EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate

Area of Science:

• Oncology
• Molecular Biology
• Drug Development

Background:

• MYC is a critical therapeutic target in human cancers, but direct inhibitors have been challenging to develop.
• Omomyc, a tissue-penetrating peptide MYC inhibitor, has shown safety and preliminary clinical activity in Phase I trials for solid tumors.
• Improving targeted delivery of MYC inhibitors could enhance their therapeutic potential in specific cancer subtypes.

Purpose of the Study:

• To investigate the potential of enhancing Omomyc's cancer targeting by conjugating it to a therapeutic antibody.
• To develop and evaluate an immunoconjugate, EV20/Omomyc, for targeted delivery of Omomyc to cancer cells.

Main Methods:

• Development of EV20/Omomyc by linking a humanized anti-HER3 antibody (EV20) to the Omomyc peptide via a bifunctional linker.
• Assessment of antigen-dependent penetration and therapeutic efficacy of EV20/Omomyc in preclinical models, specifically a metastatic neuroblastoma model.

Main Results:

• EV20/Omomyc demonstrated antigen-dependent penetration, indicating targeted delivery.
• The immunoconjugate exhibited therapeutic efficacy in a metastatic neuroblastoma model.
• This approach suggests potential for improved therapeutic activity in specific cancer indications.

Conclusions:

• Targeting Omomyc to specific cancer cells using antibody conjugates, such as EV20/Omomyc, can improve its therapeutic efficacy.
• This strategy holds promise for treating specific cancer subtypes, including pediatric cancers.
• Further development of antibody-drug conjugates for MYC inhibition warrants investigation.