The American Association for Cancer Research (AACR) annual meeting kicked off (virtually) this past weekend. On the first morning of the meeting, the synthetic biology company Synlogic presented data from the clinical trial testing their immunotherapy drug SYNB1891. The drug, a living biotherapeutic consisting of engineered bacteria that are injected intratumorally, is being developed for the treatment of solid tumors and lymphoma.

The synthetic biotic SYNB1891, being evaluated in an ongoing Phase I clinical trial (NCT04167137), is composed of an engineered strain of E. coli Nissle that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an antitumor immune response via activation of APCs and presentation of tumor antigens. The bacterial chassis of SYNB1891 also stimulates the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response. While SYNB1891 has been engineered with safety features that are designed to prevent its replication unless supplemented with specific nutrients, the bacteria remain active for several days within the injected tumor to stimulate a local immune response. Preclinical data were released last year.

Aoife Brennan
Aoife Brennan, CEO of Synlogic

The findings presented at the meeting included that SYNB1891 is safe and well-tolerated as an intratumoral injection in a heterogenous population. Also, there were no dose-limiting toxicities or SYNB1891-related infections. The dose levels through 10,000,000 live cells demonstrated target engagement as assessed by dose-dependent increases in serum cytokines, upregulation of ISGs, and presence of tumor infiltrating lymphocytes. And, evidence of durable stable disease was seen in two patients and was associated with upregulation genes tied to immune activation and increased intratumoral lymphocytes.

The presentation at AACR, “Intratumoral injection of SYNB1891, a synthetic biotic designed to activate the innate immune system, demonstrates target engagement in humans including intratumoral STING activation,” was delivered by Filip Janku, MD, PhD, associate professor, department of investigational cancer therapeutics, division of cancer medicine at the University of Texas MD Anderson Cancer Center.

These data support continued dose escalation in the monotherapy and combination arms. The combination arm of the study combines escalating dose levels of SYNB1891 with a fixed dose of a PD-L1 checkpoint inhibitor antibody to establish a recommended Phase II dose for the combination regimen. Data from both arms will continue to be reported over the course of 2021, with mature combination therapy data expected by the end of the year.