Common "driver pathogens" in many emerging infectious and chronic diseases represent a large opportunity for impact.
Spirochetes
Spirochetes are a biologically sophisticated gram-negative bacteria. They are a deeply-branching phylum of bacteria initially delineated by their serpentine shape and periplasmic flagella. Their unusual cellular ultrastructure, motility mechanism, metabolic pathways, capacity for gene regulation and ability to modulate and evade the immune system make them a challenging opponent. They are invasive, mobile, immunosuppressive and difficult to detect, culture and treat. When an infection is left untreated or unresolved (>6 mos), they often lead to immune system malfunction, lasting microbiome changes and chronic illness. All of which produce an outsized negative impact on patients, families and the healthcare system.
Spirochete-driven Diseases
Examples of spirochetal diseases: Lyme disease (Borrelia burgdorferi), syphilis (Treponema pallidum), yaws (Treponema pallidum pertinue), advanced periodontal disease (Treponema denticola and Fusobacterium) and leptospirosis (Leptospira). Each of the above pose immense, and growing, global threats to human and animal health.
Fusobacterium
Fusobacterium nucleatum (Fn) is an opportunistic, gram-negative bacteria commonly found in the oral cavity. Fn is known to cause periodontal disease but is also associated with a growing number of systemic diseases, ranging from cancer and women’s health issues to Alzheimer’s disease.
The associations between poor oral health and chronic systemic disease have been suspected for years. However, more recent research suggests that Fn, if left unchecked, can manipulate the immune system and travel outside the oral cavity, ala a Trojan horse. Fusobacterium plays a primary role in this activity but is not often alone in the process, collaborating with other microbes, like Treponema denticola (a spirochete), to effect its pathogenic action in distant tissues.
Fusobacterium-driven Diseases
Fusobacterium nucleatum (Fn) has been associated with a host of cancers, most notably, colorectal cancer (CRC) and oral cancer (OSCC). In CRC, Fn promotes tumor development by recruiting immune cells to the tumor, which creates an inflammatory environment. Fn also promotes CRC development through toll-like receptor signaling and microRNA expression. The presence of Fn has been linked to poor prognosis in a host of other tissue proliferative and inflammatory disorders, including: breast, bladder, pancreatic, and esophageal cancers. It has also been linked with debilitating women’s health issues, such as, endometriosis, infertility, pre-term birth and still birth.
Our Platform
Flightpath Biosciences uses advanced drug discovery tools to identify optimal antimicrobial therapeutic candidates to vastly improve drug targeting and safety, reduce off-target impacts on the microbiome, speed the time-to-market and reduce the risk of antibiotic resistance.
In parallel, our data science and bioinformatics partners are working hard to understand host and microbiome genetics and transcriptomics to further define the impact of our drugs on the patient’s immune system, microbiome and overall health. We believe this will lead us to new data, novel discoveries and additional targeted therapeutic candidates.
Science Driven & Data Supported
FP-100
Our breakthrough, orally bioavailable, narrow-spectrum bactericidal antibiotic leverages a unique transport mechanism (not present in mammalian cells) and a known mechanism of action to inhibit protein synthesis in gram-negative spirochetes and fusobacterium. Flightpath has demonstrated selectivity in vitro and efficacy in vivo versus standard-of-care broad spectrum antibiotic therapies. Toxicity has been evaluated at multiple ascending doses and in multiple animal species without biologically relevant events.
Manufacturing Scale-up
Flightpath has conducted extensive technology transfer to achieve product manufacturing yields similar to that of standard broad-spectrum antibiotics (e.g. penicillin). We are now manufacturing at clinical and commercial scale and completing final GMP drug substance and drug product manufacturing activities.
Sparing the Microbiome
FP-100 is a narrow-spectrum antibiotic with a favorable microbiome profile.
Standard-of-care broad-spectrum antibiotics are known to cause blooms of Enterococcus and gastroinstestinal dysbiosis that could lead to immune dysregulation, chronic diseases and health problems beyond the infection being treated (e.g. asthma, allergies, anxiety, cancer, depression, diabetes, etc). Patients with chronic Lyme disease often report having muscle and joint pain, psychological and / or neurological issues and immune system difficulties possibly associated with use of multiple, long-term, broad-spectrum antibiotics.
Drug Discovery
Flightpath and its collaborators are committed to advancing additional antimicrobial discovery research in non-traditional areas of pathogen-driven diseases with high unmet medical need.
Relevant Disease Statistics
New Lyme disease diagnoses each year (US)
New cases of adult and congenital syphilis (US)
47% of adults have periodontal disease (US)
Deaths from colorectal cancer every year (US)
New colorectal cancers diagnosed last year (US)
Males are more at risk of getting and dying from colorectal cancer than females
Women are affected by endometriosis (WW)
Hysterectomies performed per year (US)
Average cost of a hysterectomy