Electra Therapeutics starts Phase 1 of SIRPγ antibody ELA822
Electra Therapeutics has dosed the first participants in a Phase 1 clinical trial of ELA822, a fully human IgG1κ monoclonal antibody designed to bind selectively to SIRPγ, a cell surface receptor expressed predominantly on T cells. The South San Francisco company said the study is a randomised, placebo-controlled, single-ascending-dose trial in healthy volunteers, evaluating safety, tolerability, pharmacokinetics and pharmacodynamics.
ELA822 is the second development candidate from Electra's proprietary SIRP-targeted antibody library to enter human studies. The company's lead programme, ipsoprubart (ELA026), is a pan-SIRP monoclonal antibody currently in a global registrational programme for secondary haemophagocytic lymphohistiocytosis (sHLH), a severe and often fatal hyperinflammatory syndrome with no broadly approved therapies.
The science
Signal regulatory proteins (SIRPs) are a family of cell surface receptors whose expression increases upon immune cell activation, making them an attractive target for precision immune depletion. ELA822 is designed to engage only SIRPγ, with no binding to SIRPα or SIRPβ1. Because SIRPγ is expressed at high levels on activated, pathogenic T cells but at lower levels on naïve and regulatory T cells, the antibody is intended to selectively eliminate disease-driving cells while leaving protective immune populations intact.
Graham Parry, Chief Scientific Officer at Electra, noted that selective targeting of individual SIRP members has historically proved difficult, partly because SIRPγ is expressed only in primates, which constrains standard preclinical model development. Electra said it built humanised model systems to address this limitation; in those systems, ELA822 demonstrated selective depletion of activated T cells in vitro and showed activity in humanised mouse models of T cell-driven disease in vivo. In nonclinical models of giant cell arteritis and graft-versus-host disease, the antibody reduced activated T cell infiltration and inflammatory cytokine expression and was associated with improvements in disease activity measures and survival. Non-human primate tolerability studies were also described as acceptable.
Chief Medical Officer Kim-Hien Dao said the approach is designed to address a core limitation of existing treatments for chronic T cell-mediated conditions. Many current immunosuppressive therapies broadly deplete or suppress immune cells, which can create safety and tolerability problems that restrict long-term use. A more selective mechanism could, in principle, offer durable disease control without the same cumulative risk profile, though this remains to be demonstrated in human trials.
Market context
Chronic inflammatory diseases driven by T cell dysregulation, including conditions such as giant cell arteritis, graft-versus-host disease, inflammatory bowel disease and various autoimmune disorders, represent a substantial commercial opportunity that has attracted significant pharmaceutical and biotech investment. Established biologics targeting cytokines such as IL-6, TNF and IL-17 dominate current treatment algorithms, but many patients experience incomplete responses or are unable to tolerate long-term broad immunosuppression.
Precision immune cell depletion, aimed at removing only the cells responsible for pathological inflammation, is an emerging strategy with several companies pursuing different mechanistic angles. Targeting surface receptors that are upregulated specifically on activated immune populations, as Electra is doing with the SIRP family, is a relatively novel approach. The company's ability to differentiate antibody selectivity across SIRP members, from the pan-SIRP profile of ipsoprubart to the SIRPγ specificity of ELA822, gives it a modular platform that could address multiple disease contexts with different selectivity requirements.
Investors will be watching for pharmacodynamic readouts from the Phase 1 study, particularly evidence of selective T cell depletion in humans, as the first clinical proof of concept for the SIRPγ mechanism. The company has not disclosed timelines for progressing to patient cohorts or named the specific indications it intends to pursue initially in Phase 2 development.