Phase 1 clinical trial of AAV cell therapy SC291 starts enrollment

GLEAM study recruiting patients in Colorado, Seattle

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A Phase 1 clinical trial evaluating the safety and preliminary efficacy of Sana Biotechnology’s candidate CAR T-cell therapy SC291 in adults with ANCA-associated vasculitis (AAV) and other autoimmune diseases has started enrollment.

The study, GLEAM (NCT06294236), is recruiting up to 36 patients ranging in age from 18 to 75 at the University of Colorado in Aurora, Colorado, and the Swedish Medical Center in Seattle, Washington.

Eligible AAV patients are those with hard-to-treat granulomatous polyangiitis or microscopic polyangiitis — the two most common AAV types — and have failed to respond to prior treatments. Patients with certain forms of lupus, another autoimmune disease, will also take part in the study.

Preliminary data are expected this year, Sana said in a company press release. “We have four ongoing clinical trials in seven indications, and we remain on track to share initial data from each of these studies in 2024,” said Steve Harr, MD, Sana’s president and CEO.

AAV refers to a group of autoimmune diseases marked by inflammation and damage to small blood vessels due to self-reacting antibodies that attack the body’s own cells. This blood vessel damage often causes kidney problems.

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AAV cell therapy collects T-cells to target B-cells

SC291 is designed to target and deplete B-cells, the immune cells responsible for the production of not only healthy antibodies that help the body fight invaders, but also self-reactive antibodies that drive autoimmune conditions.

CAR T-cell therapy involves the collection of T-cells, another type of immune cell, and their modification in the lab to carry a chimeric antigen receptor, or CAR. This receptor protein allows the cells to home in on and attack a specific target.

With SC291, the T-cells are collected from healthy donors and are modified to carry a CAR targeting CD19, a protein that’s found on the surface of B-cells. The cells are then infused back into patients where they are expected to target B-cells for destruction.

SC291 is designed to ease disease severity of AAV and other B-cell-mediated autoimmune diseases, such as lupus, which also can affect the kidneys.

To avoid immune responses against the delivered T-cells, which can be recognized by the patient’s immune system as foreign, the cells are designed using Sana’s hypoimmune platform, which the company says is meant to “hide” the CAR T-cells from the immune system.

Sana’s goal for the year is to gain a “better understanding our hypoimmune platform, its potential to treat a number of prevalent diseases, and the impacts of clinical data on our longer-term plans,” Harr said.

The main goal of GLEAM, announced in November 2023, is to evaluate the two-year safety and tolerability of a single dose of SC291, following a process called lymphodepletion, in which chemotherapy agents are given to wipe out a patient’s disease-causing immune cells.

Secondary goals include the therapy’s preliminary efficacy, evaluated through changes in kidney function, duration of disease remission without further treatment, and time to relapse.

In AAV patients, preliminary efficacy will also be assessed via changes in disease activity, as assessed with the Birmingham Vasculitis Activity Score (BVAS), and by the proportion of patients achieving disease remission, defined as a BVAS of zero.

The study is expected to end in 2028.