Zug, Switzerland, December 6, 2018 - Auris Medical Holding AG (EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in neurotology and mental health supportive care, today announced a strategic expansion for its intranasal betahistine development program. In two related transactions, the Company has acquired an Orphan Drug Designation for betahistine in the treatment of obesity associated with Prader-Willi syndrome (PWS) and signed a binding letter of intent to in-license exclusive rights to two US Patents relating to the use of betahistine for the treatment of depression and attention-deficit / hyperactivity disorder (ADHD), respectively.
"We are very excited to address additional neurological and metabolic disorders with our intranasal betahistine program," commented Thomas Meyer, Auris Medical's founder, Chairman and CEO. "Histamine plays a key role in the regulation of a wide range of behavioral and physiological functions, including appetite, drinking, sleep, wakefulness, learning, attention and memory. Betahistine as a structural analog of histamine has been widely used outside the US for the treatment of vertigo for decades. It has also shown promising effects in preventing antipsychotic-induced weight gain, reducing excessive daytime sleepiness and improving cognitive function. While betahistine's clinical utility has been limited by poor bioavailability when administered orally, our intranasal formulation allows for significantly higher plasma exposure, which is expected to translate into better therapeutic outcomes and open up new therapeutic uses."
In Prader-Willi syndrome, a rare genetic disorder characterized by progressive obesity, behavioral issues, delayed cognition and sleep disturbances, emerging research suggests positive effects of H3 histamine receptor inhibition on cognitive disability and excessive daytime sleepiness. Betahistine acts as an H3 receptor antagonist and uniquely, also as an agonist at the H1 histamine receptor, which plays a crucial role in the regulation of food intake. In animal studies, inhibition or knock-out of the H1 receptor resulted in increased appetite and the development of obesity, while food deprivation led to activation of H1 receptors in the hypothalamus.
Betahistine is expected to offer therapeutic benefits also in the treatment of ADHD and atypical depression. ADHD manifests with symptoms, such as hyperactivity, impulsivity and inattention and is estimated to affect in the US 8.8% of children between the ages of 4-17 years and 4.4% of the adult population. In a study with 16 adult ADHD patients, treatment with oral betahistine up to 200 mg resulted in a statistically significant improvement in surrogate markers for cognitive outcomes, attentional sensitivity in the Continuous Performance Task and inhibition in the Go/No-Go task, compared to placebo (p=0.02 and 0.004).
Atypical depression is a subtype of major depression. It is characterized by mood reactivity, fatigue, excessive somnolence, increased appetite or weight gain and cognitive deficits. Estimates in both community and clinical settings suggest that 15.7% to 36.6% of patients with depression present with atypical features. Data from two clinical trials with oral betahistine provide initial evidence for therapeutic benefits in depression.,
The two transactions are expected to close before year-end and to have no impact on the Company's development plans or financial position in the near-term. As previously announced, the Company prepares for the initiation of two proof-of-concept studies with intranasal betahistine in the first quarter of 2019 - one Phase 2 trial with AM-125 in vertigo and one Phase 1b trial with AM-201 in antipsychotic-induced weight gain. Based on the outcomes from these trials and discussions with health authorities about regulatory pathways, the Company plans to initiate specific developments in the new therapeutic indications as well.
Betahistine is a small molecule structural analog of histamine, which acts as an agonist at the H1 and as an antagonist at the H3 histamine receptors. Unlike histamine, it crosses the blood-brain-barrier. It is known to enhance inner ear and cerebral blood flow, increase histamine turnover and enhance histamine release in the brain, increase release of acetylcholine, dopamine and norepinephrine in the brain and to result in general brain arousal. Betahistine for oral administration is approved in about 115 countries, with the US being a notable exception, for the treatment of vertigo and Meniere's disease. The compound has a very good safety profile, yet it is also known that its clinical utility is held back by poor bioavailability. Intranasal administration of betahistine has been shown to result in 6 to 29 times higher bioavailability.
About Auris Medical
Auris Medical is a Swiss biopharmaceutical company dedicated to developing therapeutics that address important unmet medical needs in neurotology and mental health supportive care. The company is focused on the development of intranasal betahistine for the treatment of vertigo (AM-125) and for the treatment of antipsychotic-induced weight gain and somnolence (AM-201). These projects have gone through two Phase 1 trials and will move into proof-of-concept studies in 2019. In addition Auris Medical has two Phase 3 programs under development: Sonsuvi® (AM-111) for acute inner ear hearing loss and Keyzilen® (AM-101) for acute inner ear tinnitus. The Company was founded in 2003 and is headquartered in Zug, Switzerland. The shares of Auris Medical Holding AG trade on the NASDAQ Capital Market under the symbol "EARS."
This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Auris Medical's strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, Auris Medical's need for and ability to raise substantial additional funding to continue the development of its product candidates, the ability to pursue strategic partnering and non-dilutive funding for its Phase 3 programs, the results of Auris Medical's review of strategic options and the outcome of any action taken as a result of such review, the timing and conduct of clinical trials of Auris Medical's product candidates, the clinical utility of Auris Medical's product candidates, the timing or likelihood of regulatory filings and approvals, Auris Medical's intellectual property position and Auris Medical's financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Auris Medical's capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Auris Medical's Annual Report on Form 20-F for the year ended December 31, 2017, and in Auris Medical's other filings with the SEC, which are available free of charge on the Securities Exchange Commission's website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Auris Medical or to persons acting on behalf of Auris Medical are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Auris Medical does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law.
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 For a review see e.g. Lian et al. (2016), Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications, Pharmacol Res 106: 51-63.
 Visser et al. (2014), Trends in the parent-report of health care provider diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003-2011. J Am Acad Child Adolesc Psychiatry 53(1):34-46.
 Kessler et al. (2006), The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716-723.
 Moorthy et al. (2015), Safety, tolerability and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in a phase 1 dose escalation study in subjects with ADHD. Biopharm. Drug Dispos. 36:429-439.
 For a review see e.g. Cristancho et al. (2011), Atypical depression in the 21st century: diagnostic and treatment issues. Psychiatric Times 28:42-47.
 Morozova et al. (2015), Effects and safety profile of betahistine in patients in the Russian contingent of OSVaLD, an open-label observational study in vestibular vertigo. Int J Gen Med. 8:47-53.
 Barak et al. (2016), A randomized, double-blind, placebo-controlled pilot study of betahistine to counteract olanzapine-associated weight gain. J Clin Psychopharmacol. 36(3):253-6.