About Us:

San Diego Waterfront Genoa Pharmaceuticals is a pharmaceutical company committed to developing improved therapies for the treatment of Idiopathic Pulmonary Fibrosis (IPF). Based in San Diego, Genoa's lead program (Aerodone inhaled pirfenidone) is advancing towards the clinic for the treatment of IPF. The US FDA has granted Genoa orphan-drug designation of pirfenidone for treatment of IPF.

Clinical Need:

IPF is a fatal orphan lung disease characterized by progressive scarring, reduced exercise capacity and death from respiratory failure and/or co-morbidities. With a 3-5 year survival period, IPF causes more deaths per year than breast cancer and only lung cancer has a worse prognosis. Recently, the first drugs were approved for IPF treatment; oral pirfenidone (Esbriet®) and oral nintedanib (Ofev®). While both are moderately efficacious, clinicians believe use as stand-alone therapy will only extend life by months. Compounding this limitation, each drug is associated with significant side effects further reducing their therapeutic potential. Compared to a year ago, these new therapies are a tremendous step forward in the treatment of IPF. However, this is only the beginning and a substantial unmet need remains in IPF for highly-compliant drugs enabling improved-effect stand-alone and add-on combination therapy.

IPF Disease:

Although much of the pathogenesis of IPF remains to be elucidated, airway epithelial cells and underlying fibroblasts have emerged as principal players in development of disease. Differentiated fibroblasts (myofibroblasts) accumulate in IPF lungs and produce regions of excess collagen and fibrosis. Interestingly, this process appears driven by recurrent and/or non-resolving airway injury, suggesting that communication between airway epithelial cells and fibroblasts is important. Supporting this hypothesis, several investigations indicate that IPF is initiated and propagated by injury-induced synthesis and release of key cytokines, whose communication between these two cell types is central to fibrosis development.

The Inhaled Advantage:

Although oral pirfenidone has shown promise to slow IPF disease progression, it is a low potency drug that requires a very large oral dose to achieve efficacious lung levels. While the Esbriet dose has been established at the upper safety threshold (801 mg TID, 2403 mg/day), resulting lung levels are well-below that required for optimal effect and associated-high blood levels remain poorly tolerated. Because these blood levels exist at the upper-safety threshold, oral-dose escalation for additional efficacy is not possible. Complicating matters, dose-absorbing food, first-pass metabolism, and safety-driven dose-reduction and stoppage protocols further reduce pirfenidone lung dose and interrupt required maintenance therapy.

To address these shortcomings and maximize pirfenidone's potential Genoa has reformulated pirfenidone for nebulization and inhaled lung delivery (Aerodone). By this approach, ~160-fold less device-loaded pirfenidone will deliver the same effective lung dose as Esbriet (~5 mg vs. 801 mg). With much less drug required for equivalent efficacy, pirfenidone safety and tolerability are expected to be greatly improved permitting clinical dose escalation for additional IPF efficacy. With these properties and Genoa data supporting efficient peripheral lung deposition in IPF patients, clinicians believe inhaled Aerodone will be used as a safe and well-tolerated Esbriet alternative or improved-effect stand-alone replacement. As a safe and well-tolerated product, Aerodone will also enable pirfenidone's use in preferred, but otherwise poorly-tolerated, add-on combination regimens (e.g., with Ofev).