Peter, LGND and ARIA only look alike from a VERY superficial level. I know both companies very well and if you go back far enough there are more similarities than now.
In the 80's Ron Evans, Scientific founder of LGND's IR technology was studying oncogenes primarily because one of the genes picked up by an oncogenic virus was a defective hormone receptor (the thyroid hormone receptor). In the 80's Joan Brugge, Chief scientist and founder of ARIA was also working on oncogene. She was studying the prototype oncogene, SRC, and the mechanism by which it caused cancer (phosphiorylation on tyrosines). SRC ended up being impotant in signal transduction because one end of the molecule was an enzyme that did the tyrosine phosphorylation while the other end of the molecule had a region involve with protein protein interactions. In any event, Joan went to ARIA to develop small molecules that interfere with the early molecular events in this signalling.
They also developed gene therapy that included a small reponsive element that could be turned on and off by a small molecule taken by the patient. Thus the level of a given product produced by the added gene could be turned on and off by a small molecule.
Interstingly, one of LGND's consultants (not exclusive), Bert O'Malley was also involved with another company, GENE, that did the same type of control for added genes, but he used the progesterone promotor as his target. Speaking of the progesterone promoter (or any of the wide range of intracellular receptor brings us back to Ron Evans who has studied these hormone receptors as transcription factors. He also targets small molecules that control these receptors which gave rise to one of LGND's core technologies (IR). LGND's other core technology, STAT, targets small molecules that control transcription factors for oplypeptide hormones. Interestingly, these transcription factors use the same type of sequences found on the SRC gene product studied by Joan Brugge.
For the above, its clear that there are some potential areas of overlap. However, LGND has extablished itself as the leader in transcription factors for non-polypeptide hormones, an area not really targeted by ARIA. This area is the foundation of most drugs developed by the pharmaceutical sector (and the basis for Strategic Alliances between LGND and PFE, GLX, AGN, ABT, AHP).
The polypeptide hormones are the domain of Biotechs. ARIA really targets the front end of the signalling process (hormone meets receptor on outside and transmits signal to similar receptor on the inside). LGND on the other hand, targets the back end of the process (when the signal affects the transcription factor in the nucleus).
LGND's approach is much broader because it goes after small molecules that interact with transcription factors (polypeptide and polypeptide). ARIA targets a much more descrete set of receptors and their small molecules interfer with the phospohorylation or dephosphorylation process (like SUGN, ONCS, and a host of other smaller Biotechs). |
