Cellzome last week said it plans to use a €3.5 million ($4.9 million) grant from the German government to broaden its proteomics technology for use in epigenetics-based drug discovery, and to “miniaturize” the platform for use on patient biopsies.
The funds will enable Cellzome to continue to develop and optimize its Kinobeads platform for diagnostic applications and as a tool to monitor target-drug interactions in patients. It also will be adapting the technology to extend it to other classes of drug targets. The proteomics technology was originally designed to discover and develop inhibitors for protein and lipid kinases.
With the five-year grant from the German government, “we have funds to actually improve the platform [and] make it [more] applicable to other target classes,” Gerard Drewes, vice president of discovery research for the company, told ProteoMonitor this week.
In particular, Cellzome is looking to adapt the Kinobeads platform for drug targets around epigenetic regulation, he said. Drewes pointed specifically to histone deacetylases, or HDACs, which he called an “emerging class of drugs … where our technology could play out because it’s a target class that has a number of conserved members in humans, and selectivity is probably going to be key to getting good therapeutic windows, good efficacy, [while] controlling side effects.”
According to Drewes, Merck & Co. originally validated HDACs as a promising new class of therapeutic targets when it developed Zolinza, which was approved in the US in 2006 as a treatment for relapsed or refractory cutaneous T-cell lymphoma, a kind of skin cancer. It works by destroying cancerous cells and inhibiting their growth by silencing their genes.
However, the drug is highly toxic, “probably … because it is not a very selective compound. It inhibits, I think, almost all histone deacetylases,” Drewes said. “We believe that the second generation of [HDAC-inhibitor] compounds will need higher selectivity” than Zolinza, known generically as vorinostat.
To address this, Drewes said Cellzome will make changes to the ligands on its Kinobeads to create beads with affinity for HDACs. The beads can then be used to screen compound libraries and select those with high selectivity.
Drewes said the company is also looking at other target classes for which the Kinobeads technology can be adapted, though he did not elaborate. However, he said the Heidelberg-based company will use part of the German grant for those purposes. The grant is part of the High-Tech Initiative, a program launched by the German government two years ago to support technology-based research in regions throughout the country.
“This is all based on the proteomics that is at the moment being used for the Kinobeads, but there are going to be certain changes in the Kinobeads technology in order to make it accessible for these other targets.”
“This is all based on the proteomics that is at the moment being used for the Kinobeads, but there are going to be certain changes in the Kinobeads technology in order to make it accessible for these other targets,” he said.
The Kinobeads technology comprises a mixed-kinase matrix that quantitatively measures the binding interaction of a drug simultaneously with more than 300 different kinases, providing information about the compound’s mode of action, what disease classes it may target, and its possible side effects.
Drewes said the platform is optimized and validated, and the company has brought its first therapeutic program resulting from the Kinobeads technology — directed at phosphoinositide 3-kinase gamma — into the pre-clinical development stage.
He added that the company may also use a portion of the €3.85 million award to “miniaturize” the Kinobeads technology so that it can be applied to patient biopsies.
“Proteomics always needs quite a bit of material and I think we have some ideas for work that will also be funded by this grant where we downscale … the technology,” he said. There are “some clever things [that can be done] around the mass spec detection and around the way you do your data acquisition, data interpretation.”
Another strategy may be to use antibody-based technology for protein detection instead of mass spectrometry, he added, but declined to further elaborate on what Cellzome is doing as part of that effort.
As it continued to develop its Kinobeads technology the past year, Cellzome, which was founded in 2000, has built up its operational infrastructure. In December, the company created its scientific advisory board, and in September it announced a collaboration with GlaxoSmithKline to co-develop kinase-targeted therapeutics for inflammatory diseases. In July the company extended a drug-discovery agreement for Alzheimers’s disease with Ortho-McNeil-Janssen Pharmaceuticals and its affiliate Johnson & Johnson Pharmaceutical Research & Development.
Under the alliance with GlaxoSmithKline, Cellzome will use the Kinobeads technology to identify small-molecule inhibitors against seven identified targets, and develop the most promising product candidates through to completion of a clinical proof-of-concept trial. Four of the targets were identified by the drug firm and three were to be jointly identified by Glaxo and Cellzome.
Cellzome’s extension of its agreement with Ortho-McNeil-Janssen covers two ongoing projects in which JJPRD and Cellzome are identifying and progressing novel gamma secretase modulators and jointly selecting and progressing novel targets from the amyloid precursor protein pathway, which had been mapped previously by Cellzome.
In addition, Cellzome is mapping the Tau pathway, which has been associated with Alzheimer’s.