Ann: Neuren approaching key milestones in Q4 2019, page-56

Aurel19672003

I have no problems with the positive outlook but I don’t agree with some of your assumptions. My intention isn’t to bash the company; rather to keep expectations realistic.

Assumption 1

That the results for Ph 3 Rett will be announced in 8-9 months (i.e. by June next year)

We don’t know in which month of Q4 the Ph 3 trial will commence. It may not start before December. Nor can we know how long it will take to conclude the trial or when results will be released.

The Phase 2 paediatric trial had a speedy enrollment and was said to have run ahead of schedule. 82 patients were assessed over a total 10 week period. That trial took 12 months from trial commencement to announcement of results.

The upcoming Phase 3 trial will have 180 patients. Patients will be assessed over a total 19-20 week period. This is followed by a 40 week extension trial period. I’d expect a minimum of 18 months from trial commencement until announcement of topline results, especially as another 250 patient Rett trial has recently commenced (it is expected to take a bit over 2 years to complete). Therefore, I’m not expecting trofinetide Ph 3 results before 2021, mid-2021 if we’re lucky. The company has said that it hopes to submit an NDA in 2021, with approval to follow in 2022 (see Pitt Street Research Report).


Assumption 2

That milestone payments will begin to flow in H2 2020

We don’t know what the milestone triggers are so we can’t know when they will begin to flow. If we are lucky, there could be one as early as Phase 3 trial commencement – but if there is, it will likely be very modest. Trial completion is another possible trigger but that is unlikely to occur before 2021 (see above). For many licensing deals, NDA submission is the first trigger (perhaps late 2021). Then there is what is likely to be the largest milestone, FDA approval (if indeed it is approved). Not to be expected before 2022.


Assumption 3

That FDA approval of Sarepta’s Exondys51 in DMD, despite minimal efficacy, means it’s highly likely that even inconclusive Phase 3 results will lead to approval of trofinetide.

There is definitely a perception that the bar is lowered for rare disease drug approvals, especially following the approval of Exondys51. But that approval was highly contentious and followed an initial rejection. Also worth considering is the fact that the EMA has refused to approve Exondys 51, citing inadequate data demonstrating efficacy and in addition, Sarepta very recently had their second candidate therapy, for another subset of the DMD population, knocked back by the FDA.

So, yes, there can be a measure of flexibility, but if the aim is a smooth passage to market past both the FDA and EMA, efficacy will need to be demonstrated.