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Thank you so much for the introduction and good afternoon, everybody.
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Today, I'll start giving you an overview on the Antibody Society's objectives and I'll also give you some definitions.
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Then I'll talk about trends and success rates of antibody drug conjugates with a focus on payloads, formats and targets.
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And then I'll also give you a preliminary analysis on these emerging trends that we see that on unconventional ADC development.
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The Antibody Society is a no profit trade association supporting individuals and organisations involved in antibody research and development and it has a business intelligence unit.
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And at the business intelligence unit, we continuously collect data from the public domain on antibody therapeutics.
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And we do this because we aim to determine trends in antibody therapeutic development over time.
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We aim to determine the clinical success rates for antibody therapeutic development as conducted by the biopharmaceutical industry and also to assess innovation in the biopharmaceutical industry.
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I'd like now to spend few moments giving you some definitions and talk about our inclusion and exclusion criteria.
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So for our analysis, we consider an antibody therapeutic as a recombinant protein-based molecule, which has at least one antigen binding site that is derived from an antibody gene and it is evaluated as a therapeutic.
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So this definition or excludes all polyclonal antibodies from a natural source, excludes antibody encoding DNA because that's not a protein, and FC only FC fusion proteins because of the FC of the antibody portion, they have only the FC and not the antigen binding site and everything that is just meant for diagnostics.
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Also we are interested in commercial development, so we consider for our analysis only molecules that are developed by public or private for profit entities.
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We are also interested in innovation.
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So we consider molecules which are unique in composition of matters and so this excludes for our analysis all biosimilars.
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Also, of course, for our analysis, we consider each molecule only once and we consider the molecule for its most advanced clinical status.
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And this presentation will focus on ADC antibody drug conjugates and unconventional ADCs.
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And I'd like to clarify what we mean by ADCs and unconventional ADCs.
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By ADCs for our analysis we refer to molecules where the antibody is conjugated to a cytotoxic drug, while for unconventional ADC's we refer to molecules where the antibody is conjugated to a drug or a molecule that is not a protein, is a disease relevant and is not cytotoxic.
3:33
And also we include unconventional ADC's under the big umbrella of the immunoconjugates and these include but are not limited to antibody degraded conjugates, immunostimulating antibody conjugates, antibody oligonucleotide conjugates, antibiotic conjugates, steroid conjugates and immunoliposomes.
3:57
Now some of you might argue that immunoliposomes actually do carry a cytotoxic drug.
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That's true.
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However, just to would like to clarify that we are mindful of the historical usage of the word in ADCs and is usually referred to molecules where the antibody is conjugated to a cytotoxic drug via a linker.
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While in immunoliposomes, the drug is encapsulated in the liposome and the antibodies conjugated to the lipids that form the liposome.
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So why am I here talking about ADCs?
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This is because we have detected a trend in an increase in number of ADCs being granted first approvals in the past few years.
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As you can see from this graph showing you antibodies therapeutics being granted first approvals from 2010 stratified by the type of molecule.
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In terms of format, we have naked monospecific antibodies, ADCs, bispecific and multispecific antibodies, immunoconjugates and antibody mixtures.
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If you look at the ADC's, which are the orange bar, you can see that's an increase from 2019 in the approval of these molecules.
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And if you look at those that were in review when this graph was made at the end of December 2024, this account for nearly 1/4 of the antibodies that were in review.
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This is a similar trend to what we see for bispecific antibodies in yellow.
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Also, we have detected an increase of ADCs entering clinical studies for the first time too.
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In this graph, we are showing you the unknown number of antibody therapeutics entering first in human studies, classified in the same way as I showed you before.
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And if you look at the orange bar, you can nicely see how from 2010 you see a steady increase of ADCs entering clinical studies and then from 2021, there is a bigger increase.
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And this trend is quite similar to those of bispecifics too.
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We have also calculated phase transition and approval success rates of antibody therapeutics and we are satisfied by type of molecules like I showed you before.
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And this bar charts showed you phase transition rate.
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The first four sets of bars show you the phase transition from phase one to phase two, phase two to phase three, phase three to market in approval, market in approval to approval.
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And the last sets of bar set of bars show you the overall phase one to approval success rate.
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If you look at the last set of bars, you can clearly see here see how different is the success rate depending on the type of format.
7:07
And interestingly, you can see that ADCs have a success rate of 20%, which is way lower than the success rate of bispecific antibodies or naked monospecific antibodies, which is around 30%.
7:24
And we found this interesting because the trends I showed you before in approval or in first in human studies of ADCs and bispecifics are comparable.
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So we wanted to understand why.
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And I'd like to first clarify that for this analysis, we have included only antibodies entering first in human studies between 2000 and 2019.
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So as you know is the in this 20-year time period a lot of research has been done on ADCs.
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There's been several generations of ADCs.
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So here we group them all together.
8:03
So that could be the real why the success rate is lower.
8:08
So to test this hypothesis, we have a recalculated success rate just focusing on ADCs and stratifying them depending on when they enter clinical studies.
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So as you can see here, we divided them in through groups from 2000 to 2015 and those entering from 2016 to 2019.
8:34
The groups are more or less comparable in terms of a number as you can see from the graph.
8:41
And if you look at the last set of bars, you can nicely see that ADCs that entered from 2016 to 2019 have a way higher success rate than those that entered before 2016, which makes sense.
8:58
But we wanted to dig more, so we first decided to look at the payloads of these ADCs.
9:08
And in this graph, I'm showing you the number of ADCs entering first in human studies stratified by the type of payload.
9:20
And as you can see from 2010 we see an increase of ADCs entering clinical studies mostly with tubulin inhibitors.
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And this reaches a plateau, it stays stable until 2023.
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If you look at those with the DNA binding agents as a payload, they start to appear in 2013, then they peak at 2017 and then they go down again.
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And what we found very interesting is that those we topoisomerase one inhibitors from 2021. We do see a sort of exponential increase in the number of antibodies carrying this type of payload entering first in human studies.
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So we thought of recalculating success rate stratifying this time by type of payload.
10:12
And if you look at this graph, you say, oh, that's quite striking.
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However, just like to point out the N number.
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So again, this cohort of antibodies is antibodies entering clinical studies between 2000 and 2019.
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And the big increase I showed you of ADCs with topoisomerase I inhibitors happened in 2021.
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So it makes sense that the N number of those with topoisomerase 1 inhibitors is really small.
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So this looks interesting.
10:50
However, it can't really rely on this.
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So because of the number, so we decided to include in the analysis also ADCs entering clinical studies for the first time until 2022.
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So we have recalculated success rate including those as well.
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So now if you look at the N number, this is 49, which is comparable to the number of ADCs with DNA binding agents as payloads.
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However, if you look at the percent completion, you see that's only 12.
11:27
And now I'd like to explain what the percent completion is.
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Percent completion is the percentage of antibodies for which we know the fate.
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So the percent completion of the phase one to approve a success rate is the percentage of antibodies for which we know whether they were either terminated or approved.
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And these antibodies we know that for topoisomerase 1 inhibitors, they mostly entered in 2021 and 2022.
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So it's quite unlikely that they have been approved.
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And so it's it most of them are still in clinical studies.
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That's why the percent completion is so low.
12:06
So again, we can't really say much about the overall success rate phase one to approval.
12:12
But what we thought to look at is the phase transition rate.
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So we have calculated percent complete percent completion of the Phase 1, two, phase two transition rate because of these antibodies, the latest they entered in 2022.
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So usually phase one are quite short.
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So it makes sense that we know the fate of this molecule and that's true.
12:40
So we know the fate of all the molecules in this cohort, most of them at least of 80% of these molecules.
12:51
So we can say from this result that at least the phase one to phase two transition rate in ADC is carrying a topoisomerase one inhibitor as payload is way higher than the phase transition rate of those with tubulin inhibitors or with DNA binding agents.
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And also we can say that those with the tubulin inhibitors, although have a lower phase one to phase two transition rate compared to those with the topoisomerase 1 inhibitors, they have a higher success rate compared to those with DNA binding agents.
13:30
We did the same also for the phase two to phase three transition rate.
13:34
And as you expect the number drops because not all molecules move to the next phase, but the percent completion dropped, but it's still above 60%.
13:48
So we can also say that we with a certain degree of confidence, taking into account of the percent completion, we can say that also phase two to phase three transition rate is higher in ADCs with topoisomerase one inhibitors compared to those with different types of binding of fails.
14:11
So we look forward to recalculate success rate and calculate the overall phase one to approval success rate in few years’ time and see whether we can confirm or not the data you are seeing.
14:23
Now moving to the ADCs which are currently in clinical studies at the as of February the 20th, these were 215, 86% of them in early stage and 14% in late stage studies.
14:43
We have stratified them by target.
14:47
And then here in this graph I'm going, I'm showing you the frequency of the targets in ADCs in early stage and the frequency for those in late stage.
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As you can see, the top 4 frequent targets are the same in early stage and late stage.
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We have HER2, Claudin 18.2, TROP 2 and B7-H3.
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These are followed by a Nectin 4, FR alpha, cMET and HER3 for the early stage.
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We don't see this in late stage yet and we look forward to verifying whether these antibodies transition to late stage in the next few years.
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Also we as you might have noticed from this graph here, you do see some double targets.
15:46
So these are targets for ADCs which are also bispecifics and these are mostly targeting EGFR and cMET or EGFR and HER3 or they target different epitopes on HER2.
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We wanted to calculate the percentage of ADCs which are also bispecific and this is nearly 10% and also of the bispecific ADCs, nearly 40% are biparatopic.
16:25
Looking at the payloads of ADCs in early stage and late stage, the most frequent payloads is topoisomerase one inhibitor as you might have guessed, followed by tubulin inhibitors.
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And I'd like to spend a few moments talking about unconventional ADCs.
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This is a very emerging trend that we are seeing.
16:49
But as you can see, as you can see from this graph showing you the number of first human studies, you see that the numbers are really small, but we do see an increase of these antibodies entering clinical studies especially in the past decade.
17:05
What are these antibodies and which type of indications they are designed for?
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Interestingly, unlike the canonical disease that are just for cancer immunotherapy.
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These are for a variety of indications.
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We have those for cancer, we have them for those for muscular disease, for immunity and inflammatory disorders, for infectious disease.
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And in this graph, I wanted to pair the therapeutic area and this type of molecule.
17:38
You can see that those for cancer, they are antibody steroid conjugates, degrader conjugates, ISACs or immunoliposomes.
17:47
Those for muscular disorders are only antibody oligonucleotide conjugates.
17:53
Those for immune mediated inflammatory disorders are antibody steroid conjugates and antibody oligonucleotide conjugates.
18:02
And those for infectious disease, of course, they are antibiotic conjugates.
18:08
However, look at the N number is just 23.
18:11
And if you just only look at those that are still in clinical studies, this number drops to 13.
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So that's why I'm saying this is a very preliminary analysis because the molecules are not so many.
18:26
Those who are still in clinical studies are for cancer indications and muscular disorders.
18:33
So here are my key messages.
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I showed you the antibody drug conjugates are entering clinical studies and are being granted marketing application in increased numbers recently.
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I showed you that of the ADCs entering clinical studies between 2000 and 2019, the success rate is 20%.
18:57
If we include in this cohort also ADCs entering clinical studies up to 2022 and we stratify by payload, we see that ADCs with topoisomerase 1 inhibitors as payload have a higher transition phase transition rate from phase one to phase two and also from phase two to phase three compared to ADCs with tubulin inhibitors or DNA binding agents as payloads.
19:27
Also looking at the targets, I showed you that the most frequent targets are TROP-2, HER2 and Claudin – 18.2 and the most frequent pay loading antibodies in early and late-stage studies are topoisomerase 1 inhibitors.
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And then I showed you these emerging trends of unconventional ADCs which are entering clinical studies in increased numbers.
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There are for a variety of indications and have a variety of formats.
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And I'd like to thank my colleague, Dr Janice Reichert, who is the Director of Business Intelligence at the Antibody Society and Editor in Chief of mAbs.
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And then I would like to thank the Antibody Society and all our members and our corporate sponsors for their financial support.
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Please join the Antibody Society if you haven't done that already.
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And these are all our corporate sponsors, not only these, I will show you them.
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All membership is free.
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If you are an employee of these companies, they are in alphabetical order, so have a look.
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If you see your logo, feel free to register.
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Also, registration is free for students and postdocs.
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And I thank you very much.
20:49
I'm happy to answer any questions.
