AER Antibody

AER-37 (CRA1)

• Target: Fc epsilon RI alpha subunit, a component of the high-affinity IgE receptor on mast cells and basophils .

• Function: Binds IgE-binding sites without blocking IgE interaction, enabling flow cytometry and functional assays (e.g., basophil migration studies) .

• Applications:

  • Flow cytometric analysis of peripheral blood cells (≤1 µg/test) .

  • Studying allergic responses triggered by IgE-mediated activation .

AER001 and AER002

• Target: SARS-CoV-2 spike protein receptor-binding domain (RBD) .

• Mechanism:

  • AER001: Class 1 mAb blocking ACE2 binding, neutralizing early variants (Alpha, Beta, Delta, Omicron BA.1/BA.2) .

  • AER002: Class 3 mAb binding non-overlapping epitopes, effective against Omicron BA.1–BA.5 .

• Clinical Data:

  • Phase I trial (N=42) showed 105- and 97.5-day half-lives for AER001 and AER002, respectively .

  • Nasal mucosa transudation reached ~2.5–2.7% of serum levels, critical for pre-exposure prophylaxis .

AER-051 (Anti-EMR1)

• Target: EMR1 (ADGRE1), a marker of mature eosinophils .

• Applications:

  • Western blot and live-cell imaging of eosinophils in allergic disorders .

  • Species reactivity: Human, mouse, rat .

AER-001 (Anti-Endothelin Receptor A)

• Target: Endothelin receptor A (ET-A), implicated in cardiovascular and cancer pathways .

• Applications:

  • Detecting ET-A in rat brain, lung, and cerebellum via immunohistochemistry .

  • Studying ET-A’s role in hypertension and tumor angiogenesis .

AER005 and AER800

• Target: SARS-CoV-2 variants, including EG.5.1 (AER005) .

• Development:

  • AER800: Combination of AER003 and AER004, covering >90% of RBD’s ACE2-binding site .

  • Engineered with LS mutations for extended half-life .

Comparative Analysis of AER Antibodies

Mechanistic Insights and Innovations

• Half-Life Extension: AER001/AER002 incorporate LS mutations (Met428Leu/Asn434Ser) in the Fc region, extending half-life to >90 days .

• Epitope Engineering: AER005 targets a conserved region outside RBD, resisting viral escape .

• Multispecific Formats: AER800 combines two mAbs for broader variant coverage .

Clinical and Research Implications

• COVID-19 Prophylaxis: AER001/AER002 achieved 15–26x higher neutralization than placebo in Phase I, highlighting potential for immunocompromised populations .

• Allergy and Cancer: AER-37 and AER-001 enable mechanistic studies of IgE-mediated inflammation and ET-A-driven malignancies .

• Data Integration: Initiatives like the AIRR Data Commons (9.8 billion sequences) support antibody discovery, including AER variants .

Challenges and Future Directions

• Variant Resistance: AER001/AER002 lose efficacy against later Omicron subvariants (e.g., BQ.1.1, XBB.1) .

• Delivery Optimization: siRNA conjugates (e.g., DVD-ARC) may enhance AER antibody potency in non-liver tissues .

• Commercialization: Aerium Therapeutics advancing AER800/AER005 toward IND-enabling studies .