@Goldfish this update was from the JP Morgan Conference presetaton by Acadia, which I have listened to this morning.

I don't share the market's ethusiasm this morning, and here's my rationale.

The $700m assumes a favourable EU initial ruling on approval in Q1 2026. My concern is that, even with an initial positive opinion (driven by safety and efficacy), there is a significant risk about the future reimbursement decisions in each EU jurisdiction. (Canada is the "canary in the coalmine" - "approved", but with a "do not reimburse" recommendationon, means that we won't see a material reveue contributioon from Canada, as only those able to access funding will be able to afford the treatment.)

$ACAD believe the STIX powdered formulation is going to win back some share of the patients who have discontinued. It is being trialled and we don't yet have evidence of success. I find this interesting, because my understanding of the major driver for discontinuation are the significant GI side effects. I've not seen any comments about how the GI side effects are different for the powdered formulation, beyond some remarks by the CEO and Commercial VP about the powdered formulation being preferred for taste and dietary preferences over the liquid. No doubt, $ACAD will have more to say about this as market experience with STIX unfolds.

While stating 55% persistency at 12 months is good, and a tangible development from previous statements of "greater than 50%", it is interesting to me that a longer term persistency number was not reiterated. For example, they have previously said that persistency at 18 months is "above 45%". My point being that we are yet to see any plateau or "asymptote" in longer run persistency, which continues to put a significant questionmark over the longer term value of expected cashflow per patient. At some point in 1H 2026 we should get a 2 year persistency number,

By my model, DAYBUE sales in the US for 2025 are likely to come in around $388-$390m (Guidance $385 - $400m), which by my midpoint would be +12% on 2024. I'll be looking closely at this because any move towards the upper end of guidance would indicate that we are seeing significant benefits from the sale force expansion, which we barely saw in Q3 (the expansion having taken place in Q2, and explained by $ACAD saying that there is a decision cycle between a patient or HCP first being engaged and the writing of a script.)

But let's be positive and assume we can get 3 years of 12% annual sales growth in the US. That would give 2028 sales of $540m, meaning that we only just get the next US milestone payment in 2028.

Note: Having said I'll assume 3 years of 12% annual growth, I don't think we'll see that, as we are more likely to see a progressive decline in the growth rate, as market penetration continues.

The $700m number means that EU+RoW contributes $160m by 2028. That would indicate to me some combination of lower pricing and lower penetration in RoW+EU, Note that in just 3 quarters of sales in the US, DAYBUE got to $177m. 2028 would. be Year 3 in the EU, assuming a lauch in 2026, so even though the market is much bigger in term of prevalent population, $ACAD are clearly not assuming a high price/penetration outcome. I actually think they a putting on a risked view across several scenarios - some higher, some lower, and there is a reasonable chance (given Canada) that multiple EU territories won't reimburse at all.

I'm rambling here, but I think that 2028 across US + EU + RoW is not that exciting from a $NEU revenue basis. I've haven't modelled the $NEU revenue impact yet, and I will do this when I update my model ahead of the $ACAD 2025 result, which is currently expected on 26 Feb.

Now returning to my "Note" above. If the US can't sustain 12% annual growth to 2028, then that assumes more heavy lifting by EU+RoW ... and at this stage it is just an assumption.

In conclusion, I don't know what weight to give to the $700m 2028 number. And I also don't think $ACAD management are giving it any weight. Its more a "we think sales could be $700m assuming several positive developments occur."

I remain on the sidelines with $NEU having bagged some reasonable profits last year. Of course, this probably biases me to a bearish view which risks looking out of touch as the SP breaks above $20 again. But I want to see the 2025 revenue number and the EU decision (as well as the commentary around it) before deciding whether the DAYBUE revenue base is strong enough to get back on board for the material upside which is NNZ-2591. Koala has a long way to run, so I don't need to be in a hurry to take this decision, and I am willing to accept the risk that positive EU + RoW newsflow means I never get back onboard. I think that is a balanced risk, given my view of the downsides.

Disc: Not held