Icos MAb Hu23F2G will be studied in five Phase II trials; hemorrhagic shock trial commenced in April.

ICOS MAb Hu23F2G CLINICAL PROGRAM TO INCLUDE FIVE PHASE II TRIALS, the company indicates in a prospectus for a recent public offering. The Icos development program focuses on "early acquisition of Phase II data" through "numerous appropriate Phase II clinical trials in order to increase the likelihood of identifying clinically relevant programs," the prospectus states.

Hu23F2G is a recombinant humanized monoclonal antibody designed to "block CD11/CD18- mediated cell adhesion in humans," the prospectus explains. Icos believes "that by intervening in the adhesion process, much of the inflammation-associated damage can be prevented." The Bothell, Wash. company is "producing Hu23F2G to support Phase I and Phase II clinical trials," the prospectus notes.

The first Phase II trial of Hu23F2G, in trauma-induced hemorrhagic shock, began in April at Harborview Medical Center, Seattle. Icos also plans Phase II trials for treatment of multiple sclerosis, ischemic stroke, myocardial infarction and acute peripheral arterial occlusion, the prospectus states.

Two Phase I trials in MS -- a single dose and a multiple dose study -- support the Phase II clinical program for Hu23F2G, the prospectus says. To date, 40 patients with chronic MS have been treated with the compound. "In Phase I clinical trials, Hu23F2G has been shown to bind to CD11/CD18 on the surface of leukocytes and to block subsequent movement into surrounding tissue," the document maintains.

Annual per patient revenue from Hu23F2G is estimated at $5,000 per MS patient in the company's 10-K filing for 1995. A hemorrhagic shock indication is estimated to be worth $3,000 per patient in annual revenues. Ischemic stroke, MI and acute peripheral arterial occlusion would generate $2,500 per patient annually in revenues, the 10-K estimates.

The prospectus states that Icos believes Hu23F2G could be administered to treat stroke "alone or in combination with a thrombolytic agent such as t-PA" (Genentech's Activase). Activase was approved to treat ischemic stroke June 18 ("The Pink Sheet" June 24, p. 5).

A Phase I trial of recombinant platelet-activating factor acetylhydrolase is expected "to conclude midyear," Icos said in announcing initiation of the trial in March. The trial will gather data to support rPAF-AH use in acute respiratory distress syndrome. The compound "degrades PAF," a "prominent mediator in the amplification of the inflammatory response," Icos said.

"Clinical development of rPAF-AH for the treatment of ARDS, necrotizing enterocolitis, acute pancreatitis and [inflammatory bowel disease] is slated for 1996 and 1997," the 10-K filing reports. "Very small doses of rPAF-AH are anticipated to provide high levels of PAF degradation." The document estimates annual per patient revenue at $1,500 for acute respiratory distress prophylaxis, $3,000 for ARDS therapy, $2,000 for NEC prophylaxis, $8,000 for NEC therapy, $3,000 for treatment of moderate to severe IBD exacerbations and $5,000 for acute pancreatitis.

Icos raised $49.1 mil. with its most recent public offering, which concluded May 8. The company sold 6.9 mil. shares, including the underwriters' full exercise of a 900,000 over-allotment option. Shares were priced at 7-5/8 per share, just below the company's 1991 initial public offering price of 8.

Approximately 85% of the proceeds is slated to fund R&D and clinical trials, the prospectus states. About 15% will go to expansion of facilities, equipment and general corporate purchases. The offering was underwritten by PaineWebber, Lehman Brothers, Robertson Stephens, Gerard Klauer Mattison and Regan MacKenzie.

A 21,000 sq. ft. production facility "is anticipated to begin production in late 1996," the prospectus reports. "This facility will be capable of utilizing both microbial and mammalian-based production processes."

Icos has three collaborations with pharmaceutical companies, including a 1991 alliance with Glaxo Wellcome that is developing treatments of inflammatory and cardiovascular conditions by selective modulation of phosphodiesterase activity ("The Pink Sheet" Oct. 7, 1991, In Brief). An Abbott collaboration is studying modulators of intracellular signaling ("The Pink Sheet" April 10, 1995, T&G-1). One compound, ICM3, has reached the preclinical development stage "as a potential treatment for psoriasis, GvHD and organ transplantation rejection," the prospectus states. Icos' sole 1995 revenues -- $1.5 mil. -- resulted from the Abbott agreement.

In January, Icos entered a collaboration with Gryphon Sciences. Gryphon will synthesize proteins and protein analogs related to certain molecules discovered by Icos, which will assess the molecules' biological characteristics and activities.