Our lead drug PTL-202

The lead product candidate PTL-202 is a combination of drugs that have been approved by the FDA in other indications. PTL-202 is being developed for the treatment of progressive scarring of the lung, Idiopathic pulmonary fibrosis (IPF), a $2 billion market opportunity. IPF has a prevalence in the US and Europe totalling 200,000 patients. The death rate in IPF is higher than either prostate or breast cancer.

In animal trials the combination was more effective than either of its components at reducing indicators of fibrosis. Pacific is planning to formulate the fixed dose combination and initiate a clinical trial of PTL-202 consisting of a drug/drug interaction and pilot bio-equivalency study in 2012. These studies will be followed by final formulation and bioequivalence studies prior to initiation of a Phase 2 proof of principle study.

A provisional patent was filed in the United States by the Issuer in October 2007 to cover the composition of matter and method of use of this combination. In October 2008, the Issuer filed a PCT application based on the above provisional application. The Issuer received a positive preliminary examination of the PCT application in the spring of 2009 and is now ready to formulate PTL-202 and take it into a drug/drug interaction study in humans in 2012.


Method of action

The combination is intended to negatively target several pro-fibrotic cytokines: TNF-α, TGF-α, PDGF as well as reactive oxidative species, literally, in one tablet (Fig.2)

Fig.2 Schematic description of biological action of PTL-202 on idiopathic pulmonary fibrosis



Pentoxifylline (PTX) is a member of the methylxanthine group of chemicals. It acts as pan-phosphodiesterase (PDE) inhibitor resulting in increased level of cyclic adenoside monophosphate (cAMP), important second messenger, in variety of cell types. This leads to vasodilation, improvement of blood cell flexibility and enhancement of blood flow. In addition, the increased cAMP in platelets inhibits platelet aggregation which contributes to a reduction of blood viscosity. Hence, PTX has been successfully and safely used for treatment of vascular diseases such as intermittent claudication.

There is growing evidence that PTX, in addition to its hemorrheologic properties, has significant anti-inflammatory and anti-fibrogenic effects in lung tissue. PTX decreases neutrophil sequestration, inhibits production of free oxygen radicals. More recently, PTX has been shown to inhibit both steady-state and PDGF stimulated proliferation of lung interstitial fibroblasts and myofibroblasts, as well as collagen synthesis by these cells. Moreover, PTX has been shown to decrease secretion of TNF-α, TGF-α and FGF2 by alveolar macrophages and alveolar epithelial cells. In animal studies, PTX lowered liver collagen concentration in a pig model for liver cirrhosis, prevented TNF-α induced lung injury in guinea pigs, and diminished severity of bleomycin-induced pulmonary fibrosis.

It is widely accepted that alveolar epithelial cell injury in IPF is likely mediated, at least in part, by oxidants generated at the IPF alveolar epithelial surface. In this regard, strategies to reduce oxidants are beneficial in decreasing alveolar epithelial cell injury and consequently reducing the progressive deterioration of patients with IPF. Indeed, several groups have reported preventive effects of some anti-oxidants such as alpha-tocopherol (Vit E), and erdosteine in animal models of pulmonary fibrosis.