Appili’s unique approach to drug development has enabled the Company to create an expanding pipeline that balances near-to-market opportunities with higher-risk, earlier-stage but potentially transformational programs. It also allows Appili to pursue productive collaborations with industry partners and federal government agencies with aligned objectives, while tapping non-dilutive funding sources specifically earmarked for anti-infective development programs.
Appili’s lead program, ATI-1501, may fill a significant gap in the treatment paradigm by making a proven antibiotic, metronidazole, more accessible to pediatric and geriatric patients. ATI-1501 is an oral taste-masked, liquid formulation of metronidazole. Metronidazole is a front-line oral treatment for parasitic and anaerobic bacterial infections, including Clostridium difficile. It has been available for more than 50 years and is still heavily used, with approximately 9.5 million prescriptions written annually.
However, because of its very bitter taste when crushed, many pediatric and elderly patients who have trouble swallowing pills cannot tolerate metronidazole. This leads to noncompliance, which in turn leads to reoccurrence of the patients’ infections and the potential for them to spread to others.
By leveraging the Company’s proprietary taste-mask technology, ATI-1501 could address the significant compliance issues around the current usage of metronidazole, particularly among those who are unable to swallow large pills (dysphagia). Market research among pediatricians and geriatricians, particularly those who are frequent prescribers of metronidazole or long-term care physicians in community settings, suggests that ATI-1501 would be a valuable component to their treatment armamentarium.
Appili plans to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in 2018, following the 505(b)(2) pathway.
Appili’s proprietary taste-masking technology is being tested in other drug development programs.
Appili’s second antibiotic-focused program, ATI-1503, is a drug discovery program with the potential to generate the first novel class of antibiotics since the 1980’s.
ATI-1503 is focused on generating negamycin analogues to combat the growing threat of antibiotic resistance. Negamycin has broad activity against significant Gram-negative pathogens, including those considered among the most drug resistant, significant bacterial threats: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae (CRE).
Negamycin works by targeting the ribosome in bacteria, cellular structures that are responsible for protein synthesis. Aminoglycoside antibiotics, such as gentamicin, tobramycin, amikacin, and streptomycin, have a similar mechanism of action. But negamycin analogues are a new class of drug that work differently, and thus are not predicted to be sensitive to known mechanisms of resistance that reduce the utility of aminoglycosides.
Negamycin analogue candidates may have unique properties, including favorable pharmacokinetic and toxicity profiles, as well as low resistance frequency. Appili’s ATI-1503 program builds on work done on negamycin analogues at AstraZeneca (AZ). Appili is conducting in vivo studies of proof of concept negamycin compounds.
Appili has secured funding from the Canadian National Research Council (NRC). In addition, the Company has been awarded both a $1.2 million (USD) grant from the Peer Reviewed Medical Research Program (PRMRP) and multiple National Institute of Allergy and Infectious Disease (NIAID) Services contracts related to the ATI-1503 program.
As a unique program in anti-bacterial drug development, ATI-1503 provides significant opportunities for partnering with other pharmaceutical companies.