Trial Information

A Multicenter, Double-Blind, Placebo-Controlled, Ascending-Dose, Repeat-Dose Safety and Pharmacokinetic Investigation of a Delayed-Release, Enteric-Coated Capsule Formulation of AVX 470 [Anti-TNF (Tumor Necrosis Factor) Globulin (Bovine)] in Patients With Active Ulcerative Colitis

There is a significant unmet medical need for effective oral pharmacologic therapies for
inflammatory bowel diseases such as ulcerative colitis. Current anti-TNF therapies,
including infliximab and adalimumab, are effective treatments for these conditions, but they
must be administered by intravenous or subcutaneous injection. The major safety concerns
associated with the use of injectable anti-TNF therapies are infection, demyelinating
disease, and lymphoma, all of which are the result of systemic exposure. These uncommon but
serious side effects have limited the use of systemic anti-TNF antibody therapy to patients
with severe disease that have failed to respond to first-line treatments.

AVX-470 is purified immunoglobulin (Ig) from the colostrum (early milk) of cows immunized
with recombinant human tumor necrosis factor (rhTNF). AVX-470 is formulated in
delayed-release enteric-coated capsules designed to protect the capsule contents from
gastric acids following oral administration and to provide localized delivery to sites of
inflammation in the distal intestine. Prior clinical experience with bovine Ig therapies in
other human diseases suggests that AVX-470 will not be absorbed to any significant extent,
meaning that systemic exposure could be minimized. The development of oral anti-TNF therapy
targeting local intestinal disease activity might reduce the risks associated with
injectable anti-TNF therapy and allow the convenience of oral dosing.

The present study is a first-in-human, Phase 1 clinical study. It is primarily intended to
evaluate the safety and tolerability of multiple doses of AVX-470 administered orally to
patients with active ulcerative colitis.

Animal models of ulcerative colitis using a mouse-specific TNF antibody derived from bovine
colostrum demonstrated a 50% or more reduction in tissue TNF, TNF-messenger ribonucleic acid
(mRNA), interleukin (IL)-6 mRNA, and myeloperoxidase and lowering of colonic inflammatory
activity. Twenty-eight-day toxicology studies demonstrated no clinical or histologic
findings in exposures above the intended clinical dose range.