While the field of gastrointestinal (GI) disorders is very broad, Dynogen’s current product development programs address specific indications that share several common characteristics: they are chronic diseases requiring chronic care; there are few treatment options available in each therapeutic area; and current therapies have limitations for use across a large and growing market.  Diseases that fall into this category include irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD).

Two of Dynogen’s product candidates are in development to address IBS: DDP733 for IBS with constipation (IBS-c); and DDP225 for IBS with diarrhea (IBS-d). Dynogen is the only company with late stage clinical candidates in development that address both IBS-c and IBS-d.

IBS affects approximately 12% of the U.S. population, or 27 million patients. IBS is a chronic disease characterized by abdominal pain and discomfort associated with altered bowel habit. IBS is associated with $1.6 billion in direct medical costs, and $19.2 billion in indirect medical costs in the U.S. each year. Patients with IBS miss almost three times as many days of work each year and make an average of 5.5 visits to the physician each year, compared to 1.9 visits annually for people without bowel symptoms. With a dearth of treatments for either form of IBS, Dynogen estimates that an effective treatment for IBS-c or IBS-d could reach worldwide peak sales of over $1 billion.

GERD represents one of the largest pharmaceutical markets in the U.S., with as many as 20% of adults experiencing heartburn at least once a week. NGERD, the occurrence of GERD at night, has a prevalence estimated to be as high as 10% of the U.S. population, and is often refractory to traditional GERD therapies. There are no approved therapies for NGERD, and no therapies for GERD that address the motility abnormalities central to the pathophysiology of the disease. Dynogen estimates that an effective treatment for NGERD could reach peak sales of over $700 million.

DDP733

Dynogen is studying DDP733 as a therapy for IBS with constipation (IBS-c) and as a treatment for nocturnal gastroesophageal reflux disease (NGERD). DDP733 is an orally administered small molecule which is a partial agonist of the 5-HT₃ receptor, a specific sub-type of serotonin receptor. Serotonin, a neurotransmitter, is believed to play an important role in the regulation of gastrointestinal motility.

Dynogen obtained positive results from its double-blind, placebo-controlled Phase 2a clinical trial of DDP733 as a treatment for IBS-c. DDP733 achieved an overall clinical response rate of 54% in patients receiving a dose of 1.4 mg t.i.d. compared to a 15% clinical response rate for patients receiving placebo. This result was statistically significant. The U.S. Food and Drug Administration (FDA) has previously accepted this clinical measure as the registration endpoint for IBS-c. The study also demonstrated that the drug was well tolerated. Dynogen initiated a Phase 2b study of DDP733 in patients with IBS-c in the fourth quarter of 2007.

For more information about this ongoing clinical trial, click HERE.

Dynogen is also studying DDP733 as a treatment for NGERD. Dynogen obtained positive results from its double-blind, placebo-controlled Phase 1b translational medicine clinical trial for the treatment of NGERD. In the study, the 0.5 mg dose of DDP733 achieved statistical significance over placebo in the reduction in the number of reflux events. In this study, the drug was well tolerated. Dynogen is planning a Phase 2 study of DDP733 in GERD patients.

DDP733 represents a new approach to treating NGERD as it directly impacts the reflux mechanisms of the digestive tract. Unlike current therapies which address acid supression, DDP733 enhances the motility of the gastrointestinal tract.

Dynogen licensed DDP733 from Mitsubishi Tanabe Pharma. Dynogen’s license includes exclusive rights to all preclinical, clinical and manufacturing data related to the compound, in addition to issued patents and pending patent applications. Mitsubishi had studied DDP733 in over 300 volunteers and patients with constipation and erosive esophagitis, where it demonstrated clean and favorable safety and pharmacokinetic profiles.

For specific information regarding our DDP733 patent estate, click HERE.

DDP225

Dynogen is studying DDP225 for the treatment of IBS with diarrhea (IBS-d). DDP225 is an orally administered small molecule which is a low-potency inhibitor of the 5-HT₃ receptor and of noradrenaline reuptake. Dynogen believes that the inhibition of noradrenaline reputake impacts the sensation of pain associated with IBS-d. Inhibition of 5-HT₃ receptors, a specific subset of serotonin receptors, is believed to play an important role in the regulation of gastrointestinal motility. By combining these two mechanisms, it may be possible to inhibit multiple pathways that contribute to clinical symptoms in IBS, creating more effective therapies for this underserved market.

Dynogen generated positive results in its Phase 2a trial of DDP225 as a treatment for IBS-d. In the trial, the 1 mg dose of DDP225 administered once daily for eight weeks achieved a 71% response rate compared to a 25% response rate for placebo in the clinical endpoint of adequate relief of IBS pain or discomfort. This result was statistically significant. The FDA has previously accepted this clinical measure as the registration endpoint for IBS-d. In this study, the drug was well tolerated. Dynogen is planning a Phase 2b trial of DDP225 in patients with IBS-d.

Dynogen licensed DDP225 from Mitsubishi Tanabe Pharma. Mitsubishi studied this drug candidate previously in a number of Phase 1 and Phase 2 studies for the treatment of depression and Alzheimer’s disease, providing Dynogen with complete safety and PK profiles for the compound. In Dynogen’s preclinical studies of the compound, DDP225 decreased GI motility and hypersensitivity. These data suggest that the entire symptom spectrum of IBS-d will be addressed. Dynogen expects that its dual mechanism will yield a better side effect profile than that seen with existing therapies.

For specific information regarding our DDP225 patent estate, click HERE.

Disease Background

• Chronic condition involving abdominal discomfort and bloating with altered bowel habit
• Presents as diarrhea predominant, constipation predominant, or alternating between the two
• 12% prevalence and second most common cause for sick leave
• Accounts for as much as 4% of all primary care visits
• 80% of the severe patient population is female

• Chronic condition involving acid regurgitation into the esophagus, dyspepsia, dysphasia, heartburn and difficulty swallowing
• Afflicts 20% of the population
• Affects all age groups, although older adults most often seek treatment
• Current treatment options limited to acid reducing strategies (i.e., H2 receptor antagonists and proton pump inhibitors)
• NGERD is a form of GERD occurring when lying down to sleep