Faron Pharmaceuticals, Ltd.
Vascular barrier is everything
Faron is a Finnish drug discovery company based in Turku, Finland having focus in acute organ injuries, inflammation and cancer spread, often linked to abnormal function of vasculature. The Company’s lead project Traumakine (FP-1201–lyo) could become the first pharmacologically effective treatment for the life threatening condition called acute respiratory distress syndrome (ARDS) as it has demonstrated both safety and efficacy (Bellingan et al. (2014) The Lancet Res. Med. 2: 98-107). Traumakine prevents vascular leakage of lung capillaries and is ready to move to pan-European phase III trial according to the advice company has received from the European Medicine Agency (EMA).
Faron has virtual operation model to minimize fixed costs and therefore all investments made or will be made in Faron will only go to necessary costs to advance project development. Faron expects to become a candidate to float on one or more international markets and an attractive acquisition target with significant value increase in the near future following the FP-1201-lyo pivotal trial completion.
A new mechanism to restrict acute lung injuries
Acute respiratory distress syndrome (ARDS) is serious clinical disorders, which follow a variety of severe direct and indirect lung insults. In serious life threatening situations such as infection leading to sepsis or trauma causing massive tissue injury, an escalation of the systemic inflammatory response leads to multiple organ failure including ARDS. In the case of ARDS the predominant patho-physiological result is increased vascular leakage, which has been shown to be due to the lack of adenosine, an end product of AMP degradation by 5’-nucleotidase (CD73).
Adenosine acts to enhance endothelial barrier function via adenosine receptor activation. Therefore, any biological substance, which acts to increase adenosine level, will reduce vascular leakage and be of benefit in ARDS patients. Such substances are type I interferons, and especially the interferon-beta (IFN-beta). IFN-beta has been shown to up-regulate 5’-nucleotidase (also known as a CD73 molecule and expressed abundantly by normal endothelial cells) and prevent leakage in animal models (Kiss et al. (2007) Eur. J. Immunol. 37:3334). IFN-beta is therefore a potential treatment for ARDS. The schematic drawing below (Figure 1) illustrates how the increased expression of CD73 reduces both the endothelial leakage and escalation of inflammation prior reaching the end stage of this organ damaging condition.
Figure 1: Adenosine is capable of stabilizing endothelial barrier function. Upper panels: Various pathophysiological steps of lung injury in man (leak, inflammatory cell infiltration and collagen synthesis and deposition). Lower picture: Cell surface 5’-nucleotidase (CD73) catalyzes the conversion of AMP into adenosine, which has been shown to reduce vascular leakage and leukocyte infiltration. As vascular leakage and leukocyte infiltration into the lungs are major pathophysiological events in early ALI/ARDS development, increase in 5’-nucleotidase expression with IFN beta resulting in higher adenosine levels could be of therapeutic value.
Faron has been granted an orphan drug status for the treatment of ALI/ARDS with interferon-beta by European Commission and European Medicines Agency (EMA) under the registration number EU/3/07/505. Faron has also been granted several patents both in USA, Europe and Japan, and has several pending applications in other territories for this new use of IFN’s to treat various ischemic conditions. The medical need for an effective and safe treatment of ARDS is high, since this condition is life threatening with 35-45 % mortality rate (Rubenfeld et al. (2005)
N Engl J Med 353, 1685) (Phua et al. (2009) Am J Respir Crit Care Med 179, 220) and affects close to 400.000 patients in Europe, USA and Japan alone. Currently no approved pharmacological treatment of ARDS by the regulatory authorities in Europe (EMA) or in the USA (FDA) is available. Faron together with its scientific and clinical network is a recipient of a €6 million grant for the phase III study from the FP7 EU program.
Significant decline in ARDS patient mortality with FP-1201 treatment
In a UK based FPCLI001 study looking at the mortality of ARDS patients following FP-1201 administration, a significant reduction in all cause mortality between FP-1201 treated and non-treated ALI/ARDS patients (8,1 % versus 32,2 % with p = 0,01) was observed (Figure 2). Also the secondary end points supported the view that the FP-1201 treatment improved, not only lung function but other organ functions as well. Needs for both vasopressors and hemodialysis were reduced by half compared to non-treated ARDS patients. Also the data on several biomarkers indicated positive body response to FP-1201 treatment, including a strong decline in IL-6/IL-8 plasma content following the treatment initiation (Bellingan et al. (2014) The Lancet Res. Med. 2: 98-107). High IL-6 content in serum has been previously connected to poor outcome of ARDS patients (Meduri et al. (1995) Chest 107: 1062-73).
Figure 2: Survival of FP-1201 treated patients compared to eligible non-treated control patients. Kaplan-Meier plots of all-cause mortality at day 28 of all FP-1201 treated patients (n=37) (blue line) compared to the eligible, non-treated control ALI/ARDS patients (59 patients, red line). The odds of mortality reduced more than 80 % between the groups (for details see Bellingan et al. 2014).
Pipeline expansion and company growth
Faron plans to expand the FP-1201 use to other ischemic conditions but also focus on the development of new biologics targeting other molecules like the Clever-1 (see www.faronpharmaceuticals.com). Faron has already licensed Traumakine rights in Japan and may consider other territories as well. However, Traumakine provides also an excellent possibility to create own market force, as Traumakine end users will be around 3,500 European and 5,000 American hospitals with intensive care units. Pipeline expansion could provide additional sales opportunities with limited investments in sales force.