Relief from gut injury caused by cancer therapies
The radiation used to target abdominal and pelvic cancers is an important standard of care but produces radiation toxicities that cause painful and life-threatening side effects. Up to 80% of patients receiving radiation therapies will have to reduce or cease their treatment due to the secondary effects of their radiation treatment.
There are few effective treatments for GI toxicities from radiation. Synedgen’s MIIST305 is a first-in-class drug that protects the gastrointestinal tract from the debilitating damage caused by radiation therapy. MIIST305 promotes barrier repair and modulates the innate immune activators that are responsible for propagating radiation damage along the GI tract.
MIIST305 is designed to reduce toxicity to the GI tract from cancer treatments, allowing patients to safely tolerate higher treatment doses needed to aggressively treat their cancer. In animal models, MIIST305 reduces chemical or radiation-induced mortality by reducing the activation of innate inflammatory pathways, restoring GI mucosal defenses, and preventing mucosal barrier breakdown that leads to bacterial translocation and possibly sepsis. MIIST305 has been shown to promote healing and reduce inflammation at the damaged tissue surface. In addition, this restoration of a healthy gut environment has been shown to promote normal commensal flora and prevent overgrowth of pathogenic bacteria. Expansion indications include graft-versus-host disease, and GI damage caused by acute radiation syndrome.
How MIIST305 targets immunomodulatory signaling
The cells lining the intestine are coated with a thick, natural glycopolymer layer called the glycocalyx. Radiation and chemotherapy damage the glycocalyx, reducing protective function and initiating an innate immune system response. The resulting local inflammation initiates circulating cytokines and chemokines that trigger systemic inflammation. MIIST305 acts at the mucosal surface to reduce activation of TLR’s and immune signaling, repairing and resetting the fundamental mucosal role as a protective barrier against infection and further damage.