Neuren Pharmaceuticals: Commentary

Neuren (from NI January 2009)

Neuren's Glypromate did not show an effect in Phase III, because only 20% of placebo patients post-CABG-surgery had any cognitive decline, and it was mild. As was the case for Allon Therapeutics, the absence of decline precluded any possible evidence of benefit. Glypromate has thus been discontinued. More important is NNZ-2566, the small-molecule descendant. It is being developed in cooperation with the US Army, which has provided $10 million for its development, and will move into Phase II TBI testing towards the end of 1Q:09. The other product in active development is nefiracetam, acquired via last year's buyout of Hamilton Pharmaceuticals. 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) depends on funding, and funding has been hard to find outside of the US Army. Neuren's hope is that this will have positive cognitive effects and reduce the apathy that is so frequently seen in frontally-affected stroke patients.

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.