Lamassu Biotech has announced initial safety and pharmacokinetic data from the ongoing first-in-human phase 1/2a clinical trial (LB-SA53-101) of SA53, an oral MDM2 inhibitor, at the European Society for Medical Oncology (ESMO) Congress 2026.
Across four single-patient dose-escalation cohorts (0.054 to 0.44 mg/kg/day on a 3-day dosing schedule), SA53 produced no dose-limiting toxicities (DLTs) and no Grade ≥2 treatment-emergent adverse events. MDM2 inhibition showed antitumour activity by restoring the body’s natural p53 tumour-suppression pathway. Earlier MDM2 inhibitors have been limited by severe, dose-dependent hematologic toxicities, most notably thrombocytopenia. In this initial dose escalation, SA53 has reached plasma exposures predicted by nonclinical modelling to be pharmacologically active without dose-limiting toxicity.
The findings were presented in Madrid by Peter Anderson, an investigator on the trial at Cleveland Clinic.
There were no DLTs, no grade ≥2 treatment-emergent adverse events, and no serious adverse events (SAEs) through 0.44 mg/kg/day.
Platelet nadirs were grade 1 or lower, and neutrophil counts remained within normal limits in all patients. Cmax increased approximately dose-proportionally across cohorts, and plasma exposures at the current dose level exceeded those predicted by nonclinical PK/PD modelling to be pharmacologically active.
“Targeting the MDM2-p53 interaction has long held therapeutic promise, but drug development across this class has historically been limited by severe systemic toxicities,” said Greg Palmer, co-founder and chief scientific officer of Lamassu Biotech.
“Our initial data shows that SA53 has reached exposures predicted to be pharmacologically active without dose-limiting toxicities. These early results support continued dose escalation toward defining the recommended phase 2 dose.”
SA53 is an investigational oral small molecule designed to selectively inhibit MDM2, thereby reactivating the wild-type p53 tumour suppressor protein, often termed the “Guardian of the Genome.” Functional, wild-type p53 is preserved in roughly half of human cancers. An MDM2 inhibitor that avoids the historical serious class toxicities could offer therapeutic utility across a broad cancer patient population.
The phase 1 dose-escalation portion of the multicentre phase 1/2a study remains ongoing. It aims to establish the maximum tolerated dose and recommended phase 2 dose (RP2D) and to further characterise preliminary single-agent antitumour activity. Patient screening and enrolment are active.