Investigational Treatment for Mild Traumatic Brain Injury to be Studied in Phase I Trial Later This Year

Bangkok, Thailand (April 18, 2013) - Besins Healthcare (Besins) and Shin Nippon Biomedical Laboratories (SNBL), a global leader in hormonal products, announced today that they have completed a licensing agreement to use SNBL's proprietary intranasal drug delivery system, μco™ System (muco system), to further develop its BHR-310 investigational agent containing progesterone for treating mild traumatic brain injury (TBI).

Under the terms of the licensing agreement, Besins gains access to SNBL's delivery technology, along with associated patents and know-how for delivery of progesterone. Besins will be responsible for completing the development of the product, seeking regulatory approval and commercializing the product. SNBL will be entitled to certain undisclosed milestone payments and royalties on sales.

"The overwhelming need for a treatment for concussions or mild TBI cannot be overstated," said Thomas W. MacAllister, JD, PhD, Besins Chief Development Officer. "The condition is a huge unmet medical need, especially in theaters of war and on sports fields. Partnering with SNBL will allow us to quickly accelerate our intranasal progesterone research program. They have a tremendous amount of expertise in nasal delivery and the platform we are licensing gives far superior performance than the numerous other approached we have tried."

An intranasal progesterone powder, BHR-310 is designed as a ready-for-use nasal spray treatment for wounded warriors or athletes with TBI at the site of injury. Outcomes from preclinical studies of BHR-310 in rats and monkeys conducted by Besins' research and development affiliate, BHR Pharma, LLC, (BHR), support the feasibility of a high-dose, rapidly absorbed intranasal progesterone product able to deliver clinically meaningful doses of progesterone to the brain. BHR anticipates entering the clinic in Q3 2013.

Progesterone (P4) belongs to a class of hormones called progestogens and is the major naturally occurring human progestogen. A potent, naturally occurring neurosteroid hormone, P4 is produced in both male and female brains normally and in response to brain injury. Research suggests that progesterone has a number of mechanisms of action through which it asserts neuroprotective effects by protecting or rebuilding the blood-brain barrier, decreasing development of cerebral edema (brain swelling), down-regulating the inflammatory cascade and limiting cellular necrosis and apoptosis (programmed cell death).[1]

"As we have seen in the preclinical phase, we expect that our μco™ System will safely deliver therapeutic levels of progesterone, enabling the drug to be used in a broad population of brain injured patients," said Ryoichi Nagata, MD, PhD, SNBL President and CEO. "We are pleased to partner with a company so dedicated to finding a viable treatment for this unmet medical condition. Establishment of this relationship is another important milestone in using μco™ System to provide intranasal solutions to biopharmaceutical products. With its versatility to deliver different types of compounds, we expect that there will be many more partnerships to follow."

TBI is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force[2]. According to the World Health Organization, the condition is the leading cause of death and disability in children and young adults worldwide and is involved in nearly half of all trauma deaths. The U.S. Centers for Disease Control (CDC) calls TBI a "serious public health problem"[3] and estimates that 3.5 million Americans suffer some form of TBI annually. Of that number, approximately 75 percent of all TBIs are "concussions or other forms of mild TBI," according to the CDC.

TBI is roundly regarded as the "signature wound" of the Iraq and Afghanistan wars, accounting for 22 percent of all injuries and 59 percent of blast-related injuries [4]. According to the Defense Centers of Excellence For Psychological Health and Traumatic Brain Injury, more than 230,000 American soldiers were diagnosed with TBI in the past decade. Understanding about the devastating impact of the condition on athletes at all levels of competition is growing. The University of Pittsburgh Department of Neurological Surgery estimates that in the United States, over 300,000 sports-related concussions occur annually, and the likelihood of suffering a concussion while playing a contact sport is estimated to be as high as 19 percent per year of play.

The CDC estimates that TBI's direct medical costs and indirect costs such as lost productivity total more than $75 billion annually in the United States.

Besins, a global leader in transdermal progesterone, estrogen and testosterone hormone therapy, is a fourth-generation, family-owned business headquartered in Bangkok, Thailand. Its women's and men's healthcare products are available in 93 countries around the world. Besins founded BHR Pharma, LLC in January 2008 as a wholly owned pharmaceutical research and development company. Located near Washington, DC, USA, BHR is committed to bringing to market specialty treatments that employ non-oral delivery systems, with an emphasis on unmet and underserved medical needs. BHR currently is running a 1180-patient study to test the efficacy and safety of Besins' proprietary intravenous progesterone formulation in patients suffering from severe traumatic brain injury. Enrollment is expected to complete in Q3 of 2013.

For more than 55 years, SNBL has been a leader in providing development services to biopharmaceutical companies, generating high quality data with the exceptional precision needed to rapidly advance new medical therapies and innovations that improve patients' lives. 

In addition to providing services, SNBL has a Translational Research business, which utilizes its development capabilities to develop value-adding technologies and provides them to the pharmaceutical and medical industry. Under such business, SNBL has developed μco™ System, a novel intranasal drug delivery technology platform, to provide effective delivery solutions to pharmaceutical products.

[1] Stein DG, Wright DW, Kellerman AL (2008). Does progesterone have neuroprotective properties? Ann Emerg Med; 51(2): 164-72.

[2] Brain Injury Association of America - Retrieved on Aug. 3, 2012 from

http://biausa.fyrian.com/about-brain-injury.htm#definitions

[3] Traumatic Brain Injury Center.(n.d.). Centers for Disease Control and Prevention. Retrieved May 1, 2012, from http://www.cdc.gov/traumaticbraininjury/

[4] "Injury to brain more than doubles Risk of later dementia," USA Today/Usaedition. Retrieved May 23, 2012 from http://www.usatoday.com/NEWS/usaedition/2011-07-18-Alz-brain-injury--_ST_U.htm