Dynogen’s genitourinary (GU) development programs currently focus on overactive bladder (OAB) and the most common symptoms of lower urinary tract disorders, such as urinary frequency, urinary urgency, and nocturia.

OAB is defined as urinary urgency, with or without incontinence, usually with urinary frequency and nocturia. The majority of patients diagnosed with OAB do not experience incontinence.

OAB afflicts approximately 37 million adults in the U.S., and its prevalence increases with age. Current worldwide sales for OAB drugs is over $2 billion. Only one class of drugs, antimuscarinics, is approved for the treatment of OAB. These drugs suffer from poor efficacy and side effects such as dry mouth, constipation and blurred vision, often leading patients to abandon treatment.

DDP200

Dynogen is developing DDP200 as a treatment for the non-incontinent form of OAB (OAB-Dry), with particular focus on both male and female patients with urinary frequency, urinary urgency and nocturia.

DDP200 is an oral, fixed dose, combination of gabapentin and oxybutynin. Oxybutynin is prescribed to treat symptoms of lower urinary tract disorders such as OAB, while gabapentin is prescribed for the management of postherpetic neuralgia and epilepsy. Dynogen’s combination of the two drugs has shown statistically significant synergy in Dynogen’s preclinical models of OAB, suggesting that a low dose combination of the two drugs will have improved efficacy over oxybutynin alone, without the side effects seen at higher doses. The combination of the two drugs has important characteristics: it affects both the afferent and efferent neurological pathways serving the bladder, and therefore may have benefits for both the sensory and motor aspects of OAB. Dynogen expects the synergy between the two compounds to increase the efficacy and tolerability profiles compared to market leading drugs for OAB.

Dynogen believes the development risks associated with DDP200 are substantially reduced because the two compounds that comprise DDP200 have been marketed individually for over a decade; therefore, their safety and PK profiles are well understood. DDP200 was internally discovered and thus Dynogen owes no license fees, milestones or royalties to any third parties for this program.

Dynogen completed a Phase 1, single dose study in normal volunteers which demonstrated that concurrent administration of these products did not impact their safety or pharmacokinetic profiles. The Company is planning a Phase 2b study of DDP200.

DDP225

DDP225 is a Phase 2-ready clinical candidate for the treatment of OAB. Dynogen's preclinical studies showed that DDP225 increased the volume of urine held in the bladder and reduced voiding frequency without any effect on bladder muscle contraction during normal bladder emptying. DDP225 represents a new therapeutic approach to treating symptoms of OAB, representing a different and potentially better tolerated mechanism than those targeted by currently marketed drugs.

DDP225 is an orally administered small molecule which is a low-potency inhibitor of the 5-HT₃ receptor and of noradrenaline reuptake. The inhibition of noradrenaline reuptake is known to promote bladder storage. Dynogen believes that inhibition of the 5-HT₃ receptor, a specific subset of serotonin receptors found in the lower urinary tract, may be effective at reducing the uncomfortable sensations associated with urinary frequency, urgency and nocturia. By combining these two mechanisms, the Company believes it may be possible to inhibit multiple pathways that contribute to the clinical symptoms of OAB, creating a more effective and better tolerated therapy for this large and growing market.

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, and provided Dynogen with complete safety and PK profiles for the compound.

Disease Background

Overactive Bladder (OAB)

• Symptoms include urinary frequency, urgency and nocturia
• 37 million patients in the U.S.
• Less than half are eligible for current treatments
• High growth potential with an aging population
• Despite limitations, sales for existing therapies greater than $2 billion