Lead development candidate SG-5-00455 shows potential to become first in class PAI-1/2 inhibitor that directly targets mucosal healing in patients with inflammatory bowel disease (IBD)
BRISBANE, Calif., May 24, 2022 /PRNewswire/ -- Second Genome, a biotechnology company that leverages its proprietary platform to discover and develop precision therapies and biomarkers, presented data demonstrating the Company's development candidate, SG-5-00455, improves epithelial barrier function and promotes mucosal healing by effectively inhibiting plasminogen activator inhibitor (PAI)-1/2 activity in the intestines. The data were presented at Digestive Disease Week 2022 Annual Meeting, held May 21-24 virtually and in San Diego, California.
There is a strong correlation between the upregulation of SERPINE1 (PAI-1) and chronic inflammation in IBD. Local delivery of SG-5-00455 to the gastrointestinal mucosa of diseased mice demonstrated efficacy by inhibiting PAI-1 activity, which in excessive amounts adversely impacts wound healing, immune cell modulation and tissue remodeling. By selectively targeting the PAI-1 pathway at the mucosa, SG-5-00455 improves epithelial barrier function by regulating extracellular matrix production and reducing profibrotic inflammation. SG-5-00455 demonstrates the potential to directly target mucosal healing, a key therapeutic goal in the treatment of IBD," said Joseph Dal Proto, Ph.D. "SG-5-00455 has the potential to become a first-in-class treatment for patients with IBD in which mucosal healing is inadequately addressed by current standards of care."
This data was presented during a poster session at DDW 2022. The information is provided below:
Session Title: Non-Immune Cells in Intestinal Inflammation: Epithelium and Stroma
Abstract Number: 3698252
Title: 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
In addition to SG-5-00455, Second Genome has presented data on the identification of immunomodulatory peptides with therapeutic potential using their proprietary technology-enabled platform (abstract number: 3699744) which was presented during another poster session at DDW 2022.
SG-5-00455 is an orally delivered, engineered biotherapeutic modulator of the PAI1/2 pathway that is designed to work locally within the gastrointestinal tract to promote mucosal healing and improve barrier function in IBD patients. In vitro, SG-5-00455 demonstrated direct binding to PAI-1, functional inhibition of PAI-1/2 function and improvement in epithelial barrier function. 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 found to be upregulated in IBD patient samples in multiple clinical cohorts. This 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 anticipates filing an investigational new drug (IND) application with the U.S. FDA late 2022.
The SG-5-00455 poster (#3698252) entitled, "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," and the poster on the identification of immunomodulatory peptides utilizing our proprietary technology-enabled drug discovery platform (#3699744) will be made available on the Company's website at https://www.secondgenome.com/events/.
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 gene-editing 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 Pfizer (formerly Arena Pharmaceuticals) to identify microbiome biomarkers associated with clinical response for their lead program in gastroenterology, etrasimod. For more information, please visit www.secondgenome.com.
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