Thought the news from MorphoSys was timely considering Phylogica's CD40 Ligand Program is close to going preclinical.
I've been doing some reading on the MorphoSys MOR103 antibody against GM-CSF (granulocyte macrophage-colony stimulating factor)...
About MOR103:
MOR103 is a fully human antibody against GM-CSF (granulocyte macrophage-colony stimulating factor). GM-CSF was originally identified as a growth factor for granulocytes and macrophages but has more recently been identified as an inflammatory mediator in autoimmune disorders such as RA. GM-CSF stimulates stem cells to produce granulocytes and other macrophages and subsequently activates these differentiated immune cells leading to an increased production of pro-inflammatory cytokines, chemokines and proteases and thereby ultimately to articular destruction. The antibody MOR103 blocks GM-CSF and reduces its pro-inflammatory activity.
Rheumatoid arthritis
GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (e.g. MOR103) are being developed to block GM-CSF.[8]
Other exemplified embodiments of the invention provide methods for determining a peptide that induces or prevents cytokine signaling. For example, methods are provided to determine a peptide that induces interlekin-3 (IL-3) signaling, granulocyte-colony stimulating factor (G-CSF), granulocyte/macrophage-colony stimulating factor (GM-CSF) or erythropoietin (epo).
These and other exemplified embodiments provide a model for identifying a peptide that is capable of modulating any phenotype, e.g., a phenotype associated with a disease and/or disorder. Such a peptide is useful not only for the development of new therapeutics, but also for the identification of new drug targets (e.g., a protein with which a peptide identified using the screening method of the present invention interacts).
Taken from Phylogica's technical report on the CD40 Ligand program (Feb 2012)....
The AlphaScreen® and cellular bioassays were used to filter the primary hits to identify potential drug leads (Figure4). To date, 10 peptides have been identified which have antagonistic activity in both AlphaScreen® and biological assays. For more stringent functional specificity testing, peptides were further assessed in a TNF-a dependent cytotoxicity screen and also in LPS assay, which measures CD86 upregulation in a CD40L- independent manner. Eight of the 10 Phylomer® peptides had no effect in either assay, highlighting the specificity of the primary hits for CD40-CD40L interaction. Several of these primary hits against CD40L have binding affinities in the low nanomolar to picomolar range (Figure 5 and figure 6). The drug-like properties of the Phylomer® peptides can be tuned optimised desirable affinities and pharmacokinetics. CD40L-specific bioactive peptides have been affinity-matured using a number of approaches such as mutagenesis and multimerisation. Phylomer® peptides are also amenable to half-life extension technologies employing PEGylation, PASylation and Human Serum Albumin binding. This case study demonstrates how Phylogica’s drug discovery platform can be used identify quality primary hits with potent activity against extracellular targets.
This was taken from MorphoSys MOR103 presentation....
Considering Phylogica has relationships with many prospective and current pharmaceutical partners in this space, a deal for their in-house program may not be too far away.
PYC Price at posting:
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