Development of BIO 300 Injectable Suspension to Treat Radiation-Induced Lung Injury
Abstract
Rationale: Exposure to radiation can have life-threatening consequences. Toxicities associated with radiation exposure exist as two forms: an acute syndrome, which usually occurs within hours to weeks of radiation exposure and a delayed, chronic phase, which can manifest months to years after exposure. The lung is particularly sensitive to radiation, and lung injuries from radiation exposure typically manifest as delayed effects. Current U.S. Food and Drug (FDA)-approved therapeutics that mitigate radiation-induced organ damage are only meant to mitigate acute injury and are only used after radiation exposure. This can be challenging since members of the Armed Services and first responders are likely to embark into environments with excessive levels of radiation due to nuclear attack or accident. This puts Service Members at high risk of developing radiation-induced toxicities because there are no prophylactic medical countermeasures currently available. Project and Objectives: Humanetics Corporation (Humanetics) is developing BIO 300 as a medical countermeasure to prevent or mitigate the effects of acute radiation syndrome and the delayed effects of acute radiation exposure. Currently, an oral formulation of BIO 300 is under advanced development as a prophylactic countermeasure to mitigate the acute and delayed effects of radiation exposure. However, this formulation needs to be taken daily for 2-6 days to offer optimal radioprotection, which is sufficient when there is an elevated nuclear threat, but it is not suitable for situations where there is an imminent nuclear danger. For rapid onset radioprotection, Humanetics is developing BIO 300 Injectable Suspension, which has been shown to offer protection when administered by a single intramuscular injection 12-48 hours prior to radiation exposure. Unfortunately, the BIO 300 Injectable Suspension formulation is not optimal for use during military operations. However, we hypothesize that the BIO 300 Injectable Suspension formulation can be optimized for use in an autoinjector so that the drug could be self-administered in the field. Development of an autoinjector-optimized formulation will be of great benefit since it can be self-administered prophylactically, and offer protection to troops, first responders, or civilians in the unfortunate event of exposure to high-dose radiation. Humanetics proposes to optimize the formulation of BIO 300 Injectable Suspension for autoinjector-compatibility with the Technology/Therapeutic Development Award under the topic area of Respiratory Health. The primary objective of this proposal will be to develop a BIO 300 autoinjector formulation that will be used as a prophylactic to prevent lung injury and mitigate the progression of pulmonary fibrosis due to high-dose radiation exposure. The objective of this proposal will be met with the following research projects: (1) Development of up to five candidate formulations of autoinjector-compatible BIO 300. The lead candidate will be selected through rigorous nonclinical testing to ensure that the formulation provides therapeutic levels of drug exposure, and that the formulation is able to protect the lungs in animals exposed to radiation. (2) Establish FDA-guided good manufacturing practices for the lead candidate and manufacture a lot of drug. This lot will be used for small and large animal safety and toxicity studies that will enable the translation of this formulation into future human clinical trials. (3) The body of work produced under this proposal (nonclinical testing, manufacturing, and safety/toxicity) will be presented at the end of the project to the FDA during a Type-B meeting for review. In addition, we plan to share the design of a future phase 1 clinical safety trial in healthy human volunteers. Once we gain concurrence on the clinical study design, we will be in the position to continue the advanced development of BIO 300 Injectable Suspension with future funding.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210516
Entities
People
- Michael Kaytor
Organizations
- Humanetics Corporation (United States)
- United States Army