SG-5-00455 has potential to become a first-in-class precision therapeutic that directly targets mucosal healing in IBD patients

Company expects to file an investigational new drug application (IND) in the second half of 2022, with clinical data expected in 2023

BRISBANE, CA, USA I February 18, 2022 I Second Genome, a biotechnology company that leverages its proprietary platform to discover and develop precision therapies and biomarkers, today announced preclinical data for SG-5-00455, the Company’s development candidate. SG-5-00455 is a potential novel therapeutic for the treatment of inflammatory bowel disease (IBD) that improves barrier function and promotes tissue repair through direct binding and modulation of plasminogen activator inhibitor (PAI)-1/2, a well validated pathway that plays an important role in IBD. Results also demonstrate strong precision medicine potential to identify the target patient population using PAI-1/2 pathway biomarker(s).

The data were revealed during a digital oral presentation, “DOP54: Identification and development of a 1st in class naturally-derived protein that drives mucosal healing and is orally delivered by an engineered cellular therapy targeting the gastro-intestinal tract,” during “DOP Session 6: The Arctic: IBD Basic Science” at the 17th Congress of European Crohn’s and Colitis Organization (ECCO), being held virtually February 16–19, 2022.

“We are developing SG-5-00455 as a potential first-in-class precision therapeutic with broad application for IBD patients with disrupted intestinal mucosal healing. By directly modulating PAI-1/2 activity, which in excessive amounts adversely impacts wound healing, immune cell modulation and tissue remodeling, SG-5-00455 demonstrates the potential to directly target mucosal healing, a key therapeutic goal for IBD and an important U.S. Food and Drug Administration (FDA) metric for clinical trial outcomes,” said Joe Dal Porto, Ph.D., Chief Scientific Officer of Second Genome and presenter. “As we build on the breadth of preclinical validation to target PAI, a differentiated approach from most current IBD therapies, we are also investigating a potential biomarker to identify the patient population where SG-5-00455 can make the most impact.”

SG-5-00455 development candidate was generated using a novel, naturally derived protein (SG-2-0776) from healthy microbiome, that was subsequently engineered into a Lactococcus lactis (L.lactis) drug delivery system, SG-5-00455, for oral, non-systemic, direct delivery to the gut. The naturally derived protein SG-2-0776 demonstrated direct binding of PAI-1, functional inhibition of PAI-1/2 and improvement in epithelial barrier function in vitro. In pre-clinical colitis models, oral administration of SG-5-00455 reduced pathology scores for inflammation and restored barrier function levels, as well as improved dysregulated tissue repair and fibrosis-associated gene expression and proteins levels. Mechanism of action studies revealed interaction with, and modulation of, fibrinolysis pathway members, which were also found to be upregulated in IBD patient samples in multiple clinical cohorts. This pathway will provide the basis for a potential biomarker to identify patients likely to respond to SG-5-00455. SG-5-00455 is currently in IND-enabling studies, and the Company expects to file an investigational new drug (IND) application with the U.S. FDA in the second half of 2022.

The ECCO oral presentation will be made available on the Company’s website at

On Wednesday, February 23, 2022, at 12:00 – 1:00 p.m. EST, Second Genome will host a virtual key opinion leader (KOL) panel, “SG-5-00455 and the Role of Mucosal Healing and PAI-1/2 in IBD,” with Drs. Ryan Balfour Sartor and Silvio Danese, renowned experts in the field. A link to the event will be available on the Company’s Events page at and at this direct link, and a replay will be accessible following the program.

About Second Genome

Second Genome is a biotechnology company that leverages its proprietary technology-enabled platform to discover and develop transformational precision therapies based on novel microbial genetic insights. We built a proprietary drug discovery platform with machine-learning analytics, customized protein engineering techniques, phage library screening, mass spec analysis and CRISPR, that we couple with traditional drug development approaches to progress the development of precision therapies for wide-ranging diseases. Second Genome is advancing lead programs in IBD and cancer into IND-enabling studies. We also collaborate with industry, academic and governmental partners to leverage our platform and data science capabilities. We hold a strategic collaboration with Gilead Sciences, Inc., utilizing our proprietary platform and comprehensive data sets to identify novel biomarkers associated with clinical response to Gilead’s investigational medicines. We also hold a strategic collaboration with Arena Pharmaceuticals to identify microbiome biomarkers associated with clinical response for their lead program in gastroenterology, etrasimod. For more information, please visit

SOURCE: Second Genome