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Lakewood-Amedex, Inc. is focused on leveraging next-generation science to address unmet needs in the treatment of serious infectious diseases, improving patient outcomes and significantly reducing the threat posed by antibiotic-resistant bacterial strains like MRSA and NDM-1.
The technology at Lakewood-Amedex was originally discovered and developed by Roderick M. K. Dale, PhD, a former Yale university professor of molecular biophysics and biochemistry. Following the death of Rod’s father from a MRSA infection, Rod attempted to use RNA ‘gene silencing’ to combat infectious diseases, plowing more than $6 million of profits from his successful oglionucleotide contract manufacturing company into research and development efforts. In the course of his research efforts, Rod accidently discovered that certain oglionucleotide chains reacted with bacterial cell membranes and immediately depolarized them. Rod had accidently stumbled upon the first Bisphosphocins™.
The U.S. Centers for Disease Control and Prevention (CDC) recently released a report examining the increasing threat posed by antimicrobial resistance.
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 muliple types or classes of antibiotics (antimicrobials used to treat bacterial infections). 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.Dr. Tom Frieden, MD, MPH Director, U.S. Centers for Disease Control and Prevention Antibiotic Resistance Threats in the United States, 2013
The discovery of antibiotics in 1928 is considered one of most significant factors driving the dramatic rise of average life expectancy in the 20th century, allowing physicians to cure formerly deadly illnesses such as gonorrhea and pneumonia, while also dramatically improving surgical outcomes. However, despite the availability of numerous antibiotic classes and products, serious infections remain the leading cause of death worldwide and the 3rd leading cause of death in the United States.
The increasingly widespread prevalence of antibiotic-resistant bacterial strains, such as MRSA (“Mersa”), poses a serious threat to the progress we have made over the past century. The mortality rates due to multidrug-resistant bacterial infections are increasing at a terrifying pace. Each year, more than 63,000 patients in the United States die every year from hospital-acquired bacterial infections and another 25,000 patients in the EU die from multidrug-resistant bacterial infections. The estimated pharmacoeconomic costs associated with these infections are staggering, estimated at more than 8 billion additional hospital days and approximately $28 billion annually in just the United States.
Despite significant efforts over the past few decades, the discovery of new antibiotics has proven exceedingly difficult, resulting in a steady decline in viable therapeutic options as bacteria become increasingly resistant to existing antibiotics . According to the Centers for Disease Control and Prevention (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%. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health issue. According to the World Health Organization (WHO), almost one-third of the world's population is infected with mycobacterium tuberculosis, of which an estimated 5% is resistant to most antibiotics. 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 recent identification of a strain of Streptococcus resistant to more than 18 different antibiotics highlights this fact and the obvious need for novel approaches to dealing with bacterial infections, such as Lakewood-Amedex's Bisphosphocins™.
In addition, the emergence of diseases such as SARS and West Nile Virus, the H1N1 Influenza outbreak and the re-emergence of the lethal H5N1 “avian flu” plus increased resistance of organisms to existing therapies, combined with the increased prevalence of food-borne diseases such as E.coli O157:H7 have highlighted the lack of effective therapeutics and/or vaccines to combat many of these diseases. Many experts believe that it is only a matter of time before one of these more virulent pathogens becomes more readily transmissible to humans, potentially resulting in a worldwide pandemic. In 2012, a Dutch research organization in collaboration with an American university genetically re-engineered the lethal H5N1 influenza type A virus to make it easily transmissible between humans, demonstrating that if such a virus developed through the natural pathway of mutations, it would almost certainly cause a major world health crisis.
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.
Our primary short- and intermediate-term focus is on the development of our proprietary antimicrobial Bisphosphocins™ for both topical and systemic infections. To date, Bisphosphocins™ have been shown to be rapidly bactericidal (effective) against more than 70 different bacterial strains, including the antibiotic-resistant ESKAPE strains, which together are responsible for more than 70% of hospital-acquired infections, 'SuperBug' strains, such as NDM-1, as well as numerous potentially deadly biological weapon strains, such as anthrax and bubonic plague. Bisphosphocins™ have also been shown to be both safe and well-tolerated in established animal models. In the intermediate- to long-term, we also intend to leverage our proprietary nanoRNA ‘gene silencing’ platform technology to develop targeted therapeutics for viral infections and other diseases. Our lead nanoRNA product, Influ-RNA, is an anti-influenza agent which is expected to enter clinical trials as soon as sufficient capital is available.
Lakewood-Amedex is pursuing the proven model of developing our products through proof-of-concept in humans (Phase II) in a variety of indications and subsequently partnering with one or more established multibillion-dollar biopharmaceutical companies to develop and commercialize our products for use in those indications. Through those partnerships, we expect to receive significant upfront, milestone and royalty payments, with the potential for our first partnership by late 2015. Consistent with other biopharmaceutical companies, Lakewood-Amedex’s valuation will be driven first by achieving important preclinical, clinical and regulatory milestones as well as establishing validating partnerships and, later, by revenues (in the form of royalties on sales). Operating with a small but experienced, efficient, and results-oriented management team, who have a significant shareholding, Lakewood-Amedex seeks to align the interests of all of our stakeholders (investors, management, patients and physicians) to achieve our strategic objectives and create long-term value.
Following a successful pre-IND meeting with the FDA in the fall of 2013, Lakewood-Amedex expects to initiate its first clinical trial, a Phase I/IIa trial of our lead Bisphosphocin™ compound, Nu-3, in the treatment of complicated diabetic foot ulcers (cDFU), a topical infection indication, in 3Q14, with results expected in 2H14. Shortly thereafter, Lakewood-Amedex expects to initiate another clinical trial to demonstrate the safety and tolerability of Nu-3 for the treatment of systemic infections.
Lakewood-Amedex's products are protected by an extensive intellectual property portfolio consisting of more than 70 issued composition-of-matter, method-of-use, and manufacturing process patents covering all major markets through at least 2027.
Antibiotics are the single largest biopharmaceutical market, accounting for 14% of total prescriptions, with more than 80% of Americans prescribed an antibiotic at least once each year. Despite being dominated by generics, the worldwide antibiotic market is estimated at $42 billion annually, with antibiotics accounting for an estimated 20% of total prescription drug spending and up to 50% of hospital prescription drug spending.
Despite its unmatched size, a lack of innovation over the past few decades has resulted in limited competition. The market leading antibiotics are amoxicillin, a β-lactam antibiotic, which generates more than $2.4 billion annually in generic sales, and augmentin (amoxicillin/clavulanic acid), which generates another $1.6 billion annually in generic sales. The equivalent branded sales of these products would be well over $10 billion each, making them the best-selling pharmaceutical products in the world.
Following a four-decade hiatus in innovation, four new antibiotics classes have recently been brought into clinical use: cyclic lipopeptides, such as Cubist's Cubicin™ (daptomycin), glycylcyclines, such as Pfizer's Tygacil (tigecycline), oxazolidinones, such as Pfizer's Zyvox™ (linezolid), and lipiarmycins, such as Optimer's Dificid™ (fidaxomicin), the latter of which was recently acquired by Cubist for more than $800 million.
While the discovery of these new antibiotic classes has provided physicians with the means to combat infections resistant to older antibiotics, these advantages are offset by significant safety concerns. For example, daptomycin was originally discovered in the late 1980s (more than twenty years ago!) at Eli Lilly, but further development was shelved due to daptomycin's significant adverse effects on skeletal muscle, including myalgia and potential myositis -- side effects that are only acceptable now due to the lack of viable therapeutic alternatives. Despite these limitations, Cubicin™, which is reserved for use only in the treatment of life-threatening, gram-positive infections, nevertheless generated sales of more than $900 million in 2013. Also, despite its recent entrance onto the market, daptomycin resistance is already emerging worldwide, with cases reported in Korea as far back as 2005, in the United States as far back as 2007, in Europe as far back as 2010, and in Taiwan in 2011.
Antibiotics can be broken down into two main categories: bactericidal agents, which directly kill bacteria, and bacteriostatic agents, which slow down or stall bacterial growth. The vast majority of conventional antibiotics are bacteriostatic, requiring a properly functioning immune system to combat the infection. This severely limits treatment options in immuno-compromised patients, such as chemotherapy patients or HIV+ patients. The few that are bactericidal, such as the β-lactam antibiotics (including the penams, cephems, monobactams, and carbapenemspenems) as well as vancomycin, act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. Unfortunately, this mechanism requires the bacteria to attempt to replicate (divide) to be effective -- and these compounds are also quite toxic. As a result, Bisphosphocins™ offer numerous clinically-significant advantages over conventional antibiotics, with no offsetting disadvantages.
Bisphosphocins™ are highly protonated synthetic molecules with a core acidified nucleotide carrier, modified by blocking groups, and exhibit chemical stability, acid pH resistance, and nuclease resistance allowing for multiple routes of delivery. Due to their chemical structure, Bisphosphocins™ are unlikely to function through inhibition of any nucleotide-based process. Preliminary experiments indicate a mechanism involving disruption of the bacterial cell membrane which is further supported by their in vitro effectiveness against over 70 different bacterial strains including gram-positive, gram-negative, and many antibiotic resistant, strains. Unlike conventional antibiotics, it appears impossible for bacteria to evolve resistance against the Bisphosphocin™ mechanism of action.
Our lead candidate for clinical trials, Nu-3, is being developed to treat complicated diabetic foot ulcers (cDFU). Our follow-on candidate, Nu-3, is being developed initially as a first-line systemic antimicrobial for use against Pseudomonas aeruginosa, the most common gram-negative bacteria found in nosocomial infections, and methicillin-resistant Staphylococcus aureus (MRSA), the gram-positive "Superbug" bacteria responsible for more than 500,000 surgical site infections each year and an increasing incidence of death in hospitals and the surrounding community.
Bisphosphocins™' unique combination of attributes including its mechanism of action, broad spectrum of activity (including both gram-positive and gram-negative bacteria, as well as some fungi), and a core structure based on a vital building block give them significant advantages over existing products and position them to become blockbuster drugs in a wide range of infectious disease indications. Within five years, Bisphosphocins™ could be first-line therapy for the most common and widespread bacterial infections.
We have generated unprecedented data in validated preclinical animal models. For example, Bisphosphocins™ have been shown to be an effective treatment in both a chronic rodent lung infection model, where a single aerosolized Bisphosphocin™ treatment completely cleared the infection, and a rodent burn wound model against the Utah 4 strain of P. aeruginosa, shown below, where topical or subcutaneous treatment with Bisphosphocins™ resulted in dramatic survival advantages over the near-zero survival in the control groups. And, importantly, our Bisphosphocins™ appear extremely safe and well-tolerated.
We have also demonstrated effectiveness against biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, chronic otitis media and implant- and catheter-associated infections, which are thought to affect millions of people in the developed world each year and have previously been extremely difficult-to-treat or untreatable. Biofilms greatly enhance the tolerance of microorganisms embedded in the biofilm matrix to the immune system, antimicrobials and environmental stresses, resulting in extreme resistance to factors that would easily kill these same microbes when growing in an unprotected, planktonic state. This matrix protects microbes through (1) blocking; (2) mutual protection; and (3) quiescence (i.e. hibernation). The simplest way that the biofilm matrix protects microbes is by preventing large molecules (antibodies) and inflammatory cells from penetrating deeply into the matrix, as well as acting as a diffusion barrier to small molecules such as antimicrobial agents. A biofilm matrix, particularly polymicrobial biofilms, also allows microbes to cooperate, such as by secreting protective enzymes or antibiotic-binding proteins that protect neighbouring non-antibiotic resistant bacteria, as well as by transferring genes that confer antibiotic resistance to other nearby bacteria. Finally, bacteria in biofilms become metabolically quiescent (i.e. hibernate), and because bacteria need to be metabolically active for conventional antibiotics to be effective, quiescent bacteria in biofilms are able to survive doses in excess of the maximum prescription level. Due to their unique mechanism of action which does not require bacteria to be metabolically active, Bisphosphocins™ are extremely effective against biofilm infections, as demonstrated by the following data.
There are approximately 76 million cases of food-borne infections each year in the U.S., resulting in $10 billion in unnecessary costs due to lost productivity, hospitalization, and loss of life. Of these cases, 100,000 are caused by potentially lethal Shiga-toxin-producing Escherichia coli (STEC). While the food industry continues to implement additional safeguards to protect the food chain, the number of outbreaks of food-related infections continues to increase, resulting in a significant unmet need for targeted therapeutics addressing these pathogens.
Lakewood-Amedex is developing therapeutics capable of binding deadly toxins produced by bacteria that cause severe illness and often fatalities. In March 2007, Lakewood-Amedex acquired exclusive worldwide rights from Tufts University to a panel of fully human monoclonal antibodies (MAbs) developed by Dr. Saul Tzipori to bind the exotoxins produced by Shiga-toxin-producing Escherichia coli (STEC), particularly E.coli O157:H7, a bacterial strain that has been linked to many serious food-borne infections throughout the world. These fully human monoclonal antibodies (MAbs) have been extensively tested for both their ability to neutralize Shiga-toxin and protect against the effects of E.coli O157:H7 infection.
While we believe our HUS-MAb program offers significant therapeutic benefits, it is not a near-term development priority for the Company. As a result, Lakewood-Amedex is currently seeking a partner to help support further clinical development of our proprietary HUS-MAb.
For additional information about our HUS-MAb program, please contact our VP of Product Development, Paul DiTullio.
Mr. Parkinson has more than 25 years of experience in the biopharmaceutical industry. As co-founder and CEO of TranXenoGen, Mr. Parkinson oversaw its IPO and admission to AIM in July of 2000, increasing its market value from $90M to $250M within one year. As President and CEO of CereMedix, a drug discovery and development company, he advanced their first product to clinical trials. Mr. Parkinson has raised both public and private capital, built management teams, managed M&A, in-licensed and out-licensed products/technology, and secured major industry contracts and collaborations for a number of companies including Advanced Cell Technology where he was CEO, Johnson & Johnson, PPL Therapeutics, Genzyme Transgenics and Fermetech Ltd.
Mr. DiTullio has more than 20 years of experience in the biopharmaceutical industry, with deep expertise in cell biology and the development of related products and technologies. Previously, Mr. DiTullio co-founded TranXenoGen and, as VP of Product Development, was responsible for coordinating all research and product development activities. Prior to TranXenoGen, Mr. DiTullio was employed as a Research Scientist at Integrated Genetics and Genzyme Transgenics Corporation (now GTC Biotherapeutics) where he was involved in the development of the first transgenic product approved for use in human, GTC BioTherapeutics’ ATryn (anticoagulant antithrombin). Mr. DiTullio holds an M.S. in cell biology and a B.S in biochemistry from the University of Vermont.
Mr. McAllister has more than 15 years of experience in the biopharmaceutical industry, bringing significant accounting, finance and LM&A expertise to the team, having held senior positions as a healthcare investment banker, strategy consultant, and emerging biopharmaceuticals research analyst at a number of well-known companies including H.C. Wainwright, Capital Guardian, Dragonfly Capital, Merriman Curhan Ford & Co., and Thomas Weisel Partners.
Dr. Brown is Board Certified in Otolaryngology-Head and Neck Surgery by the American Board of Otolaryngology and is a Fellow of the American College of Surgeons and American Academy of Otolaryngology. He has a Bachelor of Arts in Theology and a Doctor of Medicine from Creighton University. He completed his residency in Otolaryngology-Head and Neck Surgery at the University of Florida, Gainesville, Florida and an internship in general surgery at Carraway Methodist Medical Center, Birmingham, Alabama. Dr. Brown practices Otolaryngology, Head and Neck Surgery as well as Oral-Maxilofacial Reconstructive Surgery at Regional Medical Center Bayonet Point, in Hudson, Florida.
Dr. Miley is a physician and entrepreneur. He is graduate of University of South Florida College of Medicine and holds certifications from the American College of Surgeons, Advance Cardiac Life Support, American Board of Quality Assurance & Utilization Review and the American Board of Emergency Medicine. He is the former founder and chief executive officer of a number of healthcare-focused software companies including Axcess Medical Imaging, Physician Computer Systems, Inc., and MedHost Inc. In his over 25 years as a physician, Dr. Miley held numerous hospital affiliations and directorships at facilities such as St. Joseph’s Hospital, Lykes Memorial Hospital, Manatee Memorial Hospital, James E. Holmes Regional Medical Center, Palm Bay Family Medical Services, and Bon Secours Venice Hospital.
Dr. Cox, currently an independent consultant to the Biotechnology and Life Sciences Industry and Principal of Beacon Street Advisors, brings significant biotechnology industry experience to the company, through a number of positions as a Senior Executive and CEO, and also as a Board Director, and Chairman, of both public and private companies. Dr. Cox was employed by Genzyme Corporation for 13 years last serving as its Executive Vice President, Operations. He subsequently became Chairman, CEO and President of Aronex Pharmaceuticals Inc. and then Chairman, CEO and President of GTC Biotherapeutics Inc., before becoming a Partner with Red Sky Partners, LLC. Dr. Cox is the immediate past Chairman of MassBio, the Massachusetts Biotechnology Council, and served for a number of years on the Board of the Biotechnology Industries Association (BIO), together with the Health Governing and Emerging Companies Sections of BIO.
Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. An increasing number of governments around the world are devoting efforts to a problem so serious that it threatens the achievements of modern medicine. A post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century.
This WHO report, produced in collaboration with Member States and other partners, provides for the first time, as accurate a picture as is presently possible of the magnitude of AMR and the current state of surveillance globally.
The report makes a clear case that resistance to common bacteria has reached alarming levels in many parts of the world and that in some settings, few, if any, of the available treatments options remain effective for common infections. Another important finding of the report is that surveillance of antibacterial resistance is neither coordinated nor harmonized and there are many gaps in information on bacteria of major public health importance.
Strengthening global AMR surveillance is critical as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions and detecting new trends and threats. As WHO, along with partners across many sectors moves ahead in developing a global action plan to mitigate AMR, this report will serve as a baseline to measure future progress.
"Inhibition of Highly Pathogenic Avian H5N1 Influenza Virus Replication by RNA Oligonucleotides Targeting the NS1 Gene" Yanhua Wu, GuoZhong Zang, Yi Li, Yi Jin, Rod Dale, Lun-Quan Sun, and Ming Wang. Biochem. and Biophys. Res. Comm. (2008) vol 365, p369-374.
"Myostatin antisense RNA-mediated muscle growth in normal and cancer cachexia mice" C-M Liu, Z Yang, C-W Liu, R Wang, P Tien, R Dale, and L-Q Sun. Gene Therapy (2008) vol 15, p155-160.
"Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cachexia mice" C-M Liu, Z Yang, C-W Liu, R Wang, P Tien, R Dale, and L-Q Sun. Cancer Gene Therapy (2007) vol 14, p 945-952.
"Therapeutic efficacy of aerosolized liposome-encapsulated nubiotic against pulmonary Pseudomonas aeruginosa infection" RMK Dale, G Schnell, RJD Zhang, and JP Wong. Therapy (2007) vol 4(4), p441-449.
"Therapeutic Efficacy of “Nubiotics” against Burn Wound Infections by Pseudomonas aeruginosa" Roderic M.K. Dale, Glen Schnell, and Jonathan P. Wong. Antimicrobial Agents and Chemotherapy Aug (2004) vol 48(8), p2918-2923.
We are actively establishing collaborations with a number of different biopharmaceutical and animal health companies, as well as academic and government institutions, to enhance our research, development and commercialization capabilities.