9 Meters pipeline

pipeline

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short bowel syndrome (sbs)

What is SBS?

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), SBS is a rare syndrome related to poor absorption of nutrients resulting from a significant resection of the small intestine due to recurrent Crohn’s Disease, trauma, malignancy, or complications from abdominal surgery.

It is estimated that 15, 000 to 20,000 people in the U.S. suffer from SBS. The clinical consequences are far reaching including malnutrition, severe diarrhea, dehydration, and kidney and liver disease, leading to a poor quality of life in many patients. In addition, many patients are dependent on parenteral nutrition. Overall mortality is as high as 50% in this population depending on age and length of parenteral nutrition. Pharmacologic therapies for SBS include the short-acting daily injectable GLP-2 analogue Gattex® (teduglutide) , which is only indicated for patients currently on parenteral nutrition and does not address the other debilitating complications of SBS such as severe diarrhea. Vurolenatide is being studies in all patients with sbs regardless of the need for parenteral support.

Vurolenatide

Long-acting injectable GLP-1 analogue for short bowel syndrome (SBS)

Patients with SBS typically have compromised levels of GLP-1, which is naturally produced in a portion of the GI tract that may be removed during surgical resection. Natural GLP-1 prevents the GI tract from moving rapidly ("ileal brake"). Without this "brake", there is unregulated gut motility, causing SBS patients’ bowels to empty rapidly and frequently compromising their ability to absorb nutrients and fluids and leaving them susceptible to intractable, malabsorptive diarrhea with frequent bowel movements and excessive stool output.

Vurolenatide is intended to replace missing GLP-1 to normalize GI transit and is intended to improve intestinal absorption of nutrients and water and reduce diarrhea for all patients with any type of post-surgical SBS, regardless of their parenteral support requirements. Owing to its extended half-life, vurolenatide only needs to be dosed weekly or bi-weekly versus daily for the current standard of care (GLP-2 analogue) , thus considerably improving convenience for patients and their caregivers.

9 Meters initiated the VIBRANT study (VurolenatIde for short Bowel syndrome Regardless of pArenteral support requiremeNT), a placebo-controlled Phase 2 trial in SBS in Q2 2021., The study includes patients with all post-surgical types of SBS regardless of their parenteral support requirements.

Vurolenatide is patent-protected and has received Orphan Drug designation by the FDA.

other development programs

Larazotide

Orally administered, gut-restricted tight-junction regulator

Larazotide is in Phase 2 development for multi-system inflammatory syndrome in children (MIS-C). MISC-C is a rare but serious condition associated with COVID-19 in which different body parts become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or GI organs. MISC-C occurs when SARS-CoV-2 superantigens move through the tight junctions between gut epithelial cells into the blood stream, leading to the hyperinflammatory immune response. Larazotide’s mechanism of action as a tight junction regulator may prevent SARS-CoV-2 superantigens from entering the bloodstream. A randomized, double-blind, placebo-controlled Phase 2a study is ongoing in collaboration with the European Biomedical Research Institute of Salerno, Italy (EBRIS), which is conducting this study.

NM-003

Long-acting GLP-2 analogue

NM-003 is being developed as a long-acting GLP-2 agonist undergoing an indication selection process. NM-003 is patent-protected and has entered an IND-enabling pathway.

NM-102

Small molecule tight junction microbiome modulator

NM-102 is being developed as a potential microbiome modulator and is undergoing an indication selection process. NM-102 is a long-acting, degradation-resistant peptide, believed to be gut-restricted, and presumed to prevent gut microbial metabolites and antigens from trafficking into systemic circulation. The researchers found that NM-102 was effective alone or when combined with immune checkpoint inhibitors (ICIs) in a pre-clinical transgenic mouse model of spontaneous aggressive skin melanoma. Furthermore, the combination of NM-102 with ICIs improved survival compared to ICIs alone. NM-102 has entered an IND-enabling pathway.

NM-136

Long-acting, highly specific humanized anti-GIP monoclonal antibody

NM-136, targets glucose-dependent insulinotropic polypeptide (GIP), a hormone found in the upper small intestine that is released into circulation after food is ingested, and when found in high concentrations, can contribute to obesity and obesity-related disorders. NM-136 has been shown to prevent GIP from binding to its receptor, which in preclinical obesity models has been shown to significantly decrease weight and abdominal fat by reducing nutrient absorption from the intestine as well as nutrient storage without affecting appetite.

enhancing our capabilities with strategic partnerships

9 Meters is working to build partnerships with key GI disease and patient advocacy groups to ensure we are working to make the greatest possible difference.