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

To: Biotech Jim who wrote (23239)	7/15/1998 2:15:00 PM
From: Henry Niman	Respond to of 32384

BJ, The wording in the BioWorld article is somewhat different than the press release. In the press release Rosen said: "This is the first reported discovery of a small, non-peptide molecule that exerts the same in vivo effect as a cytokine," said Jonathan Rosen, Ph.D., Ligand senior director, Transcription Research. "Although activity for this particular compound has so far only been observed in murine systems, this discovery provides an important proof of concept and opens up the possibility for the development of orally active, small molecule mimics for G-CSF and for other cytokines." and I thought that it was carefully worded to avoid revealing the existence of a compound that worked in a human system. In BioWorld, the emphasis seemed to be on the lack of human activity. Of course it's much easier to be misquoted in an article by a third party, than by the company and LGND could be working on a smokescreen.

To: Biotech Jim who wrote (23239)	7/15/1998 3:11:00 PM
From: Henry Niman	Respond to of 32384

Jim, I did get a chance to read the BioWorld paper and there isn't much more info than the paragraph that was uploaded earlier. Of course LGND is aware of the competition and the article closes with: Rosen concluded, "This is a general approach to drug discovery that's applicable to many protein receptor systems. It's an important lesson that we learned - and I'm afraid many others will learn from our work." So of course they key question is why did LGND elect to release the news at this time. The publication appears to have been ready early this year when LGND presented data at Keytstone and/or Lake Tahoe. The press release obviously dove tailed with the Science publication and LGND clearly has filed for patent coverage. I think that they do have a human version (the article did indicate that G-CSF was "a likely first target of their aim to replace large proteins with mini-mimic molecules) and I would be surprised if it was structurally unrelated to the 526 dalton "symetrical, heterocyclic, organic compound", which I suspect is a red herring designed to keep the competition busy (although LGND does indicate that they will use the mouse specific compound to gain structural and mechanistic information of the effect, and its ability to cause receptor oligomerization).

To: Biotech Jim who wrote (23239)	7/15/1998 5:21:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

The BioWorld article on Ligand's G-CSF was good size. It took up 1/4 of page 1 and all of page 3. The article was entitled "Ligand Finds Mini-Molecule To Do G-CSF Protein's Job". The byline is "Mantra For Drug Discovery: Pill, Yes; Needle No" and was written by David Leff. The article begins be mentioning the biotechnology and pharma's version of a needle exchange program which seeks to find oral compounds capable of replacing injected drugs. Rosen is quoted extensively throughout the report (he was senior author on the Science paper and Senior Director of Transcription Research at Ligand. Background on AMGN's billion dollar a year injectable G-CSF (Nuepogen) is given and Ligand and partner SBH have "drawn a bead on G-CSF as a likely first target of their aim to replace large proteins with mini-mimic molecules. The mimic, SB247464, was discovered in SBH's defined compound collection. It "is a symetrical, heterocyclic, organic compound with a molecular weight of 526 daltons." The paper indicates that a compound such as a small molecule that can be taken orally has several advantages over the large protein or smaller peptides (5K), both of which require injection. The molecule is thought to work via receptor oligomerization, but SB247464 is mouse specific (unlike recombinant Neupogen which works on mouse and human receptors). The only real info on other molecules came from this paragraph: "Although this compound does have, we believe, incredible effects in the mouse," Rosen observed, "in the assays we've done to date we have not seen activity in human systems. so we're going back to several drawing boards, looking for related molecules from the same series as well as discovery of additional ones that will be human-active." Ligand plans to use SB247464 to study its mechanism of action by testing some hypotheses on how it actually works. in the final paragraph: Rosen concluded, "This is a general approach to drug discovery that's applicable to many protein receptor systems. It's an important lesson that we learned - and I'm afraid many others will learn from our work."