ProScript Inc. signed a $20 million deal Monday with Hoffmann-LaRoche Inc. to discover and develop compounds for muscle wasting,initially in cancer patients.

Privately held ProScript, of Cambridge, Mass., received an equityinvestment and will get research support and milestone payments thatcould total $20 million. ProScript also can get royalties on sales.

Richard Bagley, chairman and CEO of ProScript, said thecollaboration will focus not on products for building up muscle, oranabolism, such as human growth hormone. Rather it will work onthe break-down side, or catabolism.

The deal with Roche, of Nutley, N.J., is the second majorcollaboration for ProScript. A year ago the company agreed to a dealworth up to $38 million with Hoechst Marion Roussel, of Frankfurt,Germany, that involves inhibition of enzymes in ubiquitin-proteasome pathways, a biological process for cell signaling. (SeeBioWorld Today, Nov. 10, 1995, p. 1.)

That pathway plays a role through activation of NF-kappaB, which isresponsible for transcriptionally activating proinflammatorycytokines, cell adhesion molecules and enzymes. It also regulates celldivision.

In the Roche collaboration ProScript will be working on targets in theubiquitin-proteasome pathway to find targets specific to musclewasting, or cachexia.

ProScript said its approach, focused on the ubiquitination cascade, isbased on an understanding that muscle wasting results fromaccelerated muscle protein degradation that is not offset by normalprotein synthesis. The companies will apply ProScipt's cachexia-specific assays and use screening technologies, medicinal chemistryand genomic approaches to identify inhibitors in the pathway.

Bagley said cachexia is caused by the body degrading its own musclefor emergency supplies of energy. Healthy people who suffer thecondition because of trauma can replenish the muscle. But in mostAIDS patients and about half of cancer patients the "switch" doesn'tget reset, he said, and the wasting syndrome generally is what putsthese patients in the hospital.

In the Hoechst deal ProScript will receive $15 million in equityinvestments and research support, with more than half targeted asequity. Bagley said Roche's equity investment will be about half ofHoechst's.

With the two deals ProScript essentially has partnered its science inthe ubiquitin-proteasome pathway. Later Monday, however,ProScript disclosed the acquisition of two new technologies.

In one deal ProScript licensed from Harvard Medical School therights to a small molecule cancer program based on inhibitingoncogenic Ras processing. Ras oncogenes are associated with anumber of cancers.

In a second deal ProScript acquired worldwide patent rights to anovel class of matrix metalloproteinase (MMP) inhibitors. MMPs area family of enzymes that play a role in cancer growth and jointdestruction in rheumatoid arthritis and osteoarthritis.

With the new products ProScript will have four programs running incancer and three in inflammation. n

-- Jim Shrine

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