AIKO Compound	Indication	Phase
AIKO-150	IV peripheral side effects and addiction	Phase 1a Exploratory IND - Complete Phase 1b Exploratory IND - Complete Q1-2010
AIKO-151	Oral peripheral side effects and addiction	Preclinical
AIKO-152	Analgesic co-formulation for pain therapy with both reduced GI dysfunction and abuse potential	Preclinical

Market Information:
AIKO-150 is a neutral opioid antagonist targeted for the treatment of opioid-induced side effects including opioid-induced bowel dysfunction and addiction. Over 200 million prescriptions for opioids are written annually in the US, and up to 90% of patients experience constipation, nausea and vomiting, and other bowel dysfunction. The total worldwide market in 2007 was over $7.5 billion in opioid sales. Coincident with market growth, opioid abuse has tripled in the last decade.

AIKO-150 Product Profile and Clinical Data
AIKO-150's neutral characteristics, high potency, and preferential blockade of peripheral versus central opioid receptors makes it a highly promising drug candidate superior to naltrexone and other mu opioid antagonists for treatment of opioid-induced GI dysfunction and opioid and other addictions. AIKO-150 has established safety, tolerability, and pharmacokinetics as a metabolite of naltrexone in humans. Our initial dosing studies in humans have confirmed these properties.

Exploratory Phase 1a Human Trial - Completed Q3-2009:
The first human trial, with four increasing intravenous doses (0.05-1.0 mg) of AIKO-150 administered to methadone-dependent subjects, demonstrated that AIKO-150:

• Acts as a neutral antagonist in humans, resulting in relatively low potency for precipitating opioid withdrawal compared to the prototypical antagonist naloxone.
• Possesses high potency for decreasing GI transit time (at low single dose), indicating selectivity for blocking peripheral opioid effects.
• Produced spontaneous bowel movements in three of four subjects indicative of laxation and relief of constipation.
• Produced significant abdominal discomfort at high doses, which is expected of compounds that displace opioid agonists from their receptors in these highly dependent subjects.
• Displays dose-proportional pharmacokinetic parameters similar to those expected from published studies of AIKO-150 as a human metabolite of naltrexone.

Exploratory Phase 1b Human Trial: Pending Completion Q1-2010:
The Phase 1b trial is designed to test the degree of peripheral selectivity (GI motility) and potency in blocking central opioid receptors (pain measures) in opioid-naive subjects. It is expected that this trial will demonstrate that:

• AIKO-150 given IV does not interfere with analgesia at dosages that prevent opioid agonist induced inhibition of GI transit
• AIKO-150 exhibits high potency for blocking peripheral opioid-induced effects (GI transit) and lower potency for blocking central (pain relief) effects
• The drug has good safety and tolerability at higher doses (up to 20 mg)
• AIKO-150 has desirable pharmacokinetics including confirmation of a long terminal half-life (>12 hr) and predictable first order kinetics over a broad range of concentrations The primary endpoint of these trials is establishment of a dosage range that prevents the opioid inhibition of bowel motility without impeding analgesia. Results from these two trials is expected to establish the superiority of AIKO-150 over other opioid antagonists by showing in humans:
• It's neutral antagonist character that has a lower propensity to precipitate severe withdrawal while reversing undesirable side effects of opioid agonists
• Predictable pharmacokinetics
• High potency for relieving opioid-induced constipation with no interference of opioid-induced pain relief
• Potential for reducing abuse liability if taken at dosages higher than required to relieve constipation.

AIKO - 151 Clinical Data and Product Profile
AIKO - 151 is an investigational candidate therapeutic consisting of an oral administration of AIKO - 150. The product is designed for oral administration preventing the debilitating side effects common to opioid use.

AIKO - 152 Clinical Data and Product Profile
AIKO-152 is an investigational candidate therapeutic, consisting of a coformulation of AIKO-150 with an opioid analgesic. The product is designed to provide abuse-resistant analgesic properties while preventing the debilitating side effects common to opioid analgesics, such as constipation and opioid induced bowel dysfunction. AIKO-152 is the only analgesic preparation under development targeting reduction of both abuse and adverse GI effects.