ANG003 / Anagram Therap - LARVOL DELTA

Progress towards a better outcome measure to dose pancreatic enzyme replacement therapy (NACFC 2025) - "One article each compared 2 different brands of PERT, PERT + ivacaftor and PERT + proton-pump inhibitors, without differences in CFA identified. There is conflicting evidence to support CFA as a tool to distinguish among doses, however it remains the criterion standard. The O3-SACT is the only statistically significant outcome that distinguishes among therapeutic lipase doses. Thus, we aim to compare the O3-SACT to CFA in the Phase 2 dose-ranging trial of ANG003."

Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Immunology • Respiratory Diseases • Short Bowel Syndrome • Targeted Protein Degradation

ANG003, a non-porcine pancreatic enzyme replacement therapy, provides significantly higher enzymatic activity than porcine products over the range of gastrointestinal pHs and USP monograph pH 9 (NACFC 2025) - "In vitro data indicate that ANG003 lipase may improve in vivo lipolysis, calorie and nutrient absorption, by functioning at low pH and hydrolyzing key dietary fats known to be deficient in individuals with exocrine pancreatic insufficiency (EPI) or cystic fibrosis. The higher activity at low pH, higher specific activity, and ability to formulate without enteric coating provide a unique opportunity ANG003 to minimize therapeutic dose and pill burden, potentially improving compliance and outcomes in patients with EPI."

Preclinical • Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Immunology • Respiratory Diseases • Targeted Protein Degradation

Results of a clinical trial of ANG003, a non-porcine pancreatic enzyme replacement therapy, in people with cystic fibrosis. (PubMed, J Cyst Fibros) - "ANG003 lipase significantly improves DHA+EPA and total fat absorption in a dose dependent manner. Results for ANG003 protease and amylase activity suggest that doses lower than those in current porcine-derived PERTs may be efficacious."

Journal • Preclinical • Cystic Fibrosis • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation

Observations on CFTR modulators and pancreatic function in a clinical trial of ANG003, a novel pancreatic enzyme replacement therapy in people with cystic fibrosis (ECFS 2025) - P1 | "All were taking elexacaftor/ tezacaftor/ivacaftor with the exception of two subjects taking ivacaftor alone. These data add to the body of information that adults taking highly efficacious CFTR modulators are not associated with objective improvement in pancreatic function. In addition, we observed lack of conformity with guidelines on limits of pancreatic enzyme dose per day."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Phase 1 Study to Assess Safety and Efficacy of ANG003 (clinicaltrials.gov) - P1 | N=51 | Completed | Sponsor: Anagram Therapeutics, Inc. | Recruiting ➔ Completed | Trial primary completion date: Jan 2024 ➔ Jul 2024

Trial completion • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

ATUM Partners with Anagram Therapeutics to Extend Collaboration to Develop Orally Delivered Enzyme Therapies for Malabsorption and Nutrient Metabolism Disorders (Businesswire) - "ATUM...today announced an expanded partnership with Anagram Therapeutics...'We are excited by the initiation of the ANG003 clinical study, an enzyme replacement therapy engineered using our multidimensional optimization GPS platform,'...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."

Licensing / partnership • Trial status • Cystic Fibrosis • Genetic Disorders

Phase 1 Study to Assess Safety and Efficacy of ANG003 (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Anagram Therapeutics, Inc.

New P1 trial • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis. (PubMed, PLoS One) - "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."

Journal

Cystic Fibrosis Foundation Commits Up to $15.5M in Additional Funding for Potential Enzyme Therapy (Businesswire) - "The Cystic Fibrosis Foundation recently agreed to provide up to $15.5 million to Anagram Therapeutics (formerly known as Synspira Therapeutics) to conduct early-stage clinical trials of a novel enzyme replacement therapy....Anagram is planning to start a Phase 1 clinical trial of the enzyme therapy over the summer."

Financing • Cystic Fibrosis • Genetic Disorders

Synspira Therapeutics Announces Expanded Agreement with Cystic Fibrosis Foundation to Advance Promising Treatments for Cystic Fibrosis (PRNewswire) - "Synspira Therapeutics...announced today that the Cystic Fibrosis Foundation has made equity and structured investments in the company of up to $14 million in additional funding. The new funding brings the Foundation's total commitment to $22.55 million. 'This investment and development collaboration will enable Synspira to complete preclinical and initial clinical development for SNSP003 while also advancing SNSP113 through late stage clinical studies,'...the company's novel polycationic glycopolymer SNSP113, currently in Phase 2 clinical studies, for the treatment of pulmonary infections and complications. In addition, the funding will accelerate SNSP003..."

Financing • Cystic Fibrosis • Infectious Disease