A Phase 1 Open-Label, Multicenter Study to Assess the Safety and Efficacy of ANG003 in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis
Randomized, parallel, active-treatment Phase 1 study of a single dose of orally administered ANG003 with a test meal in adult subjects with cystic fibrosis-related exocrine pancreatic insufficiency. The study's overall objectives are to evaluate the safety, tolerability and effect of four dose levels of ANG003.
Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.
作者: Steven D Freedman ; Kamil Zaworski ; Kateryna Pierzynowska ; Stefan Pierzynowski ; Robert Gallotto ; Meghana Sathe ; Drucy S Borowitz
The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption.
We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase.
The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase.
The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.
Announces Initiation of Clinical Study of ANG003 in People with Cystic Fibrosis
NEWARK, Calif.--(BUSINESS WIRE)-- ATUM, a global specialist and industry leader in bioengineering solutions, today announced an expanded partnership with Anagram Therapeutics Inc., a clinical-stage biopharmaceutical company dedicated to improving the lives of people with cystic fibrosis (CF) and other rare diseases. The expanded relationship follows a successful partnership that accelerated delivery of ANG003 into a clinical study recently initiated in people with cystic fibrosis.
Together, the companies aim to advance a pipeline of orally delivered enzymes targeting malabsorption syndromes and nutrient metabolism disorders, by combining ATUM’s expertise in enzyme engineering, bioanalytics, and machine learning with Anagram’s expertise in gastrointestinal physiology and enzyme development, as well as its global clinical and scientific thought leader network.
"We are excited by the initiation of the ANG003 clinical study, an enzyme replacement therapy engineered using our multidimensional optimization GPS platform," said Claes Gustafsson, Chief Commercial Officer at ATUM. "The bioengineering platform combines systematic variance and machine learning to efficiently search almost infinite sequence space in many fitness dimensions simultaneously using only a few hundred samples. It has been an honor to work closely with the Anagram team to harness this technology for the purpose of addressing malabsorption and nutrient metabolism disorders."
The first participants have been dosed in the multicenter, randomized, parallel Phase 1 study to evaluate the safety and tolerability of orally administered ANG003 in adult subjects with CF-related exocrine pancreatic insufficiency (EPI). Additionally, the study aims to demonstrate absorption of the byproducts of digestion in plasma using sensitive biomarkers of absorption. The study design includes up to four possible combinations of orally delivered lipase, protease, and amylase administered with a test meal. A series of robust preclinical studies suggest ANG003 may improve absorption of the most beneficial fats and other key macronutrients in a dose dependent manner. This Phase 1 trial of ANG003 is being conducted through the Cystic Fibrosis Therapeutics Development Network at approximately twenty national CF care centers in the U.S.
ANG003 is a novel broad-spectrum orally delivered enzyme replacement therapy for the treatment of malabsorption and EPI. EPI is a condition which occurs when the body does not produce enough pancreatic (digestive) enzymes to break down foods and absorb nutrients. EPI can lead to malnutrition, fatty acid abnormalities, profound gastrointestinal symptoms, a significant decrease in quality of life and reduced life expectancy.
“We are pleased to have rapidly advanced ANG003 into the clinic, representing a big step toward providing a meaningful new treatment for people living with cystic fibrosis,” said Robert Gallotto, President and Chief Executive Officer, Anagram Therapeutics. “Initiating this clinical study and dosing the first patient is a significant milestone, as we continue to evolve orally delivered enzymes as therapeutics for malabsorption and nutrient metabolism disorders.”
ATUM is a fully integrated California based CRDO (Contract Research & Development Organization) biotechnology industry leader. ATUM, over the last two decades, has served life science researchers by delivering the highest quality services including but not limited to Gene Design and Gene Synthesis, Protein Engineering, Protein Production, Leap-In Transposase®, Cell Line Development, and Master Cell Banking (MCB). With a state-of-the-art machine learning platform, proprietary algorithms and thanks to its fully integrated Laboratory Information Management System (LIMS), ATUM takes you from virtual sequence to MCB with a click of a button. ATUM provides a continual commitment to innovation where services are built on bioengineered solutions to bring speed to market, supporting you from pre-clinical research through IND and beyond. Contact us today for more information at atum.bio or follow us on LinkedIn.
About Anagram Therapeutics
Anagram Therapeutics Inc. is a clinical stage biopharmaceutical company developing novel, orally delivered enzyme therapeutics for the treatment of serious diseases caused by malabsorption syndromes and nutrient metabolism disorders that prevent the body from properly processing or absorbing certain fats, sugars, proteins, vitamins, or other key nutrients. The company is leveraging proprietary enzyme technologies and expertise in gastrointestinal diseases to solve complex problems and advance a pipeline of products that can make a life-changing impact for people and their families living with cystic fibrosis and other rare diseases. ANG003, Anagram’s lead product for the treatment of malabsorption and exocrine pancreatic insufficiency, is a new class of broad-spectrum digestive enzyme replacement therapy in clinical trials in people with cystic fibrosis. Anagram is a privately held company headquartered in Framingham, MA. To learn more, visit or follow us on LinkedIn and X.