Artiva Biotherapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thanks, Josh. Thanks for having us. Look, it all started when we, together, 3 years ago, realized the power of the deep B-cell depletion approach, right? When we learned about this mechanism, and you and I talked about this early on, we realized that the name of the game was a deep B-cell depletion, and if you could achieve that, you could have really good clinical benefits in autoimmune disease. We first decided to go into autoimmune disease, focusing on the indications that SHED was pursuing, just because there was clinical proof of concept there. As we started to think more carefully about where we wanted to play, it became very clear that certain indications were just getting overly crowded, like lupus, for example.

When we think about the advantages of our product, is that based on our oncology experience, we saw that we can deliver a really deep B-cell depletion. Our oncology data was actually pretty compelling. We did not reach the median duration of response. It was close to 2 years. It hadn't been reached. So if you can deliver a deep level of B-cell depletion, if the response seems to be deep enough that you get this durable effect in oncology, combined with the safety profile that is fairly unique to NK cells, where you don't see CRS, you don't see ICANS, patients can be treated in a community setting, why not go into one of the largest autoimmune indications? We felt that a lot of companies were not pursuing RA as their initial indications because there's a lot of drugs that are approved in RA.

Many of those modalities cause CRS. Many of them are still being used in a hospital setting today in order to get treatment. Because we were not constrained by that, we could think about going into these broader indications. So today we're in a phase III trial that has paid off because we believe we are ahead of everyone else. Nobody else has announced a phase III trial. Nobody else has announced a phase II trial. So we really do think that if things go according to plan and we deliver in our RCT as we expect, efficacy continues to look strong, safety profile continues to be accepted, we could be the very first deep B-cell depleting product to enter the RA market since RINVOQ was approved actually in 2019.

Look, I think we mistakenly talk about NK cells as if they are very similar. Let us remember that there has probably been three or four sizable enough trials for people to make determinations as to whether durability is there or not. We have had iPSC-derived NK cells. We have had CAR-NKs. Those are all very different than what we are doing. We are using NK cells that are not genetically modified, and because we do not genetically engineer them, we use a monoclonal to actually do the targeting. We believe, based on our internal work, that that activation of NK cells via the Fc portion of a monoclonal is one of the most powerful ways to activate NK cells. Based on our data generated in oncology, which is exactly the place where people first became disappointed with NK cells, that data was actually really strong.

Just like we do in every other area, you have to look at each product individually. Given that we think we achieved a really deep level of B-cell depletion, which explains the durability in oncology, this is why I think we are seeing pretty compelling data in autoimmune disease. I think that now that we are a phase III RA company, the NK cell is just the how we do it. But what matters is what does the data look like? What does the safety look like, and can we really be first in a compelling new market?

Well, I think that can be ascertained just by speaking with physicians. RA is interesting because historically, take the development of RINVOQ, for example. It took over 1,000 patients required to be treated in order for RINVOQ to get an approval. This is because historically, most of the drugs that have been approved have been approved either for right after you fail methotrexate or for after you fail, for example, a TNF. Those are first-line settings, second-line settings, where your opportunity to have such a much better result than the available agents are actually fairly low. If you're a company targeting a first-line agent in RA or second-line agent in RA, you have a very long development path ahead of you because you have to demonstrate that you're better than other agents that work pretty well.

What we know from the literature and speaking with physicians and registries and a lot of the papers out there is by the time you have failed two distinct biologic or targeted synthetic DMARDs, your opportunity for a response is actually very low. You talk to a physician and you ask the question: what is the unmet need in RA? There are two different ways they look at it. As you know, Josh, a lot of times when patients come to a physician, they want to leave there with a script. If that is their objective, you can always give them a new drug that has been approved in RA because there's been many of them that have been approved.

But if you ask them the question, after a patient has failed two targeted classes, do you have high expectations that they'll respond to a third, a fourth, or fifth? They don't. That is exactly the population that we're going after. Now that we ran the phase II trial and we saw the pretty high ACR50 rates that we're seeing in this refractory population, we feel really convicted that if you are the first to get into that market targeting this refractory population, that you are addressing a big unmet need. The final thing I'll say is we're beginning to share more information on our specific patients that are being treated. For example, our very first patient, now we have more information about her background and lifestyle. This is a patient that has had RA for over a decade.

They have been on two or three different biologic or targeted synthetics. Leading up to our trial, this patient had 11 knee taps. Then they were on our drug, and as of the last update that we provided in April, they had not been on any drugs for 18 months. They were back riding their motorcycle, using their hands. It really is a big unmet need, but you have to ask the question: what do you do, physician, if your patient has already failed two distinct classes? What are your hopes of them getting a response? That's where drugs targeting refractory RA can have an impact.

Cyclophosphamide and fludarabine. We have to understand how this notion of separating cyclophosphamide and fludarabine from these regimens and talking about them in a vacuum first emerged, right? Because historically, what we do in biotech is clinical results come out, you look at the efficacy, you look at the side effects, and then you talk about the regimen. Here, because you have some therapies that use Cy/Flu, therapies that do not use Cy/Flu, we started asking people in industry and physicians, what are your thoughts on Cy/Flu? That is a difficult question to ask, because if you have the same exact efficacy and the same exact tolerability, but one product uses Cy/Flu, the other one does not, who is not going to want the product without Cy/Flu?