Our Science

More than 30 years of groundbreaking scientific research highlights the importance of intestinal integrity to human health and the medical complications that can occur when the intestinal epithelial barrier is disrupted. Palisade Bio is applying 15 years of the company's own internal efforts to develop novel therapeutics designed to improve human health by guarding the intestines. Protecting intestinal integrity is a cornerstone of human health and plays a key role in both acute critical-care medical conditions and burdensome chronic diseases.

The intestinal epithelium is a layer of cells which forms the protective inner lining of the intestinal tract. It helps facilitate nutrient absorption while also protecting the abdomen from the harsh environment of the intestine, whose contents includes corrosive digestive enzymes, invasive pathogens and potentially harmful dietary antigens. If compromised, the intestinal epithelium can allower potent digestive enzymes to damage the GI tract and surrounding organs and trigger widespread complications.

Escape of digestive enzymes from a compromised intestinal barrier can cause a range of complications including:

  • Damage to the intestinal epithelium leading to additional gut permeability and enzyme translocation into the peritoneal (abdominal) cavity and circulatory system
  • Local nerve and muscle damage and inflammation resulting in loss of bowel motility and ileus
  • Proteolytic damage to the mesothelial surfaces leading to adhesion formation
  • Circulating proteases can cause damage to peripheral tissues (lungs, heart, and liver) and metabolic injury through digestion of signaling receptors.

A wide variety of events can cause the breakdown of the intestinal mucosal barrier:

  • physical injuries resulting from incisions and mechanical manipulations during abdominal surgery
  • metabolic injuries resulting from prolonged low blood flow (hypoperfusion) during CV surgery
  • damage resulting from the body’s natural response to life-threatening infections, shock and sepsis
  • acute respiratory distress syndrome, as well as chronic inflammatory diseases.

Two common types of surgery often lead to disruption of the mucosal barrier and GI complications:

  • During cardiovascular surgery, the surgeon has to stop the heart and lungs, diverting blood flow through a cardiopulmonary bypass pump to allow blood, oxygen, and nutrients to circulate throughout the body. The cardiopulmonary bypass pump preferentially directs blood to the vital organs, such as the brain, heart, and lungs causing a prolonged period of low blood flow to the intestines that can lead to damage.
  • During GI and abdominal surgeries, surgeons handle, manipulate and often make incisions in the intestines. As a result, surgical patients may experience a delayed return of normal bowel function, impaired motility (called ileus), and scar tissue formation (called adhesions). These complications can increase recovery time and hospital readmissions.

Lead asset LB1148 is a protease inhibitor with potential to both reduce abdominal adhesions and help restore bowel function following surgery. LB1148 is designed to temporarily inhibit the activity of digestive enzymes, mitigating the risk of complications resulting from post-operative damage to surrounding tissues.

Our Approach

Your Intestines and Your Health

Protecting intestinal integrity is a cornerstone of preserving human health.

The gastrointestinal tract is home to enzymes, microorganisms, chemicals, nutrients and mucus that keep us healthy. This intestinal environment — as well as the tissues and barriers that protect the rest of the body from these potent elements — are critical to your health.

When digestive enzymes, called proteases, escape the intestine during major surgery they cause serious damage to GI tissues. This can result in interruption of GI function and cause multiple health problems and increase the duration of hospital stay. In addition to the immediate concern of reduced bowel function, issues such as formation of post-surgical scarring (called adhesions) or other surgical complications can also present themselves. Research also suggests that the damage caused by digestive enzymes can also contribute to a wide range of chronic conditions including obesity, diabetes, and hypertension.

Therapeutic Solutions

Palisade Bio is a late-stage biopharma company advancing therapies that help patients with acute and chronic gastrointestinal (GI) complications stemming from post-operative digestive enzyme damage.

Lead asset LB1148 is a protease inhibitor with potential to both reduce abdominal adhesions and help restore bowel function following surgery. LB1148 is currently being advanced for potential approval in multiple indications: accelerating return of post-op GI function and reducing post-surgical adhesions. Palisade Bio also intends to pursue development of LB1148 and other protease inhibitors for a range of additional acute and chronic medical conditions resulting from disruption of the intestinal epithelial barrier.

Additional Solutions for Intestinal Integrity

Oral protease inhibitor therapies have potential to treat a variety of blockbuster indications such as inflammatory bowel disease and autoimmune diseases. Palisade Bio is also leveraging its expansive collection of preclinical research for the development of novel therapies and diagnostic technologies to address a range of chronic conditions associated with disruptions in intestinal integrity.