SUBA™ itraconazole   

SUBA-itraconazole is a super-bioavailable formulation of itraconazole, a synthetic broad-spectrum anti-fungal agent.  Itraconazole is marketed worldwide by Johnson and Johnson companies using the brand SporanoxÒ.  In 2005 the process patent for Sporanox in the US expired.  Global sales of SporanoxÒ and generic itraconazole formulations are in excess of US $600 million.

Due to its low aqueous solubility, itraconazole is difficult to formulate as an oral product.  Most formulations have relatively low bioavailability (that is a high dose must be administered to ensure sufficiently high blood levels).  Currently available itraconazole formulations also exhibit a significant food effect and carry an “administer with food” label.

SUBA-itraconazole has been developed using patented technology to overcome the inherent difficulties in formulating itraconazole.  SUBA-itraconazole has significant advantages for patients over current formulations:

Half dosage
SUBA-itraconazole achieves similar blood concentrations of itraconazole as the leading brand at fifty percent of the dose.  The smaller oral dose of itraconazole may result in an improved safety profile, including reduced gastro-intestinal side effects.

Small capsule
SUBA-itraconazole is presented in a small capsule making it easy to swallow and reducing the impact of impaired oesophageal transit associated with elderly patients.

Stable pharmacokinetic profile
SUBA-itraconazole’s patented formulation provides low intra-subject and inter-subject variability.  This can improve medication reliability and increase doctor and patient confidence in treatment.

No food effect
Pharmacokinetic studies suggest SUBA-itraconazole can be taken with or without food which is an important consideration in patient compliance and reducing intra-patient variability. 

No gastric acid effect
SUBA-itraconazole’s delivery system does not require an acidic gastric environment.  Dissolution studies suggest SUBA-itraconazole can be used safely by achlorhydric patients and those taking medication that increase gastric pH.

Technology
SUBA technology uses a molecular dispersion to improve the bioavailability of poorly soluble drugs. 

Matrix core of active
(x600)	(x400)
Itraconazole crystals microcapsule cross section

Clinical Development
Five human pharmacokinetic studies have been conducted with SUBA-itraconazole. HalcyGen is working with regulatory authorities around the world to design and implement a clinical program that will lead to the marketing approval of SUBA-itraconazole.

Intellectual Property
HalcyGen has global exclusive licences for SUBA itraconazole in respect of the patents (and patent applications) set out in the following table: 

Territory	Patent number	Status
Australia	782469*	Granted
Canada	2396380	Awaiting examination
Europe	1239831	Awaiting examination
Japan	2003-518483	Awaiting examination
United States	6881745	Granted
United States	20030086976	Under examination