Neuren Pharmaceuticals: Commentary

Neuren (from July/August 2008 NI)

Neuren's lead drug, Glypromate, encountered some good news in a blinded analysis of its post-CABG MCI trial, and that's something seldom if ever heard in a neuroprotection trial. The interim analysis showed much smaller variance and many fewer dropouts than initially expected, which means they have already enrolled the 320 patients they need to power the study. Results should available near year-end, which will be a huge event for this under-the-radar company.NNZ-2566 is the small-molecule descendant, being developed in cooperation with the US Army for TBI, which covers half of the costs. The IND will be filed this quarter, and enrollment of the 200 patients will begin in October. Neuren's acquisition of nefiracetam via Hamilton Pharmaceuticals has set the stage for a Phase II in post-cortical stroke patients, with enrollment (goal is 200 patients) likely to begin in the next couple of months.

Neuren (from January 2008 NI)

Neuren's lead drug, Glypromate, finally started its 600pt Phase III trial in post-CABG cognitive impairment. Enrollment should be completed about a year from now, though a blinded interim analysis (no statistical penalty) could extend that if they need to increase the sample size. NNZ-2566 is the small-molecule descendant, being developed in cooperation with the US Army, which covers half of the costs. A Phase II trial in nonmilitary mild-moderate TBI patients will start mid-08, and a severe TBI Phase IIa should start then, funding permitting. An oral formulation is also in development, and eventually could be made available for combat-zone acute intervention. During 2007, Neuren also acquired Hamilton Pharmaceuticals, an inept shell of company with one asset, nefiracetam, which had been licensed from Daiichi. Nefiracetam is a chemical relative of Keppra, and showed signs of benefit in a Phase IIa trial of post-stroke patients. A larger Phase II in post-cortical stroke patients (therapeutic window of 90 days) could begin in May or June if funding is obtained. This is an interesting molecule, while it broadly increases monoamine levels presynaptically, it has a post-synaptic effect on nicotinic alpha beta 2 receptors, reminiscent of Abbott's Phase II nicotinic agonist. Neuren's belief is that this will have positive cognitive effects and will reduce the apathy that is so frequently seen in frontally-affected stroke patients.

Now, Neuren has revamped its management group to reflect its new emphasis upon clinical trials (they should have four Phase II trials going in 2008). The general antipathy towards programs aimed at stroke or TBI has certainly impeded their fundraising prospects, and bureaucratic incompetence has blocked their access to the hefty funding Congress allocated for programs relevant to combat TBI. This program has as good a chance as any to disprove the belief that 'neuroprotection is dead'.

Neuren (from July-August 2007 NI)

Neuren (from July 2006 NI)

Neuren (ASX:NEU): Neuren is quietly building an important neuroprotection franchise with its lead drug, Glypromate (which is a derivative of IGF-1), and a small-molecule version, NNZ-2566. The former is being brought into a 520pt CABG-MCI pivotal trial. Glypromate has shown very well in preclinical models, providing 90% infarct reduction with (and this is where it differs from so many drugs whose protection came when given before an infarct) a seven hour window. We have questioned whether the FDA would be receptive to a CABG/MCI drug, but thus far they have apparently been open to the concept. The safety margin for this drug has been impeccable; even at the equivalent of two grams or more, no toxicity has been shown, and the FDA has accepted that they can only provide a maximum ‘feasible’ dose, based on how much can be absorbed. Perhaps even more interesting is the small-molecule descendent, which is being developed in cooperation with the US Army. The Army’s interest is pragmatic: the Iraq War is producing a horrific harvest of young soldiers with both closed and (increasingly) penetrating head wounds. While the Army retains no control over NZZ-2566, they are providing funding for the program, which has both IV and oral formulations. This is currently in Phase I.