Artiva Biotherapeutics, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Yeah. Thanks, Emily, for having us. Artiva is a phase III company pursuing refractory RA. As you mentioned, we are one of the companies that is pursuing the very exciting mechanism of deep B-cell depletion. We have differentiated ourselves by actually pursuing refractory rheumatoid arthritis as our lead indication, and if we are successful, based on the current competitive landscape, we should be the first of any deep B-cell depleting product to actually get to market if we are successful. And probably the very first approval in RA since 2019 when RINVOQ was approved. We will come back to the RA market in a little bit and explain why it is so compelling. Artiva uses NK cells to actually kill the B cells. So unlike auto CAR T, allo CAR T-cell engagers in vivo, we do not use T cells to actually do the killing, we use NK cells.

We do not engineer our NK cells, and there is a number of advantages of not engineering them. But because we do not engineer them with a CAR, we actually use a monoclonal antibody as part of our regimen. So a monoclonal antibody binds to the B cell, and then the Fc portion of the monoclonal activates our NK cells, which then does the killing. So we have been running a phase II trial, a basket study that includes RA as well as Sjögren's, scleroderma, and myositis, and after a recent meeting with the FDA, we aligned on a registrational single phase III trial. We raised $300 million of capital, which takes us through the end of the phase III trial into 2029. And we are located in San Diego.

Yeah. That's a natural question because rituximab is part of our regimen, right? People always want to know, what are you doing above and beyond what rituximab does? Now that we have phase II results with really encouraging results, high degrees of responses, significant decreases in disease activity across the board, it's pretty clear that the level of activity that we're having is above and beyond rituximab. But there's more ways in which we can describe that. The first way is the mechanism that we're going after is deep B-cell depletion. We utilize an assay, it's currently available, but very few companies have reported using that assay. But it's an assay that actually detects B cells in the periphery with a limit of detection of 0.1 to 0.2 cells per microliter. Most of the B-cell depletion charts that everybody shows has a 5 to 10.

If you look at rituximab specifically with assays that are that sensitive, one realizes that the average patient on rituximab still has B cells after they are treated with rituximab. Whereas in our patients, we showed a series of all of our RA patients, not a single one had detectable B cells using that assay. So that, combined with the efficacy that we have already seen so far, I think is pretty strong evidence that it works significantly better than rituximab. The final piece of evidence that we're going to be generating is our phase III trial is actually a randomized control trial against rituximab.

One of the reasons we did choose to do a randomized control trial as opposed to an open label study is because if we were to come out with a very strong degree of efficacy, specifically ACR50, which is our regulatory endpoint, people would always ask that question, I wonder what rituximab would do in that population. By running a randomized control trial against rituximab, then we will have very clear evidence of what we do above and beyond rituximab, assuming we're successful.

Yeah. One of the biggest advantages of NK cells, I would say it's the biggest advantage of NK cells and why they matter, is because whether you're talking about auto CAR T, Allo CAR T, TCEs, or in vivo CAR T, these all use T cells, and these all rely on T cells expanding in order to actually kill the B cells. When T cells expand, they cause cytokine release syndrome, CRS, they cause ICANS. We've recently seen with auto CAR T that there's other syndromes that they can also cause. AlloNK, our NK cells do not cause CRS, they do not cause ICANS. Because of that, it has a safety profile that's very differentiated compared to the T-cell approaches. We have actually treated the vast majority of our patients in a community setting. A community setting is not the Outpatient infusion clinic at Harvard.

It's a community rheumatology practice where there's only one or two practitioners, and he or she is utilizing his or her infusion chair to treat the patients, and then the patients are going home. This tolerability profile really differentiates NK cells from T cells. Now, the one drawback of NK cells is that because they don't expand, you have to give very high doses. We, for example, give 8 billion NK cells as part of our regimen compared to something like 60 million T cells, which is the regular regimen that's given. Thankfully, we have a highly scalable manufacturing process, and because we don't engineer our NK cells, we're actually able to manufacture our cells in a way that the COGS look a lot more like a biologic than they do to traditional cell therapy.

This is the one thing that I feel like investors a lot of times don't appreciate with regards to our cells is the way you would use our cells in a community practice is you pretty much get a kit as part of the clinical trial. You get our cells in a Dewar, which you thaw by the bedside, and then you connect it straight to the IV. There's no specialized pharmacy. You receive the cyclophosphamide and fludarabine in an IV bag that, again, goes straight into the IV that you're administering, and then you use rituximab the way these clinics use rituximab. There is no specialized pharmacy, no liquid nitrogen, no need for complex monitoring. It really is as simple as cell therapy gets when you compare it to a biologic.

Yeah. We shared data on 21 patients that had 12 or more weeks of follow-up, and we honed in on the ones that had six months because ACR50 at six months is our regulatory endpoint. What we were able to show is that across the board, for the vast majority of the patients, we were causing clinically significant disease activity reduction and specifically the ACR50. Out of the seven patients that were ACR50 evaluable, five out of the seven achieved an ACR50, which mathematically is 71%, but those are small numbers. Our bogey, the target that we are going after, is actually achieving a 50% or higher ACR50 compared to approximately 20% for rituximab. We would like to show as part of the RCT that we can, in a way, double what the response is that rituximab offers.

Rituximab, as some people may know, you are retreated every six months with rituximab, which means you keep the B cells low for this entire period. When that happens, the patient is relatively immunocompromised compared to somebody whose B cells recover. In our case, the B cells are able to recover. They recover with a naive phenotype, and then the patient is off any other biologic or targeted synthetic, potentially giving the patient an opportunity to be less at risk of infection than if they were on any other chronic therapy.