GL-0719 is a recombinant Fc fusion protein designed to selectively inhibit the classical and lectin complement pathways, leaving the alternative pathway intact, which it does through a novel mechanism of action that may lead to much lower dose requirements compared with monoclonal antibodies. In addition to inhibiting two complement pathways, GL-0719 also increases the generation of anti-inflammatory blood factors.

Because GL-0719 works upstream in the complement pathway, it is expected to be useful not only in classical or lectin pathway diseases that form downstream membrane attack complex (MAC) but also in diseases where the opsonins C4b, C3b, C1q, and iC3b target cells for destruction by phagocytosis.

In a publication by Sun et al (J Autoimmunity, 2017), G211 (GL-0719) demonstrated efficacy in the prevention and/or treatment of three distinct disease models in rats whose pathophysiology is dependent on aberrant complement activation:

  • Wistar rat acute intravascular hemolysis model
  • Anti-THY-1 glomerulonephritis treatment model
  • Passive Heymann nephritis (both prophylaxis and treatment models)

The combination of biologic activities exhibited by GL-0719 provides development opportunities in a broad range of complement-associated diseases in hematologic, neurologic and renal indications.

The pharmacological, pharmacokinetic, and toxicological profiles of GL-0719 have been characterized in a variety of in vitro studies and in vivo studies. GL-0719 is being dosed in a phase 1 study in healthy participants to assess safety, tolerability, pharmacokinetics, and pharmacodynamics (NCT05318534). We are striving for GL-0719 to deliver targeted inhibition of complement at small, convenient, subcutaneous doses for the treatment of an array of complement-mediated diseases.

If successfully commercialized, GL-0719 could be well positioned to offer a patient-friendly combination of specific complement inhibition and dosing convenience.