Therapeutic Areas

Snowdon is focused on three therapeutic areas that address significant medical needs in the nation and the world, including pain, neurological disorders, and infectious diseases.

Acute and Chronic Pain
The development of pharmaceutical agents that are safe, effective and long acting truly represents the "Holy Grail" of pain management. Pain can be divided into two broad types: acute and chronic. Acute pain is usually caused by a traumatic event, such as a broken bone, back injury, skin burn, or severe headache, whereas chronic pain often arises from a degenerative disease such as cancer or arthritis or from damage to the nervous system (neuropathic pain). Some familiar causes of neuropathic pain are herpes zoster (shingles), diabetes (diabetic neuropathy), fibromyalgia, and multiple sclerosis, to name only a few. In many cases, the specific causes of chronic, neuropathic pain are unknown.

The need for pain medications is substantial and growing rapidly, driven in part by the increasingly aging population. To address this need, Snowdon is developing novel treatments for chronic and neuropathic pain. Snowdon's leading preclinical candidate, SND-121, has demonstrated positive results in rat models as a treatment for neuropathic pain. Further preclinical studies are underway at Snowdon on prodrugs of SND-121 with improved water solubility and GI permeability for enhanced systemic uptake when administered orally.

Neurological Disorders
Excessive transmission of chemical signals between neurons in the brains of humans is associated with a host of neurological and psychiatric disorders, including schizophrenia, autism, epilepsy, amyotrophic lateral sclerosis (ALS), drug addiction, Alzheimer's disease and Parkinson's disease. Specifically, an increasing body of evidence has implicated glutamate excitoxicity as a common mechanism of neuronal death in both acute and chronic neurological diseases.

Snowdon is actively developing novel medical treatments that will reduce this excessive transmission of glutamate between neurons back to normal levels. Several novel molecules have been discovered that show encouraging results in laboratory studies and in animal models. These preliminary results offer hope for the development of safe and effective medicines for these intractable diseases and disorders.

Infectious Diseases
Infectious diseases usually occur by natural causes, but there is growing awareness that infectious agents can be spread through deliberate efforts as acts of terrorism. Both routes of infection represent major threats to our national security and to global health and stability. Snowdon is investigating two drug prospects, SND-159 for tuberculosis and SND-226 for toxoplasmosis.

Treatments for Tuberculosis: Tuberculosis (TB) is a major global pandemic that is estimated to infect one-third of the world population at any given time. The disease causes more deaths than any other single infectious agent in the world. Over 9 million new cases of TB occurred in both 2006 and 2007, and about 2 million deaths were attributed at least in part to TB in 2007. While TB disproportionately affects developing nations such as Africa, China, and India, the disease remains a serious and costly problem in industrialized nations including the US. According to the World Health Organization (WHO), the economic cost of TB in sub-Saharan Africa alone has been estimated at $40 billion annually.

The current first-line TB drug regimen consists of combinations of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). These TB drugs entail a wide range of side effects including nausea, vomiting, constipation, psychotic episodes, and hepatitis. Moreover, effective treatment requires prolonged (6-9 months) antibiotic chemotherapy. The occurrence of these debilitating side effects, and the long duration of treatment, leads to lack of patient compliance. This, in turn, leads to disease management problems and the onset of drug-resistant disease. Thus, the discovery of new types of drugs which effectively control TB and which possess a minimum side-effect profile is urgently needed.

The emergence of drug-resistant, Multiple Drug-Resistant (MDR) and Extensively Drug-Resistant (XDR) TB strains of the pathogen have developed and present challenges for therapeutic management. MDR-TB is generally treatable, but requires two years of treatment with more costly and less safe second-line anti-TB drugs. XDR-TB is more severe as it comprises MDR plus resistance to fluoroquinolone, and at least one of the second line injectable drugs such as capreomycin, kanamycin or amikacin.

Another major challenge is the treatment of Latent Tuberculosis Infection (LTBI), which must be addressed to reduce the risk that TB infection will progress to disease. The current "gold standard" treatment of LTBI in the US is 9 months of INH. The risk of hepatotoxicity with INH, together with the protracted treatment regimen, underscores the need for alternative TB treatments that are safer, more effective, and shorter in duration.

Snowdon, working with researchers at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School (UMDNJ-NJMS), has discovered a small-molecule compound designated SND-159 that is effective in inhibiting the tuberculosis bacterium (including a MDR-TB strain) under various culture conditions in the laboratory. Encouragingly, SND-159 also significantly decreased the viability of latent TB strains. Unlike the current first-line and second-line TB drugs, SND-159 is very safe and offers the advantage of a minimal side effect profile. Studies to date suggest that the mechanism of action of SND-159 is unique compared with other TB drugs. Snowdon is investigating SND-159, alone or in combination with current TB drugs, as a novel TB drug therapy that is safe, effective, and faster acting.

Treatments for Toxoplasmosis: Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects both immune-competent and immune-compromised individuals, and is the leading cause of severe congenital neurological and ocular disease in humans. Toxoplasmosis causes substantial morbidity and mortality worldwide, and is a major opportunistic infection, producing illness, disability and death in those with AIDS. Approximately 10% of HIV/AIDS patients in the U.S. and 30% in Europe die from toxoplasmosis. Toxoplasmic encephalitis (TE) is still the most significant opportunistic neurological infection in HIV-1 infected patients. Although survival of HIV patients with TE has improved markedly since the introduction of highly active anti-retroviral therapy (HAART), persistent neurological deficits are often present in surviving patients. In the developing world where both T. gondii infection and HIV infections are common and retroviral therapy is not available, TE remains a major cause of morbidity and death for those with AIDS.

T. gondii infection is also involved in ocular disease, congenital toxoplasmosis, as well as primary, acute and chronic infection in the immune-competent individual. Treatments for toxoplasmosis do exist; however, the medicines that are available have significant toxicity including neutropenia with pyrimethamine, and C. difficile diarrhea with clindamycin. There is frequent hypersensitivity secondary to treatment with sulfonamides. In addition no medicine currently available eliminates the encysted form of the parasite which is the cause of recrudescent disease making relapse when CD4+T cell counts diminish an ongoing risk. No vaccine is available for humans. Therefore an urgent medical need and commercial opportunity exists for safer and more effective medicines for toxoplasmosis therapy.

Snowdon, working in collaboration with toxoplasmosis expert Rima McLeod, M.D., of the University of Chicago Medical School and funded by the NIH, is developing a novel family of small-molecule inhibitors of toxoplasmosis. Several lead compounds have been discovered in laboratory studies with sub-500 nM inhibitory activity against the causative agent T. gondii. At least one lead compound, SND-226, has demonstrated sub-100 nM inhibitory activity. Snowdon is conducting further studies on SND-226 and related lead compounds with the aim to confirm these encouraging results in animal models.