Antibody-Drug Conjugates Technology

Antibody-drug conjugates (ADCs) are one of the most actively pursued therapeutic classes in oncology due to their high specificity and potency. The conjugates have two components: an antibody allowing the delivery of drug to tumors in a highly targeted manner, and a potent cytotoxic agent to directly kill tumor cells. 

Despite the high degree of specificity and potency for ADCs, there are continued challenges that limit their success:

  1. Narrow therapeutic windows limit dose levels that can be delivered and often result in toxic effects prior to peak efficacious doses 
  2. Limited control over conjugation of the toxin can lead to heterogeneity which results in pharmacokinetic and efficacy issues that hinder clinical development
  3. Unstable linkers result in leakage of the toxin during circulation

SOTIO’s ADC platform, which is being developed in partnership with NBE-Therapeutics, is based on NBE’s proprietary site-specific sortase mediated antibody coupling (SMAC) conjugation platform. The ADCs utilize an anthracycline toxin called PNU, a highly potent cytotoxic agent derived from doxorubicin, that leads to immunogenic cell death and elicits a long-lasting immune response. 

SOTIO’s ADCs have been designed to address the limitations of current ADCs: 

  1. In preclinical studies, these have demonstrated a long half-life with a broad therapeutic window, resulting in efficacy at concentrations much lower than doses where toxicity is observed
  2. The SMAC conjugation platform creates homogenous ADCs that have a higher yield in the conjugation process and potentially higher efficacy
  3. The linker chemistry delivers a stable product, limiting toxin leakage during circulation