ISH0339, a tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life.

ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile.

ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs.

Pharmacokinetic analysis of ISH0339

An indirect antigen ELISA assay was used for the detection of ISH0339 in rat serum (Medicilon).

Pharmacokinetic analysis of single-dose ISH0339 administration was conducted by Medicilon.

Extended toxicity study of single-dose ISH0339 was conducted by Medicilon.

Reference:

Huabing Yang, et al. Preclinical evaluation of ISH0339, a tetravalent broadly neutralizing bispecific antibody against SARS-CoV-2 with long-term protection. Antib Ther. 2023 Mar 6;6(2):97-107. doi: 10.1093/abt/tbad003.