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Biotech / Medical : Regeneron Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (925)	6/7/2004 10:16:28 PM
From: Miljenko Zuanic	Respond to of 3559

<<Anyone know when final results are expected?>> By the year 200X, or 20XX, IF we are lucky. Unless,... well I will not continue in this tone. Yes, some stabilization and maybe minor respond should be expected with 800 mcg/kg/week or 1600mcg/kg/week. But, that it is not the point. Avastin didn't have any objective respond in multiple PI. What make me angry is slid #15 from ASCO presentation. regeneron.com IF target minimal effective plasma level for Trap was 10 mcg/mL, what was an idea going with 25-200 mcg//Kg dose. Second, IF VEGF blood level is measured with ng/mL, and Trap Kd is few pM, than why they need mcg/ml level to bind VEGF? Most likely Trap is highly bound to plasma proteins (albumin), long t1/2, and only small part of the circulating Trap is available to bind VEGF. This is not that important, IF one know what is coming, but failing with formulation designee and waste time and money on long PI has no excuse. Positive is that Aventis is now in control. New IV trial have ONLY TWO dose (every second week) before PK and safety data are collected and trial continue with higher dose cohort, while extension protocol looks on further tolerability/activity. Miljenko PS: One who continue to bleed with his misfortune investment

To: tuck who wrote (925)	10/6/2004 3:58:41 PM
From: keokalani'nui	Read Replies (1) \| Respond to of 3559

Final results of the study will be presented. 2004 eort-aacr. I didn't notice a PR from the co. Abstract 132: A phase I and pharmacokinetic clinical trial of subcutaneous (sc) VEGF Trap in advanced solid tumor patients Citation: European Journal of Cancer Supplements Volume 2, No.8, September 2004, page 43 J. Dupont1, L. Schwartz1, J. Koutcher1, D.R. Spriggs1, M.S. Gordon2, D. Mendelson2, J. Murren3, A. Lucarelli4, J.M. Cedarbaum4 1Memorial Sloan-Kettering Cancer Center, Medicine, New York, USA 2Arizona Cancer Center, Medicine, Scottsdale, USA 3Yale University, Medicine, New Haven, USA 4Regeneron Pharmaceuticals Inc, Medicine, Tarrytown, USA Background: VEGF Trap is a potent angiogenesis inhibitor comprised of portions of the human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (KDR) extracellular domains fused to the Fc portion of human IgG. VEGF Trap binds VEGF-A 100- to 1000-fold more tightly than monoclonal antibodies (Kd <1 pM) and neutralizes all circulating and tissue VEGF-A isoforms plus placental growth factor. Methods: In this phase I trial, successive cohorts of pts with relapsed or refractory solid tumors received 1 (or 2) doses of sc VEGF Trap, followed 4 weeks later by 6 weekly (or twice weekly) doses. Pts without disease progression subsequently entered a long-term extension study. Study endpoints included safety, pharmacokinetics, and immunogenicity. Antitumor activity was assessed by CT scan. Results: A total of 38 pts were treated across 7 dose levels: 0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg weekly, and 0.8 mg/kg twice weekly. Potentially drug-related grade 3 or 4 adverse events (AEs) encountered included hypertension (n=2), proteinuria (n=1), afebrile neutropenia (n=1), and pulmonary embolism (n=1). Other than HTN, no dose-related pattern of AEs emerged. The maximum tolerated dose was not reached. No pts have developed anti-VEGF Trap antibodies, including those pts treated for ³6 mos. Plasma VEGF Trap levels associated with antitumor activity in animal models were approached in the 0.8 mg/kg once and twice weekly dose groups. Objective partial or complete responses were not achieved, but 17 of 35 evaluable pts, including 8 of 12 pts treated with ³0.8 mg/kg/week, maintained stable disease (SD) for at least 10 weeks and entered the extension study. Conclusions: VEGF Trap has a favorable safety and tolerability profile. Consistent with previous findings with an anti-VEGF antibody, VEGF Trap may be associated with dose-dependent hypertension. Eight of 12 (67%) of evaluable pts treated with 0.8 mg/kg once or twice weekly, compared with 9 of 23 (39%) who received lower doses, maintained SD at the end of the 10-week study. Final results of the study will be presented.