Synlogic and Roche Partner to Evaluate Synthetic Biotic SYNB1891 in Combination with PD-L1 Inhibitor Tecentriq for Advanced Solid Tumors

Recently, Synlogic, a synthetic biology company co-founded by renowned scholar Professor Lu Guanda, announced a clinical development collaboration with Roche. The partnership aims to explore the efficacy of combining SYNB1891, developed by Synlogic, with Roche’s PD-L1 inhibitor Tecentriq (atezolizumab) for the treatment of patients with advanced solid tumors. SYNB1891 is a dual innate immune agonist designed using synthetic biology technologies. Synlogic plans to submit an Investigational New Drug (IND) application to the U.S. FDA in the second half of 2019, enabling the company to conduct open-label Phase 1 clinical trials to evaluate SYNB1891 both as a monotherapy and in combination with atezolizumab.

A hallmark of tumors is their ability to employ multiple mechanisms to suppress or evade immune responses. Although immune checkpoint inhibitors have demonstrated remarkable efficacy in certain cancer types, a substantial proportion of patients do not respond to these therapies. Research has shown that simultaneous activation of both the innate and adaptive components of the immune system is crucial for generating an effective anti-tumor immune response.

SYNB1891 is a non-pathogenic Escherichia coli strain engineered using synthetic biology technologies to express a STING agonist, thereby activating the innate immune system. Upon phagocytosis by antigen-presenting cells, the intracellular STING signaling pathway is activated, inducing a type I interferon (IFN) response and initiating and promoting tumor-specific T cell responses.

Moreover, the bacterial shell of SYNB1891 can activate the innate immune system through other mechanisms, including binding to Toll-like receptors. This may further enhance the overall intensity of the immune response. In combination with atezolizumab, SYNB1891 has the potential to simultaneously activate both the innate and adaptive immune systems, thereby promoting tumor shrinkage.

Following IND approval, Synlogic plans to conduct an open-label, multicenter Phase 1 clinical trial to administer SYNB1891 via intratumoral injection in patients with advanced/metastatic solid tumors. The primary objectives of this trial are to evaluate the safety and tolerability of SYNB1891, determine the maximum tolerated dose (MTD) as monotherapy, and establish the recommended Phase 2 dose (RP2D) when used in combination with atezolizumab. Additionally, the study will explore efficacy endpoints, including immune biomarkers and objective response rate (ORR). Synlogic will lead the clinical study, while Roche will provide the clinical supply of atezolizumab.

“This collaboration represents a significant step toward advancing SYNB1891 as a potential therapy for refractory tumors, enabling us to leverage atezolizumab, a key immune checkpoint inhibitor,” said Aoife Brennan, President and Chief Executive Officer of Synlogic. “We believe SYNB1891 offers a novel approach to combating cancer, with the potential to enhance the efficacy of immune checkpoint inhibitors when used in combination.”

References:

[1] Synlogic Announces Clinical Collaboration to Evaluate SYNB1891 in Combination with PD-L1 Checkpoint Inhibitor in Patients with Advanced Solid Tumors. Retrieved May 22, 2019, from https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-clinical-collaboration-evaluate-synb1891

[2] Synlogic. Retrieved May 22, 2019, from https://www.synlogictx.com/

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