Artiva's Autoimmunity Trials

In this Pharmaceutical Executive video interview, Fred Aslan, MD, CEO, Artiva Biotherapeutics, discusses the company’s current trials for autoimmune indications in the US. The first is a company-sponsored trial focusing on lupus, while the second is an investigator-initiated trial exploring four conditions: lupus, rheumatoid arthritis, pemphigus vulgaris, and vasculitis. This second trial is uniquely being conducted in a community setting to assess the practicality of outpatient treatment.

Pharmaceutical Executive: Artiva Biotherapeutics currently has two ongoing trials for autoimmunity indications in the US. Can you tell me about them?
Fred Aslan: At the moment, we are running two trials in the US. One trial is a company sponsored trial where we are treating patients that have lupus, with-or-without lupus nephritis. Some of the original data of utilizing cell therapy in autoimmune disease was done with patients specifically with lupus nephritis, as well as lupus more broadly. We felt that was a good place to start to understand and evaluate the efficacy of our NK cell therapy in the same populations that were treated with auto CAR-T that was part of the academic study.

The second study is an investigator-initiated trial which is exploring patients with four different autoimmune diseases, including lupus (with-or-without lupus nephritis), rheumatoid arthritis, pemphigus vulgaris, and vasculitis. While the company sponsored trial is mostly being done initially in academic sites, we are running this investigator-initiated trial in a community setting. This way, we can test the feasibility of a community rheumatologist treating patients with our product in their infusion chair, and then managing those patients on an outpatient basis as they are evaluated for the benefits of the drug.

PE: Can you elaborate on the specific mechanisms by which AlloNK differs from traditional B-cell depletion strategies?
Aslan: What I would call the traditional B-cell depletion strategies are actually monoclonal antibodies. The first monoclonal antibody to specifically deplete an antigen on a B-cell was rituximab. Since then, we've seen other monoclonals come into the space. Very recently, there's been a lot of excitement around obinutuzumab or Gazyva in patients with autoimmune diseases. When we look at the available clinical data utilizing cell therapy, the mechanism that those cells utilize to actually kill B-cells is a cytotoxic cell, and it is engineered with a chimeric antigen receptor (CAR). This allows the cell to find the antigen that it's interested in. When it does, it activates the cell and kills the B-cell. You can think about those two approaches, the traditional one and an engineered cell therapy product, as almost being like two separate extremes. We're somewhere in the middle.

It is very well understood that when you're using a monoclonal antibody to kill B-cells, the monoclonal antibody binds to the B-cells, but it needs to be binding on the opposite end to an NK cell so that the NK cell can be activated. It's the NK cell that actually kills the B-cell. Even monoclonal antibodies utilize NK cells to do the B-cell depletion. Our hypothesis for AlloNK is that our endogenous NK cells are just not around in sufficient numbers or with sufficient activity to really drive the activity of the monoclonal antibodies. Our cell therapy involves a two-step process. First, we will give a traditional monoclonal antibody. Then we give high doses of active, allogeneic NK cells. This allows the monoclonal antibodies to bind to the B-cell to drive up the cytotoxicity that those B-cells will experience.