SYNB1891 / Synlogic - LARVOL DELTA

Safety and Tolerability of SYNB1891 Injection Alone or in Combination With Atezolizumab in Adult Participants (clinicaltrials.gov) - P1 | N=32 | Terminated | Sponsor: Synlogic | N=70 ➔ 32 | Recruiting ➔ Terminated; Business reasons

Combination therapy • Enrollment change • Metastases • Trial termination • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

"STING activation can be enhanced within the #TumorMicroenvironment with intratumoral injections of SYNB1891, a live, modified strain of the probiotic E. coli Nissle 1917. https://t.co/7jycpMMnfi @jasonlukemd @aoifemlbrennan @davehava @FilipJankuMD" (@CCR_AACR)

Biomarker • Tumor microenvironment • Oncology • STING

Phase I Study of SYNB1891, an Engineered E. coli Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies. (PubMed, Clin Cancer Res) - P1 | "In addition, a dose-related increase in serum cytokines was observed, as well as stable disease in 4 participants refractory to prior PD-1/L1 antibodies. Repeat intratumoral injection of SYNB1891 as monotherapy and in combination with atezolizumab was safe and well tolerated, and evidence of STING pathway target engagement was observed."

Journal • Metastases • P1 data • Infectious Disease • Oncology • STING

Phase I Study of SYNB1891, an Engineered E. coli Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies (Clin Cancer Res) - P1 | N=70 | NCT04167137 | Sponsor: Synlogic | "Twenty-four participants received monotherapy across six cohorts, and 8 participants received combination therapy in two cohorts. Five cytokine release syndrome events occurred with monotherapy, including one that met the criteria for dose-limiting toxicity at the highest dose; no other SYNB1891-related serious adverse events occurred, and no SYNB1891-related infections were observed. SYNB1891 was not detected in the blood at 6 or 24 hours after the first intratumoral dose or in tumor tissue 7 days following the first dose. Treatment with SYNB1891 resulted in activation of the STING pathway and target engagement as assessed by upregulation of IFN-stimulated genes, chemokines/cytokines, and T-cell response genes in core biopsies obtained predose and 7 days following the third weekly dose."

Cytokine release syndrome • P1 data • Oncology • Solid Tumor

"Excited for pub of SYNB1891 (E coli expressing #STING agonist) +/- PDL1. #Synbio Data expand the field & emphasize anti-tumor STING effects. Translational findings support type I interferon activators as major players in #immunotherapy! https://t.co/MWEhWldaco" (@jasonlukemd)

Oncology • PD-L1

Phase I study of SYNB1891, an engineered E coli Nissle strain expressing STING agonist, with and without atezolizumab in advanced malignancies (Clin Cancer Res) - P1 | N=70 | NCT04167137 | "Twenty-four participants received monotherapy across 6 cohorts, and 8 participants received combination therapy in 2 cohorts. Five cytokine release syndrome events occurred with monotherapy, including one that met the criteria for dose-limiting toxicity at the highest dose; no other SYNB1891-related serious adverse events occurred, and no SYNB1891-related infections were observed. SYNB1891 was not detected in the blood at 6 or 24h after the first IT dose or in tumor tissue 7 days following the first dose."

P1 data • Oncology

Phase I study of SYNB1891, an engineered E coli Nissle strain expressing STING agonist, with and without atezolizumab in advanced malignancies. (PubMed, Clin Cancer Res) - P1 | "Repeat IT injection of SYNB1891 as monotherapy and in combination atezolizumab was safe and well tolerated and evidence of STING pathway target engagement was observed."

Journal • Metastases • P1 data • Infectious Disease • Oncology • STING

SYNB1891, a bacterium engineered to produce a STING agonist, demonstrates target engagement in humans following intratumoral injection (SITC 2021) - P1 | "Durable, stable disease was observed in two patients treated with SYNB1891 monotherapy refractory to prior PD-1/L1 antibodies with vulvar melanoma (1x106 live cells; RECIST -28%) and small cell lung cancer (1x107 live cells; RECIST -12%). Conclusions Repeat IT injection of SYNB1891 as monotherapy and in combination atezolizumab in this ongoing study is safe and well-tolerated up to at least 1x108 live cells, and shows evidence of STING pathway target engagement."

IO biomarker • Lung Cancer • Melanoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Vulvar Cancer • CD4 • CXCL10 • CXCL9 • GZMA • IFIT1 • PD-L2 • STING • TNFSF10

Treating tumors with SYNB1891 to overcome anti-PD1 resistance (YouTube) - "Jason Luke, MD...outlines SYNB1891, an investigational drug designed by Synlogic to drive an immune response for the intra-tumoral treatment of solid tumors and lymphoma."

Video

[VIRTUAL] Intratumoral injection of SYNB1891, a synthetic biotic designed to activate the innate immune system, demonstrates target engagement in humans including intratumoral STING activation (AACR 2021) - P1 | "Repeat IT injection of SYNB1891 as monotherapy is safe and well-tolerated up to at least 3x107 cells and shows evidence of STING pathway target engagement. These data support the continued dose escalation of SYNB1891 as monotherapy, and initiation of Arm 2 in combination with atezolizumab."

IO biomarker • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Vulvar Cancer • CD4 • CXCL10 • CXCL9 • GZMA • IFIT1 • IFNG • IL1R1 • IL6 • PD-L2 • STING • TNFA • TNFSF10

Synlogic Presents Data from SYNB1891 Phase 1 Trial at American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - P1, N=70; NCT04167137; Sponsor: Synlogic; “Synlogic, Inc…presented data on SYNB1891 for the treatment of solid tumors and lymphoma during the American Association for Cancer Research (AACR) annual meeting, April 10-15, 2021….SYNB1891 is safe and well-tolerated as an intratumoral injection in a heterogenous population. No dose limiting toxicities or SYNB1891-related infections. Dose levels through 1e7 live cells demonstrate target engagement as assessed by dose-dependent increases in serum cytokines, upregulation of ISGs and presence of tumor infiltrating lymphocytes. Evidence of durable stable disease was seen in 2 patients and was associated with upregulation genes tied to immune activation and increased intratumoral lymphocytes…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.”

P1 data • Lymphoma • Oncology • Solid Tumor

Synlogic Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Business Update (PRNewswire) - “Advancement of SYNB1891 into combination arm dosing with PDL1 checkpoint inhibitor in an ongoing Phase 1 clinical study in patients with advanced solid tumors or lymphoma…An update on the study will be shared at the American Association of Cancer Research (AACR) meeting in April 2021. Data from both arms will continue to be reported as appropriate over the course of 2021, with mature combination therapy data expected by the end of the year.”

P1 data • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

SYNB1891 + Tecentriq: Data from P1 trial (NCT04167137) for metastatic solid tumors and lymphoma in late 2021 (Synlogic) - Chardan's 3rd Annual Microbiome Medicines Summit

P1 data • Lymphoma • Oncology • Solid Tumor

Synlogic Outlines Upcoming Clinical Milestones (PRNewswire) - "Synlogic anticipates clinical proof of concept data in 2021 across two metabolic programs...as well as continued advancement of SYNB1891 for the treatment of solid tumors and lymphomas...Synlogic anticipates additional data from cohorts in both arms will be available in mid to late 2021."

P1 data • Lymphoma • Oncology • Solid Tumor

Synlogic Announces Advancement of SYNB1891 to Combination Arm Dosing with PD-L1 Checkpoint Inhibitor in the on-going Phase 1 Study for the Treatment of Solid Tumors and Lymphoma (PRNewswire) - P1, N=70; NCT04167137; Sponsor: Synlogic; "Synlogic...announced SYNB1891 has advanced into the combination therapy stage of the ongoing Phase 1 trial...Enrollment of additional monotherapy dose escalation cohorts will continue...Study results to date across four dose cohorts of SYNB1891 monotherapy demonstrate: SYNB1891 is safe and well-tolerated at currently evaluated dose levels, as an intratumoral injection in a heterogenous patient population with no dose limiting toxicities or infections to date...Evidence of durable stable disease was observed in two patients being treated for metastatic melanoma and metastatic small cell lung cancer. Both patients experienced disease progression on immunotherapy with anti- PD-1/PDL-1 antibodies prior to enrollment in the study....Results of the SYNB1891 Phase 1 study will be presented at a future medical meeting."

Enrollment status • P1 data • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Synlogic Reports Third Quarter 2020 Financial Results and Provides Business Update (PRNewswire) - “SYNB1891 is currently in Phase 1 clinical development in patients with advanced solid tumors or lymphoma. Enrollment in the Phase 1 trial continues per plan. Synlogic expects to share an update on the initial dose cohorts of the monotherapy arm of the Phase 1 clinical study before the end of the year, per plan. Initiation of the combination arm of the Phase 1 clinical study, with the anti-PD-1 antibody Tecentriq (atezolizumab), is expected in the first half of 2021.”

Enrollment status • P1 data • Trial status • Lymphoma • Oncology • Solid Tumor

SYNB1891+Tecentriq: Initiation of study arm of P1 trial (NCT04167137) for solid tumors and lymphoma in early 2021 (Synlogic) - Q2 2020 Results: Data from study arm of P1 trial for solid tumors and lymphoma in late 2021

P1 data • Trial status • Lymphoma • Oncology • Solid Tumor

Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity. (PubMed, Nat Commun) - "SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine."

Journal • Oncology

SYNB1891: Data from P1 trial (NCT04167137) for solid tumors and lymphoma in late 2020 (Synlogic) - Q2 2020 Results

P1 data • Lymphoma • Oncology • Solid Tumor

Synlogic Reports Second Quarter 2020 Financial Results and Provides Business Update (Synlogic Press Release) - "Continuation of the monotherapy arm of the Phase 1 clinical study of SYNB1891 in patients with advanced solid tumors or lymphoma…Synlogic expects to share data from the monotherapy arm of the Phase 1 clinical study before the end of the year."

P1 data • Lymphoma • Oncology • Solid Tumor

Publication in Nature Communications highlights the preclinical development of SYNB1891 and its potential as a dual innate immune activator to stimulate an immune response in difficult to treat tumors (PRNewswire) - "The work describes preclinical studies that demonstrate anti-tumor activity and generation of immunological memory by SYNB1891 in mouse models of cancer, as well as its robust activation of human antigen presenting cells (APCs) that are key to the generation of an anti-tumoral immune response."

Preclinical • Oncology

Synlogic reports first quarter 2020 financial results and provides business update (PRNewswire) - "Evaluation of data from the monotherapy arm of the Phase 1 clinical study of SYNB1891 in patients with advanced solid tumors or lymphoma....While this clinical trial and most clinical sites have remained open and enrolled patients have continued on study, Synlogic expects slower enrollment of new patients as a result of the coronavirus pandemic, which has the potential to impact the availability of data in 2020."

Enrollment status • P1 data • Hematological Malignancies • Immunology • Lymphoma • Oncology • Solid Tumor

Synlogic outlines upcoming milestones for clinical programs and unveils new preclinical pipeline programs (Businesswire) - “SYNB1891 is being evaluated as a monotherapy in a Phase 1 open-label, multicenter, dose escalation clinical trial (NCT04167137) in patients with refractory solid tumors and lymphoma. Three U.S. sites have been activated to enroll and the first subject has been dosed. Synlogic expects to have data from the monotherapy arm of this study in 2020. After establishing a maximum tolerated dose (MTD) for SYNB1891, Synlogic will initiate a second arm of the trial in which subjects will receive escalating dose levels of SYNB1891 in combination with a fixed dose of the checkpoint inhibitor, atezolizumab (Tecentriq®), to establish a recommended dose for the combination regimen.”

P1 data • Trial status

Safety and Tolerability of SYNB1891 Injection Alone or in Combination With Atezolizumab in Adult Subjects (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Synlogic

New P1 trial

Synlogic provides program and business update and reports third quarter 2019 financial results (Businesswire) - "Synlogic has initiated a Phase 1 open-label, multicenter, dose escalation trial of its STING-agonist producing bacterial strain, SYNB1891, for the treatment of refractory solid tumors. The study’s primary objectives are to evaluate safety and tolerability of escalating doses of intratumorally administered SYNB1891 as a monotherapy...Synlogic expects to have data from the monotherapy arm of the study in 2020."

New P1 trial • P1 data