Spherics Presents Proof-of-Concept Studies Demonstrating Advantages of Oral Delivery Platform Technologies; Human and Preclinical Studies Presented at Controlled Release Society Meeting

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LINCOLN, R.I.--(BUSINESS WIRE)--June 21, 2005--Spherics, Inc., announced today the results of proof-of-concept studies with three marketed compounds demonstrating the potential of the company's polymer-based oral delivery platform and Phase Inversion Nanotechnology to improve the drugs' oral bioavailability. The four studies, which involved human and preclinical studies with itraconazole, and preclinical studies with acyclovir and paclitaxel, are being presented at the 2005 annual meeting of the Controlled Release Society, in Miami, Florida.

"Each of these drugs has distinct and challenging bioavailability issues that limit effectiveness, increase potential for adverse effects, or in the case of paclitaxel, preclude use as an oral agent," said Avinash Nangia, Ph.D., Vice President of Research and Development at Spherics and one of the study's authors. "In these studies, we have shown we can significantly enhance the oral bioavailability profiles of these drugs, providing strong proof-of-concept for our oral drug delivery technology platform."

“Acyclovir only enters the bloodstream through the upper portion of the small intestine, and as a result there is a limited window for absorption”

Spherics has developed advanced drug delivery systems with a focus on oral delivery. The company's technologies are designed to increase drug residence time at target sites within the gastrointestinal tract, thereby improving bioavailability. The platform includes bioadhesive polymer-based delivery systems. The company's Phase Inversion Nanotechnology ("PIN") process generates nano-size drug particles for systemic absorption of drugs with low solubility and poor permeability.

Spherics is using the platform to establish a proprietary pipeline of products and the company expects to collaborate with partners in life-cycle management. Spherics' pipeline is focused principally on drugs to treat central nervous system disorders, gastrointestinal diseases, and cancer. The company expects to outlicense other products, such as itraconazole and acyclovir.

Study Details

Spherics' Itraconazole Bioadhesive Formulations (Spherazole(TM) and Spherazole(TM) CR) Show Increased Bioavailability, and Improved Reliability

Spherics presented results of a Phase I healthy volunteer study with Spherazole(TM) -- an immediate release, bioadhesive formulation of the antifungal agent itraconazole -- demonstrating improved bioavailability and reduced intersubject variability compared with a commercially available itraconazole product.

The study was a single-dose, randomized, two-way crossover trial involving 16 healthy volunteers, who received either 100 mg of a commercial itraconazole product or Spherazole(TM) after a standard meal. Spherazole(TM) had about 20 percent increase in area under the curve (AUC), a measure of the amount of drug absorbed into the bloodstream. The study also showed a 17 percent reduction in the variability of the maximum plasma concentration (Cmax) and 37 percent reduction in AUC variability. Spherazole(TM) was safe and well tolerated.

A preclinical, pharmacokinetic study of four controlled release tablet formulations of itraconazole (Spherazole(TM) CR), demonstrated the feasibility of once-a-day dosing with bioadhesive formulations. In controlled studies, the Spherazole CR formulations had equivalent or superior AUC compared with itraconazole alone and also significantly reduced variability. Effective plasma concentrations were maintained for up to 24 hours.

"Itraconazole has low bioavailability due in part to low aqueous solubility," noted Jules Jacob, Spherics' Director, Research and Development and the studies' lead author. "As a result, oral absorption can vary widely, potentially increasing the risk of toxicity if blood levels are too high as well as diminished efficacy if they fall below minimally effective concentrations. Our strategy was to design a formulation that resides in the stomach for longer duration, making it less prone to gastric emptying and allowing the drug to be released in a controlled and reproducible manner."

Preclinical Studies with Oral Acyclovir, Paclitaxel Yield Improved Dosing Potential with Spherics' Formulations

With the anti-herpes drug acyclovir, Spherics researchers reported preclinical data with two controlled release formulations (BioVir(TM)) demonstrating the feasibility of reducing the frequency of daily dosing from four times to two times per day while maintaining effective concentrations of the drug.

"Acyclovir only enters the bloodstream through the upper portion of the small intestine, and as a result there is a limited window for absorption," said Mr. Jacob. "Spherics' strategy was to develop bioadhesive formulations that targeted the absorption site and remained there for six to eight hours to increase drug uptake."

The researchers compared the pharmacokinetic profiles of 400 mg of acyclovir, administered four times per day, with 400 mg BioVir(TM), formulated as a 400 mg controlled release tablet (CR-I) or with 100 mg immediate release plus 300 mg controlled release portions (CR-II).

The maximum concentration of the CR-I formulation was approximately half that of acyclovir, while demonstrating a 20 percent increase in AUC. The CR-II formulation showed a 70 percent increase in AUC compared with commercial acyclovir. Repeat dosing studies over 24 hours demonstrated that the AUC of BioVir CR 400 mg tablets administered twice per day was comparable to 200 mg commercial acyclovir administered four times per day.

Through its PIN technology Spherics is developing oral paclitaxel as a maintenance therapy for cancer. Currently, the drug is administered as an intravenous infusion. Its bioavailability is very low due to poor aqueous solubility and to a known molecular resistance mechanism that pumps the drug back into the intestinal tract.

"The nanoparticles, below one to two microns, enables uptake of the drug," said Mr. Jacob. "In these studies, we were able to achieve greater than 20 percent bioavailability, a significant level with our NanoTaxel(TM) formulation. Studies are underway to define the dose levels and dosing intervals for achieving optimal anti-tumor activity."

About Spherics

Spherics is an emerging pharmaceutical company focused on applying its proprietary oral drug delivery platform to develop products with improved therapeutic profiles. The Company's novel delivery technologies improve drug performance by increasing absorption and residence time in specific regions of the gastrointestinal tract. Spherics' business strategy is to further its proprietary pipeline of drugs, while working with pharmaceutical companies in life-cycle management and product line extension. For more information, visit www.spherics.com.

Contacts

Spherics, Inc.
Ze'ev Shaked, Ph.D., 401-334-7800
President & CEO
or
RMG Associates
Robert Gottlieb, 857-891-9091

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