NTP is developing a pipeline of compounds for disorders of the nervous system. Research into novel chemistries and the structure activity relationships (SAR) are being used to create compounds that have shown highly significant activity in multiple indications. These efforts have resulted in novel series of compounds which are protected by composition of matter patents and other intellectual property.
Pain Efficacy
Positive, predictive and highly significant results in models of epilepsy, pain (neuropathic, acute and inflammatory)
and anxiety
NTP compounds have demonstrated significant efficacy in a variety of pain models, including those representing neuropathic, inflammatory and nociceptive (acute) pain.
In the preclinical setting, NTP compounds have shown an impressive and often complete reversal of pain. In a screen of neuropathic pain (Formalin Paw; Late Phase), NTP compounds showed near 100% pain reduction; the results of which were superior to the positive control gabapentin (Neurontin®) and at a lower molar dose. In a model of neuropathic pain resulting from nerve injury/ligation (Chung), NTP compounds produced a significant and dose-dependent reversal of pain. Additionally, in a model of chemotherapy-induced neuropathic pain (Taxol-induced Peripheral Neuropathy), complete relief of pain was demonstrated in the treated group.
In a model of sub-acute inflammatory pain (Carrageenan Paw), dose dependent and complete pain relief was demonstrated with NTP compounds. Overall, these results were superior or comparable to morphine.
NTP’s compounds are quite unique as they also have strong effects in acute/nociceptive pain, in which gabapentin and most other chronic therapies for neuropathic pain are known to demonstrate no effect. In a model of nociceptive pain (Tail Flick), the activity of NTP compounds were comparable or superior to that of morphine. Further, the NTP compounds demonstrated a much more favorable behavioral safety profile and have no potential for addiction.
Epilepsy Efficacy
NTP compounds have also shown consistent and significant efficacy in models of epilepsy. In a rigorous model of treatment-resistant, or refractory, complex partial epilepsy (MTLE – Mesial Temporal Lobe Epilepsy), NTP compounds have shown near complete suppression of discharges and dose-dependent activity. In this model, the NTP compounds reduced seizure activity well beyond that of all four positive controls, each of which is a blockbuster drug currently used in epilepsy.
Other Efficacy
NTP compounds have shown positive results in preclinical studies of other nervous system disorders as well. Efficacy has been demonstrated in three models of anxiety (Vogel Conflict, Light/Dark Box and Marble Burying). Further, in a model of migraine, a strong and dose-dependent response was observed.
Safety Pharmacology
A consistent lack
of sedative and cognitive side effects as predicted by the mechanism and supported by
in vivo data
NTP’s compounds have shown a favorable safety pharmacology profile in various safety and toxicology studies performed to date. It is important to note that NTP’s compounds have repeatedly shown a lack of the sedative and cognitive side effects which are typically observed with traditional therapies to treat pain and epilepsy. It is believed that this is due to the compounds’ mechanism of action, which has been shown to reduce neuronal excitability at specific (rather than broad) receptor sites in the brain and only act during states of abnormal neuronal excitability. This is in contrast to existing therapies, which tend to act widely across the central nervous system and at all times, thus leading to sedation and similar effects.
Study Plan
NTP raised a financing which will support the company’s pipeline development and compound screening, generate multiple clinical candidates, and advance one compound through multiple Phase 2a studies in pain and epilepsy. The company will concurrently review and consider the compounds’ potential application in other indications.
The company plans to initiate a Phase I study in early 2013. Additional compounds could be advanced into human clinical studies through corporate partnerships.
Conclusion
In preclinical studies, NTP’s compounds have exhibited a greater level of efficacy than multiple approved compounds which are widely used in the market today. They have also shown no evidence for sedating activity after administration of pharmacodynamically active doses in numerous animal models. While yet to be supported by human clinical data, these compounds have the potential to dramatically improve upon existing care for numerous neurological disorders without the potential for addiction.
