Translating AlloNK Efficacy Across Autoimmune Diseases

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: Given the different underlying disease mechanisms in autoimmune diseases, what specific data points are you prioritizing to demonstrate that results from these trials will translate to similar efficacy across a range of autoimmune conditions?
Fred Aslan: One of the things that iscompelling about this academic study isthat the investigator didn't just treat patients with lupus, he treated patients with lupus with-and-without lupus nephritis, along with patients with myositis or scleroderma. Since then, there's been other conditions that have also been investigated by this academic group. What’s remarkable about that initial readout is this notion that a deep B-cell depletion could actually be transformational in patients across multiple different conditions, which is something that was interesting and not seen before.

Now the challenge (and good news) for the industryis that there arethese indications that one can interrogate and pursue. The one commonality across all these diseases, which we believe is the mechanism of action of how these therapies are working, is the depletion ofthe B-cells. When these cells reconstitute, they do so with a naïve phenotype.

When investigating different autoimmune diseases, they each have their own specific endpoints. The standard of care for each of these diseases is different. You must do a disease-by-disease evaluation specifically looking for those endpoints (particularly ones that are accepted by FDA and industry as most relevant) to measure the efficacy of the product and its clinical impact on the patient. Safety is something that you can look at across all the different diseases; the safer your product is, the more accessible it’ll be for a variety of different patients.

Finally, in some indications, patientsare more exposed to drugs, like steroids, that can have negative consequences more so than other indications. Seeing the degree of medication reduction in different specific indications is also important. Looking at it from an indication-to-indication basis is going to give bigger hints that it is active. The goal that we're trying to see is if this mechanism can be as broadly applicable as shown in the academic study and that as drugs start moving through development and into the market, we will see a variety of those drugs being used across different indications.