DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Development of BIO 301: An Encapsulated Nanogenistein Therapy

Principal Investigator: KAYTOR, MICHAEL D
Institution Receiving Award: HUMANETICS CORPORATION
Program: PRMRP
Proposal Number: PR161175
Award Number: W81XWH-17-1-0584
Funding Mechanism: Technology/Therapeutic Development Award
Partnering Awards:
Award Amount: $3,811,222.00


PUBLIC ABSTRACT

Humanetics Corporation (Humanetics) is developing a new drug, named BIO 300, as a medical countermeasure (MCM) to prevent or mitigate the effects of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE). Symptoms of these syndromes occur throughout the body when someone is exposed to harmful radiation. Among the various organ systems affected by radiation, the lung tissue is of particular concern because it is a relatively large and vital organ system. In particular, the lungs are susceptible to both radiation-induced acute lung injury and pulmonary fibrosis, the latter of which is defined by the slow accumulation of scar tissue in the lung and compromises a person’s ability to properly breathe. In addition, the lung tissue has a low regeneration potential, making treatment options often ineffective. Given this significant current gap in treatment options, Humanetics is focused on developing BIO 300 to protect and benefit the lungs in people that are exposed to radiation.

BIO 300 has a long-standing history with the Department of Defense (DoD). The radioprotective efficacy of the active compound in BIO 300, genistein, was originally discovered by Dr. Michael Landauer at the Armed Forces Radiation Research Institute (AFRRI), an organization within the Department of Defense (DoD) whose mission it is to identify new drug candidates capable of preventing or mitigating radiation-induced harm. The DoD subsequently licensed Dr. Landauer’s patent for the use of genistein as a MCM to Humanetics to develop it as a pharmaceutical drug to protect against radiation exposure. Humanetics is pursuing this effort for uses that encompass both MCM and commercial markets, including protection for Warfighters and civilian populations as well as mitigating the side effects of radiation therapy in cancer patients who are receiving radiation treatment for solid tumors.

To optimize genistein’s therapeutic potential, Humanetics developed a new nano-formulation of genistein, called BIO 300. This formulation is superior to standard genistein in mitigating the deleterious effects of radiation exposure. After a series of successful preclinical experiments, Humanetics has initiated a clinical trial to evaluate BIO 300’s ability to protect lung cancer patients from the side effects of radiation therapy. The BIO 300 formulation used to treat lung cancer patients is a liquid that is administered by an oral syringe. Cancer patients often have compromised ability to swallow as a side effect of their treatment and a liquid drug is optimal. However, such a formulation leaves much to be desired for Warfighters and mass civilian distribution in the event of a nuclear or radiological event.

The purpose of this proposal is to re-develop BIO 300 for use by Warfighters and also for the unfortunate possibility of a nuclear or radiological incident that would affect civilian populations. These situations require a drug in a compact, stable form, and also require a flexible administration process of the drug outside the aid of medical personnel or a hospital setting. Accordingly, we propose to compare various technologies capable of transforming our liquid nano-genistein technology into an encapsulated or tablet formulation. While some of these processes simply crystalize our current liquid formulation into a solid form, others could potentially enable unique biophysical properties of the drug, thus not only enabling a different dosage form, but also perhaps an improved bioactivity. We will compare these candidate drug formulations in multiple validation experiments, characterizing them by their bioavailability and by their ability to mitigate radiation induced damage to the lung. Upon selecting the best formulation, we propose to develop a pilot-scale Good Manufacturing Practices (GMP) manufacturing scheme, which is a requirement for manufacturing drugs for human consumption.

In summary, the work proposed hereafter would enable an unbiased approach to redevelop the dosage form of our radioprotective therapy, with the specific goal of optimizing it for field deployment and strategic stockpiling in order to protect Warfighters and first responders at risk of -- or in response to -- unintended radiation exposure.