Thursday, January 15, 2009
Cedric Francois MD, PhD, President/CEO of Potentia Pharmaceuticals describes his company’s novel anti-AMD compound (POT-4) in a conversation with Dr. Sophie Bakri.
After trying many approaches, complement inhibition was viewed as being the best way to modulate the activity of macrophages in the back of the eye. The role of macrophages in the chronic inflammatory disease process is well understood and has been shown to be a factor in dry Macular Degeneration. The role of complement in macular degeneration was established in 2005 as the first breakthrough discovery resulting directly from the human genome project.
Compstatin is a potent complement inhibitor first characterized by John D. Lambris, PhD at the University of Pennsylvania 12 years ago. Compstatin is a small peptide with favorable properties of being able to be formulated in a sustained release configuration and also worked on C3 protein of the complement cascade. POT-4 is a much more active version of the original compound. Early work shows that the safety of POT-4 is really quite good.
The ASaP trial, “assessment of safety of POT-4”, is a phase I, randomized, dose-escalation trial at 6 sites. Pts with disciform scars and are no longer candidates for Avastin and Lucentis. Pharmacokinetic evaluation of POT-4 is showing that expected dosing targets have been achieved and importantly that the sustained presence of the drug is being demonstrated. In a non-human primate model (at 4 dosing levels) sustained release was demonstrated for as long as nine months.
The next clinical study will focus on geographic atrophy as an end point, with wet-form AMD in patients who are not responsive to Lucentis or who have developed geographic atrophy in spite of years of therapy. Preventing the exudative process is the objective.