Kos Reports on Promising Data Presented at AHA: New Compound Reverse-D4F, a Novel Apo A-I Mimetic Peptide, May Reduce the Progression of Atherosclerosis

-- Reverse-D4F, a Novel Apo A-I Mimetic Peptide, Showed 46% Reduction in Atherosclerotic Lesion Area in a Preclinical Animal Model

-- The Data Indicate that Reverse-D4F is at Least as Effective as D-4F in Reducing the Progression of Atherosclerosis at Early Stages of Lesion Formation in Apo E-null Mice

-- Data Represents Early Productivity in the Area of Potential New Chemical Entity Design Through Kos' Sponsored Research Agreement With Arisaph

Kos Pharmaceuticals, Inc. (Nasdaq: KOSP) today commented on theresults of a study presented at the 2005 Scientific Sessions of theAmerican Heart Association (AHA) meeting. The results, presented byDr. Moti L. Kashyap of VA Healthcare System and the University ofCalifornia at Irvine, showed that Reverse-D4F (Rev-D4F), an apo A-Imimetic peptide, significantly reduced atherosclerotic lesion areacompared with the L-4F mimetic peptide and placebo (water as acontrol) in an atherosclerotic animal model and demonstrated potentanti-inflammatory properties, in vitro.(1) Rev-D4F was developed onbehalf of Kos through its sponsored research agreement with ArisaphPharmaceuticals, formerly known as Triad Pharmaceuticals, Inc.

The study evaluated the effects of Rev-D4F, D-4F, L-4F mimeticpeptides and placebo (water as a control) on atherosclerosis inapolipoprotein E-knock-out mice, a well-established animal modelsimulating human atherosclerosis. Following six weeks of treatment,measurements of the atherosclerotic lesion showed that both Rev-D4Fand D-4F significantly decreased lesion area by 46% and 33%,respectively, compared to control. Animals treated with Rev-D4F showedthe greatest reduction in lesion area, although the differencecompared with D-4F was not statistically significant. The animalsreceiving L-4F showed no difference in lesion size compared withplacebo. Additionally, Rev-D4F showed potent anti-inflammatoryproperties, in vitro, by significantly inhibiting LDL oxidation byendothelial cells, monocyte chemotactic proptien-1 expression, andmonocyte chemotaxis, important inflammatory events that are involvedin atherosclerosis.(2)

"We are proud of our pioneering developments in the cholesterolmarket, specifically with Niaspan(R) and Advicor(R), highlydifferentiated products aimed at increasing HDL-C and providingbroader dyslipidemic control," said Adrian Adams, President and CEO,Kos Pharmaceuticals, Inc. "As one of the fastest growingpharmaceutical companies in the USA, we see tremendous opportunity tosustain growth and build on our leadership position in the HDL-Cmarket by leveraging our heritage and our extensive cardiovascularknowledge to create potential new chemical entities through oursponsored research programs. This is part of a synergistic strategy tobroaden our research and development efforts with measured,cost-effective investments in our core therapy areas."

The focus on Rev-D4F is part of a multi-pronged HDL research anddrug discovery program led by Kos in conjunction with Arisaph and anumber of lead investigators. In addition to Rev-D4F, Kos' sponsoredresearch program has made considerable progress in identifying twoadditional promising leads to improve HDL, including niacin-relatedanalogs and inhibitors of enzymes specific to atherogenesis. Thiscomes at a time when HDL-C is an increasing focus of the scientificand clinical community and bodes well for Kos' growth strategy tomaintain its leadership position in the area of HDL-C.

About L-4F, D-4F and Rev-D4F

The HDL protein facilitates "reverse cholesterol transport," andis like a "cleaning service" for the blood, removing plaque build-upout of the artery wall and through the liver to the gastrointestinaltract where it is removed from the body.(3) L-4F and D-4F have beenshown to make HDL more functional and reduce atherosclerosis lesionsin mice, but can be broken down by enzymes in the body when takenorally before the full benefits of the compound can be observed.Rev-D4F is not an HDL-C raising strategy, but the compound seems tohelp existing HDL function better.

Study Details

The study evaluated the effects of Rev-D4F, D-4F, L-4F mimeticpeptides and placebo on atherosclerosis in apolipoprotein E-knock-outmice, a well-established animal model simulating humanatherosclerosis. The study consisted of four groups of four-week oldApo E-knockout mice (Apo E was genetically removed to induceatherosclerosis), that were all fed chow diets, but separatelyadministered water or Rev-D4F, D-4F or L-4F orally in drinking water.Following six weeks of treatment, measurements of the atheroscleroticlesion showed that both Rev-D4F and D-4F significantly decreasedlesion area by 46% and 33%, respectively compared with placebo.Atherosclerotic lesions were assessed by quantitative morphometry ofaortic root cross sections stained with oil-red O performed with theNational Institutes of Health (NIH) software.(4)

About Kos

Kos Pharmaceuticals, Inc. is a fully integrated specialtypharmaceutical company engaged in developing, commercializing,manufacturing and marketing proprietary prescription products for thetreatment of chronic diseases with a particular focus on thecardiovascular, metabolic and respiratory disease areas. The principalproduct development strategy of the Company is to reformulate existingpharmaceutical products with large market potential to improve safety,efficacy, and patient compliance. The Kos strategy also includesmaking increased, measured investments in new chemical entity researchthrough in-house and sponsored research, scientific in-licensing andgeneral corporate development activities. The Company currentlymarkets Niaspan(R), Advicor(R), Azmacort(R), Cardizem(R)LA,Teveten(R), and Teveten(R)HCT. Kos has a strong and growing researchand development pipeline encapsulating proprietary drug deliverytechnologies in solid-dose, inhalation and aerosol metered-dose deviceadministration to help fuel sustained, organic sales growth into thefuture.

About Arisaph

Arisaph, located in Boston, Massachusetts, is an emerging drugdiscovery and design biopharmaceutical company with active developmentprograms to develop differentiated therapies for diabetes, cancer andcardiovascular disease. Arisaph utilizes proprietary drug discoveryplatforms to develop "ultra-smart" drugs that are efficacious and acton select targets. Arisaph has successfully applied its specificityprofiling and retro-inversal chiral chemistry technology platforms tosynthesize promising candidate drugs for six different targets,including lead candidates for DPP IV inhibition to treat type IIdiabetes and for reverse D-4F, an orally active apo A-I mimeticpeptide for treatment of atherosclerosis. Through a license agreementwith Tufts University, the Company has exclusive worldwide rights toseveral important issued patents in the diabetes area and to allintellectual property generated by the Company.

Certain statements in this press release, including statementsrelating to results of the Rev-D4F study, the Company's ability togrow and strengthen its research and development pipeline andcholesterol franchise, the Company's ability to sustain its growth,are forward-looking and are subject to risks and uncertainties whichmay cause actual results to differ materially from those projected ina forward-looking statement. These risks and uncertainties include,the Company's ability to grow revenue and control expenses, theprotection afforded by the Company's patents and those related to theacquired and licensed products, the ability to build awareness forNiaspan(R), Advicor(R), Azmacort(R), Cardizem(R)LA, Teveten(R) andTeveten(R)HCT within the medical community, the continued success ofthe alliances with Takeda, Merck KGaA, Oryx, Barr and Biovail, thecontinuing growth of the cardiovascular and respiratory markets, theCompany's ability to maintain its compliance with FDA regulations andstandards without adversely affecting the Company's manufacturingcapability or ability to meet its production requirements or profitmargins, the Company's ability to attract and retain salesprofessionals and successfully integrate the sales force obtained fromBiovail, ensure compliance with prescription drug sales and marketinglaws and regulations, changes in the regulatory environment governingthe Company's compliance with the FDA, PTO, tax and competitionissues, the impact of a possible generic version of the Cardizem LAproduct or other products sold by the Company, the ability of thirdparty suppliers to the Company continuing to be able to perform theirsupply obligations, the Company's ability to achieve regulatoryapprovals for its products under development in a timely manner, suchas the modified formulation of Niaspan and others, the Company'sability to establish a footprint and generate sales in thehypertension and angina markets, the Company's ability to successfullynegotiate additional important strategic business developmentopportunities, the progress of the Company's research and developmentpipeline, fluctuating buying patterns by the Company's wholesalers anddistributors, the Company's ability to maintain coverage of itsproducts by government agencies, such as the Centers for Medicare andMedicaid Services, the effect of conditions in the pharmaceuticalindustry and the economy in general, as well as certain other risks. Amore detailed discussion of risks attendant to the forward-lookingstatements included in this press release are set forth in the"Forward-Looking Information: Certain Cautionary Statements" sectionof the Company's Annual Report on Form 10-K for the year endedDecember 31, 2004, filed with the Securities and Exchange Commission,and in other reports filed with the SEC.

(1) Qin S. Reverse-D4F (Rev-D4F), an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in Apolipoprotein E-null Mice (Abstract)

(2) Qin S. Reverse-D4F (Rev-D4F), an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in Apolipoprotein E-null Mice (Abstract)

(3) The Difference Between LDL and HDL Cholesterol. American Heart Association. 2005. Available at www.americanheart.org; accessed 10/31/05

(4) Qin S. Reverse-D4F (Rev-D4F), an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in Apolipoprotein E-null Mice (Abstract)