Immunosynthen is our proprietary immunostimulatory ADC platform designed to take ADCs beyond delivery of traditional cytotoxic drugs to immunomodulatory molecules that can stimulate an anti-tumor innate immune response. Through the safe and efficient delivery of immunomodulatory molecules, ADCs created with our Immunosynthen platform have the potential to address the challenges of systemic delivery and tolerability. The Immunosynthen platform utilizes a novel agonist of the Stimulator of Interferon Genes (STING), which has emerged as an innate immune pathway capable of inducing anti-tumor immune activity. Preclinical datashow that our STING agonist ADCs result in a greater than 100-fold increase in in vitro activity compared to a free agonist. In addition, treatment with our STING agonist ADCs resulted in complete regression of in vivo tumors after a single, well-tolerated dose in a variety of preclinical tumor models. Increased immune cell infiltration and cytokine expression profile within the tumor after dosing was also observed after treatment, consistent with the activation of STING. We expect to disclose our first Immunosynthen ADC development candidate and path forward in the second half of 2020.
ADCs are ideally suited to overcome the limitations of free STING agonists
- Systemic Administration with Targeted Delivery: ADCs have the convenience of systemic administration while providing targeted delivery specifically to the tumor, including metastatic lesions.
- Improved Therapeutic Index: Conjugation of the STING agonist provides protection in the systemic circulation to minimize off-target effects while simultaneously providing targeted delivery to maximize effects in the tumor and metastatic lesions.
- Enhanced Pharmacokinetic (PK) Properties: The prolonged PK of ADCs and active uptake through targeting can overcome PK and permeability issues of the free agonists, resulting in sustained delivery and activation of the innate immune response.