Therapeutic Platform Pathway 1:
Clinical Program 1: The primary and immediate focus of CP-1 is to further the commercialization of a promising approach comprised of our lead compound NHPN=1010 compound. NHPN-1010 is a combination of two well understood and safe compounds; HPN-07 and NAC.
The target indication will be as an otoprotectant to prevent and treat acute noise-induced hearing loss.
Background: When it is considered that a combination of two compounds might lead to therapeutic effect in humans each compound must be thoroughly studied independently, and then studied as a combination. Since there is extensive clinical data available to our team on the independent studies of HPN-07 and NAC, our main objective is to prove clinical efficacy with the combination of the two compounds. It should be noted that NAC is currently approved by the FDA for other indications and that HPN-07 has successfully completed phase III clinical studies for another indication. Note that AstraZeneca, in partnership with Centaur Pharmaceuticals (RA Floyd, co-founder) from 1998 to 2002, carried out human Phase I, Phase IIa and IIb as well as Phase III (4900 patients total) for the treatment of acute ischemic stroke using NXY059 (same compound as HPN-07). The compound was shown to be a very safe drug. We have shown in preclinical studies that HPN-07 alone, administered orally, does provide over 50% protection from NIHL. Therefore, Otologic Pharmaceutics can take advantage of the extensive FDA approved safety studies to reap enormous savings in developmental costs and progress more rapidly to clinical trials.
Dr. Kopke and Dr. Floyd have been funded over the last five years by the Office of Naval Research to conduct research that promotes an understanding of noise-induced hearing loss (NIHL) and to explore treatment approaches. Over the years, several laboratories including our own have demonstrated that free radical processes cause NIHL. Drs. Kopke and Floyd discovered in chinchillas, as the experimental model, that administering our two are nearly 100% effective in treating permanent hearing loss.
Since NAC alone is effective, we expect the combination of HPN-07+NAC will be efficacious in a synergistic manner. Therefore the drug combination may provide a much more rapid and less expensive development path for a therapeutic to treat noise-induced hearing loss.
Clinical trial with NAC: Marine Corp Recruit Depot Clinical Study: This study was a prospective, randomized, double blind, placebo-controlled investigation of the safety and efficacy of, NAC, to prevent noise-induced threshold shift in 566 healthy subjects exposed to military noise during a 16-day period of weapons training. During weapons training, all subjects received standard hearing protection devices. Hearing status was assessed prior to weapons training and two weeks following the end of training using conventional and high frequency pure tone audiometry and distortion product otoacoustic emissions.
In a post hoc analysis, using Navy criteria for threshold shift, the threshold shift rate was significantly reduced in the NAC group compared to placebo for the right ear, trigger hand ear, and right ear for right-handed shooters.
Over 1000 (566 completed) enrollees have been involved in clinical trials with NAC since 2003 with the target indication of prevention of hearing loss from acute acoustic trauma. No other compound has been so thoroughly studied in humans for our target indication and has found to be safe.
