My name is Mark Dysinger. I am a development scientist in the Bioanalytical and Biomarker Group at Alexion Pharmaceuticals located in New Haven, Connecticut. The overall goals of Alexion is to provide treatments for people who suffer from rare and ultra-rare disease.
These are people who have high, unmet medical need. There are over 7,000 identified rare diseases, and only 5% of them actually have treatments that make an impact on people's lives. From a bioanalytical perspective, we focus in ligand-binding assays and mass spectrometry. Mass spectrometry has been used for small molecule quantification. It's also been used for problematic proteins that are not readily measured by protein-protein interaction.
What we do with the ligand-binding assays, rely on protein-protein interaction. We measure pharmacokinetics which is how much of the drug is in the system at any given point in time. We measure pharmacodynamics which is what the drug is actually doing with regards to method of action. And we also measure antidrug antibodies, which with protein therapeutics is a measure of whether or not that foreign protein in your body elicits an immune response.
And that immune response could cause health issues that could also neutralize the drug and not allow it to do what it's meant to do. Specifically for Alexion Pharmaceuticals, we have found the greatest advantage for the Gyros technology is in the measurement of free targets. Traditionally, ligand-binding assays in the microtiter plate format have challenges when it comes to measuring free target in that they tend to overestimate the amount of free target which makes the drug look less effective than it actually is.
We traditionally capture with the drug or a protein antibody that has affinity match to it, and this sample is incubated. What can happen in the microtiter well, as a matter of kinetics in equilibrium, is that the drug used as a capture agent can complete and pull the target from the drug that's actually in the sample.
And then this can lead to an overestimation of the amount of free target making your drug look less effective than it actually is. Gyros counters this problem by having a very rapid sample incubation. These samples pass across the microstructure in a matter of seconds. So there is little to no opportunity for this, what is called "back dissociation," for the capture reagent to compete the target from the drug in the sample.
The second challenge with microtiter plates is the sample dilutions tend to be relatively high. And when you dilute a matrix sample, you tend to perturb the equilibrium which leads to dissociation of the target from the drug and in the sample. And it is then available to be measured by the capture reagent in the assay. Gyros gets around this by having very high matrix tolerance.
Because the samples go across the microstructures so quickly, there's little to no opportunity for any matrix effects to occur. So we generally dilute our samples 1 to 2 in our 50% matrix. There is very little perturbation of the target from the drug in that scenario. So microtiter plate, prolonged sample incubation and high sample dilution tends to lead to an overestimation of the target that is actually free in the sample, makes your drug look less effective than it is.
Gyros' rapid sample incubation and minimal sample dilution cause very little, if any, opportunity for the target to be dissociated from the drug in the sample and measured in the assay. That is what we want your drug to be able to reflect. You want your assay to be able to reflect your drug's true potency, and this is data upon which we base our label of claims for target engagement.
When you are doing clinical studies with rare disease, you have a very finite patient population. Sometimes we've had clinical trials with only 2 or 3 dozen people in them. In that case, every sample is vitally important to be able to measure. The far, far reduced sample volume requirements that Gyros has, compared to other platforms, means that a single sample from a patient can be used across multiple, different types of assays.
The Gyros platform allows for rapid method development. It's user friendly, and it can generate data, in many cases, in an hour. You can get 112 data points in an hour. And it is, for regulated work, it is compatible with Watson LIMS. It has Part 11 compliant audit trail.
It has been validated in our area for regulated use. It's a validated instrument and computer system, and it has enabled us to develop assays in-house that are readily transferrable to external partners, so they can validate it at their labs and provide study support that we don't have infrastructure to when there are thousands of samples to be analyzed.
So it's very easily transferrable to other places and very robust technology. The future bioanalytical development at Alexion is actually quite broad. We have very aggressive goals across multiple projects, multiple therapeutic areas, multiple drug candidates. We will continue pressing forward with seeking treatments for ultra-rare and rare disease.
We're going to continue to need to use various analytical platforms to achieve our goals. But our partnership with our CRO lab partners and our other vendors are going to make the process easier, and that process is facilitated by having technologies such as Gyrolab where the assays are easily transferrable and becoming much, much more ubiquitous than external labs.
