Biotech firm KineMed said this week that it has signed a research collaboration agreement with Pfizer to investigate therapies for metabolic diseases, particularly type 2 diabetes.
Under the agreement, KineMed will use its Dynamic Proteomics platform to study the impact of drug candidates on various metabolic pathways related to the disease. That platform uses wide-scale isotopic labeling combined with mass spectrometry to track the kinetics of protein activity, providing insight into biological pathways and disease processes.
With this technology, the Emeryville, Calif.-based firm aims to fill what it sees as a gap in conventional proteomics work, Marc Hellerstein, the company's co-founder and chairman of its scientific advisory board, told ProteoMonitor. KineMed was founded in 2001, but its Dynamic Proteomics technique, he said, has come to the fore "in the last year or two, and particularly the last six months."
He added that the company is near closing a Series B financing round that is "fully subscribed" and will raise around $5 million.
"The idea [of the Dynamic Proteomics platform] is to build on contemporary proteomics," said Hellerstein, who is also a professor of nutrition and toxicological sciences at the University of California, Berkeley. "What we do is add a labeling step [that] perturbs the isotopic pattern, the ratio of masses in the [sample] peptides … and from that we can learn everything we want to know about the kinetics [of a given protein] – the synthesis rate, the breakdown rate, transport – all kinds of interesting things that reflect the dynamics of these peptides and the proteins they came from."
Focusing on protein dynamics, as opposed to expression levels, could provide pathway data that is easier to interpret, Hellerstein suggested. "The beauty of –omics techniques is that they are so broad, they interrogate systems at a global level," he said. "The difficulty is that … you're often left with a lot of informatics and very little insight."
"With proteome dynamics, when the cell makes or breaks down a protein, that is a proactive decision on a cell's part, and often it is interpretable in an intuitive way," he said. "If you know what these proteins do and whether they are being made or broken down, the underlying factors that can be inferred from that can often be highly informative."
Hellerstein cited cholesterol homeostasis as an example, noting that, for instance, "if you have a cell that's making LDL receptors, that's making HMG-CoA reductase, that's making cholinesterases, you would know that that cell thinks it has low cholesterol and is trying to upregulate it. So you can infer the regulatory signals not from the level of proteins, but from their breakdown or synthesis rates."
Financial and other terms of the Pfizer diabetes agreement were not provided, but KineMed has published past research using its technology to study the disease, including a paper in the current issue of Diabetologia investigating the mechanisms of glucose lowering with the diabetes drug colesevelam – marketed as Welchol by Daiichi Sankyo, which funded the study.
It also published a paper in 2008 in the Journal of Lipid Research detailing a study funded by Takeda Pharmaceutical North America on the effects of the drugs pioglitazone and rosiglitazone – marketed, respectively, by Takeda as Actos and by GlaxoSmithKline as Avandia – on lipogenesis in type 2 diabetes.
The company has inked pharma deals covering a variety of other indications, as well, including an agreement with Bristol-Myers Squibb for research into Alzheimer's and other neurodegenerative diseases. The two firms agreed to extend this collaboration in March of last year (PM 3/11/2011).
The Dynamic Proteomics technique requires subjects – either animal or human – to ingest deuterium or another stable isotope labeled tracer, which is then incorporated into proteins made by the subject. By measuring these labeled proteins via mass spec, the firm is then able to study the dynamics of a target pathway.
According to John Price, a scientist at KineMed, the company is currently using the Dynamic Proteomics platform largely for exploratory efforts, looking at the kinetics of hundreds or thousands of proteins.
For this work it has used primarily either Thermo Fisher Scientific Orbitrap instruments or an Agilent 6520 Q-TOF, Price told ProteoMonitor, noting that the Orbitrap has proved most effective for experiments where the researchers are able to use a labeling strategy that enables high levels of enrichment. For experiments that use lower levels of enrichment – such as work in humans with deuterium – he said the Q-TOF instrument has been more effective.
KineMed has also been using the Q-TOF for more focused analyses of hits identified by their discovery work, Price said. The company is considering using selected-reaction monitoring-style assays for such work, but, he said, "we haven't moved into SRM because we need to go through and validate at almost every step of the way that we're measuring accurate isotopic distribution, and that takes a while."
The company aims to apply its Dynamic Proteomics work "throughout the entire value chain of drug development, from very early pathway analysis [through to] preclinical all the way through to phase IV post-marketing types of studies," Scott Turner, KineMed's vice president of R&D, told ProteoMonitor.
"Our preferred approach is to do large co-development deals with drug companies," Hellerstein said, noting that these are not fee-for-service arrangements. "We go in and work with [the pharma firm's] scientists closely on target identification and biomarker identification."
The company has also "begun exploring some diagnostic applications" internally, he said. Although, he noted, "diagnosis is a long road, and we don't have a sales force, so we would have to partner that."
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