IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, today announced its progress in two Phase 1 clinical trials evaluating IGM-6268, an anti-SARS-CoV-2 IgM monoclonal antibody, for the treatment and prevention of COVID-19.
The first, a Phase 1 clinical trial in the U.S., is a multi-center, randomized, double-blinded, placebo-controlled single (SAD) and multiple (MAD) ascending dose study to assess the safety, tolerability, and pharmacokinetics of IGM-6268 administered intranasally in healthy volunteers. The first two dose cohorts of healthy volunteers have been successfully cleared in the U.S., and data from the study are expected in the first half of 2022.
The second, a Phase 1a/1b clinical trial in South Africa, is a multi-center, randomized, double-blinded, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of IGM-6268 administered intranasally first in healthy volunteers, once an appropriate dose cohort has been cleared, in outpatients with mild to moderate COVID-19. The first dose cohort of healthy volunteers has been cleared in the South Africa study, and data from the study are expected in mid-2022.
IGM today also announced that results from in vitro pseudovirus testing conducted by a widely recognized, commercial laboratory indicate that IGM-6268 exhibits neutralization of the Omicron (B.1.1.529) variant at an IC50 of 230 ng/mL, as well as potent in vitro neutralization activity against all other SARS-CoV-2 Variants of Concern (VoC) and Variants of Interest (VoI) tested to date, including the Delta variant. This indicated IC50 for the Omicron variant is expected to be well below the concentrations achievable by intranasal administration in key sites of infection and viral replication, based on previous observations from animal studies. These results expand upon data previously published in Nature, in which IGM-6268 exhibited significantly increased potency against wild type SARS-CoV-2 relative to an IgG antibody with the same binding domains and exhibited potent neutralization against the Alpha (B.1.1.7), Gamma (P.1), and Beta (B.1.351) variants, as well as other receptor-binding domain mutants that conferred resistance to several IgG antibodies authorized for emergency use.
“IgM antibodies are the first antibodies produced by the immune system when a virus attacks, and they demonstrate very high avidity, or overall binding strength, against the viral antigens they target,” said Chris Takimoto, MD, Ph.D., Chief Medical Officer of IGM Biosciences. “Our in vitro neutralization data suggest that engineered IgM antibodies, because of their inherently enhanced avidity and engineered specificity, offer resilience against the emergence of resistant variants of SARS-CoV-2, while demonstrating superior potency over an IgG antibody with the same binding domains.”
IGM-6268 is an engineered IgM antibody that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. This humanized pentameric IgM antibody has 10 binding sites to the spike protein. IGM-6268 is being developed as a treatment or prophylaxis for symptoms associated with mild to moderate COVID-19 with administration by intranasal plus intraoral spray once for 1 day (SAD), or once or twice each day for 5 days (MAD). The primary mechanism of action of IGM-6268 is to block the binding of the SARS-CoV-2 RBD on the spike protein to human angiotensin converting enzyme 2 (hACE2), the cellular receptor for SARS-CoV-2. By blocking this binding, IGM-6268 neutralizes the infectivity of the virus. In preclinical studies, IGM-6268 has been shown to be highly effective in preventing and treating COVID-19 after intranasal administration. Due to its ability to bind to SARS-CoV-2 with greater strength, IGM-6268 offers advantages over an IgG antibody with the same binding domains, including 50-500x greater neutralizing potency against wildtype virus and greater ability to effectively neutralize certain Variants of Concern and Variants of Interest, such as the Delta and Omicron variants, as compared with an IgG antibody with the same binding domains.