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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
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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
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
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
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 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
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
Neuropathic Pain Efficacy – Chemo-induced PN NTP-2014 demonstrated the maximum pain relief possible in this model Nine rats per treatment group In a Taxol-induced model of neuropathy, NTP-2014 completely reversed chemotherapy-induced pain at a lower equimolar dose than gabapentin. CONFIDENTIAL
Oral Nociceptive Efficacy – Tail Flick NTP-2014 showed extremely robust efficacy after oral administration 8-10 mice per treatment group 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
Development Timeline NTP plans to initiate human clinical trials in 2Q10 Form / CMC (2014) Phase IIa - Neuropathic Pain (2014) IND Creation (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) Ph I MD (2nd Cmpnd) IND Creation (2nd Cmpnd) Ph I SD (2nd Cmp) Dec 2009 Dec 2010 Dec 2011 Dec 2012 NTP’s development plan will reduce risk and be highly capital efficient through use of multiple Phase IIa proof-of-concept studies.