OK, here's the potential early strike. I've worked with mitogenic anti-CD2 pairs, integrating antibody 9-1 from Bob Knowles (Sloan Kettering) in particular. CD2 is a magic molecule, and Bazin (the inventor of BTI-322) is a very respected immunologist. Throw in David Sachs, and you've got, IMO, a potential big winner.
The royalty from MEDI is double digit, so, together with the partnered programs, this company represents, IMO, biotech's best bargain. MEDI has initiated clincals for psoriasis, kidney transplantation, and GvHD. The near-term downside is effectively near zero, given that the company is selling for cash. The programs (gene therapy and mixed bone marrow chimerism) supported by Novartis are, IMO, top notch and based in solid science.
It has recently been argued that there is little chance for near-term revenues. I would counter that we are one phase II result (Medimmune, a proven regulatory powerhouse) away from big upside..... the project addresses the entirety of transplantation and autoimmunity.
A unique chance for a 10 bagger and more, compare MEDI-507 to anti-CD40 ligand......
J Immunol 1998 Apr 15;160(8):3797-3804
Potent apoptotic signaling and subsequent unresponsiveness induced by a
single CD2 mAb (BTI-322) in activated human peripheral T cells.
Dumont C, Deas O, Mollereau B, Hebib C, Giovino-Barry V, Bernard A,
Hirsch F, Charpentier B, Senik A
Centre National de Recherche Scientifique, UPR 420, Villejuif, France.
Manipulation of CD2 molecules with CD2 mAb pairs has been shown to
deliver apoptotic signals to activated mature T cells.
We show that BTI-322, a CD2 mAb directed at a peculiar epitope of CD2,
can trigger on its own the apoptotic death of
IL-2-activated peripheral T cells and of OKT3-stimulated T cells,
contrasting in this respect with a series of other mouse or rat
CD2 mAb. F(ab')2 fragments were as potent as the whole Ab.
BTI-322-induced apoptosis proceeded in a few hours and was
independent of the Fas/Fas ligand system. Less than 5 ng/ml of BTI-322,
added at the beginning of culture, were able to
eliminate within 4 days most CD3+ cells from OKT3- and IL-2-stimulated
lymphocytes, the only cells remaining being
CD16+CD2- NK cells. T cell proliferative responses induced by a
mitogenic CD2 mAb pair or by PHA-P (which mainly
binds to CD2) were not inhibited by BTI-322. In this case, the apoptotic
effect was successfully counteracted by simultaneous
enhancement of T cell divisions. Thus, the killing effect of BTI-322 was
most effective when T cells were exclusively stimulated
through the CD3/TCR complex. Apoptosis of the responding T cells may
explain why T cells recovered from a primary MLC
performed in the presence of BTI-322 responded to third party cells but
not to the primary stimulatory cells. These data
constitute the rational basis for the use of BTI-322 for inducing
tolerance in human allotransplantation. |
