Avalo Therapeutics 3rd Annual Guggenheim Healthcare Innovation Conference

Thank you for inviting me, Yatin.

Great. No, we're doing very well against all of our milestones and objectives at Avalo. After we had the very positive data from the LOTUS trial in the beginning of May, we were able to raise $430 million worth of capital, which is really helpful these days in the market. We reported that we still have $462 million at the end of September, which is enough to get us through our top line for phase III in 2029. We do not need to do any additional raises right now, and it also funds our soon-to-be-announced second indication, which will get us into a new therapeutic area, add more value to our overall program, as well as funding our AVTX-010 program, which is our engineered antibody with the extended PK, which is going to get into the clinic in 2027.

We were very pleased with the results that we had from LOTUS, and obviously the market recognized that at the time, showing a really consistent depth of response and consistent between the two doses that we tested, very consistent over time, and very consistent across all of the secondary endpoints. That has given us and continues to give us great confidence for going into phase III. We have been working hard on getting all of these programs going in parallel, upsizing the company a little bit. We are being very careful with our capital, but making sure we have the resources to do what we need to do. We have got our packages before the FDA and the EMA. We will have our feedback from those agencies before the end of the year. We have got our CROs lined up, CMO lined up. Everything is going great on the CMC.

We will be ready to hit the ground running early in 2027 once we get the feedback from FDA, and we are very, very excited. Also, we have seen there have been a number of interesting developments in the HS space, as you expect. There have been a number of entrants, people trying different mechanisms.

Yeah I guess we will talk a little bit more about that.

So we're very convinced, and there's very solid data showing the central role of IL-1β specifically, but not IL-1α, but IL-1β and the NLRP3 complex in driving the disease in a very substantial number of patients. IL-17 is also important, we know that, but the IL-1β has a more central role in the inflammatory cascade, which we think is very important in the disease, specifically around the control of neutrophils, which are important in the disease, macrophages, which also release TNF-α, but also with a secondary role on control of IL-17, in particular IL-17F. So, which seems to be the more important target on the T-cell side in the disease. We've seen this both with measurement of protein in the lesions in these patients. You can see massively increased CRP levels in these patients, consistent with that NLRP3-driven inflammatory response.

We've also seen this in RNA expression as well, and we've done a lot of work on that, looking at different profiles for RNA complex expression, and we're still actually doing deep analysis on our biomarker set. So we've been very convinced about the target, and we've seen now there hasn't been, with the two AbbVie phase II trials, their recent phase III trial, and the LOTUS trial, there hasn't been any failure yet in an IL-1β-targeted trial. I think what we do know that IL-1α doesn't work, and looking at the results of the INTREPID study, lutikizumab, I think it lays the issue to rest about the value of targeting IL-1α, which may, if anything, may be a detriment rather than an advantage.