Peer Reviewed Medical
Development of BIO 301: An Encapsulated Nanogenistein Therapy
Posted October 13, 2020
Michael Kaytor, Ph.D., Humanetics Corporation
Dr. Michael Kaytor
U.S. military personnel may encounter a wide variety of dangers during their performance of duty, including chemical, biological, radiological, or nuclear (CBRN) hazards. While CBRN hazards have various origins, some may cause similar health effects. For example, exposure to ionizing radiation and coronavirus disease of 2019 (COVID-19) infection may each cause damage and scarring in the lung tissue (i.e. lung fibrosis). Lung fibrosis in both cases can lead to long-term impairment of lung function and severe decreases in quality of life. A team of researchers led by Dr. Michael Kaytor at Humanetics Corporation (Humanetics) previously conducted efforts to make genistein, a compound that stimulates DNA damage protection and repair, an effective treatment to prevent the negative health effects of radiation treatment for lung cancer, including lung fibrosis. The radioprotective effects of genistein were originally discovered by researchers at the Armed Forces Radiobiology Research Institute and the National Institutes of Health, and subsequently licensed to Humanetics for further development and ultimately, US Food and Drug Administration approval. Genistein has shown promise for radioprotection but has eluded drug developers for decades due to its poor solubility and low oral bioavailability. Dr. Kaytor’s team successfully developed a nanoparticle oral suspension formulation of genistein, BIO 300, which showed promise in reducing pulmonary injury in a National Cancer Institute (NCI)-sponsored Phase 1b/2a clinical trial for patients receiving radiation therapy for lung cancer (NCT02567799). During this time, Dr. Kaytor also received a Fiscal Year 2016 (FY16) Technology/Therapeutic Development Award from the Peer Reviewed Medical Research Program (PRMRP) to develop a new, solid dosage formulation of genistein that is more appropriate than an oral suspension as a radiation medical countermeasure for protection of U.S. military personnel.
Supported by their FY16 PRMRP award, Dr. Kaytor’s team designed a new formulation, BIO 300 Oral Powder (previously known as BIO 301), which is amenable to a solid dosing form (tablet, capsule, etc.) to better suit the needs of deployed Warfighters. The researchers rapidly developed and screened over 100 formulations, one of which (an amorphous dispersion) exhibited vastly improved oral bioavailability compared to BIO 300 Oral Suspension in animal studies and was sufficiently stable for further development efforts. The amorphous dispersion can be formulated into a variety of shelf-stable forms that are suitable for field operations and early formulations have demonstrated promising radioprotection efficacy. The current oral powder that is being tested can easily be further processed into a variety of easy to administer oral products. Additionally, because the active pharmaceutical ingredient in BIO 300 Oral Powder matches that of BIO 300 Oral Suspension, the team is able to use the oral suspension data to support the rapid development and regulatory approval of BIO 300 Oral Powder. Findings from this award were further supported by an FY18 Joint Warfighter Medical Research Program award to advance the development of this solid formulation of BIO 300. Included in this award are required human safety studies with the new more bioavailable BIO 300 Oral Powder.
Lung injury due to COVID-19, which has been reported in as many as 50% of patients at the time of hospital discharge, appears similar to lung injury caused by radiation therapy. For comparison, two studies found that approximately 30%-45% of infected patients developed pulmonary fibrosis within 12 months following the Severe Acute Respiratory Syndrome (i.e., SARS) epidemic of 2003. In addition to developing a solid formulation for BIO 300, the studies conducted with the FY16 PRMRP award improved understanding of the pharmacokinetic and pharmacodynamic properties of the original BIO 300 Oral Suspension. These data, along with the promising results of the NCI-sponsored clinical trial, led to support for another clinical trial in patients recovering from COVID-19, this time sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). In this NIAID-sponsored clinical trial, patients will self-administer BIO 300 or placebo for 12 weeks following discharge from the hospital, and they will be followed for 1 year to assess lung function, exercise capacity, and quality of life. In addition to studying the therapeutic effects of BIO 300, this study will evaluate long-term effects following COVID-19 infection. The ability of BIO 300 Oral Powder to reduce the inflammatory response associated with COVID-19 disease severity will be studied in transgenic mice through an FY20 PRMRP Expansion Award that was recently recommended for funding. These studies by Dr. Kaytor and his team highlight the progress towards essential treatments for lung fibrosis, especially due to emerging threats such as COVID-19 infection, which could ultimately benefit both U.S. military personnel and the American public.
Last updated Monday, January 3, 2022