Flightpath is developing proprietary oral formulations of two previously FDA-approved drugs for the treatment of acute Lyme disease (FP-101) and Post-Treatment Lyme Disease (FP-102).
Our scientific team screened 8000+ compounds and identified FP-101 and FP-102 as effective drugs against Borrelia burgdorferi (Bb). Unlike doxycycline, a bacteriostatic (Bb growth-inhibiting) drug that is standard of care, FP-101 and FP-102 are bactericidal (Bb killing) drugs.
Azlocillin has a historically clean safety profile and has demonstrated efficacy against Borrelia burgdorferi both in vitro and in vivo.
Azlocillin was approved as Azlin® by the FDA on September 3rd, 1982 as a semisynthetic broad spectrum penicillin antibiotic to treat Pseudomonas aeruginosa via intravenous administration. Commercially, the drug was safe and well tolerated and had a limited side effect profile, with warnings and contraindications related only to a patient history of penicillin sensitivities.
In laboratory plate experiments, our scientific team demonstrated that azlocillin significantly inhibited the growth of drug-tolerant Borrelia burgdorferi (Bb) bacteria in a manner far better than doxycycline (the standard of care).
Azlocillin also reduced Lyme disease related inflammation in mice infected with Bb for seven days, compared to the saline control, telismartin, and doxycycline. Upon completion of additional pharmacokinetic and efficacy studies in animals at Tulane University, we hope to advance FP-101 into clinical trials in acute and PTLDS indications in the near future.
Commercially available disulfiram is an atypical antimicrobial drug with demonstrated antibiotic, antiparasitic and anti-inflammatory properties in animal models of Lyme disease, but its side-effect profile is suboptimal.
Disulfiram (tetraethylthiuram disulfide) was first synthesized in 1881 and used in the rubber industry to hasten vulcanization (i.e., the process of stiffening rubber). In the 1940s, doctors discovered that disulfiram could form chelates with copper leading to the death of parasites. During World War II, disulfiram became a popular therapy to treat scabies and intestinal worm infections. Later, physicians discovered its utility as an alcohol- deterrent for use in treating alcoholism and branded it “Antibus(e)”.
However, the drug also fell into disrepute due to the fatal reactions caused by exorbitantly high doses. The drug also suffered from reports of the neurological, hepatic, and cutaneous side-effects which later on were attributed to diethyldithiocarbamate, one of its metabolites.
In 2016, Jayakumar Rajadas, PhD and his colleagues at Stanford Medicine’s Biomaterials and Advanced Drug Delivery laboratory were the first to discover that disulfiram was extremely effective at eradicating Borrelia burgdorferi in vitro and later with a proprietary formulation of the drug in animal models. This landmark discovery by the Rajadas lab opened up a new line of research into new formulations of disulfiram that could be useful to potentially retain the efficacy of the drug but vastly reduce the negative side-effects.
Flightpath has licensed these proprietary disulfiram formulations and is pursuing the preclinical and clinical path to FDA approval for use in Lyme disease patients with Post-Treatment Lyme Disease (PTLD). Flightpath Bioscience’s proprietary oral formulation of disulfiram is named, FP-102. The company intends to initiate human clinical trial(s) as early as 2020.
Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening. Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim KM, Samineni A, Parekh M, Tayebi L, Rajadas J*. Drug Design, Development and Therapy. 2016, 10, 1307–1322. PMID: 27103785. doi:10.2147/DDDT.S101486
Late Disseminated Lyme disease. Associated Pathology and Spirochete Persistence Posttreatment in Rhesus Macaques. Nicholas A. Crossland,* Xavier Alvarez,z and Monica E. Embers*. The American Journal of Pathology, Vol.188, No. 3, March 2018
Pal A, Pattanayak RD, Sagar R. Tracing the journey of disulfiram: From an unintended discovery to a treatment option for alcoholism. J Mental Health Hum Behav [serial online] 2015 [cited 2019 Oct 7];20:41-3. Available from: http://www.jmhhb.org/text.asp?2015/20/1/41/164826