Snowdon Inc.

Therapeutic Area: Acute and Chronic Pain

The choice of pharmaceutical agents for pain management depends on multiple factors, including the type, severity, and duration of the pain. Milder forms of pain may be relieved by over-the-counter medications such as acetaminophen or NSAIDs such as aspirin and Aleve. Topical pain relievers such as capsaicin and the “caine” drugs (lidocaine, benzocaine) are also available over-the-counter as creams, lotions, or sprays that are applied to the skin to relieve pain from sore muscles and arthritis.

If these non-prescription drugs do not provide pain relief, then prescription drugs such as muscle relaxants, anti-anxiety drugs, antidepressants, prescription NSAIDs such as Celebrex, or a short course of opioid painkillers (codeine, percocet, vicodin) may provide temporary relief. In some cases, steroid injections can be applied by the physician at the site of a joint problem to reduce swelling and inflammation.

For more severe and acute pain, strong opioid analgesics such as morphine and oxycodone remain the mainstay treatment. Like all narcotics, however, opioids entail a wide range of serious side effects as described below.

For neuropathic pain, the current drugs of choice are the anticonvulsants gabapentin (Neurontin) and pregabalin (Lyrica). These drugs are often prescribed for the treatment of fibromyalgia, diabetic neuropathy, and herpes zoster (also called shingles).

Despite the apparent variety of treatments available for pain management, all of the medications described above suffer from limitations. In short, these medications either lack sufficient potency or produce serious side effects. For example, the inherent potency of aspirin is insufficient to give pain relief for a broken arm regardless of the amount of aspirin ingested. On the other hand, the potency of morphine is sufficient to provide relief for severe pain such as a broken arm. As with all narcotics, however, morphine produces a multitude of serious side effects such as respiratory depression, constipation, nausea, tolerance and addiction. In addition, opioids are generally ineffective for the treatment of neuropathic pain.

Snowdon's Approach: Clearly there is a major need for the development of medications that relieve acute and chronic pain without the serious limitations of the opioid narcotics and other prescription drugs. Snowdon is developing medical treatments that address this challenge.

Treatments for Neuropathic Pain: Glutamic acid is the major excitatory neurotransmitter in the mammalian peripheral nervous system (PNS) and central nervous system (CNS). Glutamate mediates a variety of neurological, psychiatric, and physiological processes, by binding to two different receptor types: ionotropic glutamate receptors (iGluRs), and metabotropic glutamate receptors (mGluRs). The Group I mGluRs, specifically mGluR1 and mGluR5, play a key role in pathological peripheral nervous system (PNS) processes, including non-provoked pain behavior, mechanical hyperalgesia, visceral pain emanating from the gastrointestinal tract, and gastroesophageal reflux disease (GERD).

Negative allosteric modulators (NAMs) of Group 1 mGluRs have been recognized as having potential value in mediating these disorders. Recently NAMs of mGluR1 and of mGluR5 have demonstrated interesting preclinical activity in a growing number of studies directed toward understanding how the modulation of these receptors might furnish therapy for central and peripheral nervous disorders. As yet, however, there are currently no approved Group 1 mGluR NAM drugs on the market for CNS or PNS disorders.

Snowdon is developing therapeutic modulators of peripheral disorders associated with pain and discomfort. Our leading candidates, SND-223 and SND-225, exhibit potent in vivo activity in a rat model of neuropathic pain. These molecules are also well tolerated in animals. Snowdon is actively pursuing pre-clinical development of both SND-223 and SND-225, in anticipation of filing an Investigation New Drug Application (INDA) with the FDA in 2011.

Treatments for Acute Pain: There are three major subtypes of opioid receptors: μ (mu), κ (kappa), and δ (delta). Morphine and most other opioid analgesics exert their analgesic, and adverse, effects primarily through the mu receptor. Recent observations confirm that the mu and delta opioid receptors interact with each other, and that these interactions permit cross-talk between the two receptors. The clear implication of these findings is that delta receptor agonists and antagonists may improve the pharmacological profile of mu analgesics to minimize common opioid-induced side effects, such as tolerance and narcotic addiction.

Snowdon is developing both agonists and antagonists of the delta opioid receptor. Discovery-stage studies reveal that these molecules produce fascinating pharmacological properties, suggesting that they may enhance the analgesic effects of mu agonists and mitigate their adverse effects.

Therapeutic Areas: Cancer | Acute and Chronic Pain | Neurological Disorders| Infectious Diseases