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

To: Harold Engstrom who wrote (195)	5/7/1999 12:04:00 PM
From: scaram(o)uche	Read Replies (2) \| Respond to of 52153

Harold..... as you know, I don't pay much attention to companies that actually sell stuff. However, here's something to further torture you........ 315 HIGH LEVELS OF STABLE MULTI-LINEAGE HEMATOPOIETIC CBIMERISM AND DONOR-SPECIFIC ALLOGENEIC SKIN GRAFT TOLERANCE WITH T-CELL COSTIMULATORY BLOCKADE Background: The induction of mixed hematopoietic chimerism by bone marrow transplantation leads to donor-specific tolerance if host T-cells are adequately depleted during conditioning. Because of its potential toxicity in the chemical setting, we sought to avoid T-cell depletion in the host conditioning. Methods: C57BL/6 mice received a non-myeloablative dose of 3Gy whole body irradiation (do) and were injected with 15x10^6 fully MHC-mismatched, unseperated bone marrow cells from B10.A donors on the same day. In addition, hosts were injected with a single dose of an ant+CD40L antibody (MR1; 0.45mg/mouse) and CTLA4Ig (0.5mg/mouse) either alone or in combination on d0 and d+2, respectively. A control group received anti-CD4 and anti-CD8 T-cell depleting antibodies on d-5 and d-1. Donor chimerism in peripheral blood was followed by flow cytometric analysis at multiple time points, and donor and third party (A.SW) skin grafts, were placed 3-10 weeks after bone marrow transplantation. Results: Treatment with the combination of MRI plus CTLA4Ig led to high levels of multi-lineage chimerism (>40% donor cells in the T-cell, B-cell and myelold lineages) that was sustained throughout the observation period of more than 7 months. MRI alone, in contrast, led to initially high levels of donor representation, which, however, were not stable over time. Treatment with CTLA4Ig alone did not result in chimerism detectable by flow cytometric analysis. MRI plus CTLA4Ig led to indefinite donor skin graft survival (>lOO days in 12 of 14 mice), while third party grafts were rejected within 2 weeks. In the control group receiving T-cel1 depleting antibodies, 3 of 5 donor grafts survived for 100 days. CTLA4Ig alone did not permit prolonged skin graft survival. MRI alone prolonged survival, but 7 of 9 grafts were rejected before day 100. Conclusion: Treatment with anti-CD40L antibody plus CTLA4Ig allows the induction of high levels of stable mixed chimerism and skin graft tolerance without T-cell depletion or myeloablation of the host T Wekerle, MH Sayegh, J Hill, A Chandraker, KA Swenson, G Zhao and M Sykes. Transplantation Biology Research Center/Massachusetts General Hospital and Laboratory of Immunogenetics and Transplantation/Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02129, USA ***************** So, how in the world to you sell stock in a company that has anti-CD40L coming along? :-) BTW.... for those who are watching this issue, yes, that's the BTRN-alligned crew. The CD2 epitope defined by 507 is only expressed on human, gorilla and chimp, so this study doesn't worry me from that stand. I do not know if there's a potential to sneak through with an anti-CD40L-related use patent for this application (human chimeras).

To: Harold Engstrom who wrote (195)	5/7/1999 5:22:00 PM
From: Biomaven	Read Replies (1) \| Respond to of 52153

Harold, Nothing like a nice, easy question, right? Well I'll take a shot, anyhow. My answer is long, so I'll take a few posts. (If you are impatient, where I come out is that if you are very confident in BGEN's fundamentals and aren't too risk averse, you should buy more, but should probably hedge your position against some other stocks). There are really two separate (but related) questions. The first (and harder) is "Is this stock good value in absolute terms?" and the second is "Is this stock good value in relative terms?" By "good value" I mean some sort of risk-adjusted valuation and by "relative terms" I mean in comparison with some other set of identifiable stocks. The way I look at it, there are really three factors that go into determining a stock price. The first is the fundamentals of the company, the second is peoples' perceptions of these fundamentals, and the third is what the market will pay for a stock with given perceived fundamentals (call this "market attitude" for want of a better term). BGEN is currently off 20% from last month's high. I don't believe there has been much change in either of the first two factors - all that has changed is market attitude - how much the market will pay for a BGEN-type stock. BGEN is also over double what it was a year ago. I would say this move is about half each changed (improved)fundamentals and changed (also improved) market attitude. Now biotechs (particularly early-stage biotechs) can have a huge gap between fundamentals and market perception of these fundamentals. I don't think this is particularly the case with Biogen, given its current fairly high valuation. Clearly the market has priced it assuming it is going to continue to perform fairly well. To be continued ... Peter