Privately held NPS Pharmaceuticals Inc. has attracted a major corporate partner to aid in its search for drugs to treat osteoporosis.

In a multimillion dollar collaboration announced Tuesday, NPS and SmithKline Beecham agreed to explore the potential of NPS's technology in calcium receptors to develop and commercialize orally active drugs for treating osteoporosis and related bone and mineral disorders. NPS of Salt Lake City will receive an up-front payment from SKB of $6 million, as well as an equity investment of $7 million from SKB's venture capital affiliate, S.R. One (which had previously made a $2 million investment in NPS). NPS also will receive further cash payments and research funding from SKB on the achievement of certain milestones.

SKB gets the exclusive worldwide rights to products developed through the collaboration and will pay royalties to NPS on product sales. For its part, NPS will have the option to co- promote products with SKB in the U.S., and under certain conditions may obtain exclusive worldwide rights to products not commercialized by SKB.

NPS Pharmaceuticals was founded in 1986 as Natural Product Sciences Inc; it was renamed in March 1992. A month later the company raised $5 million in its initial round of venture financing led by Domain Associates and Biotechnology Investments Ltd. That summer it raised another $4.75 million -- $2 million from S.R. One, $2 million from Chancellor Management and $750,000 from JAFCO America Ventures Inc. -- explained Hunter Jackson, NPS's chairman and chief executive officer.

NPS's drug discovery efforts are focused on the role of calcium and its receptor in bone-related diseases and disorders. In particular, researchers have found that calcium ions can function as extracellular signals. In fact, a wide variety of cell types appear capable of sensing external changes in calcium concentrations. The most important of these seems to be the parathyroid cell because the hormone it secretes is primarily responsible for regulating the level of plasma calcium.

Scientists from NPS, in conjunction with their collaborators at Case Western Reserve University and Brigham and Women's Hospital, have expressed, cloned and sequenced the calcium ion receptor from the surface of parathyroid cells (the results will appear shortly in the journal Nature). The receptor is a member of the G-protein receptor super family and the encoded polypeptide exhibits the classic seven transmembrane domain motif common to all such receptors.

The research and development program between NPS and SKB involves three separate approaches to developing drugs that interact with the calcium receptor, explained Jackson. Two of those involve devising means to limit or prevent the resorption of bone that is common in osteoporosis; the other involves efforts to replace the bone.

Bone structure is maintained by a balance between the actions of osteoclasts, which dissolve bone, and osteoblasts, which lay down bone. But a negative feedback loop appears to be at work; according to Jackson, as the bone is dissolved the large amount of calcium released acts to turn off the osteoclast.

"We're seeking to turn that (negative feedback loop) into a therapeutic advantage," Jackson told BioWorld. "We want to mimic that action with small orally active drugs." And although calcium receptors have not been cloned from osteoclasts per se, there is physiological evidence that such a receptor exists, he added.

As for the third approach of actually trying to replace bone tissue, that goal is "the holy grail," commented Jackson.

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.