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 : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Henry Niman who wrote (14854)	2/12/1998 2:55:00 PM
From: squetch	Respond to of 32384

This is a VERY bullish paper in IMUntrainedO. I think it will lead to more off label usage when Targretin is approved. I had a hard time buying the off label arguement as doctors seem a conservative lot. Not sure how it translates to human, but >>the chosen doses of TAM were similar to doses that have been shown to be efficacious therapeutic doses in this (rat) model.<< The therapeutic numbers for stand alone treatment are encouraging. 72% is the headline number, but 30 mg regressed 27.8% of primary tumors as compared to 33.3% w/ 800 ug Tam. The combo data I posted to tonyt of Tam + Targ is very encouraging. I would intuitively think less Tamoxifen generating 27.8% CR would generate a serious look by Oncologists. The press release mentions, but doesn't get into, other areas which are also encouraging. These are the areas of secondary tumor burden and cellular proliferation. Looking at the graph of Mean Secondary Tumor Burden, both doses of Tam reduced burden by about 72% compared to control. 10 mg of Targ reduced the burden 24%. 30 mg of Targ was 75% reduction and 100mg was -81% of control group. Control had 3.63 mean tumors per animal. 150 ug Tam had ~1.8, 800 ug had 1.33 per animal. 10 mg of Targ ~2.4 per, 30 mg had ~1.4, 100 mg had 0.69 per animal. So 30 mg would appear in this study to have better to equal control of tumor burdens when compared to Tam doses. Something not mentioned in the release was >>after 6 weeks of treatment, LGND 1069 therapy resulted in complete regression of all tumors, or cures, in 46% of treated animals; in contrast, only 29% of TAM-treated animals achieved complete cures.<< Note after reading some posts, cure was in the paper and so not added by me The second exciting area was cellular proliferation. >>Histopathological analysis of H&E-stained slides from Targretin-treated rat mammary tumors indicated noticeably fewer features of malignancy, as characterized by a decrease in stromal and surrounding tissue invasion, a decreased number of cell layers, and a decreased cellular pleomorphism, as compared to control tumors. TAM-treated tumors also exhibited a decrease malignant phenotype, when compared to vehicle-treated controls; however, these effects were not as promient as in Targretin-treated tumors(data not shown)<< Another point you might be interested in Henry is both Targ-treated and control tumors had high amount of apoptosis. >>Thus a sharp decrease in proliferation, combined w/ a basal level of apoptosis, accounts for a large part of the rapid therapeutic effect of Targ on mammary tumors.<< Seems very positive study to me especially when you add in little or no retinoid associated toxicities in cancer trials at doses of less than or equal to 350mg/mm/day.