BACKGROUND

The Infectious Diseases Society of America (IDSA) recognizes antimicrobial resistance as “one of the greatest threats to human health worldwide”.

While the discovery of antibiotics is considered to be one of the most significant factors driving the dramatic rise of average life expectancy in the 20th century, serious infections remain the leading cause of death globally and the third leading cause of death in the United States, despite the availability of numerous antibiotic classes and products. The increasingly widespread prevalence of antibiotic-resistant bacterial strains poses a serious threat to the progress we have made over the past century.

Nucleotide parent of bisphosphocins, thymidine.

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In 2013, Dr. Tom Frieden, MD, MPH, Director at the U.S. Centers for Disease Control and Prevention (CDC), stated, “Antimicrobial resistance is one of our most serious health threats. Infections from resistant bacteria are now too common, and some pathogens have even become resistant to multiple types or classes of antibiotics […] The loss of effective antibiotics will undermine our ability to fight infectious diseases and manage the infectious complications common in vulnerable patients undergoing chemotherapy for cancer, dialysis for renal failure, and surgery, especially organ transplantation, for which the ability to treat secondary infections is crucial.”

Mortality rates due to multidrug resistant (MDR) bacterial infections are increasing at a terrifying pace. Each year, more than 63,000 patients in the United States die from hospital-acquired bacterial infections and another 25,000 patients in the EU die from MDR bacterial infections. In the US alone, associated annual additional costs of infections caused by resistant organisms are estimated to be between $21 billion and $34 billion.

Despite significant efforts over the past few decades, the discovery of new antibiotics has proven exceedingly difficult, resulting in a steady decline of viable therapeutic options as bacteria become increasingly resistant to existing antibiotics. According to the CDC, the number of hospital-acquired infections that are resistant to at least one antibiotic is almost 70% and those resistant to at least three antibiotics almost 40%.

No other factor highlights the need for a greater effort into the research and development of novel anti-bacterial compounds than the ever-increasing ability of bacteria to rapidly acquire resistance to existing antibiotics and their newer derivatives.

The opportunity for novel anti-infectives is massive, the need is unmet and the healthcare community is increasingly desperate for new therapeutics. Lakewood-Amedex is poised to quickly emerge as a leader in the development of novel biopharmaceuticals for the treatment of a wide range of infectious diseases.

BISPHOSPHOCIN 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.

Bisphosphocins were first discovered by Dr. Roderick M. K. Dale, a former Yale University professor of molecular biophysics and biochemistry and Founder of Lakewood-Amedex, as a result from his pioneering research into the use of gene silencing RNA oligonucleotides to treat antibiotic-resistant infections.

Preclinical efficacy studies in animals have shown that bisphosphocins are safe and efficacious against a broad range of bacterial infections, including the most multidrug-resistant pathogens, dramatically depopulating infection sites within short exposure times. In vitro biochemical analysis by independent laboratories has confirmed that the bactericidal activity of bisphosphocins is mediated by depolarization of the negatively-charged bacterial cell membrane, with no effect on mammalian cells. In vitro challenge assays exposing large populations of pathogenic bacteria in culture to bisphosphocins has demonstrated very short kill times, within fifteen minutes or less.

A study at Tufts University demonstrated that bisphosphocin compounds are also able to penetrate through bacterial biofilm and kill the biofilm-encased bacteria within ten minutes of exposure. This is crucial data both medically and commercially, since the ineffectiveness of most current antibiotics against biofilm-forming bacteria has become a major factor in the number of deaths attributable to hospital-acquired 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 1/2a 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.