Privately held NPS Pharmaceuticals Inc. has attracted a majorcorporate partner to aid in its search for drugs to treatosteoporosis.

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

SKB gets the exclusive worldwide rights to products developedthrough the collaboration and will pay royalties to NPS onproduct sales. For its part, NPS will have the option to co-promote products with SKB in the U.S., and under certainconditions may obtain exclusive worldwide rights to productsnot commercialized by SKB.

NPS Pharmaceuticals was founded in 1986 as Natural ProductSciences Inc; it was renamed in March 1992. A month later thecompany raised $5 million in its initial round of venturefinancing led by Domain Associates and BiotechnologyInvestments Ltd. That summer it raised another $4.75 million-- $2 million from S.R. One, $2 million from ChancellorManagement and $750,000 from JAFCO America Ventures Inc.-- explained Hunter Jackson, NPS's chairman and chiefexecutive officer.

NPS's drug discovery efforts are focused on the role of calciumand its receptor in bone-related diseases and disorders. Inparticular, researchers have found that calcium ions canfunction as extracellular signals. In fact, a wide variety of celltypes appear capable of sensing external changes in calciumconcentrations. The most important of these seems to be theparathyroid cell because the hormone it secretes is primarilyresponsible for regulating the level of plasma calcium.

Scientists from NPS, in conjunction with their collaborators atCase Western Reserve University and Brigham and Women'sHospital, have expressed, cloned and sequenced the calcium ionreceptor from the surface of parathyroid cells (the results willappear shortly in the journal Nature). The receptor is amember of the G-protein receptor super family and theencoded polypeptide exhibits the classic seven transmembranedomain motif common to all such receptors.

The research and development program between NPS and SKBinvolves three separate approaches to developing drugs thatinteract with the calcium receptor, explained Jackson. Two ofthose involve devising means to limit or prevent the resorptionof bone that is common in osteoporosis; the other involvesefforts to replace the bone.

Bone structure is maintained by a balance between the actionsof osteoclasts, which dissolve bone, and osteoblasts, which laydown bone. But a negative feedback loop appears to be atwork; according to Jackson, as the bone is dissolved the largeamount of calcium released acts to turn off the osteoclast.

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

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

-- Jennifer Van Brunt Senior Editor

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