Celldex Therapeutics 3rd Annual Guggenheim Healthcare Innovation Conference

Absolutely. Thank you. We really appreciate you having us here today. Yatin, as you know, Celldex has this deep heritage in the antibody space, and we have applied that over the last several years to drive new science around mast cell depletion and mast cell modulation. You saw top-line phase III results from our barzolvolimab program in September, which Diane will talk about in much greater detail with you over the course of this. We are very excited about that, and we are moving forward to probably the biggest milestone for us, BLA submission in 2027.

Yeah. We are thrilled with our phase III data, and we have been sharing it with outside experts who are also giving us very positive feedback and are really just as excited about what they call best in disease efficacy as we are. When I think about it, we have shown in these trials a number of things that nobody else has demonstrated to date. We're the first studies that have had a complete response rate in the majority of patients, the first studies that have prospectively set out to show angioedema clearing at 12 weeks. We've shown that omalizumab refractory patients respond as well as the overall population, and we have one of our regimens with all these improvements only requires seven doses in a year.

When you take these data together with our phase II data, where in the 76-week data, we showed this unprecedented off-therapy prolonged response, we really have a unique profile and a profile that can really serve a lot of CSU patients. I don't know if Terri wanted to comment on the competitive profile.

Sure. As Diane said, in our interactions with the HCPs indicate barzolvolimab can really be a practice-changing therapy. All of our conversations continue to come back to these five big differentiators for HCPs and patients. Number one, that complete response number. Up till this point, patients and HCPs have settled for some improvement in symptoms, but what they really want is complete clearance of symptoms, and that's the difference with that complete response in a majority of patients. Second, the effect is rapid, durable, and actually deepens over time. Third and four, the ability to address patient populations that none of the other therapies currently can, that first-line patient with severe disease and angioedema, and then the biologic refractory patients. Number five, that dosing regimen, right?

Both the flexibility of Q4 or Q8, but importantly with Q8, the only therapy that offers as few as seven dosing days a year. That's a very compelling package from just the 24-week top-line data.

We do expect to have that in the label in some form, which we have to negotiate with the FDA. As we said, we designed the study to be able to specifically look at that subgroup, and so it's highly statistically significant. It's a matter of where it would go in the label, but we expect it to.

Mm-hmm. Optionality is a real advantage. The intention is to fit seamlessly into HCPs' practices and into patients' lives. There are HCPs who prefer that monthly interaction with the patient, and that fits into their practice, and there are patients who prefer to not think about their disease when they don't have to, so the fewer dosing days per year is a real advantage. Because after the loading dose, it's the same amount of drug over the course of a year, payers will be supportive of this optionality. It really reflects real-world treatment paradigms.

Yeah. Just to take a step back, we were very pleased with the overall safety profile that we saw in the studies. The most common adverse events were the KIT-mediated events that are mostly mild to moderate and expected to be reversible. In terms of serious adverse events and grade 3 and 4 adverse events, the rates in placebo and barzolvolimab were the same. We had two adjudicated cases of probable anaphylaxis in the phase III study. They both occurred after the first dose of barzolvolimab, and as we pointed out, these are the only two probable cases adjudicated in the entire subcutaneous program, which is 2,400 patients. There was another case that was adjudicated as anaphylaxis, but occurred with a dose of placebo, not with barzolvolimab. The other cases were not adjudicated as anaphylaxis.