Researchers say inflammation is key TBI culprit, page-21

Mountsbay, not too be rude but your interpretation that the rejection of Breakthrough Designation ("BTD") equates to a rejection of the Retts Phase II by the FDA is simply wrong. The Phase II exceeded expectations and subsequently the FDA granted Orphan Drug Designation and the results will advance Neuren to a Phase III and ultimate approval.

Few specific comments. Point 3. clarifies the sample size point you raised:

(1) Only 30% of BTD application have been granted, this number is closer to 15% for neuro drugs. There are 38 pharmas/biotechs publicly listed as having received BTD. Some have received multiple designations. Of these, 31 (82 %) are American companies. Of the 7 non-American companies, 2 are from Switzerland, 1 is from Germany, 1 from the UK, 1 from Denmark, 1 from Japan and 1 from Taiwan. Of the 7 non-American companies, 5 are Top 20 pharma – Novartis, Roche, GSK, Boehringer Ingelheim and Takeda. That leaves just 2 non-US, non-big pharma companies which have received BTD from the FDA. Not sure why the market bet on a positive outcome for BTD since it was approx a 1 in 10 chance and rejection doesn't really change a thing. just slows things by approx 6 months or so.
(2) The company has reconfirmed that their Phase 2 clinical trial of NNZ-2566 successfully demonstrated clinical benefit in Rett syndrome and so does the FDA who granted Orphan Drug Designation. From the Chairman's Letter in the recent Annual Report: "The data we submitted from our Phase 2 trials of 54 subjects was considered to be of insufficient statistical power to meet the FDA's requirement for Breakthrough Therapy at this time. This does not alter our view of the clinical benefit that was observed in the trial or our commitment to move our Rett syndrome program forward. We and our expert consultants remain confident that we have a strong case for Breakthrough Therapy and we may submit further data to the FDA in the future” So while BTT was rejected the Rett Phase II results still exceeded expectations and NEU are on track for expeditious market approval via Orphan Drug Designation and Fast Track Status.
(3) Finally, on patient numbers required your doctor friends are quoting rule of thumb for common diseases, not orphan drugs for rare diseases. It is important to note that in all phases of clinical trials, the number of patients required for studying rare diseases i.e. Fragile X and Rett syndrome are much lower than for other diseases. For example, whereas a Phase III study of a common disease such as diabetes may require thousands of patients, a Phase III study of a rare disease may include fewer than 100 patients. A Phase II of 50 for a rare disease is plenty for drug approval, just not for Breakthrough which was a slim chance at any rate.

Hope that is helpful.

Cheers,