Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Elan Corporation, plc (ELN) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (3440)	10/27/2002 2:12:50 PM
From: scaram(o)uche	Respond to of 10345

>> be much more helpful if you could explain the difference between Antegren and MLN02 - which seem to employ very similar approaches - and tell us why you think the first one will "work" why the other evidently didn't. << Erik: I was an Athena shareholder, and have followed antegren since it was conceived. I supervised the integrin projects at a competitive biotech, and I'm an investor in Dr.Butcher's "subsequent to LeukoSite" endeavor. I was also V.P. R&D at a reagents company at a time where there was a big-time focus on integrins. We made significant and independent efforts to discriminate among their tissue distributions. I was retained by an underwriter that participated in the IPO for LeukoSite, and I did formal dd on LDP-02. Given this background, I am nonetheless only capable of expressing an enthusiastic "lean" toward antegren. As you know, trials with anti-selectin and anti-integrin agents have largely failed to date. As I've expressed elsewhere at SI, I was also "leaning" positive for LDP-02 (MLN-02). But!!!...... an anti-beta7 is, IMO, not as powerful for gut indications as an anti-alpha4. Anti-beta7 completely misses any blockade of VLA-4 (alpha4beta1) interaction with VCAM-1. Moreover, an anti-alpha4 hits alpha4beta7, as did LDP-02. My "gut lean" (vbg), therefore, has always been stronger for antegren than for LDP-02. For demyelinating diseases? That doesn't address your question, but the literature is crammed with encouraging data from preclinical models. Hope that helps. Rick

To: Icebrg who wrote (3440)	10/27/2002 5:01:36 PM
From: scaram(o)uche	Read Replies (2) \| Respond to of 10345

I've been trying to find a striking study that would focus attention on the "clinical potential difference" between antegren and LDP-02. I can't. But I did find an abstract that will provide some focus (below). I presume that you know this...... major ligand for alpha4beta1 (VLA-4) is thought to be VCAM-1. major ligand for alpha4beta7 is thought to be mucosal addressin cell adhesion molecule (MAdCAM). while I believe that it's naive to assume that lymphocytes can't use alternative receptors to home to the gut, it should be apparent that an anti-beta7 (LDP-02) doesn't cover one of two of the biggies, while anti-alpha4 hits them both. studies to date indicate that the alpha4 epitope recognized by antegren is "relevant"..... the antibody not only reacts with both integrins, but also appears to block interaction of a4b1 with VCAM-1 and of a4b7 with MAdCAM. I can't personally testify to this. Am J Physiol Gastrointest Liver Physiol 2002 May 29; [epub ahead of print] Spatial heterogeniety of TNF-{alpha}-induced T-lymphocyte migration to the colonic mucosa is mediated by MAdCAM-1 and VCAM-1. Watanabe C, Miura S, Hokari R, Teramoto K, Ogino T, Komoto S, Hara Y, Koseki S, Tsuzuki Y, Nagata H, Granger DN, Ishii H. Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan. Relatively little is known about how recirculation of lymphocytes through the inflamed intestinal mucosa is regulated. The aim of this study was to investigate the dynamic process of T-lymphocyte-endothelial cell adhesion in tumor necrosis factor (TNF)-alpha challenged murine colonic mucosa by intravital microscopy. T lymphocytes from spleen (SPL) and intestinal lamina propria (LPL) were fluorescence labeled and their adhesion to microvessels in the colonic mucosa was observed. In TNF-alpha (25 micro g/kg)-stimulated colonic venules, an enhanced adhesion of SPL and LPL was demonstrated, with dominant recruitment of LPLs. The magnitude of the increased LPL adhesion was more significant in the colon than in the small intestine. These T-lymphocyte interactions in the colonic mucosa were significantly reduced by blocking mAbs against either MAdCAM-1, VCAM-1, alpha4-integrin, or ss7-integrin, but not by anti-ICAM-1. Immunohistochemistry revealed significant MAdCAM-1 expression in the lamina propria and VCAM-1 expression in the submucosa of TNF-alpha-treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha-challenge may promote specific T-lymphocyte recruitment in the inflamed colonic mucosa.