OVERVIEW

Bisphosphocins are novel small protonated nucleotide derivative molecules that exert their antibacterial activity by depolarization of the bacterial cell membrane, causing rapid bacterial cell death. Preclinical studies have demonstrated efficacy against more than 70 bacterial strains, including the ESKAPE pathogens and clinically isolated strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA). Due to the nature of the rapid bactericidal mechanism, challenged bacteria have been unable to develop resistance to bisphosphocins. Serial passage of MRSA in sub-inhibitory bisphosphocin concentrations (0.1x minimum inhibitory concentration (MIC) and 0.2x MIC) failed to generate any detectable change in the MIC out to 30 days, whereas the bacteria demonstrated resistance to ampicillin after only one day. This indicates that after 30 days of exposure the bacteria were unable to develop a resistance to bisphosphocins.

In 2017, Lakewood completed a Phase 1/2a clinical study testing its proprietary Nu-3 for the treatment of patients with infected diabetic foot ulcers (iDFU). Nu-3 was well-tolerated, with no reported adverse events related to treatment. While this dose-escalating, exploratory study was not powered to generate statistically significant efficacy data, it did reveal a trend toward efficacy. Patients treated with 2% Nu-3 for seven days had a 65.5% reduction in ulcer area versus a 29.9% reduction in the placebo arm, as measured 14 days after treatment began. In addition, 62.5% of patients treated with 2% Nu-3 saw a reduction in the microbiological load, versus 20% in the placebo. After Nu-3 is reformulated into a gel, an additional placebo-controlled, dose-escalating, adaptive arm Phase 2a study is planned. This study will extend treatment time from 7 days to 21 and will probe for further dose-escalation effects in 2, 5, and 10% formulations.

This promising first-in-human data support the insights found in the extensive body of preclinical work on the fast-acting antimicrobial activity of bisphosphocins. With evidence that bisphosphocins are effective against all antibiotic-resistant clinical strains tested, and that these strains have not been able to generate resistance to bisphosphocins, Lakewood-Amedex is rapidly expanding our pipeline to four additional indications of urgent medical need where patients are routinely plagued by multidrug resistant infections.

Bisphosphocins may well represent a broadly effective weapon against antibiotic-resistant and biofilm-forming pathogenic bacteria. Hence, Lakewood’s proprietary bisphosphocins technology platform represents the opportunity to build a substantial new anti-infectives company with a diversified development pipeline that addresses the most critical current needs for new anti-microbial and anti-fungal therapeutics.

The company has progressed significantly beyond preclinical validation, to achieve the first safety and preliminary efficacy signals in humans in a Phase 2a clinical trial in infected diabetic foot ulcers, and to develop a second generation of bisphosphocins that are significantly more druggable and better suited for a broad range of clinical indications.