Pherin Pharmaceuticals lead program PH94B nasal spray, a Phase 3 ready product, is being developed for the acute treatment of Social Anxiety Disorder under USFDA guidance.

Pherin Pharmaceuticals

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More Effective than Hormone Replacement Therapy

Hot flashes are the most common symptom of menopause and are a significant quality-of-life and workplace issue because substantial numbers of women experience symptoms that are debilitating. Pherin Pharmaceuticals is conducting trials of an effective therapy delivered as a nasal spray.

Hot Flashes

In the U.S. approximately 40 million women are at or near menopause, and some 45 million are beyond menopause. Up to 80% of women may experience hot flashes during the perimenopause transition or after menopause.

Currently available therapies to treat hot flashes include hormone replacement therapy (estrogen with or without progesterone, or a synthetic progestin), gabapentin, SSRIs, clonidine, and herbal products. These therapies have well-known side effects (hormonal treatments, SSRIs, gabapentin, clonidine) or have been proven ineffective to treat menopausal hot flashes (herbal products).

Although estrogens have been proven to relieve hot flashes, use in the U.S. became sharply curtailed after 2002 with concerns about breast cancer and cardiovascular events associated with chronic treatment. At present, there is no alternative prescription medication approved by the US Food and Drug Administration for the treatment of menopausal hot flashes.

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Nasal Spray Study

Pherin Pharmaceuticals conducted a Phase 2 exploratory randomized study in 40 eligible volunteers age 45-65 years, to compare the effectiveness and tolerability of 1.6 micrograms PH80-HF nasal spray for the acute management of daily menopausal hot flashes. Study medication or a placebo was administered six times daily for two consecutive weeks. The primary outcome measures were the significant improvement in the severity, number of hot flashes, and the following objective parameters: body temperature, electrodermal activity, and skeletal muscle tension. Secondary endpoints included tolerability and safety of Salubrin-HF nasal spray.

The results of this study showed rapid onset of action of PH80 (35-65 sec) after intranasal spray administration of 1.6 micrograms. Physiologic parameters that were increased during the occurrence of hot flashes improved significantly better than placebo after administration of Salubrin-HF: body temperature (p < .02), electrodermal activity (p < .01) and muscle tension (p < .04).

PH80-HF (1.6 micrograms) improved the severity (p < .02) and the number (p < .07) of daily hot flashes along the 14-day in-house treatment period. Intranasal administration of PH80-HF was safe, and there were no reports of local (nasal) or systemic side effects and severe adverse effects during the treatment period and the follow-up period.

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Cognitive Improvement

Cognitive deficits are characterized clinically by progressive loss of memory, cognition, reasoning, judgment and emotional stability that can gradually lead to profound mental deterioration. In an example of such disorders, Alzheimer's Disease (AD) is a common cause of progressive mental failure (dementia) in aged humans. Such disorders have been observed in different races and ethnic groups worldwide and present a significant current and future public health problem. These disorders are currently estimated to affect about two to three million individuals in the United States alone.

A large number of healthy individuals (seniors, menopausal women, individuals suffering from general tiredness and stress) also complain annually of decreased performance or cognition. Several studies have shown that individuals complaining of insomnia due to several different causes score very low when challenged with cognitive performance situations. In the United States, these conditions address a market estimated to be $2 billion annually.

Nasal Spray Studies

PH15 is in early-stage development for the treatment of cognitive impairment. In vitro and in vivo pharmacological studies revealed that PH15 binds to GPC-peripheral receptors in the nasal passages in a dose-dependent manner. In vitro and in vivo toxicology studies showed that PH15 is well tolerated in laboratory animals at concentrations 100-fold higher than the dose proposed to use in clinical studies. FMRI studies in human volunteers performed at the Institute of Neuroscience of Stanford University, California, revealed that intranasal administration of PH15 activates human brain areas related to the anterior gyrus cingulate (hippocampus, hypothalamus, limbic system, anterior thalamus, frontal and temporal cortex) in a dose-dependent manner and this effect is significantly better than the impact of placebo-control.

Pherin Pharmaceuticals conducted a double-blind, randomized, placebo-controlled pilot study in sleep-deprived healthy volunteers (N=10) to compare the effects of its proprietary pherine PH15 nasal spray, placebo and orally administered caffeine, using quantitative computer simulation tests for assessment of cognitive performance and reaction time. The results show that intranasal administration of 1.6 micrograms PH15 nasal spray improved cognition. This was revealed by a faster reaction time to identify synchronously and randomly presented visual stimuli in volunteers treated with the PH15 nasal spray. This effect was statistically significantly better than the result of placebo, and also than that of 400 milligrams of caffeine administered orally.

Of particular interest is the significant effect produced by PH15 nasal spray during a cognitive challenge when the volunteers had to identify stimuli administered randomly, a situation that requires increased attention. The reaction time after intranasal administration of 1.6 mg PH15 was faster and statistically significantly more regular than the reaction time after administration of placebo or 400 mg oral caffeine. Due to the rapid onset of effect of PH15 nasal spray, the low dose needed to obtain significant improvement and the absence of side or adverse effects reported in the study; we expect that PH15 nasal spray will have the considerable market potential for cognitive enhancement.