AVX-470 / Circle33 - LARVOL DELTA

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