NEO6860

TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 (TRPV1) ANTAGONIST

Treatment of pain related to neuropathic pain

Stage of development: Human Proof Of Concept

Indications

Neuropathic pain
Osteoarthritis (OA) pain
Visceral pain / chronic pancreatitis

Mode Of Action

Potent, reversible, selective, and orally available vanilloid receptor-1 (TrpV1) ion channel antagonist

Main Advantages

  • Unique pharmacological profile that distinguishes it from other TrpV1 antagonists: blocks only the channel’s activation by capsaicin, not heat or pH
  • This profile should provide effective analgesia, without affecting body temperature and sensitivity to heat which are adverse effects associated with non-selective blockade of TrpV1

Disease Facts / Medical Need

  • Chronic pain is mediated by the activation and sensitization of nociceptors innervating affected tissue. Despite the availability of various medication, such as pregabalin, NSAIDS, COX-2 inhibitors, and opioids there remains, as a result of the limited efficacy and side effects associated with these treatments a continued need for a non-opioid, effective and safe treatment for neuropathic pain, OA pain and other chronic pain.

Pre-Clinical Data

NEO6860 is a potent and selective inhibitor at the human TrpV1 channel for capsaicin stimulation.

It does not affect channel activation by either pH or heat.

In primate DRG neurons, NEO6860 blocks only the capsaicin-, not heat-, evoked currents. It does not increase heat thresholds of primate unmyelinated C-fibres.

NEO6860 has successfully completed the GLP IND-enabling toxicology package, which included 28-day rat and primate toxicology studies. In the 28-day primate study, NEO6860 did not affect body temperature.

Clinical Data

Phase I clinical trial – SAD completed

Objective/Design:

  • A double-blind, placebo controlled, single and multiple oral dose, safety, tolerability, pharmacokinetic and pharmacodynamic study in healthy male and female subjects
  • 64 subjects in eight groups of eight with six subjects in each group receiving NEO6860 and two subjects, placebo; each group was fasted and received respectively 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg dosed once per day, and 500 mg dosed twice daily at 12-hr intervals. A non-fasted and female group were included in the 200 mg dose

Outcome:

  • Good safety profile with mostly mild Adverse Events (AEs) ; some moderate AEs at the higher doses
  • Specific AEs seen with other TrpV1s, hyperthermia and a reduced capacity to perceive heat as painful, were not seen with NEO6860
  • Very good pharmacokinetic profile with a dose-dependent increase in exposure
  • Clear pharmacodynamic evidence of target engagement

 

Phase II PoC-Clinical Proof of Concept

Objective/Design:

  • A randomized, double-blind, placebo & active control, crossover study assessing NEO6860 in patients with pain associated with osteoarthritis of the knee
  • A total of 54 patients were evaluated
  • Each patient was exposed to NEO6860 (500 mg dosed twice at 12-hr intervals), Naproxen (500 mg dosed twice at 12-hr intervals), and placebo in a crossover design

Primary endpoint:

  • Mean change in numerical rating scale (NRS, 0-10) from baseline following a staircase test

Outcome:

  • Robust study in terms of patients characteristics and study design
  • No effect on core body temperature and noxious heat perception
  • NEO6860 exhibits analgesic properties

Perspective:

  • Multiple dose study in OA, with a reduced dose is expected to have a more favorable benefit/safety ratio
  • Combination/add on therapy with NSAIDS to be explored

 

Next Step

  • NEOMED’s intent is to perform another phase II study in patients with neuropathic pain and pain associated with chronic pancreatitis.

 

For more information

Dan Chiche

Chief Medical Officer

514-375-3334 dchiche@neomed.ca
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