Stingthera Announces Clinical Collaboration With Merck to Evaluate SNX281 in Combination With KEYTRUDA in Certain Patients With Advanced Solid Tumors & Lymphoma

Stingthera, Inc. recently announced it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the US and Canada) to evaluate the combination of SNX281, Stingthera’s investigational small molecule activator of the Stimulator of Interferon Genes (STING) protein, and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced solid tumors and lymphoma who have relapsed on or have become refractory to prior immune checkpoint therapy.

Under the terms of the agreement, Stingthera is responsible for conducting the clinical trial, which was initiated with the SNX281 monotherapy arm in late November 2020.

The Phase 1 open-label, multi-center, multi-dose clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SNX281 as a monotherapy and in combination with KEYTRUDA, Merck’s anti-PD-1 (anti-programmed death receptor-1) therapy, in patients with advanced solid tumors and lymphoma who have relapsed on or have become refractory to prior immune checkpoint therapy. After determination of the optimal dose of SNX281 as a single-agent and in combination with KEYTRUDA, expansion cohorts to further evaluate safety and efficacy in specific populations will be examined. This includes colorectal and ovarian cancer in the monotherapy arm and refractory or relapsed tumors on checkpoint inhibitors in the combination arm. For more information about the SNX281 clinical trial (NCT04609579), please visit: https://clinicaltrials.gov.

“We are pleased to collaborate with Merck to evaluate SNX281 in combination with KEYTRUDA as treatment for people with solid tumors or lymphoma who have relapsed on or have become refractory to prior immune checkpoint therapy, as these are patients for which there are limited treatment options available and their overall survival remains low,” said Humphrey Gardner, MD, FCAP, Chief Medical Officer, Stingthera. “We look forward to further evaluating the potential clinical utility of this combination, in an effort to improve outcomes for patients with a number of different cancers.”

Activation of STING provides two critical anti-tumor responses: the “spark” for initiating a robust innate immune response as well as the priming and induction of a robust tumor directed T cell response, providing sustained antitumor immunity. First generation clinical compounds are structural mimetics of endogenous cyclic dinucleotides (CDNs) STING agonists and cannot be delivered systemically, thus limiting use to local delivery via intra-tumoral injection.

SNX281 is a unique, small molecule STING agonist with drug properties permitting intravenous delivery, immunoactivation and antineoplastic activities, and displays antitumor efficacy in patients following systemic administration. The compound was discovered using the molecular design and computational physics platform at Silicon Therapeutics.

SNX281 is potent, specific and active against all prevalent human isoforms of STING, rapidly activating downstream signaling and induction type I interferon (IFN). Treatment of primary immune cells from human donors results in the maturation and activation of antigen presenting cells. In vivo, SNX281 stimulates cross-presentation, antigen-specific T cell response and rapid multi-lineage anti-tumor immunity.

In preclinical disease models, treatment with SNX281 results in complete regression of tumors in mice harboring colorectal tumors (CT26) with a single intravenous dose. This anti-tumor activity was shown to be immune-mediated, as it did not occur in immunocompromised mice. Further, the combination of an anti-PD-1 antibody with SNX281 demonstrated both enhanced anti-tumor activity as well as increased survival in a variety of additional tumor models. SNX281 drug characteristics and STING pharmacology allow for a unique dosing paradigm with robust tumor regression after a short duration of exposure, and durable anti-tumor immunity.

Located in Boston, Stingthera, Inc. is a new independent, privately-held biotechnology company focused on the development of small molecule Stimulator of Interferon Genes (STING) compounds for the treatment of cancer. The company’s lead program SNX281 is a highly differentiated STING agonist for the treatment of cancer. SNX281 was discovered using the molecular design and computational physics platforms at Silicon Therapeutics and is wholly owned by Stingthera.