Biomarker Discovery Programme of OMO-103, a First-in-modality MYC Inhibitor - Biognosys

Biomarker Discovery Programme of OMO-103, a First-in-modality MYC Inhibitor

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Biomarker Discovery Programme of OMO-103, a First-in-modality MYC Inhibitor

Sandra Martínez-Martín, Phd (Peptomyc)

The MYC family of oncoproteins is deregulated in up to 70% of human cancers through various mechanisms, functioning as master modulators of the cancer transcriptome. Despite the broad therapeutic utility anticipated for a clinical MYC inhibitor, MYC remains considered undruggable, and no direct MYC inhibitor has been approved for clinical use.

Omomyc is a first-in-modality recombinant mini-protein that completed a Phase I clinical trial in October 2022, demonstrating excellent safety and target engagement. Omomyc acts as a MYC dominant-negative, sequestering MYC away from its target genes on DNA.

Here, we describe the transcriptional reprogramming exerted by Omomyc supporting target engagement in preclinical models of various solid tumours, suggesting its applicability in multiple oncological indications. Importantly, to characterise the PK/PD relationship, we quantified the amount of functional Omomyc present in tumour tissue and serum of treated mice using a targeted proteomic approach and observed that 2h after intravenous administration, the drug reached higher concentrations in the tumours compared to serum, and persisted there at higher levels at least for 72h after dosing. Notably, we confirmed the presence of Omomyc in the biopsies from the first-in-human MYCure trial.

Our results show evidence of the long-lasting half-life of functional Omomyc in patient-derived tumour tissues, suggestive of a different PK profile between serum and tissue. We also demonstrate in vivo target engagement and the therapeutic utility of this pan-MYC inhibitor in lung, colon and breast cancer models.

Short Bio Sandra Martínez-Martín:

 

Dr. Martínez-Martín graduated in Health Biology (Universidad de Alcalá, 2014) and obtained a Master’s degree in Biomedicine (Universidad Autónoma de Madrid, 2015). She has a PhD in Biochemistry, Molecular Biology and Biomedicine (Universidad Autónoma de Barcelona, 2020) and a course in Health and Biotech Project Management (LaSalle, 2022). Her PhD project opened a completely new research line for Dr. Soucek’s laboratory, focused on studying the effect of different MYC inhibitors, including Omomyc, for the treatment of multiple myeloma and Burkitt lymphoma. She has co-authored seven peer-reviewed publications, two of which were as a first author. As Peptomyc’s Biomarker Project Manager, Sandra has assisted with the coordination and performance of the activities aimed at discovering pharmacodynamic biomarkers in response to Omomyc treatment, both preclinically and clinically, since 2020, when she first joined the company. More recently, she has also been involved in the pipeline expansion project to develop new MYC inhibitors based on Omomyc.

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