...without bothering anyone, it would be enough to postpone the...

...without bothering anyone, it would be enough to postpone the start of the studies of 2591 for a few months, because we are in the presence of the classic case where there is no money in the short term, but even abundant in the medium term.

Actually, Sillazze, it would bother me if Neuren postponed the start of studies of NNZ-2591 until after it had received milestone payments related to trofinetide.

Firstly, postponement would have to be for more than just a few months. The first milestone payment is likely not due until an NDA is filed for trofinetide in Rett syndrome. Currently, Acadia anticipates Phase 3 trial completion in October 2021, so NDA submission may well not occur until H1 2022. That’s not only a long time to expect shareholders to wait, are NEU staff expected to sit around twiddling their thumbs for the next two years while remaining funds are whittled away? Also, one needs to take into consideration that there is no certainty that an NDA will be filed and it is possible that even if it is, any milestone might be less than $20 million.

It would also bother me if the Company suddenly postponed after consistently advising shareholders for close to a year that it planned to commence Phase 2 studies in NNZ-2591 in H2 this year. Failing to execute on these plans would not reflect well on the credibility of the Board.

Then there is the unpalatable fact that the Company has already dragged its feet on NNZ-2591 development for a very long time.

Here’s where the compound was at when Richard Treagus joined the NEU Board in early 2013

NNZ-2591 NNZ-2591 is the lead molecule in Neuren’s diketopiperazine (DKP or cyclic dipeptide) portfolio. It is a synthetic analogue of the DKP cyclo-(Gly-Pro) which occurs naturally in the brain and has been described as having neuroprotective, anxiolytic and nootropic (memory enhancing) effects. NNZ-2591 has been shown to be neuroprotective in vitro in cytotoxicity tests, reduce infarct size in rodent models of stroke and hypoxiaischemia, improve behavioural outcome following repeated treatment in Parkinsonian rats, exhibit nootropic effects in cognitively-impaired rats and provide significant protection against the development of peripheral neuropathy. Like NNZ-2566, NNZ-2591 significantly attenuates activation of microglia following injury. The molecule has excellent oral bioavailability (~100%) and is currently being assessed as a clinical candidate for the treatment of chronic neurological disorders. NNZ-2591 has been protected for composition of matter and therapeutic use in issued patents and pending applications.

For the October 2013 $23.5 million capital raise, one of the stated use of funds was for advancing Neuren’s second drug product NNZ-2591 through pre-clinical development. Following, in August 2014, the Company announced that it had initiated activities to support filing of an IND with the FDA and subsequent clinical development of NNZ-2591, with initial focus on optimisation of manufacturing processes and physical attributes. Yet, here we are in 2020, with Neuren stating last week that it was continuing the manufacturing development and non-clinical studies required before submitting an Investigational New Drug (IND) Application for NNZ-2591 in the United States.

Does this set a world record for duration of IND-enabling studies?

A further concern I would have is that a substantial postponement would hand a free kick to any competitors in the three targeted indications.

Finally, what if the stars don’t align and the Phase 3 trofinetide results are “light green”, resulting in an extended period of data analysis, negotiation with the FDA e.t.c., e.t.c.
Or worse, red.

In that event, would it not be preferable to already have results for the Phase 2 studies in NNZ-2591?