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