Pharvaris N.V. Ordinary Shares Morgan Stanley 24th Annual Global Healthcare Conference

Thank you, Max. Good to be here.

Mm-hmm. Sure. Actually, our journey, or my personal journey in HAE started 23 years ago, not with Pharvaris, but with the company that developed icatibant. I worked there together with Jochen Knolle, who is the inventor of icatibant. Then in, as we all know, Shire took over in 2008, and it then became, and still is, the most widely used acute therapy for subcutaneous injection. But already back then, we knew that patients were looking for better treatments and already then we were just starting to think about the vision for an oral therapy. Then a couple of years later in 2015, starting operations in 2016, Jochen and I started Pharvaris, with the idea to develop an orally available B2 receptor antagonist, really from chemistry square one, really from scratch.

We are really excited to what we see today with what came out of that, is deucrictibant. The properties of that molecule makes it very different from icatibant, that it is a B2 receptor antagonist, but it is, to our knowledge, the first and only orally available B2 receptor antagonist. It also has the properties that make it half-life and so on, that makes it suitable for prophylactic development, unlike icatibant. Looking at the therapeutic area for over more than two decades, you see the big unmet need for an efficacious oral therapy option, and that there is still nothing approved out there. We are of course hoping that deucrictibant is going to be the first orally available B2 receptor antagonist, an oral therapy with a high level of efficacy for people living with HAE.

Yeah. You saw the data. We had a remarkable 87% efficacy in the type 1, type 2 population of hereditary angioedema. The study included as also part of the overall protocol, patients with normal C1 inhibitor, other mutations. The primary endpoint included a small number of such patients and that total primary endpoint and efficacy attack reduction was 83%. That really means that we are in the area of what we can call injectable-like efficacy. If you look at the other injectables in the prophylactic space therapies out there all seems to be almost like a ceiling. I was thinking more or less, maybe not coincidence, but there seems to be like there is a maximum level of efficacy at around 87%.

We are very happy to see that with deucrictibant, and it really puts us in a very differentiated position vis-à-vis the others. As I said, we see a huge unmet need for an oral therapy that really provides that level of efficacy.

Mm-hmm. Yeah, the baseline characteristics are very similar to other therapies. In terms of attack frequency, they range from, I think the lowest is the TAKHZYRO with 1.7, and the highest is ORLADEYO indeed. We were sort of in the little over 2.1, I think it was in our case. It's all very similar. These are fairly severe patients.

Yeah. Yeah. I think that's very comparable.

I'll add on that those were our placebo rates in the full 24-week study. For the baseline characteristics leading into the study, our average attack rate was about 3.6, so that is a more severe patient population. We were incredibly impressed to see the 87% attack reduction given the severity of the patients that we were treating.

Yes, happy to. In our study, we did see two grade 3, level 2 liver enzyme elevations. As you mentioned, Max, one of those patients did have fatty liver disease. That was also a normal C1 patient. That person ended up discontinuing the study drug but stayed on the study, so we were able to continue their lab assessments. The second patient had previously used androgens. They actually stayed on study and completed the study and then rolled over onto the open label extension. Both of those patients neither were symptomatic and neither saw elevated bilirubin, so we were pleased to see that.