Pacgen is conducting a number of preclinical studies with PAC-G31P, a novel recombinant protein, to evaluate its potential in the prevention and the treatment for a number of acute and chronic inflammatory diseases characterized by non-beneficial neutrophil recruitment.
THE DRUG CANDIDATE
PAC-G31P is a novel peptide that is a synthetic derivative of the human cytokine, Interleukin-8 (IL-8). IL-8 is one of several alarm signal cytokines that stimulate neutrophil recruitment from circulation to the site of infection or injury. Based on the biological mechanism of action of PAC-G31P, ARDS has been identified as a possible lead clinical indication. Other inflammatory lung diseases such as pneumonia, asthma and chronic obstructive pulmonary disease may also be therapeutic targets for PAC-G31P.
MECHANISM OF ACTION
PAC-G31P acts by binding to two specific cell surface receptors, CXCR-1 and CXCR-2, found on neutrophils, that detect alarm signal cytokines. When PAC-G31P binds to the receptors, it blocks (or modulates) the actions of the cytokines responsible for neutrophil recruitment. In conditions such as ARDS where over-recruitment of neutrophils is part of the disease process, PAC-G31P is expected to block the receptors, overcome the excessive alarm signal, and restore a level of neutrophil recruitment that is appropriate to respond to the lung injury or infection.
The development program for PAC-G31P will be very complex and will address multiple acute and chronic market opportunities. For that reason, Pacgen expects to seek to partner this program at an earlier stage of development than its other programs.
The development program for PAC-G31P will be very complex and will address multiple acute and chronic market opportunities. For that reason, Pacgen expects to seek to partner this program at an earlier stage of development than its other programs. PAC-G31P will also require extensive early commercial planning to optimize the value of the program. The treatment/prevention of ARDS, among other inflammatory diseases, is estimated to be a $3 billion market opportunity. Pacgen plans to partner the compound at a late preclinical or early clinical development stage.
Preclinical results to date suggest PAC-G31P has potential to reduce neutrophil recruitment to the injured lung. In preclinical models of inflammatory disease a bacterial lipposaccharide (LPS) is used to cause significant peripheral blood, pulmonary and airway neutrophilia which is similar to that observed in acute lung injury in humans. Treatment with PAC-G31P significantly reduced neutrophil infiltration into lung airways and tissues.