Amylyx Pharmaceuticals 3rd Annual Guggenheim Healthcare Innovation Conference

Sure. Yes, we had a really exciting year. We had the phase III readout from LUCIDITY where we met our pre-specified primary endpoint with a p-value of 0.000003, which we're incredibly excited about. That measured the rate of level 2 and level 3 hypoglycemia. These are severe hypoglycemic events. Level 3 is basically when somebody's rendered so incapacitated that they need kind of third-party assistance. Level 2 is a level that's been picked by the ADA where your brain is at a severe lack of sugar and you start to have major problems. We met that pre-specified primary endpoint. We also met all of the secondary endpoints with a kind of consistent and highly statistically significant result across those two, with a favorable safety profile as well.

With that in hand, we're now working towards our NDA submission by the end of the year, planning for a launch, if approved, in 2027. I think just the more we've dug into the PBH market, the more excited we've gotten. About 90% of people who have PBH describe themselves as disabled. When you have this condition, it really takes over your whole life. It's really hard to live with and manage. I think in line with that, both from physicians and patients, we hear an incredible excitement for the potential of a therapy. As we've continued to do claims-based work and dig into the market, we estimate there are about 160,000 people living with PBH, and today there's no therapy for them. We're very excited about this.

We had a big year this year, but I hope we have an even bigger year next year.

Well, thanks, and I appreciate the nod to our prior launch. We are very proud of the work we did there, but of course, there are always lessons learned, so we hope to do even better this time. That being said, each market is different, and so we are approaching this with the right level of diligence. I think first and foremost, it always starts with people. I think you really need the right leadership on down, especially as you are building a new market, as we are with PBH. Huge unmet need, but there has never been an FDA-approved treatment for people with PBH. So, this is new. There is a lot of education needed. I think on the people side, given the strength of the prior results going into LUCIDITY, we started to build that leadership team both on the medical affairs and commercial side.

We have a really strong leadership in medical affairs and commercial in place. They have been doing great work. I think this past year, we spent a lot of time really understanding the market, understanding the patient journey, going through multiple different claims analyses to recognize where people are, how are they treated, who is treating them, figuring out what future call points and those things will be. So really getting a sense of the landscape. I think right now there is a lot of focus on disease education. We have an ongoing campaign both for people with PBH as well as for healthcare professionals, and those efforts will continue to ramp up as we go into anticipated launch next year. I think overall, the way we are approaching this is a rare disease, but of course, it is a large rare disease. We estimate there are about 160,000 people in the U.S.

I think generally what we have seen so far is that the concentration in the market is similar to what you might see in other rare diseases, but the overall numbers are just higher, given the size of the population. We are doing a lot of payer preparation work now. We are starting to work on our various campaigns that we will have. So we are in full launch preparation mode, but I think it is going to be really important that while this is a high unmet need, there are well-educated centers, and we need to make sure we are partnering with them. There is also a market to build, and so I think we are really trying to make sure we get both of those aspects right.

Yeah. I think I touched on a little bit, but I think first, just the meaningfulness of these outcomes. When you think of level 2 and level 3 hypoglycemia, these are severe, dramatic events for patients, and being able to reduce them is just a very, very big deal for this disease. I would also add just the consistency of data, the consistency of data between this trial and the previous trials, as well as the consistency of the data within this trial. Not only did we hit our composite of level 2 and level 3, but we hit level 2 and level 3 individually. We also hit level 2, whether you measured it by finger stick or by continuous glucose monitoring.

I think it just, the kind of strength of the data comes from the fact that no matter how you look at it, sort of no matter how you slice it, you see a strong and consistent benefit that also matches what we have seen in prior trials.

I would add too, I think, is we have had a few opportunities to have ad boards show the data to different key opinion leaders. The totality of the data, I think, has been really important for physicians, both from an efficacy perspective, as Josh was talking about, but the safety and tolerability as well. The profile is very consistent with what we have seen in prior trials. We did not see any evidence of weight gain or sort of things that people could be concerned about mechanistically. We never thought that that might be a concern, but again, nice to see the 16-week data to support that.

I really think it is that totality of data that physicians have found very encouraging, because again, there has never been an FDA-approved treatment for people with PBH before, and I think it is that totality of data that has physicians very excited that they may finally have something to offer their patients.