AVX-470 / Circle33 - LARVOL DELTA

Anti-Inflammatory Peptides as Promising Therapeutics Agent Against Inflammatory Bowel Diseases: A Systematic Review. (PubMed, JGH Open) - "Oral AVX-470 (bovine-derived anti-TNF antibody) reduced enterocyte TNF, MPO, and apoptosis levels...However, their therapeutic potential is limited by protease degradation, poor bioavailability, and possible cytotoxicity. Future research should enhance their stability, delivery systems, and pharmacokinetic properties to optimize their clinical applicability and safety."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Structural features of bovine colostral immunoglobulin that confer proteolytic stability in a simulated intestinal fluid. (PubMed, J Biol Chem) - "We evaluated the stability of AVX-470, a bovine colostral anti-tumor necrosis factor (TNF) polyclonal antibody used in early clinical studies for treatment of ulcerative colitis, using conditions that mimic the human small intestine. This infliximab-bovine IgG1 chimera (bovinized infliximab) retained the antigen binding and neutralization activity of the wild-type sequence but was degraded 9-fold more slowly than the unmodified infliximab. This remarkable increase in stability with as few as 18 amino-acid substitutions suggest that this "bovinization" process is a means to enable oral delivery of proven therapeutic antibodies, as well as novel antibodies to targets that have been previously inaccessible to therapies delivered by injection."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Targeted Protein Degradation • Ulcerative Colitis • TNFA

AVX-470: A novel orally-administered anti-TNF antibody therapeutic for IBD: in vitro pharmacology (DDW 2013) - Presentation time: Tuesday, 8:00AM - 5:00PM; Abstract #Tu1662; "In affinity measurements, TNF neutralization, and apoptosis studies, AVX-470 was comparable to infliximab. AVX-470 cross-reactivity to non-human primate TNF has enabled a toxicology study in cynomolgus monkeys."

Preclinical • Inflammatory Bowel Disease

BARDA supports development of new drugs to treat radiation injury (Apogee-Biotechnology) - U.S. Department of Health & Human Services’ Biomedical Advanced Research & Development Authority (BARDA) recently released information about award; Under two-year, $2M contract Apogee Biotechnology will conduct preliminary studies of ABC294640 to evaluate the drug’s efficacy in reducing gastrointestinal injury caused by radiation exposure; Two-year, $2.9M contract with Avaxia Biologics supports preliminary efficacy studies for AVX-470; Studies are the next step in drug development process & are needed before proceeding to clinical trials & pivotal efficacy studies

Award • Inflammatory Bowel Disease

Avaxia Biologics receives IND clearance from FDA to initiate clinical program to evaluate AVX-470 as therapy for ulcerative colitis (Avaxia Biologics Press Release) - "...Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for AVX-470 for the treatment of ulcerative colitis...The Company expects to initiate a Phase 1b clinical trial of AVX-470 in patients with active ulcerative colitis in the near term."

Anticipated new P1 trial • IND • Inflammatory Bowel Disease

Avaxia Biologics receives FDA Orphan Drug Designation for AVX-470 for the treatment of pediatric ulcerative colitis (Businesswire) - "Avaxia...announced today that the US Food and Drug Administration (FDA) granted Orphan Drug Designation to AVX-470 for the treatment of pediatric ulcerative colitis. AVX-470 is a gut-targeted anti-TNF antibody, which earlier this year successfully completed a Phase 1b clinical trial in adults with active ulcerative colitis."

Orphan drug • Inflammatory Bowel Disease

Evaluation of an oral anti-TNF antibody in patients with active ulcerative colitis (clinicaltrials.gov) - P1, N=24; Sponsor: Avaxia Biologics; Recruiting; New P1 trial; Pipeline shift: Preclinical -> P1.

New P1 trial • Phase shift • Crohn's Disease • Inflammatory Bowel Disease