Phase II Amount
$1,796,643
Malabsorption syndromes occurs when the body is not able to properly digest or absorb macronutrients fromingested food. Malabsorption results from impaired secretion of pancreatic enzymes [exocrine pancreaticinsufficiency (EPI)], disturbed GI transit, critical loss of intestinal mucosa or changes in gastric, duodenal, liver,bile or gallbladder physiology or secretion. Malabsorption syndromes can be life-threatening conditions resultingfrom cystic fibrosis, chronic pancreatitis, pancreatic cancer, or other diseases. Currently the only treatment ispancreatic enzyme replacement therapies (PERTs) derived from pig pancreas processed in slaughterhouses.PERT rarely eliminates maldigestion or severe GI symptoms and patients continue to not meet target nutritionalstatus in-spite of chronic use with significant groups of non-responders. PERT requires enormous volumes oflarge pills to be taken daily (20-40) and does not provide a liquid formulation dramatically limiting its effectivenessfor infants, children or those with difficulty swallowing pills. Synspira is developing SNSP003 to provide superiorperformance and make a life-changing impact for the people who require PERT. SNSP003 is a mixture of thethree critical enzymes (lipase, protease and amylase) necessary to aid digestion and absorption of keymacronutrients. SNSP003 has been developed to improve fatty acid abnormalities (specifically physiologicallyrelevant LCPUFAs), protein and carbohydrate malabsorption, clinical outcomes, GI symptoms and QoL. Thelipase in SNSP003 has been improved through enzyme engineering to be build stability against low pH andproteolytic degradation directly into the enzyme without the need for enteric coating. The stability of theengineered lipase will allow it to digest fats in the stomach and through the small intestine while also allowing fora liquid compatible formulation. Synspira intends to create a Rapidly Disintegrating Tablet (RDT) formulation,that can be given as a liquid treatment option for infants, children suffering from rare diseases or adults who areunable to swallow the requisite large volume of capsules. SNSP003 will only require one pill per meal and providethe novel RDT formulation both aimed at reducing treatment burden, simplifying therapy, improving adherence,QoL and provide an opportunity for patients who otherwise would not be able to use pancreatic enzymes. ThisRDT is novel and will solve a problem that has been unmet for 50-years providing a dramatic improvement inpatient care. In this study, Synspira will reformulate the lipase, protease and amylase in the existing SNSP003mini-tablets for use in the RDT formulation. The effectiveness of the RDT formulation will be tested using an EPIporcine model demonstrated to be a sensitive tool for the evaluation of macronutrient absorption by determiningfatty acid uptake in plasma, RBCs, tissues and stool. Analytical testing will then be performed using highthroughput analytical methods measuring free fatty acid release (C14-C24), amino acids and glucose. Synspirawill conduct a 28-day toxicology study for SNSP003 to inform clinical studies and evaluate the base enzymes(lipase, protease and amylase). SNSP003 will have manufacturing capacity to ensure supply and meet demand.
Public Health Relevance Statement: NARRATIVE
Malabsorption syndromes (e.g., cystic fibrosis, chronic pancreatitis, pancreatic cancer) can be life-threatening
conditions that occur when the body is not able to digest or absorb nutrients from food. Currently the only
treatment is pancreatic enzyme replacement therapies derived from pig pancreas processed in slaughterhouses
which are not fully affective and require large volumes of pills to be taken with each meal or snack, an
impossibility for children. Synspira intends to create a Rapidly Disintegrating Tablet formulation, with a mixture
of enzymes (lipase, protease and amylase) to aid digestion and absorption, that can be given as a novel liquid
treatment option for infants, children suffering from rare disease (e.g., cystic fibrosis) or adults who are unable
to swallow the requisite large volume of capsules required.
Project Terms: <21+ years old><0-11 years old> 