Radius in-licensed from Karo Bio AB a class of selective androgen receptor modulators (SARMs) aimed at promoting both bone and muscle growth, and is prepared to pay up to $17 million for the rights.

Under the terms, Radius gains exclusive worldwide right, except for the Nordic countries, to the preclinical compounds for initial development in osteoporosis and frailty associated with muscle loss. In exchange, Radius agreed to pay milestones of up to $17 million to Karo Bio for one product, and would pay royalties. Karo Bio also would be entitled to payments related to the development of the SARMs for other indications.

Described as orally active small-molecules, SARMs are designed to modulate the androgen receptors, and preclinical studies have demonstrated high anabolic activity in bone and muscle.

"There is a great synergy between the activity on muscle and bone," said Richard Lyttle, president and CEO of Cambridge, Mass.-based Radius, "so that you can reduce fracture potentially by increasing bone mineral density and help fortify that bone with increased muscle mass."

The SARMs from Karo Bio also have demonstrated that they do not stimulate the androgen receptors in prostate and uterus tissues, and appear to avoid problems associated with androgen therapy.

Many of the compounds in the osteoporosis space are antiresorbers, such as Indianapolis-based Eli Lilly and Co.'s marketed drug Forteo (teriparatide), a recombinant form of human parathyroid hormone (PTH). NPS Pharmaceuticals Inc., of Salt Lake City, also is working on a PTH compound, Preos, which received an approvable letter in March, and Bothell, Wash.-based Nastech Pharmaceutical Co. Inc., is in Phase I with its nasal spray formulation of PTH.

While those products have been shown to prevent the resorption of bone, "it would be a big market boost if you could have an agent that could actually build bone," Lyttle told BioWorld Today. That means, in addition to osteoporosis, SARMs could have the potential to treat sarcopenia, muscle loss associated with aging.

Radius has narrowed the number of compounds in the SARM series and is shooting for an investigational new drug application submission for a lead candidate "sometime in 2008," Lyttle said.

About 44 million men and women in the U.S. suffer from low bone mass, according to Bart Henderson, senior vice president and chief business officer for Radius, "so there's a very large need for new therapies."

In addition, sarcopenia affects roughly 9 million people nationwide, and there are "a number of chronic conditions associated with muscle loss and frailty," such as chronic obstructive pulmonary disease and chronic renal failure, Henderson added.

Radius' new acquisition is a good fit for its growing pipeline, which is led by BA058, an injectable parathyroid hormone-related protein that just finished up a Phase Ib study in osteoporosis and is expected to move into Phase II early next year. That product is aimed at promoting new bone formation without causing resorption.

Behind BA058 is a selective estrogen receptor modulator aimed at relieving hot flashes and preventing bone loss caused by osteoporosis in postmenopausal women. Radius is preparing to start IND-enabling studies on that compound, RAD-1901, Lyttle said.

The company licensed rights to RAD-1901 from Tokyo-based Eisai Co. Ltd. in June. Terms were not disclosed. (See BioWorld Today, June 30, 2006.)

Radius also has an early stage collaboration with the University of Illinois focused on small-molecule estrogen receptor beta agonists for endometriosis and other inflammatory diseases.

Karo Bio, which retains the right to develop and market the SARM products in several countries - Denmark, Finland, Iceland, Norway, Sweden, Estonia, Lithuania and Latvia - also retains rights to the compounds in cancer and benign prostatic hypertrophy.

In separate news, the Huddinge, Sweden-based firm entered Phase I development with an estrogen receptor compound discovered through its collaboration with Whitehouse Station, N.J.-based Merck & Co. Inc. In that agreement, Karo Bio granted Merck exclusive worldwide rights to the compound in exchange for milestone payments and royalties.