0:00
It's a very packed programme.
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Oxford Global just do a wonderful job putting together a great lineup of speakers.
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There's a lot of competing talks.
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So I really appreciate your time.
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So for the next 20 minutes, I'm going to walk through validation of our new whole slide imaging approach for our MultiOmyx platform.
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Now this has been our dedicated spatial proteomics platform.
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We've actually had it in house since 2012 and since that time it's been region of interest analysis.
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We've got well over 100 publications.
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But now we've moved into that realm of whole slide imaging and really as part NeoGenomics because we are a CAP clear accredited central laboratory there's a lot of work that goes into that validation approach.
0:49
So that's really what we're going to go through today.
0:51
So I'm going to cover just a very quick overview of what we do within pharma services at NeoGenomics.
0:56
But I'm really going to spend the time with what we call our bullet points 2-3 and four, which is really some of our spatial solutions that we can use today for your clinical trials, but also preclinical approaches to addressing the changes within the tumour microenvironment and also some of the validation approaches that we have applied now for our whole slide imaging.
1:20
So again, just very briefly, we actually have 3 divisions associated with NeoGenomics.
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I am part of the Pharma Services division.
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So really we're supporting everything from your preclinical workflows all the way through to CDX development and certainly with incorporation of spatial proteomics.
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There's a lot of that within the realm of early phase 1A, phase 1B for example, and there's a lot of publications to address the use of multicomics in that realm.
1:49
We also have a data solutions division.
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So this would be your real world data.
1:54
We have a wealth of genomic data associated with NeoGenomics and that includes outcomes.
2:00
And so that's certainly something that can be accessible to you, especially as part of some of your coordinated trials.
2:07
And then, of course, we have our clinical division, which supports ongoing oncology diagnostics today.
2:16
And so when we think about what it is that we provide as part of NeoGenomics pharma services, we're really focused in at least in 2025 and probably for the foreseeable future, especially with the interest in ADC development right now.
2:32
But we're supporting 3 specific areas, and these are supported not only by the services that we offer, but also with our clients and really the majority of clinical trials today under the idea of cell therapy.
2:45
And that would include not just CAR T, but there's a lot of recent interest, especially in other CAR designs, specifically CAR NKs as well as CAR macrophages.
2:55
We just had a really nice paper that we highlighted last week, you know from Carisma Therapeutics looking at CAR macrophages and some of the spatial qualification of their specific assets. But also ADC's as I've highlighted and then molecular targeted therapies which includes some of those signalling modalities, especially kinase signalling and addressing specifically EGFR mutations.
3:18
So what we have to support that under lab services.
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Of course, a lot of our business is IHC based, aspects of which I'll discuss today because it's certainly part of our qualification and validation of some of our antibodies, but also flow cytometry certainly used within the realm of cell therapy.
3:36
FISH Cytogenetics.
3:37
What I've been discussing today is really our spatial analysis and what specific platforms we use to support that.
3:43
Of course, genomics and pathology are certainly utilised within the realm of spatial as well as IHC.
3:49
So today, we support 3 platforms and I'll spend today talking about our MultiOmyx platform.
3:55
As I said, we've transitioned from region of interest selection now through whole slide imaging using the RARE CYTE Finder.
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And I know RARE CYTE are here today as well.
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So certainly feel free to visit their booth also.
4:09
We also have the Akoya Phenolmager here, and that's certainly much further along.
4:13
If you're considering a potential CDX using spatial, we can have discussions around that and of course the NanoString GeoMx.
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And if you're in the space right now of looking at discovery-based approaches, I would certainly recommend the use of that.
4:31
Now when we think about end-to-end services, you have to have dedicated pathology support and so we have over 200 pathologists and these are very indication specific pathologists as well.
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You have to have that on the front end.
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And so we have a lot of access to that as part of NeoGenomics.
4:51
But certainly some of the technologies and that's especially true for the GeoMx, you have to include molecular expertise in that, especially some of the data analysis with regard to the sequencing.
5:01
And it is about the informatics and it is about the data.
5:04
You have to have that full workflow and that's something that we've specifically developed for the MultiOmyx technology that I'll discuss.
5:12
So again, end to end, this is certainly a phrase that many companies use.
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And what does it really mean?
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You have to be very cognizant of your verification process.
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And we have spent over 10 years verifying these specific antibodies for use in a multiplexed approach.
5:31
Now there were questions earlier for the earlier talk asking about the specific chemistry.
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We also do a cyclic immunoflorescence.
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We have our own proprietary dye and activation step.
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This is not a bleaching approach and this is not a quenching approach.
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This is a very specific dye and activation.
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We make sure we have cleared that signal before we move into the next round.
5:59
Now we can go up to 60 specific markers.
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In fact, we can actually go up to much larger than that.
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We kind of cap off at 60 because it becomes a little bit cost prohibitive.
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But certainly I would say for most of our clients, they're looking at that target size of say 10 to 20 where it's you want to just look for example, maybe at functional targets.
6:19
We also want to look at the immune response.
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So I would say most of the publications that we've had today are in that type of Plex.
6:26
And again, if you want to do discovery, there are other approaches for that.
6:29
And I would certainly recommend the GeoMx DSP for that. Classification quantification as well as our integrated visualisation analysis.
6:39
We've developed a proprietary pipeline for that.
6:42
So this is specific image analysis that we have developed in house and we've developed specific AI tool for that as well.
6:49
So again, very specific for our MultiOmyx, again, you have to have that full end to end approach and that's something that we have again developed in house.
6:57
So we have the spatial solution at NeoGenomics in regards to that.
7:04
So I'm not sure because I was sitting at the back early and it was really difficult to see some of the image and some of the resolution of the images.
7:12
So again, for anybody that's interested or more than happy to share with you PowerPoint or PDF, as I said, we now work with Rarecyte and using their CyteFinder.
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So we can accommodate 80 samples at any given time.
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So we do all our upfront cyclic immunoflorescence and that's accommodated on the lyca bond, which also does 80 samples.
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And then we can take that and move that into the imaging and scanning on the Rarecyte, again 80 samples.
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So again, this certainly accommodates some of the need, particularly when you're in early phase trials.
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We're looking at pretreatment biopsies, post treatment biopsies and you need to go through a wealth of sample numbers.
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So it's useful to have obviously had a platform that can accommodate large, a large number of samples.
7:59
So again, from the image that I'm showing you there, this is one of our kind of first forays into using this particular platform and we accommodated that using the NSCLC samples.
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And I'm going to address some further analysis that we did on that.
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But that larger image shows expression of PD-L1.
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We've also got macrophage in green.
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I don't know if you can see that at the top as well as the functional marker Ki67.
8:25
I'm just homing in again, in that top right, that's PDL1 as well as macrophage.
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And then in the bottom right, you have Ki 67 and Macrophages.
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So one thing that we do really well, as I said, we've developed our own, what we call our NeoLYTX advanced analysis and we've developed an AI tool.
8:44
It's not enough to know enough about region segmentation for example.
8:49
As with anything in life, you have to know who your neighbours are and that's truly important in spatial biology.
8:55
I would say proximity analysis and neighbourhood composition as well as your nearest neighbours are probably the most frequently requested asks from an analytical perspective.
9:05
It's not just about knowing the composition of cytotoxic T cells in a tumour.
9:11
You know what is that Co expression with again?
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Maybe you've got an immune suppressed tumour microenvironment which is often the case as clinical trials proceed.
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So that's really important to know.
9:24
So I'm just going to update you again.
9:25
This was our, if you look on the right hand side, we had our former workflow for region of interest selection and a lot of integration with our pathologists on site for that.
9:35
Now we've moved into the more automated whole side imaging workflow.
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So proof and principle.
9:43
We did a 16 marker panel.
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You can see the markers that we used.
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We've obviously optimised what round those markers should be on and we've obviously optimised what fluorophore they should be on.
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And we've done that for over 200 markers at this point.
10:01
So you can certainly cherry pick if you want to create your own panel in that regard.
10:06
And I've shown you the chemistry at the bottom there.
10:08
Again, there is the cyclic immuno fluorescence 2 fluorophores and we do up to 80 samples.
10:15
So again just some of our whole slide imaging workflows.
10:18
We create what's called a virtual H&E, but there's no reason why you can't provide us with H&E slides already, but we create that virtual H&E and again other spatial providers also do this.
10:29
It really is a pseudo blend of both your DAPI stain as well as what comes up in the auto fluorescence channel.
10:35
And then we really involve our pathologists at this juncture really to select some of the more tumour relevant regions.
10:43
Of course, you want to take into account any tissue for artefacts and it's still a problem in the spatial realm and in pathology realm, you want to take into account any potential folds, necrosis areas of that tumour as well as potential tissue loss.
10:57
And then we do our AI based approach for that segmentation and biomarker classification moving into concordance.
11:04
This is hugely important as part of the validation step.
11:08
I can't stress that enough.
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We certainly titrate in all our markers.
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We know the right concentrations, we know the right fluorophore, but we certainly test it not just with DAPI, but we also do on the chromogenic scene.
11:20
You can see that in both the Ki67 PD-L1 and we test it in IHC and you can see the concordance now with what we're calling our MultiOmyx 2.0.
11:31
Again that's our whole slide imaging multi omics.
11:34
So again highly concordant, almost close to 1 and really in biology to get anything over 0.75 you're doing really well.
11:42
So over 0.9 is great results to see, again you want to be able to see concordance with what we've done before we've amassed a multitude of publications using region of interest selection.
11:56
So can we get concordance results now using the whole slide imaging approach?
11:59
So we've certainly done that.
12:01
We've taken sequential slides, we've stained in the traditional workflow and then we've gone and done the sequential slide in the whole slide imaging workflow.
12:09
And you can see here looking at T cells, Myeloid cells and endothelial cells that again you almost get superimposable results.
12:16
Again, the concordance to this is 0.96 which is very high.
12:20
But right now we are working through all our previously annotated off the shelf panels that we created using the region of interest staining and now we're moving into whole slide imaging staining.
12:32
Your assay has to be robust.
12:34
It has to be robust to be part of a clinical trial, has to be robust enough for longitudinal clinical trials.
12:40
So the repeatability of an assay as well as the reproducibility of that assay is really key.
12:47
So what we've done here is we've taken 9 serial sections from tumour blocks and we've run this assay 3 independent times over the course of many months and also the triplicate staining.
12:59
So again in that regard and you can see superimposable data almost again with a really high CV again across all these different sections, Again it was over 0.95.
13:11
Again it has to meet that acceptable criteria.
13:14
Your coefficient of variance has to be less than 25%.
13:18
But again, to get anything over that 75 is fantastic.
13:24
So again, right now we're kind of characterising NSCLC samples for ACR, ASCO and future conferences.
13:33
We'll be doing further characterization and other tumour indications as well as showcasing some of our clinical trials that we're doing right now using the whole slide imaging approach for clients.
13:44
But again, it's important to, it's not just about the prevalence, for example of looking at T cells or even the prevalence of cytotoxic T cells.
13:52
It's the co-expression of some of these markers.
13:55
So here we've shown the co-expression of the cytotoxic T cell in combination with PD1 as well as Ki 67 with macrophages.
14:05
And then of course, you've got PD-L1 again with some of the macrophages and I'm not sure if you can see the images very well at the back.
14:11
But as I said, more than happy to share with you PDF that. Again some of our validated markers and validated panels, every single one of the panels now has been moved into whole slide imaging.
14:23
But all these markers are available today and we have over 200 validated markers in our portfolio that will continue to grow over 2025 and beyond.
14:35
And I just want to showcase just some very recent publications.
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We had a really nice paper in January from BioNtech.
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They utilised our MultiOmyx and correlated that really well to some CT imaging pre and post biopsy.
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So there's tangible data from a spatial perspective as to why you had tumour shrinkage using their novel approach.
15:01
Again, it was a neo-antigen specific autologous T cell product.
15:06
I did mention the Carisma study earlier.
15:08
They did a very nice both MultiOmyx as well as RNAscopes.
15:12
We're talking about both RNA and proteomics on the same slide again testing out their novel CAR mechanism of action.
15:21
So again, these are CAR macrophages.
15:22
So I think for solid tumours, we're moving a little bit away from CAR T therapy.
15:27
It's been problematic for solid tumours.
15:30
We're moving into the realm of CAR macrophages and CAR NK cells.
15:36
So really nice paper.
15:37
And then of course GSK used us for several of their studies over the last few years as well.
15:45
So just to conclude again, we're very excited about our whole slide imaging approach highly concordant with what we previously published and worked on with regard to our region of interest.
15:57
A lot of precision analysis went into this.
16:01
We're going to put together a white paper, it should be ready by the end of April that will coincide with the ACR.
16:07
So we'll be more than happy to share that.
16:09
And so I think this really does provide you with that histological context and it's really about providing now that unbiased spatial approach.
16:21
It's not that we were biased in our region of interest, certainly that is really guided by the pathologist.
16:27
But now with the use of slides and provide and for example, clients providing us that slide, now we get that unbiased insight with our spatial proteomic workflows.
16:40
So I mean, it's all about greater insights and certainly greater insights with regard to your immune response.
16:46
And we can see that born out of publication.
16:48
So I'm more than happy to take any questions.
16:51
And again, if you want to stop by our booth, we've got our team on hand.
16:54
Anything in regard to any of your clinical trials, we'll be more than happy to discuss.
16:58
So thanks everybody.
