San Francisco-based anti-infectives company Achaogen completed a $56 million Series C financing round led by new investor, Frazier Healthcare Ventures. The company says that the funds will be used to push on with development of its pipeline of antibacterial products including the early clinical-stage, next-generation aminoglycoside, ACHN-490.
“This financing, together with nondilutive capital that we have secured through partnerships with various government agencies will enable us to advance multiple clinical programs, including conducting a Phase II study in complicated urinary tract infections of ACHN-490, our lead candidate for multidrug-resistant bacterial (MDR) infections,” comments Kevin Judice, Ph.D., CEO and CSO.
Recent studies suggest that over 20% of Gram-negative bacteria strains worldwide are now resistant to one or more currently marketed aminoglycosides, according to Achaogen, creating a critical need for innovative new drugs to treat MDR bacterial infections effectively. The firm has chemically engineered lead product, ACHN-490, along with other next-generation aminoglycosides, or neoglycosides, to overcome existing aminoglycoside-resistance mechanisms. The result is a pipeline of broad-spectrum agents that are effective against aminoglycoside-resistant bacteria as well as those that are resistant to other commonly used classes of drugs including fluoroquinolones, cephalosporins, carbapenems, and glycopeptides, the company reports.
ACHN-490 is currently in Phase I trials. The firm is concurrently developing membrane biosynthesis inhibitors targeting LpxC, an oral beta-lactam antibiotic with activity against MRSA, and broad-spectrum fluoroquinolones against resistant Gram-positive and Gram-negative bacteria.
The company’s work on SOS pathway inhibition has led to a class of compounds that it believes inhibits the rate of bacterial mutation and thus the emergence of drug resistance when administered in combination with antibiotics. In vitro and in vivo studies have shown that SOS inhibitors also hypersensitize bacteria to existing antibiotics, making resistant bacteria susceptible again, Achaogen points out. Research has also demonstrated that these inhibitors attenuate bacterial virulence in vivo, reducing the severity and duration of an infection, the firm adds.
Achaogen’s antibiotics that inhibit outer membrane biosynthesis work via a previously unexploited target known as LpxC. These first-in-class agents reportedly have a novel mechanism of action and are potent against a broad spectrum of MDR Gram-negative bacteria with no pre-existing clinical resistance.
Antibacterial activity has been demonstrated against MDR P. aeruginosa and MDR E. coli as well as other clinically important Gram-negative pathogens including what it calls weaponizable bacteria such as Y. pestis. The compounds also have the potential to be administered orally as well as intravenously, Achaogen adds. IND filings for an LpxC-targeting candidate and a SOS pathway inhibitor are expected to be made this year.