BIO 300

A New Medical Radiation Countermeasure

BIO 300 is a non-synthetic single molecular agent for the treatment of Acute Radiation Syndrome, (ARS) and is in a class of drugs known as medical radiation countermeasures. Medical radiation countermeasures are used in the event of, or threat of, a radiation or nuclear event caused by terrorism or accident. Currently, there are no approved drugs for use as medical radiation countermeasures for the prevention or treatment of Acute Radiation Syndrome.

We are developing BIO 300 under a worldwide exclusive license from the Department of Defense and the National Institutes of Health. Since 2003, we have been working with researchers at the Armed Forces Radiobiology Research Institute (AFRRI), to develop BIO 300 and other safe, effective, non-synthetic, simple molecular agents to prevent ARS. AFRRI, located in Bethesda, Maryland, is part of The Uniformed Services University of the Health Sciences, or USU, an institution of higher learning within the Department of Defense, and is recognized as the nation’s premier center for radiation injury countermeasure research.

BIO 300 is highly unique in that it has a history of safety; it can be self-administered; it is cost effective and easily stored in environmental conditions; and can be safely administered without the need for medical supervision. Competing radiation countermeasures for ARS generally require an injection or intravenous administration by medical personnel, use of medical facilities, have undesirable side effect profiles, are higher cost, and may require refrigeration or special handling for storage.

BIO 300 is being studied for its use both before and after a nuclear event. Due to widespread chaos caused by a nuclear event that would cripple transportation, communication, and healthcare systems in a wide geographic region, we believe conventional post-exposure therapies would be largely inaccessible to most civilians. As a result, a majority of the global civilian population currently has no means to protect themselves from harm caused by radioactive nuclear fallout. A material point of differentiation provided by a self-administered agent such as BIO 300 is the ability to offer mass civilian populations a safe, inexpensive solution that may be distributed in advance for easy access and self-administration by individuals at home, work, or in transit. BIO 300 is also uniquely useful by first responders or military personnel who are entering known risk areas and need protection from ARS.

BIO 300 – Mechanism of Action

BIO 300 has shown efficacy as amedical radiation countermeasure through multiple routes of administration in nonclinical animal experiments conducted at the Armed Forces Radiobiology Research Institute (AFRRI). The mechanism of action through which it achieves this effect involves multiple factors such as stimulation of hematopoietic cell growth and differentiation, inhibition of protein tyrosine kinase-triggered apoptosis, and potent antioxidant activity. BIO 300, as an inhibitor of protein tyrosine kinase, has been shown to prevent radiation-induced cell death, or apoptosis. The potent antioxidant potential of BIO 300 also likely plays a role in preventing cell damage due to oxidative free radicals during and after exposure to ionizing radiation.

Advantages of Self-Administered Drugs

Humanetics has focused its development program for medical radiation countermeasures on bioactive non-synthetic compounds with a high safety profile that can improve or protect human immune function. These countermeasures can be safely self-administered by large civilian populations without the need for medical supervision.

BIO 300, our lead candidate, is highly unique in that it can be self-administered and has a history of safety; is cost effective; cand be easily stored in environmental conditions; and can be safely administered without the need for medical supervision. Competing radiation countermeasures for ARS generally require an injection or intravenous administration by medical personnel, use of medical facilities, have undesirable side effect profiles, are higher cost, and may require refrigeration or special handling for storage.

BIO 300 is being studied for use both before and after a nuclear event. Due to widespread chaos caused by a nuclear event that would cripple transportation, communication, and healthcare systems in a wide geographic region, we believe conventional post-exposure therapies would be largely inaccessible to most civilians. As a result, a majority of the global civilian population currently has no means to protect themselves from harm caused by radioactive nuclear fallout. A material point of differentiation provided by an agent such as BIO 300 is the ability to offer mass civilian populations a safe, inexpensive solution that may be distributed in advance for easy access and self-administration by individuals at home, work, or in transit. BIO 300 is also uniquely useful by first responders or military personnel who are entering known risk areas and need protection from ARS.

BIO 300 - Preclinical Program

Substantial preclinical testing of BIO 300 has been conducted in collaboration with the researchers at the Armed Forces Radiobiology Research Institute (AFRRI). Its efficacy as a radioprotectant for Acute Radiation Syndrome (ARS) has been demonstrated in mice using AFRRI’s radiation source facilities and established expertise in radiation countermeasure research. The endpoints are survival, hematological parameters, and resistance to infection. Various ranges of radiation doses, compound doses, and dosing schedules are evaluated to determine each compound’s administration parameters. As shown in the chart, the survival rates for irradiated BIO 300 were 88 percent for subcutaneous administration and 81 percent for oral administration, compared with survival rates for mice given a placebo of 31 percent and 6 percent, respectively.

In 2006, a hematologic biomarker experiment was conducted at AFRRI using BIO 300 in irradiated mice. BIO 300 was administered subcutaneously 24 hours prior to irradiation. The mice were exposed to a sublethal dose of whole body gamma irradiation and followed over a 28-day period. Blood analysis for hematologic parameters was obtained at 8 time points. The hematologic endpoints included a complete blood count with differential and reticulocyte count. The results of the study revealed a significant improvement in all hematological endpoints with BIO 300 administration compared to the control irradiation group (p<0.002). At Day 14, the nadir for the BIO 300 treatment group was 332 percent higher than control for the total white blood cell count, 250 percent higher than control for the total platelet count, and 425 percent higher than control for the absolute neutrophil count. The results from this study indicate that BIO 300 administration results in accelerated hematologic recovery in irradiated mice.

In addition to proof of efficacy work at AFRRI, BIO 300 has been the subject of multiple preclinical and clinical trials for the assessment of safety, pharmacokinetics, absorption, distribution, metabolism, and excretion as well as drug interaction studies. Preclinical assessments for genotoxicity, acute safety, sub-chronic safety, chronic safety, reproductive safety, skin irritation, skin sensitization, and eye irritation have been completed and demonstrate a favorable safety profile. In addition, preclinical evaluations of the absorption, distribution, metabolism, and excretion of orally administered BIO 300 have been completed, resulting in a well understood metabolic pathway for the compound. Drug interaction studies with BIO 300 predict that interaction with drugs metabolized via the cytochrome P450 isoenzymes in humans is not expected.

BIO 300 – Clinical Safety Trials

BIO 300 has been previously studied in two human safety trials. The first trial was a randomized, sequential-group study in healthy volunteers (n=40) to determine the safety, tolerability, and pharmacokinetic data of BIO 300 in four single ascending doses. No clinically meaningful adverse events were noted in any group. BIO 300 was further evaluated for safety in a second study in healthy volunteers (n=30) to determine the safety, tolerability, and pharmacokinetic data associated with oral administration at three ascending dose levels for 14 days. No clinically meaningful physical changes, chemistry laboratory parameters, vital sign changes, or electrocardiogram, or ECG, changes were noted in this study. None of the reported adverse events were serious or unexpected.

Government Research Collaborations

Humanetics entered into a Master Cooperative Research and Development Agreement (CRADA) with the Uniformed Services University of the Health Sciences (USU) and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). The Congressionally-chartered USU is a fully-accredited graduate-education university operated by the Department of Defense (DoD) and is located in Bethesda, Maryland. HJF, located in Rockville, Maryland, is a private, not-for-profit organization chartered by Congress to support medical education and research at USU and throughout the military medical community.

Under the Master CRADA, Humanetics is sponsoring a new research program with two components of USU, the Armed Forces Radiobiology Research Institute (AFRRI), the nation’s premier center for radiation injury countermeasure research, and the F. Edward Ebert School of Medicine. Capitalizing on this DoD expertise, Humanetics plans to develop and commercialize bioactive, non-synthetic compounds that show promise in supporting and protecting the immune system against challenges from exposure to radiation resulting from terrorist attack or nuclear accident. Humanetics and AFRRI are currently pursuing a number of target compounds - some of which have already been shown to be effective in increasing survival in mice receiving lethal doses of radiation. These compounds would be developed for use by the military, first responders and civilians in major metropolitan areas that are vulnerable to a terrorist attack.

To learn more about the Armed Forces Radiobiology Research Institute (AFRRI), click here.