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Speedel Group Release: SPP301 Phase IIb Results In Diabetic Nephropathy Presented At ASN


11/14/2005 10:39:21 AM

BASEL, Switzerland and BRIDGEWATER N.J., Nov. 12 /PRNewswire-FirstCall/ -- Speedel announced today that positive Phase IIb results of SPP301 in diabetic nephropathy (diabetic kidney disease) were presented on 11 November 2005 at the 38th Annual Meeting of the American Society of Nephrology (ASN) in Philadelphia, Pennsylvania, USA. The results were presented by Professor Rene Wenzel, principal investigator of the Phase IIb trial and Head of Internal Medicine at Zell am See Hospital, Austria. These results showed that SPP301, a once-a-day oral endothelin-A receptor antagonist (ERA) being developed by Speedel, decreases urinary albumin excretion rate (UAER) and total cholesterol in patients with diabetic kidney disease when administered on top of standard treatment. Diabetic nephropathy (DN) represents a large and growing unmet medical need with a high mortality rate affecting an estimated 8.0 million people(1) diagnosed with diabetes in the US, Europe and Japan.

Professor Wenzel commented: "The compelling results of this trial offer real hope for the treatment of diabetic nephropathy, the leading cause of end stage renal disease, for which treatment options are limited and the mortality rate unacceptably high. SPP301 may provide physicians with a novel approach to treating diabetic patients with nephropathy effectively and safely."

Dr. Jessica Mann, Medical Director of Speedel, commented, "These Phase IIb results are very encouraging as they demonstrate that SPP301, when administered on top of standard treatment, may offer a medical breakthrough for patients with diabetic kidney disease. SPP301 is the only ERA currently in development for this indication and we are now undertaking an extensive Phase III clinical programme to bring this novel therapy to patients."

Phase IIb results demonstrate strong efficacy and good safety

A total of 286 patients were enrolled in this randomized, placebo- controlled, double-blind, parallel design trial. It investigated the effects on UAER of 12-week therapy with SPP301 (5 mg, 10 mg, 25 mg or 50 mg) or placebo, administered once daily on top of standard treatment (consisting of angiotensin converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]. Compared to placebo, all doses of SPP301 decreased UAER significantly (p<0.001), with the highest two doses (25 mg, 50 mg) demonstrating the greatest reduction in UAER. There was also a significant reduction in total cholesterol at all doses (p<0.001) compared to placebo.

SPP301 was shown to reduce proteinuria by at least 30% on top of standard treatment for 55% of all patients across all dose groups. This is a remarkable additive effect in patients already receiving ACE inhibitors or ARBs, since these drugs are known to have strong antiproteinuric-effects on their own. Importantly, data from the US National Kidney Foundation(2) suggests that such a significant reduction in proteinuria by SPP301 could impact morbidity and mortality in patients with diabetic kidney disease.

SPP301 also has a good safety profile and whereas other ERAs have previously been associated with liver toxicity, SPP301 has not been associated with this side effect so far. In this trial, no significant increases in liver enzymes, aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) were observed with SPP301 compared to placebo.

The abstract(3) of the presentation made by Professor Wenzel can be accessed at: http://asn- online.org/education_and_meetings/Renal%20Week/Renal%20Week%202005/abstracts.a spx

Based on these very encouraging results, Speedel has taken SPP301 into a Phase III programme.

Phase III pivotal trial - ASCEND(4)

The Phase III pivotal morbidity and mortality trial, which began in July 2005, is a randomized, placebo-controlled study with over 2000 patients, designed to assess time to doubling of serum creatinine, ESRD or death in type II diabetic patients with nephropathy. The study, which has been discussed and agreed with the FDA and the EMEA, is being conducted in Europe, USA and other countries and is expected to be completed within approximately 3.5 years. The FDA has granted Fast Track status for SPP301 in this indication and has agreed a Special Protocol Assessment defining the design and endpoints for this Phase III trial.

About SPP301

SPP301 is a once daily oral endothelin A receptor antagonist that Speedel licensed from Roche in October 2000. SPP301, a second generation ERA, was developed out of Roche's endothelin research and drug discovery program, and was specifically optimised for improved liver safety. Speedel took the compound through a number of Phase I and exploratory Phase IIa clinical trials before selecting the novel indication of diabetic nephropathy for a Phase IIb clinical trial, the headline results for which were announced in March 2005. A Phase III study began in July 2005. Speedel has exclusive worldwide development and commercialisation rights under the licensing agreement with Roche.

About Diabetic Nephropathy

Diabetic Nephropathy is a new indication for this class of compound, and the positive Phase II results for SPP301 indicate considerable additional benefit on top of current therapies taken by patients suffering from this chronic disease. Current therapies include - amongst others - drugs that work on the renin-angiotensin system such as ACE inhibitors and ARBs, which have an antihypertensive effect as well as a renoprotective effect and have been shown to slow disease progression. However, 20-40% of patients with markers of early disease still progress to advanced kidney damage and eventually End Stage Renal Disease and death(5).

Definition: Diabetic nephropathy refers to any deleterious effect on kidney structure and/or function caused by diabetes mellitus. More specifically, diabetic nephropathy is thought of in stages, the first being that characterized by microalbuminuria (30-300 mg urinary albumin per 24 hours). This may progress to overt nephropathy or macroalbuminuria (>300 mg urinary albumin per 24 hours). Later still, progressive renal functional decline is characterized by significant decreases in glomerular filtration rate accompanied by rises in serum creatinine, the final result of which is End Stage Renal Disease.

Prevalence: According to the WHO in 2000, some 177 million people around the world had some form of diabetes, including undiagnosed cases. About 20-40% of patients with type 1 or type 2-diabetes develop nephropathy(6). Current treatments (primarily antihypertensive treatment and inhibition of the renin angiotensin system) slow progression of DN, but it remains an unmet medical need, with a high mortality rate.

About Endothelin Receptor Antagonists

Pharmacological blockade of the endothelin system constitutes a relatively new concept for modulating haemodynamic and cellular functions. Substantial evidence from animal testing and clinical studies suggest that endothelin plays a pivotal role in several diseases such as hypertension, chronic heart failure, and chronic nephropathies. Endothelin triggers renal vasoconstriction, decreases glomerular filtration rate and modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, by mechanisms that are still unclear. Endothelin also stimulates the renin angiotensin system and atrial natriuretic peptide release and inhibits vasopressin-mediated water re-absorption in the collecting duct. In preclinical testing, chronic administration of Endothelin Receptor Antagonists protected animals, including those with induced diabetes, from developing renal injury.

About Speedel

Speedel is a biopharmaceutical company that seeks to create value for patients, partners and investors by developing innovative therapies for cardiovascular and metabolic diseases. Speedel is a world leader in renin inhibition, a promising new approach with significant potential for treating cardiovascular diseases. Our lead compound SPP100 (Aliskiren), the first-in- class renin inhibitor, is partnered with Novartis for Phase III development and commercialisation in hypertension with filing for registration expected in 2006. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 in Phase III, SPP200 in Phase II, SPP635 in Phase I, and several pre-clinical projects.

Speedel develops novel product candidates through focused innovation and smart drug development from lead identification to the end of Phase II. We either partner with big pharma for Phase III and commercialisation in primary- care indications, or we may ourselves complete Phase III development in specialist indications. Candidate compounds for development and the company's intellectual property come from our late-stage research unit Speedel Experimenta and from in-licensing.

Our team of approximately 70 employees, including over 30 experienced pharmaceutical scientists, is located at our headquarters and laboratories in Basel, Switzerland and at offices in New Jersey, USA and Tokyo, Japan. Since being founded in 1998, we have raised gross proceeds of CHF 239 million (approximately EUR 154 million or USD 191 million) from private placements of equity securities and two convertible loans and we have had total revenues, principally from milestone payments, of CHF 57.7 million (approximately EUR 37 million or USD 46 million). The company's shares were listed on the SWX Swiss Exchange under the symbol SPPN on 08 September 2005.

(1) Decision Resources, October 2004 (2) Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis. 1999 May; 33 (5): 1004-10 (3) The ETA - selective anatagonist SPP301 on top of standard treatment reduces urinary albumin excretion rate in patients with diabetic nephropathy. Presented at 38th Annual Meeting of the American Society of Nephrology, 11 November 2005, Philadelphia. Rene Wenzel, Jessica Mann, Christiane Jurgens, Ilknur Yildirim, Heike Bruck, Thomas Philipp, Anna Mitchell. (4) Avosentan on doubling of Serum Creatinine, ENd stage renal disease and death in Diabetic nephropathy (5) Diabetes Care, American Diabetes Association 2004 (6) Diabetes Care, American Diabetes Association 2004 Forward looking statements

This press release includes forward-looking statements that involve substantial risks and uncertainties. These forward-looking statements are based on our current expectations and projections about future events. All statements, other than statements of historical facts, regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management are forward-looking statements. The word "may" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations described in these forward-looking statements and you should not place undue reliance on them. There can be no assurance that actual results of our research and development activities and our results of operations will not differ materially from these expectations. Factors that could cause actual results to differ from expectations include, among others: our or our partners' ability to develop safe and efficacious products; our or our partners' ability to achieve positive results in clinical trials; our or our partners' ability to obtain marketing approval and market acceptance for our product candidates; our ability to enter into future collaboration and licensing agreements; the impact of competition and technological change; existing and future regulations affecting our business; changes in governmental oversight of pharmaceutical product development; the future scope of our patent coverage or that of third parties; the effects of any future litigation; general economic and business conditions, both internationally and within our industry, including exchange rate variations; and our future financing plans.

Speedel

CONTACT: Nick Miles, Director Communications & Investor Relations ofSpeedel, +41-61-206-40-00, direct, +41-61-206-40-14, fax, +41-61-206-40-01,mobile, +41-79-446-25-21, nick.miles@speedel.com, or Frank LaSaracina,Managing Director of Speedel Pharmaceuticals Inc, +1-732-537-2290, fax,+1-732 537-2292, mobile, +1-908-338-0501, frank.lasaracina@speedel.com


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