PHERINES AS PHARMACEUTICAL AGENTS

Pherin has discovered a new class of substances termed pherines, and has gathered a large body of human data that indicate these compounds can have significant applications as pharmaceuticals. Pherines are not ingested or injected, but rather are self-administered by the patient with a metered nasal spray. Once they have been administered intranasally, Pherines modulate the hypothalamus and limbic areas of the brain and have a rapid onset of effect.

Pherines affect key areas of the brain. These compounds do not need to circulate in the bloodstream in order to produce an effect. Instead, they initiate neural impulses that are transmitted by specific pathways that directly and rapidly affect brain function.

As a consequence of binding to receptors, Pherines can influence the regulatory functions exerted by the hypothalamus and limbic system. These regulatory functions are potential therapeutic targets for pherines.

WHAT ARE PHERINES?
The term "Pherine" refers to odorless substances that have a physiological or pharmacological effect as a consequence of binding to specific peripheral chemosensory receptors in the human nasal passages.

PROPERTIES OF PHERINES

Pherines affect key areas of the brain. These compounds do not need to circulate in the bloodstream in order to produce an effect. Instead, they initiate neural impulses that are transmitted by specific pathways that directly and rapidly affect brain function.

As a consequence of binding to receptors, Pherines can influence the regulatory functions exerted by the hypothalamus and limbic system. These regulatory functions are potential therapeutic targets for pherines.

Figure 2. Brain activation induced by a pherine in a human subject, revealed with functional magnetic resonance imaging (fMRI). The orientation of brain images is shown top to right. Images 1 and 2 had no activation and are not shown. Images 3-8 in the three conditions (sham, low concentration, high concentration) are shown from top to bottom, respectively. A robust increase in activation from the low concentration to the high concentration conditions is evident. Regarding regions of interest, activation is evident in the cingulated gyrus (images 3-8), in the inferior frontal gyrus (images 4-8), in the hypothalamus (image 5), in the limbic amygdala (image 6), in the thalamus (images 7-8).

Pherines

The term "pherine" refers to odorless substances that have a physiological or pharmacological effect as a consequence of binding to specific peripheral chemosensory receptors in the human nasal passages.

The various functions of the hypothalamus define the possible indications for treatment with pherines. Pherin’s intellectual property portfolio includes composition of matter (novel compounds) and methods of use patents covering over 1,000 pherines, genes encoding pherine receptors and pharmaceutical applications of pherines.

Pherines act locally by binding to peripheral chemosensory receptors. By virtue of this local action, pherines have a very rapid onset of action, as they do not require systemic absorption and distribution or crossing the blood-brain barrier to initiate their pharmacological effect. This is likely to provide pherines with a significant therapeutic advantage compared to current therapies that require access to the systemic circulation followed by uptake into the brain in order to exert any effects.

The local action of minuscule quantities (nanograms) of a pherine in peripheral chemosensory receptors leads to site-specific communication via a triggering of physiological responses in the hypothalamic-limbic regions of the brain. This targeted delivery and localized effect is in contrast to the broadcast-type communication, and more global effects within the brain and throughout the body that results when drugs are administered systemically.

The very low dosages at which pherines are likely to be effective, together with their ability to be administered locally and the resultant limited anticipated exposure of the systemic circulation to these compounds provide an additional important potential therapeutic advantage for pherines. There is minimal, if any, side effects or toxicity in laboratory animals. In addition, results of clinical trials indicate that pherines are well tolerated and have a broad safety profile in humans. Finally, pherines are administered by a non-invasive nasal spray, which is a convenient and well-established route of administration with a clear advantage for the patient.

Pherin’s research efforts are focused on those aspects of the chemistry, molecular biology and pharmacology of pherines that hold promise for development into efficacious and safe therapeutic applications. The Company’s scientific advisors and consultants provide ongoing advice as well as carry out projects in support of company objectives in their areas of expertise.