)

Phase IIa - Acute Nociceptive Pain(2014)

Phase IIa – Epilepsy(2014)

Dec 2009 Dec 2010 Dec 2011 Dec 2012

Form / CMC(2014)

Early Signal(2014)

NTP plans to initiate human clinical trials in 2Q10

NTP’s development plan will reduce risk and be highly capital efficient through use of multiple Phase IIa proof-of-concept studies.

Platform Development

Ph I SD(2nd Cmp)

Ph I MD(2nd Cmpnd)

IND Creation(2nd Cmpnd)

Efficacy, PK, Toxicology, Form / CMC(2nd Compound)