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EMBARGOED FOR RELEASE UNTIL 12:30 P.M. (CDT) ON SEPTEMBER 23, 2005

NOVEL COMPOUND PROTECTED AGAINST BONE LOSS IN MONKEY MODEL OF OSTEOPOROSIS

Nashville (Sept. 23, 2005) – A compound developed by Novartis, AAE581, prevented the loss of bone mass and strength in monkeys with osteoporosis, according to findings presented today at the 27th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR). AAE581 inhibits cathepsin K, the key enzyme responsible for the breakdown of bone matrix. Approximately 60 percent of the weight of the bone is mineral. The rest is water and matrix, which is formed before the mineral is deposited, and can be considered the scaffolding for the bone.

Christopher P. Jerome, Ph.D., and his colleagues at SkeleTech Inc., in Bothell, WA, along with researchers at Novartis International AG in Basel, Switzerland, analyzed data on 100 female monkeys who were treated with placebo or with low, medium or high dosages of AAE581 for 18 months. Prior to receiving the compound, 80 monkeys underwent surgical removal of their ovaries, inducing bone fragility similar to that seen in postmenopausal women with osteoporosis. A control group of 20 monkeys had sham surgery and were treated with placebo.

AAE581 treatment, especially in medium and high dosages, resulted in increased bone mineral density and strength at the spine, femur and hips of ovariectomized monkeys to levels equal to or greater than those measured in the sham nonovariectomized group. Bone mineral density and strength were assessed using bone density analysis and mechanical loading tests of bone samples.

Many antiresorptive drugs, such as bisphosphonates, treat osteoporosis by inhibiting bone resorption or breakdown. However, they also significantly reduce bone formation. In contrast, AAE581 appeared to prevent bone resorption while it maintained the overall rate of bone formation. While the rate of bone formation decreased on surfaces within the bones, at the outer surface of long bones, AAE581 actually appeared to stimulate bone formation.

Dr. Jerome noted that an osteoporosis treatment that added bone where additional bone could improve resistance to fracture would be a welcome addition to the arsenal of osteoporosis therapies. However, he indicated that more information is needed about AAE581 to better understand and draw conclusions about its effect on bone formation.

ASBMR President-Elect Elizabeth Shane, M.D., notes: “These data in a non-human primate model are exciting because they suggest that this is another potential therapy for osteoporosis with novel and divergent effects on bone resorption (which was decreased) and bone formation (which was increased). Deposition of new bone on the outer surface of long bones increases their diameter and increases their resistance to fracture. If cathepsin K inhibitors prove to be safe and effective in humans they may provide another option for the prevention and treatment of osteoporosis.”

Please note that the results of a preliminary safety study of AAE581 in humans are also being presented at the ASBMR’s September 23rd press conference. (See “Potential Osteoporosis Treatment Well Tolerated, Effective in First Human Study.”)

Disclosures: The study discussed in this press release was funded by Novartis. Dr. Jerome has received research funding from Novartis.

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