Grant: Project Grant

Bacteria and viruses may enter the uterus during pregnancy, causing infection and fetal inflammation. Inflammation can permanently damage the organs of the fetus and cause preterm birth. Although antibiotics can treat the infection, they cannot stop the intrauterine inflammation that hurts the fetus and causes early labour. Our team designed, synthesized, and tested extensively in human tissues and several animal models a very effective novel small molecule inhibitor of the receptor of the cytokine, Interleukin-1 (IL-1), rytvela. Unfortunately, rytvela is unattractive for investors because its composition of matter patent expires this year. This led us to design LIV-010, an IL-1 receptor antagonist that is superior to rytvela and has patent protection until 2041. Guided by thirteen years of experience with rytvela, we are in a strong position to rapidly perform the required preclinical tests for regulatory approval of LIV-010 from the FDA and Health Canada. Our objective is to complete all steps necessary to hold an IND meeting. Experimental Aims: 1. Use LIV-010 to block the inflammatory response to a bacterial stimulant in a human fetal membrane explant model; 2. Demonstrate that LIV-010 blocks preterm birth in the pregnant mouse better than rytvela and protects the fetus and newborn from inflammatory harm; 3. Perform small animal toxicity and PK/PD studies on LIV-010. Commercialization Objectives: A. Validate LIV-010's target product profile; B. Clarify the global patent position for LIV-010; C. Demonstrate investor and market interest in LIV-010 by derisking it for safety and efficacy profiles; D. Scale-up LIV-010 production; E. Hold an IND meeting with Health Canada and the FDA. Significance: An IND meeting will increase the value of LIV-010 and will stimulate further investment into its development for use in patients. If successful, LIV-010 will be the most significant advance in fetal/newborn therapeutics since surfactant.