Avalo Therapeutics, Inc. Common Stock Stifel 2026 Virtual Immunology and Inflammation Forum

With that, Garry. Thanks, Alex, and thanks for having us again.

Avalo is focused on developing therapies targeting IL-1 beta for immune-mediated inflammatory diseases where there remains significant need. Our lead asset is abdakibart, formerly AVTX-009, a highly potent and selective anti-IL-1 beta monoclonal antibody. We acquired the molecule through the Almada Bio transaction of 2024 because we saw a compelling combination, strong biology supporting IL-1 beta as a central driver of HS, and an attractive safety profile for the IL-1 beta class. The molecule we believed would have a differentiated efficacy and dosing profile, and that's playing out. The LOTUS Phase II results significantly strengthened that conviction. Both doses met the primary HiSCR 75 endpoint response rates of 42.2%, 42.9% respectively, and we saw very consistent activity across multiple clinically meaningful secondary endpoints. In fact, all of the secondary endpoints were positive.

Importantly, the 300 milligram every four-week regimen performed essentially identically to the every two-week regimen. Our number one priority is straightforward, execute the registrational phase III program in HS, which we plan to initiate the first half of 2027. At the same time, we're building beyond abdakibart with AVTX-010, our next generation long-acting anti-IL-1 beta antibody, and we plan to submit an IND for that program in the first half of 2027 as well. I'd characterize the next 12 months as being about execution, moving abdakibart into phase III, looking at additional indications, and beginning to build a broader IL-1 beta franchise.

It is very vibrant, very dynamic. There is increasing recognition of the huge need. Patients are getting earlier diagnosis and better diagnosis than they ever had before because of the availability of some new products. They are getting on biologics much earlier with the recognition that allowing the disease to progress is not really optimal medical care. We are seeing the market growing. It is probably already in excess of $3 billion, and we have it pegged to grow to over $10 billion by the mid-2030s, and that may be an underestimate for it. It has been very easy to enroll these trials because of the availability of patients who are seeking better treatment options, and that is why we do need to explore and provide new mechanisms such as abdakibart to these physicians that look after them and the patients.

Because even though there has been a lot of progress, there still remains a lot of need. Patients are not completely satisfied, and until we get a mature market like psoriasis where the majority Yeah of patients are achieving clear skin, I think we are not done yet.

IL-1 beta is really a central inflammatory driver. From an efficacy point of view, it really makes a lot of sense. There are very, very high levels of IL-1 beta in these HS lesions, more than any other cytokine. The second most commonly expressed would be IL-17, which we know is well-validated with approved drugs on the market. It also has an effect, IL-1 beta has an effect on a variety of other mechanisms, such as the matrix metalloproteinase system, direct effects on the neutrophil and macrophage, which are really super important, also upstream of TNF. All of that taken together leads to a really great profile, potentially of being able to help more patients also get into healing in draining tunnels and fistulas. That is really critical for it. At the same time, it has a really great safety profile.

Yeah IL-1 beta, it is not a pro immune stimulator.

It is an inflammatory molecule. Blocking it gives you an anti-inflammatory effect, but you do not get into opportunistic infections or Yeah increased cancer risk, which has been a little bit of a problem or an impediment to the safe use of some of the other products that are used in this disease.

In fact, if you look at the historical data from the CANTOS trial with Ilaris, which is a much less potent drug than ours and not being developed in HS, but it did show that there was no increased cancer risk. In fact, quite the opposite. There was a markedly reduced cancer risk and cancer mortality risk in that three-year study since most cancers, epithelial cancers especially, arise on a background of inflammation. You also saw a decrease in cardiovascular risk with long-term treatment with it. I think those are both very reassuring when you are looking at the long-term safety profile of a drug like abdakibart.

Yeah. The LOTUS was on approximately 250- Yeah patient study.