Immune Reset in SLE/LN: Data and Trial Assessments

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: What preclinical or early clinical data supports the concept of an 'immune reset' in SLE/LN, and what are you tracking in trials to assess the potential for achieving this?
Fred Aslan: An immune reset was first described as part of a German academic study that was utilizing auto CAR-T in patients with autoimmune disease. The hypothesis that was put forth in the paper is that utilizing a cell therapy to very deeply deplete the B-cells that a patient has eliminates all the existing B-cells and forces the patient’s body to reconstitute new ones. What they saw is that when those B-cells came back, they were what the author called “naive B-cells.” Think about them as the B-cells that you are born with. Individuals are generally born with naïve, healthy B-cells. However, individuals who develop autoimmune disease end up developing these pathological B-cells that can produce auto antibodies, and that ends up leading to a lot of the negative consequences of autoimmune disease.

The immune reset is this notion of eliminating all the existing B-cells so that they can reconstitute with naive cells. How do we measure that? First, we determine if there’s a clinical benefit in patients. What was remarkable about the academic study was the notion that by deeply depleting the B-cells, you could drive to a state of having drug free disease remission. Not only were they able to improve the clinical symptoms dramatically, but they were able to take the individuals off steroids and other medications, which oftentimes is what actually causes a lot of the negative consequences of having autoimmune disease. Patients have two things working against them: the disease itself, but also the medicine, including steroids, to treat the autoimmune disease. If you take them chronically, it can be a problem.

You’re looking for both clinical benefit and a number of serological markers. For example, you can look for double stranded DNA in lupus patients actually going down, complement levels going up, and the B-cells reconstituting with a naive phenotype. There's a number of clinical and biomarkers that you would look for to feel confident that you addressed the patient's pathology and drove them into a remission—hopefully in a state where they don't have to take all the medications that they were taking prior to receiving the therapy.