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Antibodies to watch in 2025
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Antibodies to watch in 2025
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Segment:0 .
Hello, everyone, and thank you for attending today's webinar. Antibodies to watch in 2025. I'm Tristan fry, senior editor at biotechniques, and I'll be your host for today's event.
Before I introduce you to our speakers, I'd like to quickly cover a few housekeeping items. Firstly, all the information about today's webinar can be found on the right hand side of your screen, including the Q&A tab. You'll have the opportunity to submit questions to today's presenters by typing your questions into the Q&A box on the side of the window. You may send in your questions at any time during the presentation, and you'll find all of your asked questions in that tab.
Please note that other attendees will not be able to see your questions. We'll collect these and address them at the end of the webinar. If you encounter any technical problems during the webinar, please use the online chat support function, which can be found by clicking on your profile icon. Navigate to the help desk desk and clicking on the chat with support icon. Alternatively, contact us at client projects at TNF UK for further support.
Lastly, please let us know your thoughts on today's webinar by tweeting us at bioanalysis zone using the hashtag BTN. Webinars and an on demand version of today's webinar will be available approximately one hour earlier after the webinar, and can be accessed using the same audience link that was sent to you earlier. So we are delighted to have Janice Reichardt and Sylvia christley presenting for us today.
Janice is the director of business intelligence at the antibody society and is an internationally recognized expert in the development of antibody therapeutics. She is a founder and editor in chief of the peer reviewed medical journal mabs, which focuses on topics relevant to antibody research and development. She has published extensively on development trends for antibody therapeutics, and presented her research results as an invited speaker at conferences held worldwide.
Sylvia is a consultant for the antibody society since 2021. She has co-authored the antibodies to watch articles published in mabs. Her research interests focus on antibody therapeutics development for both cancer and non-cancer indications, as well as on different areas of cancer immunology and immunotherapy, including antibody discovery, antibody engineering, and glyco engineering. Thank you again for joining us today, everyone.
I'll now hand over to Janice and Sylvia to start today's presentation. Thank you so much for the introduction, Tristan. And good morning or afternoon, everyone, and welcome to our antibodies to watch in 2025 webinar today I am going to start giving you an overview on the antibody society's objectives. And then I will also give you some definitions on antibody therapeutics and our inclusion exclusion criteria for our analysis.
Then I will present our latest analysis on trends and success rates of therapeutic antibody formats in terms of first approvals, success rates and first in human studies. Then my colleague Jan will discuss about first approvals of antibody therapeutics granted in 2020. For those that have been approved so far in 2025 and those currently in regulatory review.
And then she will give you an overview on the antibodies to watch for possible transition to regulatory review by the end of 2025. And she will conclude with an outlook for the future. The antibody Peabody Society. The business intelligence department of the antibody society continuously collects data on antibody therapeutics from the public domain, with the aim to determine trends in antibody therapeutic development over time.
We annotate each antibody molecule with information about the molecular characteristics and also clinical development, and this allows us to perform our analysis overall or focus on particular aspects of these antibodies, like a specific therapeutic area or formats or targets or mechanism of action. We also aim to determine clinical success rates for antibody therapeutic development as conducted by the biopharmaceutical industry.
We calculate clinical phase transition rates overall marketing approval rates. Phase lengths. And last but not least, we aim to assess innovation in the biopharmaceutical industry. I'd like now to spend a few minutes giving you some definitions, and discussing about our inclusion and exclusion criteria.
So as an antibody therapeutic. We for antibody therapeutic. We mean a recombinant protein based molecule which has at least one antigen binding site that is derived from an antibody gene and that is evaluated as a therapeutic. So this definition excludes all polyclonal antibodies from a natural source antibody, including DNA, because it's not a protein.
And those molecules which are FC only FC fusion proteins because of the antibody, they have only the Fc portion and not the antigen binding site and everything that is just meant for diagnostics. Also, we are interested in commercial development, so we are focusing on molecules which are developed by a public or private for profit entities. We are also interested in innovation. So we only focus on molecules which are unique in composition of matter.
And this excludes all biosimilars. And also for our analysis we count each molecule only once. And we consider the molecule for its most advanced clinical study. Also throughout this presentation, we will often mention first in terms of events. So first approval first time a regulatory review first in human studies. And so this excludes all second and third, and so on and events.
So for the analysis I'm going to present to you today, as I mentioned before, we can focus on a specific aspect of antibody therapeutic development. So we focus the focus this analysis on therapeutic antibody formats. And before jumping to the actual graphs, I'd like to spend a few minutes to describe the classification method.
We used to stratify our antibodies for performing our analysis. So as I mentioned before us, our definition of antibody therapeutic is a recombinant protein based molecule which has at least one antigen binding site derived from an antibody gene. And this definition is quite broad and includes, of course, a full length antibodies like the one depicted in this picture here.
So the classic Y shaped immunoglobulin, composed by 2 heavy chains and two light chains and two fab domains one FC domain, but also includes antibody fragments, which are molecules composed by one or multiple immunoglobulin domain, fragments containing an antigen binding site, or fragments FC, which are composed by one or multiple immunoglobulin domain fragments containing an antigen binding site that is fused to an immunoglobulin FC, and appended immunoglobulins, which are full length antibodies fused to one or multiple immunoglobulin domain fragments containing antigen binding site.
However, the situation is even more complicated. So an antibody can be monospecific, specific or can be by specific or multi specific, can be naked, or can be chemically conjugated to a molecule or fused at the genetic level with a known antibody. Protein domains. So for antibodies which are chemically conjugated to cytotoxic drugs, we call them antibody drug conjugates ADCs antibodies which are conjugated either to a isotope or a chelator.
We call them antibodies for immunotherapy. So which includes conjugate and conjugates. And then we placed all the other chemically conjugated and antibodies fused to known antibody protein domains under the big umbrella of conjugates. So this is a very heterogeneous group which includes both antibodies chemically conjugated to other molecules and antibody fused to other non-protein.
Non non antibody protein domains. The chemically conjugated molecules are. Include, but are not limited to. Antibodies for immunotherapy antibodies which are pegylated or biopolymer conjugated to increase half life, and also those antibodies which are also classified as unconventional ADCs like antibody degraded conjugates, Isaac's antibody oligonucleotide conjugates, antibiotic conjugates and steroid conjugates, and among the antibodies which are fused to non antibody protein domains, we have immunotoxins cytokines and those molecules, which we call bispecific or multi-specific conjugates.
And these are molecules where the fuse portion is a receptor. For example, antibodies fused to a recombinant TCR or antibodies fused to a recombinant TGF beta receptor two ectodomain. Antibodies can be also formulated as one molecule or as a mixture of antibodies. They can have canonical mechanism of action like blocking, agonist antigen clearance, cell mediated effector function, or payload delivery, or they can be designed as vaccines and they can have canonical antigen binding properties, or they can be conditionally activated.
So based on this classification, we have stratified our molecules and to perform our analysis. So in the graph I'm showing you here I'm showing you the first approval of antibody therapeutics approved between 2010 and 2024, and those that were in review as of the 31st of December, 2024. So, as you can see from this graph, where each bar is stratified according to the molecular category of the antibody, we can see that since 2019, we see an increase in antibody therapeutics with an unconventional format.
And then since 2021, we see that these antibodies with an unconventional format account for nearly a third of the antibodies approved each year or in regulatory review. And these are mainly composed by ADCs, bispecifics, and in conjugates and antibody mixture. In this other graph, I'm showing you the annual number of antibody therapeutics entering first in human studies between 2010 and 2023, again stratified by general molecular category.
And as you can see here, we see an increase of antibody therapeutics with an unconventional format. Since 2010 and since 2021, the total number of antibodies with an unconventional format accounts for nearly half of the antibodies entering the clinic each year, and these are mainly ADCs, bispecifics, and conjugates.
We also calculated the phase transition and approval success rates of antibody therapeutics. And as you can see here in this graph, we have a bar chart and the bars are grouped depending according to the phase transition that they are describing. So we have phase one to phase two, phase two to phase three, phase three to marketing approval, marketing approval to approval.
And the last set of bar bars is the overall phase one to approval success rate. So if you look at the last set of bar bars, you see how the overall success rate vary depending on the type of format. You have the highest success rate for bispecific and multispecific antibodies 32% followed by the one for naked monospecific antibodies 30% The lowest is instead for antibodies for radioimmunotherapy, followed by antibodies, which are conjugate, which is just 14% while the antibodies for radioimmunotherapy is 0% I'd like to point out that although there are two antibodies, which are radio conjugates, which have been granted marketing application, these analysis only.
Consider antibodies entering clinical studies between 2000 and 2019 and the antibody radio conjugates approved enter clinical studies way before 2000. That's why they weren't included here. And that's why the success rate is zero. And I'd like now to focus on the completion that is shown here. The completion is the percentage of antibodies for which we know the fate.
So the antibodies can be either approved or terminated. And this gives you an idea on how reliable the success rate value is. And as you can see, the completion is above 60% for most of the groups. For all. For all the groups. And there is a much different across the groups. And these also give us a certain degree of confidence in comparing the success rates.
And now I will hand it over to my colleague Dan who will tell you all about our proof. Antibodies antibodies regulatory review and antibodies to watch. Thank you very much Silvia. In the next section of the presentation, as you mentioned, briefly review the first approvals for antibody therapeutics that occurred in 2024. I'll also as a preview, tell you about the antibodies that are currently in regulatory review and ones for which we expect marketing application submissions by the end of the year.
Also, to keep you up to date, I will mention those approvals that have been received so far in 2025. In 2024, as I move into these tables, I want to note that the total number of global approvals was 24. And in the tables you'll see 11 that are for non-cancer indications and 13 that are for cancer indications.
Half of those approvals occurred outside the US or the EU. So we do segregate the information into tables here. There's a lot of information. Information for nearly 70 molecules to keep the time reasonable. I will focus only on aspects that we consider innovative compared to the approved products, so the presentation will be available for your later reference, so don't worry about missing any of the lovely details, the lovely details that we include in all of these tables in the tables you see coming up.
We start with the US or the EU relevant data first and the molecules are stratified into non cancer and cancer indications. So we do them the same for molecules that are approved in what we call the rest of the world. R.o.w so you also see that listed on the slides coming up in this particular table. If you look at the headers, we include information on the international nonproprietary name as well as the brand name target and format the indication, as well as the country or region of first approval.
We are also interested in subsequent approvals that occur in the same year. So you may see multiple countries listed in that last column in terms of innovative molecules. We would mention donanemab, which is the first antibody targeting a disease modified form of amyloid beta in particular. That's the pyroglutamate at position 3 of the n-terminus. In addition, it was the first approved antibody targeting CSF 1 receptor.
Continuing with the non-cancer indications, these are approvals. You see most of them are in China. So outside of the US or EU, we do have one approved in Russia. And that particular molecule is, in fact, the only one here that is novel compared to previously approved molecules.
Now moving on to us or EU approvals for antibody therapeutics for cancer. And again emphasizing these are first approvals that occurred in 2024. If an additional country did approve it subsequently, we've included that. You see that in this case is only relevant to Zoll rituximab, which is the first antibody approved that targets claudin 18.2. We are tracking many anti claudin 18.2 molecules that are currently in clinical studies.
And in fact, there's around 40 of them. So we do anticipate that there may be more anti claudin 18.2 antibodies that gain marketing approvals in the future. In terms of innovativeness again tala is the first approved antibody targeting DLL3 DLL3 as well as the combination of D3 and CD3. In addition, the combination of HER2 and HER3 3 is unique among the approved antibodies.
Now moving on to approvals that occurred outside the US or the EU first. All of these approvals are in Asia. Most of them in China. In terms of being innovative. We would mention Ivan zmab, which is the first approved antibody targeting the combination of PD 1 and VEGF.
This very nice map summarizes all of the data that was just presented. It also shows whether an antibody approved in 2024 is also in review in another country or region. Those countries or regions are listed on the y-axis. The approvals are shown in the dark blue. Those in regulatory review are shown in the light blue of the products approved in the US.
You'll notice the majority were also approved or they are in regulatory review and either the EU, UK, Canada or Japan. However, you also notice that there's relatively little overlap between the products approved in China and those approved elsewhere. Two keep you up to date. I will just mention the molecules that have received an approval so far in 2025, and that is a first approval.
Again emphasizing we are focusing primarily on first approvals for innovativeness. We would mention Gardasil, which targets factor 12. A was recently approved in Australia just a couple of weeks ago. It's also in regulatory review in a number of countries and the EU. Moving on.
I'll now discuss the investigational antibodies that are currently in regulatory review in at least one country. That total is 28 with 17 for non-cancer indications and 11 for cancer. So again here to conserve time, there's a lot of molecules to cover. I'll just touch on the high points. This table shows the antibody therapeutics for non-cancer indications that are in regulatory review in either the US or the EU, potentially another country, if we know about it.
Ventrosa Mab is actually novel in the sense of being an anti-drug antibody. It targets and counteracts a drug that's given as an anticoagulant. Narsoplimab is the first antibody targeting masp two that has entered regulatory review. Recently, scholar rocks anti myostatin antibody was announced as being in regulatory review. And that target is unique compared to the currently approved products.
So here we're looking at the antibody therapeutics and regulatory review in the US or the EU. But these are for cancer regarding novelty. So here I'll focus on the combination of the target and the format. So NCME and her three are not in and of themselves unique targets. But these particular molecules that target those antigens are unique in that they are anti-drug conjugates.
Antibody drug conjugates. The Fibronectin extra domain B is a unique target. And this particular product candidate is a unique in being a mixture of cytokines. So the next two tables focus on the antibodies undergoing regulatory review in outside the US or the EU. But interestingly, they are all in review in China for non-cancer indications.
We would note that tetanus toxin is a novel target. We are not aware of a recombinant monoclonal antibody that's been approved that targets that particular antigen. Or the cancer indications. We note again here. These are all undergoing regulatory review in China. So we are tracking a tremendous amount of activity going on in China. In terms of novel lymphocyte.
Alpha is unique in being an antibody targeting the combination of pd-l1 and TGF beta is also a bispecific immunogen conjugate. Here we're looking at a map that again summarizes the table you just saw with the two antibodies approved in 2025, shown in the dark blue. And those excuse me. So the approvals are in the dark blue.
Again, as we saw before, those in review are shown in the light blue. As before, the relevant country is on the y-axis. We do note several interesting points here. Majority of these are for non-cancer indications. It's typical that cancer makes up about half of the totals. But here at this point in time, the majority are for non-cancer indications. And as we saw before with the approvals, there's a lot of other activity going on in China, but there's currently relatively little overlap between the molecules that are in regulatory review in China and in regulatory review outside of that country.
Now moving on to the antibodies to watch. So those would be antibodies in late stage clinical developments where we believe based on the information available, that it may enter regulatory review by the end of 2025. Currently 16 with 11 for non cancer and 5 for cancer indications. So again, you see a prevalence of the antibodies for non-cancer indications at this point in time in this table.
In the following ones we've indicated the estimated timing of the market application submission and the relevant country if known. Here we show two antibodies for non-cancer indications that we think may have first half of 2025 submissions, and both of these molecules target antigens that are unique compared to the approved products.
So here we have non-cancer indications again. But the timing of the possible submission is not known just at some point in 2025 or it's in the second half of 2025. Unique targets here include IL 33, as well as its receptor. And both of the antibodies that target those antigens are for COPD. Insulin receptor also represents a unique target compared to the approved antibodies.
So in the final table, we show five antibodies for cancer, for which we anticipate possible marketing application submissions in 2025. Two unique targets are included toom three and TIGIT. We do recognize that not all clinical data for these particular antibodies to watch have been positive, but they remain, as all of them will. They'll remain on our watch list as long as the company indicates they are pursuing development.
So with that, I'll now move on to the final graph. So looking towards the future, what do we think. Well, we can look to history a little bit in order to justify our projection for the future. So in terms of the outlook for the future, it's certainly true that I have been tracking late stage pipeline of antibody therapeutics for quite some time, and it does continue to impress.
This graph shows the number of antibodies that were counted, as in late stage clinical studies, in each of the annual antibodies to watch papers the year shown on the x-axis is the year named in the title. So an antibodies to watch in 2010. You can see on the far left hand side of this graph the number was 26. So really not a whole lot of work for me in the antibodies to watch to in 2010 paper.
However, if I direct your attention all the way to the far right, you'll see an antibodies to watch in 2025, we counted nearly 180. So this is quite impressive, but it's Additionally impressive because that substantial increase occurred at the same time, of course, that molecules were moving into regulatory review. And some may of course, have been terminated. So as a consequence of seeing that happen over a long period of time, I and I have no reason to believe that would stop.
My outlook for the future is thus quite good. We may see plateaus in the future in terms of the number in late stage clinical studies, but it's certainly true that antibodies are well suited as therapeutics, and there's an abundance of unmet medical need, and therefore an abundance of need for safe and effective drugs.
So with that, we'll now conclude with a few simple messages, which we hope are clear from the presentation. So first, antibody therapeutics are certainly entering clinical studies and being approved in increasing numbers. In evaluating the success rates, we've shown that rates do vary according to the format. We'll continue to track these rates into the future, particularly the rate for the antibody drug conjugates.
In terms of the global first approvals, it did reach an all time high in 2024, and we do see continued success in the future with 28 antibodies in regulatory review. Of course, the timing of approvals does very much depend on the review process. We've identified at least 16 molecules that may enter regulatory review soon. This is only February.
We do expect to hear about more than these in the months ahead. Overall, we think our results and we hope you agree. We think our results support the statement that antibody therapeutics development as conducted by the biopharmaceutical industry is robust and increasingly successful. We would definitely like to thank our antibodies to watch in 2025 co-authors for their participation.
Creating the paper every year is a massive amount of work. So we are very appreciative of their contribution of time and their considerable expertise. We also thank the antibody society and their sponsors for their support. In addition. We want to encourage you to join the antibody society if you're not already a member.
The society is a non-profit trade association. We do a lot of work in business intelligence, as you've just seen, and we do disseminate this information in various ways, including by webinars. We have searchable tables of antibodies to watch content on the antibody society's website, and we keep those up to date during the year. So we encourage you to go look at that for continued updates. We also provide pipeline data to our sponsors.
And speaking of those sponsors, I want to wrap up by mentioning that membership is free for people who work at sponsor companies. So I'll show the sponsor logos, which are in alphabetical order, very quickly. If you happen to see your company's logo here, please do feel free to go to the antibody society's website and register for your free membership.
And with that, I thank you very much for your kind attention. Brilliant well, thank you very much for that presentation, Janice and Sylvia. If you were at home watching, do you have any questions for our presenters. And please continue to submit them using the Q&A button at the side of your window, and we'll now start addressing some of your questions.
Just a quick technical one that was posed on whether or not this webinar will be available to watch on demand. Absolutely it will be roughly an hour after the webinar is concluded. You'll be able to watch the recording. So straight in then to questions for Sylvia and Janice. So how will AI driven antibody discovery shape the future of antibody development in 2025 and beyond.
Sylvia, you want to jump in on the discovery side. Yeah Hi. Well, I believe so. Now we hear more and more talking about AI driven antibody discovery. And I think we will continue to hear more and more because AI and machine learning approaches can be used for different steps in the discovery process. Early stage discovery process, but also making sure that then what has been discovered, it complies with the CMC.
And and I believe that we will hear more and more talking about these. And I can't I can't tell you what will happen, of course, but definitely we are going to watch this space and. Yes just a couple of other things is the. Older of the two of us the one thing so I so I'm the voice of caution here.
So absolutely I will have immediate effects. It's already of course on the discovery space. But again pointing out that whatever comes out of that discovery efforts and even through the preclinical, the true test of it will be what survives the clinical trials process. So I may give you better design. It may give you an antibody that you might not have thought of before.
But if it's not proven in traditional clinical studies to be safe and effective, then it's going to fail. So that's the it's really that the true test is always what does it do in human. Fantastic so probably following on from that, I mean relatively new tool of AI in this field. Do you think that growth in the field is sustainable. At the rate that it's going at the moment. I do.
And and really that's based not only well, it's based on several of the graphs that we showed. The first is continuing increase in the number of antibodies entering clinical studies, but also that they are making it through in larger numbers to the late stage clinical studies. And we see, of course, this infiltration of the technologies into other countries where they're being uptaken and loads more work is being done than even the past, say, five years or so.
We've been tracking the very tremendous activity going on in China for quite some time. It was not so impressive in the 2015 to 2019 range, but it's really taken off and I can see that there's tremendous potential there still for a lot more activity, but also potentially additional work being done in other countries. And that increases the number globally of antibodies that are in development and potentially then making it through to patients in due time.
Fantastic and so kind of following on about the growth and the success rates, how are these success rates actually calculated by the antibody society. So can I let me I have a slide so that you can see. So basically what we did. Yeah so what we did for our analysis is that we. For each molecule, we are assigned a status, a status.
There are nine possible status 1, 2, three marketing approval. So we read the antibody is regulatory review or approved. And then it could be terminated in phase one, phase two phase three and the regulatory review stage. So what we did is that we took the antibodies which entered clinical studies between 2000 and 2019. We have signs that each one a status.
And then we applied. And then we calculated the success rate this way. So we calculated the number of antibodies moved to the falling phase, divided by the sum of the number of antibodies which moved to the falling phase, plus those which have been terminated at that phase. And then we.
So we did this for each phase transition. So phase one to phase two. Phase two to phase three. Phase three marketing approval and marketing approval to approval. And then when we calculated the overall phase one to approval success rate, we simply did the mathematical product of the different phase transition rates as shown here in the slide.
I just want to remind you that so the way this success rate is calculated, basically we only consider the molecules for which we know the fate. So either transition to the falling phase or terminated. So we always also calculate together with success rate we calculate the completion in the cohort, which is calculated as the antibodies that have been approved plus those that have been terminated divided by the total number of antibodies in the cohort.
So antibodies for which we know the fate divided by the number of antibodies in that cohort. And these give us an idea of how reliable is the value that we are calculating. So one thing that I'll point out about that is that it was an antibodies to watch in 24. I believe we did a compare contrast with our approach and our results, with the reports that was put out by, and it uses a commercially available database.
But I would encourage you, if you're interested in this and how these calculations were done, I would encourage you to look at that paper. But in particular, one thing that we note is that the calculations by the other group were done differently. So it's very important when you're looking at success rates to understand how they were calculated. What do they actually represent.
Because you can do the calculations in various ways. You can construct your cohort in various ways. And if you just look at the final numbers, I think the number is like 5% It was very low, very low compared to ours. But we explain the difference in the calculations and why it would be lower. So it's not that theirs is wrong or and ours is right, it's that the calculations were done differently.
They tell you something different. So it's just important to understand that, especially for people who are using these success rate to, for example, justify their development programs. Fantastic and then just. Yeah following on from that question about the success rates, do you think that the rates are likely to change in the future.
Yes so the success rates I showed let me show let me find the slide. I showed how the success rate varied between antibodies with different formats. And I don't know whether you notice that the success rate of antibody drug conjugates doesn't really look so great in this graph.
But just to point out that this analysis has been done on antibodies that have entered clinical studies between 2000 and 2019. But now when you look at the trends in first in human study that I showed here, you see that there is an increasing number of antibody drug conjugate entering the clinic. And you think why. Why?
if the success rate is so great, why they keep entering the clinic. Because what we noticed is that the anti-body especially antibody drug conjugates. Have undergone. There's been a lot of research on antibody drug conjugates and they found a way to implement them. And reduce toxicity especially varying the type of payload.
What we noticed is that there's been an increase lately in antibody drug with the different types of payloads compared to first generation antibody drug conjugates. And we haven't shown it here, but our preliminary analysis, because the numbers are still very little, we see that the success rates of antibodies with that type of payload, which is topoisomerase one inhibitors, is much, much higher than the classic payloads like tubulin inhibitors and DNA binding payloads.
And so we do expect the success rate of ADCs to improve in time, because we do see an increased number, especially of these ADCs with the top inhibitor, which in our preliminary analysis is showing such a very nice success rate. And also I want to say something about the antibodies for radioimmunotherapy. So here I'm showing a success rate of 0. But as I explained before, this is only because we are considering antibodies entering the clinic between 2000 and 2019.
Now we do see antibody which are already conjugates. And in clinical studies we do see them is the pink bar. And what we've noticed is that again like for ADCs the payload has changed. So now the majority of conjugates entering the clinic have an isotope, which is an alpha emitter which apparently shows a lower tissue penetration.
And it seems that is causing less damage to the surrounding tissue. So it should cause less toxicity and more be able to target the tumor better. So the numbers are still very, very low. So we hope we might see a decrease in the success rate for these type of molecules as well. Fantastic and does the antibody society track the model or method that the proteins are made for instance mouse strains or dromedary type for example.
Yes, we definitely have that information for some. So bear in mind that the overall data set that we have exceeds 2900. And the origin of the molecules is not always revealed immediately. It can take quite some time to find that information in the public domain. So I would say of the antibodies in the late stage development through to approval.
We may have the majority of that information, but for antibodies that, well, certainly antibodies that are preclinical, forget about it. You probably do not know. Potentially, though, people do like to mention when they're so so maybe for those we have a comprehensive list and certainly ones in phase one, just the information is not available. So we're not able to do analysis that we have confidence in the origin, but we do have the information for at least some of the molecules.
Fantastic and sorry what are your data sources as well. Oh well we do have lots. We do not rely. In fact, I don't believe that there is a single source you could go to and just say, Oh, well, I'll just go and find all this information. It'll be so easy. And no, I've been collecting this kind of data for well over 10 years.
I feel like I'm a little like a little bird, a little magpie that goes around and collects up little shiny bits of information. And then I tuck them into my data set, and that's what we use for the analysis. But the data comes from all over the place. We do want to rely on sources that are reliable. And that would include the company first and foremost. What are they saying in their press releases.
What are they saying in their presentations. What are they presenting in abstracts at various meetings. So we would start with the company. And then of course, you also have other reliable sources such as the World Health Organization. When they're finally given an in. Then there's a lot of information embedded in the information the WHO puts out, of course, regulatory agencies for anything that may be in review, or certainly those that are approved.
Ema does put out very nicely a monthly list of what's undergoing regulatory review. So we do look at that every month. FDA is not quite so accommodating. They do not have a similar list. So we can't say with FDA. It's only if the company chooses to disclose the information that we would know. There are also some public databases that we like to use.
And that would include imgt as well as their sabdam, of course, also published literature. So anything that appears in papers, we would look at that also very definitely the clinical trials registries, but of course, not just clinicaltrials.gov. We're looking at registries that are in China where you look at the Australia New Zealand registry. We look at the Japan registry. So we're looking through all of that data cells.
We do not like to rely on a second or secondary source for key information that we really need to. We need to verify everything that we see we like to verify it with, with, like I said, a trusted source, such as the company, regulatory agencies or the clinical trials registries. And do you have data or an idea on how long the phase transition and approval have changed throughout the years.
Well, I mean, certainly it's easy to point out where things started to change. And that was with the immune checkpoint modulators. It was very common for clinical studies to take anywhere from 8 to 10 years. But the immune checkpoint modulators came through much faster. I mean, as quick as 4 or 4 and a half years for some of those molecules.
And then also as we get additional antibodies that target well validated antigens, I think there's a chance there to speed up the clinical studies, because you have data from previously approved molecules is something as a guide, you can't copy what was done before. It's not ever going to be exactly the same. These are not biosimilars. They are unique molecules.
But it does. The previous knowledge does help in the clinical trials process. Also, the additional experience gained by the regulatory agencies also help because of course, companies don't just go off and run their clinical studies without extensive consultation with the various regulatory authorities. So I think things have moved forward such that the clinical trials can take less time, certainly for the antibodies that are against well validated targets.
You may still be going at a somewhat slower pace than for antibodies against novel targets or with unique, truly unique mechanisms of action. And so you mentioned biosimilars there. Do you also study the rates of approval for biosimilars for those molecules. We do not. We do not. Biosimilars are specifically excluded from our analysis.
Not that we don't like them or think there's no value in them. Quite the opposite. There's a lot of value in them. And I still am super impressed by celltrion's approval of the first biosimilar. They always get a shout out from me for going that route and really doing what people did not think could be done before. It was astounding. Really, really amazing.
Good job. So of course that was some time ago. But in any event, the reason, of course, is because they do have that benefit of being the same as something that was approved before. So you do have an abundance of knowledge about how clinical studies were done before the expected results of the clinical studies. And so I do think that helps shorten the clinical trials process.
You can go immediately from a phase one to a phase three. You normally aren't doing that with an innovative molecule. And so there is a big difference there. And and so we exclude them to keep them separate from the innovative molecules. But there's so many innovative molecules, we don't really have the time to track the biosimilars. Somebody else is doing that though, so we don't have to. Fantastic And what is it that causes some of the biologics license applications to be delayed.
Sylvia, you looked at that comment. Let me let me again. We have a slide I can show you. So this was published in our paper. So basically what we did is that here in this graph we plotted the number of antibodies approved by the FDA and those in review.
And we stratified the molecules according to whether they were approved after one cycle or review or they are still in the first cycle of review or they have a complete response letter. And also we annotated whether the complete response vector was due to CMC issues or other. So as you can see here, we start to see first of all, an increase in the antibodies approved by having received a complete response letter since 2019.
We start to see them. And since 2022 we really see an increase. And also what we see is that the majority of these complete response letters seem to be due to manufacturing issues, and this is the same for the antibodies that are currently. Well, they were very relevant to review as of December 31, 2024 because now the situation has changed. It's just one month.
So you see half of the antibodies in review by the FDA have received a complete response letter, and the complete response letter can delay. So they issue a complete response letter when they have a concern about the marketing application. And this can delay the approval by six months or more. So Yeah, this is what is causing this delay. And so we, we, we really recommend the companies to make sure they manufacture inside comply with the, the FDA standards for manufacturing and CMC.
Fantastic well thank you very much, Janice and Sylvia for answering all of our audience questions. I'm afraid that's all we've got time for today, but if there are any others that we haven't managed to get around to, we'll address them offline. If you do have any other questions for Janice and Sylvia, please feel free to send them across to client projects at UK.
And I would now like to once again thank our wonderful presenters Janice and Sylvia, as well as you, our listeners for your time and questions. If you, you'll receive an email with how to watch this webinar on demand shortly. And don't forget to visit us at ww.com for more webinars. Thank you again for attending everyone and goodbye. Thank you. Thank you.
Bye bye.
Segment:0 .
Hello, everyone, and thank you for attending today's webinar. Antibodies to watch in 2025. I'm Tristan fry, senior editor at biotechniques, and I'll be your host for today's event.
Before I introduce you to our speakers, I'd like to quickly cover a few housekeeping items. Firstly, all the information about today's webinar can be found on the right hand side of your screen, including the Q&A tab. You'll have the opportunity to submit questions to today's presenters by typing your questions into the Q&A box on the side of the window. You may send in your questions at any time during the presentation, and you'll find all of your asked questions in that tab.
Please note that other attendees will not be able to see your questions. We'll collect these and address them at the end of the webinar. If you encounter any technical problems during the webinar, please use the online chat support function, which can be found by clicking on your profile icon. Navigate to the help desk desk and clicking on the chat with support icon. Alternatively, contact us at client projects at TNF UK for further support.
Lastly, please let us know your thoughts on today's webinar by tweeting us at bioanalysis zone using the hashtag BTN. Webinars and an on demand version of today's webinar will be available approximately one hour earlier after the webinar, and can be accessed using the same audience link that was sent to you earlier. So we are delighted to have Janice Reichardt and Sylvia christley presenting for us today.
Janice is the director of business intelligence at the antibody society and is an internationally recognized expert in the development of antibody therapeutics. She is a founder and editor in chief of the peer reviewed medical journal mabs, which focuses on topics relevant to antibody research and development. She has published extensively on development trends for antibody therapeutics, and presented her research results as an invited speaker at conferences held worldwide.
Sylvia is a consultant for the antibody society since 2021. She has co-authored the antibodies to watch articles published in mabs. Her research interests focus on antibody therapeutics development for both cancer and non-cancer indications, as well as on different areas of cancer immunology and immunotherapy, including antibody discovery, antibody engineering, and glyco engineering. Thank you again for joining us today, everyone.
I'll now hand over to Janice and Sylvia to start today's presentation. Thank you so much for the introduction, Tristan. And good morning or afternoon, everyone, and welcome to our antibodies to watch in 2025 webinar today I am going to start giving you an overview on the antibody society's objectives. And then I will also give you some definitions on antibody therapeutics and our inclusion exclusion criteria for our analysis.
Then I will present our latest analysis on trends and success rates of therapeutic antibody formats in terms of first approvals, success rates and first in human studies. Then my colleague Jan will discuss about first approvals of antibody therapeutics granted in 2020. For those that have been approved so far in 2025 and those currently in regulatory review.
And then she will give you an overview on the antibodies to watch for possible transition to regulatory review by the end of 2025. And she will conclude with an outlook for the future. The antibody Peabody Society. The business intelligence department of the antibody society continuously collects data on antibody therapeutics from the public domain, with the aim to determine trends in antibody therapeutic development over time.
We annotate each antibody molecule with information about the molecular characteristics and also clinical development, and this allows us to perform our analysis overall or focus on particular aspects of these antibodies, like a specific therapeutic area or formats or targets or mechanism of action. We also aim to determine clinical success rates for antibody therapeutic development as conducted by the biopharmaceutical industry.
We calculate clinical phase transition rates overall marketing approval rates. Phase lengths. And last but not least, we aim to assess innovation in the biopharmaceutical industry. I'd like now to spend a few minutes giving you some definitions, and discussing about our inclusion and exclusion criteria.
So as an antibody therapeutic. We for antibody therapeutic. We mean a recombinant protein based molecule which has at least one antigen binding site that is derived from an antibody gene and that is evaluated as a therapeutic. So this definition excludes all polyclonal antibodies from a natural source antibody, including DNA, because it's not a protein.
And those molecules which are FC only FC fusion proteins because of the antibody, they have only the Fc portion and not the antigen binding site and everything that is just meant for diagnostics. Also, we are interested in commercial development, so we are focusing on molecules which are developed by a public or private for profit entities. We are also interested in innovation. So we only focus on molecules which are unique in composition of matter.
And this excludes all biosimilars. And also for our analysis we count each molecule only once. And we consider the molecule for its most advanced clinical study. Also throughout this presentation, we will often mention first in terms of events. So first approval first time a regulatory review first in human studies. And so this excludes all second and third, and so on and events.
So for the analysis I'm going to present to you today, as I mentioned before, we can focus on a specific aspect of antibody therapeutic development. So we focus the focus this analysis on therapeutic antibody formats. And before jumping to the actual graphs, I'd like to spend a few minutes to describe the classification method.
We used to stratify our antibodies for performing our analysis. So as I mentioned before us, our definition of antibody therapeutic is a recombinant protein based molecule which has at least one antigen binding site derived from an antibody gene. And this definition is quite broad and includes, of course, a full length antibodies like the one depicted in this picture here.
So the classic Y shaped immunoglobulin, composed by 2 heavy chains and two light chains and two fab domains one FC domain, but also includes antibody fragments, which are molecules composed by one or multiple immunoglobulin domain, fragments containing an antigen binding site, or fragments FC, which are composed by one or multiple immunoglobulin domain fragments containing an antigen binding site that is fused to an immunoglobulin FC, and appended immunoglobulins, which are full length antibodies fused to one or multiple immunoglobulin domain fragments containing antigen binding site.
However, the situation is even more complicated. So an antibody can be monospecific, specific or can be by specific or multi specific, can be naked, or can be chemically conjugated to a molecule or fused at the genetic level with a known antibody. Protein domains. So for antibodies which are chemically conjugated to cytotoxic drugs, we call them antibody drug conjugates ADCs antibodies which are conjugated either to a isotope or a chelator.
We call them antibodies for immunotherapy. So which includes conjugate and conjugates. And then we placed all the other chemically conjugated and antibodies fused to known antibody protein domains under the big umbrella of conjugates. So this is a very heterogeneous group which includes both antibodies chemically conjugated to other molecules and antibody fused to other non-protein.
Non non antibody protein domains. The chemically conjugated molecules are. Include, but are not limited to. Antibodies for immunotherapy antibodies which are pegylated or biopolymer conjugated to increase half life, and also those antibodies which are also classified as unconventional ADCs like antibody degraded conjugates, Isaac's antibody oligonucleotide conjugates, antibiotic conjugates and steroid conjugates, and among the antibodies which are fused to non antibody protein domains, we have immunotoxins cytokines and those molecules, which we call bispecific or multi-specific conjugates.
And these are molecules where the fuse portion is a receptor. For example, antibodies fused to a recombinant TCR or antibodies fused to a recombinant TGF beta receptor two ectodomain. Antibodies can be also formulated as one molecule or as a mixture of antibodies. They can have canonical mechanism of action like blocking, agonist antigen clearance, cell mediated effector function, or payload delivery, or they can be designed as vaccines and they can have canonical antigen binding properties, or they can be conditionally activated.
So based on this classification, we have stratified our molecules and to perform our analysis. So in the graph I'm showing you here I'm showing you the first approval of antibody therapeutics approved between 2010 and 2024, and those that were in review as of the 31st of December, 2024. So, as you can see from this graph, where each bar is stratified according to the molecular category of the antibody, we can see that since 2019, we see an increase in antibody therapeutics with an unconventional format.
And then since 2021, we see that these antibodies with an unconventional format account for nearly a third of the antibodies approved each year or in regulatory review. And these are mainly composed by ADCs, bispecifics, and in conjugates and antibody mixture. In this other graph, I'm showing you the annual number of antibody therapeutics entering first in human studies between 2010 and 2023, again stratified by general molecular category.
And as you can see here, we see an increase of antibody therapeutics with an unconventional format. Since 2010 and since 2021, the total number of antibodies with an unconventional format accounts for nearly half of the antibodies entering the clinic each year, and these are mainly ADCs, bispecifics, and conjugates.
We also calculated the phase transition and approval success rates of antibody therapeutics. And as you can see here in this graph, we have a bar chart and the bars are grouped depending according to the phase transition that they are describing. So we have phase one to phase two, phase two to phase three, phase three to marketing approval, marketing approval to approval.
And the last set of bar bars is the overall phase one to approval success rate. So if you look at the last set of bar bars, you see how the overall success rate vary depending on the type of format. You have the highest success rate for bispecific and multispecific antibodies 32% followed by the one for naked monospecific antibodies 30% The lowest is instead for antibodies for radioimmunotherapy, followed by antibodies, which are conjugate, which is just 14% while the antibodies for radioimmunotherapy is 0% I'd like to point out that although there are two antibodies, which are radio conjugates, which have been granted marketing application, these analysis only.
Consider antibodies entering clinical studies between 2000 and 2019 and the antibody radio conjugates approved enter clinical studies way before 2000. That's why they weren't included here. And that's why the success rate is zero. And I'd like now to focus on the completion that is shown here. The completion is the percentage of antibodies for which we know the fate.
So the antibodies can be either approved or terminated. And this gives you an idea on how reliable the success rate value is. And as you can see, the completion is above 60% for most of the groups. For all. For all the groups. And there is a much different across the groups. And these also give us a certain degree of confidence in comparing the success rates.
And now I will hand it over to my colleague Dan who will tell you all about our proof. Antibodies antibodies regulatory review and antibodies to watch. Thank you very much Silvia. In the next section of the presentation, as you mentioned, briefly review the first approvals for antibody therapeutics that occurred in 2024. I'll also as a preview, tell you about the antibodies that are currently in regulatory review and ones for which we expect marketing application submissions by the end of the year.
Also, to keep you up to date, I will mention those approvals that have been received so far in 2025. In 2024, as I move into these tables, I want to note that the total number of global approvals was 24. And in the tables you'll see 11 that are for non-cancer indications and 13 that are for cancer indications.
Half of those approvals occurred outside the US or the EU. So we do segregate the information into tables here. There's a lot of information. Information for nearly 70 molecules to keep the time reasonable. I will focus only on aspects that we consider innovative compared to the approved products, so the presentation will be available for your later reference, so don't worry about missing any of the lovely details, the lovely details that we include in all of these tables in the tables you see coming up.
We start with the US or the EU relevant data first and the molecules are stratified into non cancer and cancer indications. So we do them the same for molecules that are approved in what we call the rest of the world. R.o.w so you also see that listed on the slides coming up in this particular table. If you look at the headers, we include information on the international nonproprietary name as well as the brand name target and format the indication, as well as the country or region of first approval.
We are also interested in subsequent approvals that occur in the same year. So you may see multiple countries listed in that last column in terms of innovative molecules. We would mention donanemab, which is the first antibody targeting a disease modified form of amyloid beta in particular. That's the pyroglutamate at position 3 of the n-terminus. In addition, it was the first approved antibody targeting CSF 1 receptor.
Continuing with the non-cancer indications, these are approvals. You see most of them are in China. So outside of the US or EU, we do have one approved in Russia. And that particular molecule is, in fact, the only one here that is novel compared to previously approved molecules.
Now moving on to us or EU approvals for antibody therapeutics for cancer. And again emphasizing these are first approvals that occurred in 2024. If an additional country did approve it subsequently, we've included that. You see that in this case is only relevant to Zoll rituximab, which is the first antibody approved that targets claudin 18.2. We are tracking many anti claudin 18.2 molecules that are currently in clinical studies.
And in fact, there's around 40 of them. So we do anticipate that there may be more anti claudin 18.2 antibodies that gain marketing approvals in the future. In terms of innovativeness again tala is the first approved antibody targeting DLL3 DLL3 as well as the combination of D3 and CD3. In addition, the combination of HER2 and HER3 3 is unique among the approved antibodies.
Now moving on to approvals that occurred outside the US or the EU first. All of these approvals are in Asia. Most of them in China. In terms of being innovative. We would mention Ivan zmab, which is the first approved antibody targeting the combination of PD 1 and VEGF.
This very nice map summarizes all of the data that was just presented. It also shows whether an antibody approved in 2024 is also in review in another country or region. Those countries or regions are listed on the y-axis. The approvals are shown in the dark blue. Those in regulatory review are shown in the light blue of the products approved in the US.
You'll notice the majority were also approved or they are in regulatory review and either the EU, UK, Canada or Japan. However, you also notice that there's relatively little overlap between the products approved in China and those approved elsewhere. Two keep you up to date. I will just mention the molecules that have received an approval so far in 2025, and that is a first approval.
Again emphasizing we are focusing primarily on first approvals for innovativeness. We would mention Gardasil, which targets factor 12. A was recently approved in Australia just a couple of weeks ago. It's also in regulatory review in a number of countries and the EU. Moving on.
I'll now discuss the investigational antibodies that are currently in regulatory review in at least one country. That total is 28 with 17 for non-cancer indications and 11 for cancer. So again here to conserve time, there's a lot of molecules to cover. I'll just touch on the high points. This table shows the antibody therapeutics for non-cancer indications that are in regulatory review in either the US or the EU, potentially another country, if we know about it.
Ventrosa Mab is actually novel in the sense of being an anti-drug antibody. It targets and counteracts a drug that's given as an anticoagulant. Narsoplimab is the first antibody targeting masp two that has entered regulatory review. Recently, scholar rocks anti myostatin antibody was announced as being in regulatory review. And that target is unique compared to the currently approved products.
So here we're looking at the antibody therapeutics and regulatory review in the US or the EU. But these are for cancer regarding novelty. So here I'll focus on the combination of the target and the format. So NCME and her three are not in and of themselves unique targets. But these particular molecules that target those antigens are unique in that they are anti-drug conjugates.
Antibody drug conjugates. The Fibronectin extra domain B is a unique target. And this particular product candidate is a unique in being a mixture of cytokines. So the next two tables focus on the antibodies undergoing regulatory review in outside the US or the EU. But interestingly, they are all in review in China for non-cancer indications.
We would note that tetanus toxin is a novel target. We are not aware of a recombinant monoclonal antibody that's been approved that targets that particular antigen. Or the cancer indications. We note again here. These are all undergoing regulatory review in China. So we are tracking a tremendous amount of activity going on in China. In terms of novel lymphocyte.
Alpha is unique in being an antibody targeting the combination of pd-l1 and TGF beta is also a bispecific immunogen conjugate. Here we're looking at a map that again summarizes the table you just saw with the two antibodies approved in 2025, shown in the dark blue. And those excuse me. So the approvals are in the dark blue.
Again, as we saw before, those in review are shown in the light blue. As before, the relevant country is on the y-axis. We do note several interesting points here. Majority of these are for non-cancer indications. It's typical that cancer makes up about half of the totals. But here at this point in time, the majority are for non-cancer indications. And as we saw before with the approvals, there's a lot of other activity going on in China, but there's currently relatively little overlap between the molecules that are in regulatory review in China and in regulatory review outside of that country.
Now moving on to the antibodies to watch. So those would be antibodies in late stage clinical developments where we believe based on the information available, that it may enter regulatory review by the end of 2025. Currently 16 with 11 for non cancer and 5 for cancer indications. So again, you see a prevalence of the antibodies for non-cancer indications at this point in time in this table.
In the following ones we've indicated the estimated timing of the market application submission and the relevant country if known. Here we show two antibodies for non-cancer indications that we think may have first half of 2025 submissions, and both of these molecules target antigens that are unique compared to the approved products.
So here we have non-cancer indications again. But the timing of the possible submission is not known just at some point in 2025 or it's in the second half of 2025. Unique targets here include IL 33, as well as its receptor. And both of the antibodies that target those antigens are for COPD. Insulin receptor also represents a unique target compared to the approved antibodies.
So in the final table, we show five antibodies for cancer, for which we anticipate possible marketing application submissions in 2025. Two unique targets are included toom three and TIGIT. We do recognize that not all clinical data for these particular antibodies to watch have been positive, but they remain, as all of them will. They'll remain on our watch list as long as the company indicates they are pursuing development.
So with that, I'll now move on to the final graph. So looking towards the future, what do we think. Well, we can look to history a little bit in order to justify our projection for the future. So in terms of the outlook for the future, it's certainly true that I have been tracking late stage pipeline of antibody therapeutics for quite some time, and it does continue to impress.
This graph shows the number of antibodies that were counted, as in late stage clinical studies, in each of the annual antibodies to watch papers the year shown on the x-axis is the year named in the title. So an antibodies to watch in 2010. You can see on the far left hand side of this graph the number was 26. So really not a whole lot of work for me in the antibodies to watch to in 2010 paper.
However, if I direct your attention all the way to the far right, you'll see an antibodies to watch in 2025, we counted nearly 180. So this is quite impressive, but it's Additionally impressive because that substantial increase occurred at the same time, of course, that molecules were moving into regulatory review. And some may of course, have been terminated. So as a consequence of seeing that happen over a long period of time, I and I have no reason to believe that would stop.
My outlook for the future is thus quite good. We may see plateaus in the future in terms of the number in late stage clinical studies, but it's certainly true that antibodies are well suited as therapeutics, and there's an abundance of unmet medical need, and therefore an abundance of need for safe and effective drugs.
So with that, we'll now conclude with a few simple messages, which we hope are clear from the presentation. So first, antibody therapeutics are certainly entering clinical studies and being approved in increasing numbers. In evaluating the success rates, we've shown that rates do vary according to the format. We'll continue to track these rates into the future, particularly the rate for the antibody drug conjugates.
In terms of the global first approvals, it did reach an all time high in 2024, and we do see continued success in the future with 28 antibodies in regulatory review. Of course, the timing of approvals does very much depend on the review process. We've identified at least 16 molecules that may enter regulatory review soon. This is only February.
We do expect to hear about more than these in the months ahead. Overall, we think our results and we hope you agree. We think our results support the statement that antibody therapeutics development as conducted by the biopharmaceutical industry is robust and increasingly successful. We would definitely like to thank our antibodies to watch in 2025 co-authors for their participation.
Creating the paper every year is a massive amount of work. So we are very appreciative of their contribution of time and their considerable expertise. We also thank the antibody society and their sponsors for their support. In addition. We want to encourage you to join the antibody society if you're not already a member.
The society is a non-profit trade association. We do a lot of work in business intelligence, as you've just seen, and we do disseminate this information in various ways, including by webinars. We have searchable tables of antibodies to watch content on the antibody society's website, and we keep those up to date during the year. So we encourage you to go look at that for continued updates. We also provide pipeline data to our sponsors.
And speaking of those sponsors, I want to wrap up by mentioning that membership is free for people who work at sponsor companies. So I'll show the sponsor logos, which are in alphabetical order, very quickly. If you happen to see your company's logo here, please do feel free to go to the antibody society's website and register for your free membership.
And with that, I thank you very much for your kind attention. Brilliant well, thank you very much for that presentation, Janice and Sylvia. If you were at home watching, do you have any questions for our presenters. And please continue to submit them using the Q&A button at the side of your window, and we'll now start addressing some of your questions.
Just a quick technical one that was posed on whether or not this webinar will be available to watch on demand. Absolutely it will be roughly an hour after the webinar is concluded. You'll be able to watch the recording. So straight in then to questions for Sylvia and Janice. So how will AI driven antibody discovery shape the future of antibody development in 2025 and beyond.
Sylvia, you want to jump in on the discovery side. Yeah Hi. Well, I believe so. Now we hear more and more talking about AI driven antibody discovery. And I think we will continue to hear more and more because AI and machine learning approaches can be used for different steps in the discovery process. Early stage discovery process, but also making sure that then what has been discovered, it complies with the CMC.
And and I believe that we will hear more and more talking about these. And I can't I can't tell you what will happen, of course, but definitely we are going to watch this space and. Yes just a couple of other things is the. Older of the two of us the one thing so I so I'm the voice of caution here.
So absolutely I will have immediate effects. It's already of course on the discovery space. But again pointing out that whatever comes out of that discovery efforts and even through the preclinical, the true test of it will be what survives the clinical trials process. So I may give you better design. It may give you an antibody that you might not have thought of before.
But if it's not proven in traditional clinical studies to be safe and effective, then it's going to fail. So that's the it's really that the true test is always what does it do in human. Fantastic so probably following on from that, I mean relatively new tool of AI in this field. Do you think that growth in the field is sustainable. At the rate that it's going at the moment. I do.
And and really that's based not only well, it's based on several of the graphs that we showed. The first is continuing increase in the number of antibodies entering clinical studies, but also that they are making it through in larger numbers to the late stage clinical studies. And we see, of course, this infiltration of the technologies into other countries where they're being uptaken and loads more work is being done than even the past, say, five years or so.
We've been tracking the very tremendous activity going on in China for quite some time. It was not so impressive in the 2015 to 2019 range, but it's really taken off and I can see that there's tremendous potential there still for a lot more activity, but also potentially additional work being done in other countries. And that increases the number globally of antibodies that are in development and potentially then making it through to patients in due time.
Fantastic and so kind of following on about the growth and the success rates, how are these success rates actually calculated by the antibody society. So can I let me I have a slide so that you can see. So basically what we did. Yeah so what we did for our analysis is that we. For each molecule, we are assigned a status, a status.
There are nine possible status 1, 2, three marketing approval. So we read the antibody is regulatory review or approved. And then it could be terminated in phase one, phase two phase three and the regulatory review stage. So what we did is that we took the antibodies which entered clinical studies between 2000 and 2019. We have signs that each one a status.
And then we applied. And then we calculated the success rate this way. So we calculated the number of antibodies moved to the falling phase, divided by the sum of the number of antibodies which moved to the falling phase, plus those which have been terminated at that phase. And then we.
So we did this for each phase transition. So phase one to phase two. Phase two to phase three. Phase three marketing approval and marketing approval to approval. And then when we calculated the overall phase one to approval success rate, we simply did the mathematical product of the different phase transition rates as shown here in the slide.
I just want to remind you that so the way this success rate is calculated, basically we only consider the molecules for which we know the fate. So either transition to the falling phase or terminated. So we always also calculate together with success rate we calculate the completion in the cohort, which is calculated as the antibodies that have been approved plus those that have been terminated divided by the total number of antibodies in the cohort.
So antibodies for which we know the fate divided by the number of antibodies in that cohort. And these give us an idea of how reliable is the value that we are calculating. So one thing that I'll point out about that is that it was an antibodies to watch in 24. I believe we did a compare contrast with our approach and our results, with the reports that was put out by, and it uses a commercially available database.
But I would encourage you, if you're interested in this and how these calculations were done, I would encourage you to look at that paper. But in particular, one thing that we note is that the calculations by the other group were done differently. So it's very important when you're looking at success rates to understand how they were calculated. What do they actually represent.
Because you can do the calculations in various ways. You can construct your cohort in various ways. And if you just look at the final numbers, I think the number is like 5% It was very low, very low compared to ours. But we explain the difference in the calculations and why it would be lower. So it's not that theirs is wrong or and ours is right, it's that the calculations were done differently.
They tell you something different. So it's just important to understand that, especially for people who are using these success rate to, for example, justify their development programs. Fantastic and then just. Yeah following on from that question about the success rates, do you think that the rates are likely to change in the future.
Yes so the success rates I showed let me show let me find the slide. I showed how the success rate varied between antibodies with different formats. And I don't know whether you notice that the success rate of antibody drug conjugates doesn't really look so great in this graph.
But just to point out that this analysis has been done on antibodies that have entered clinical studies between 2000 and 2019. But now when you look at the trends in first in human study that I showed here, you see that there is an increasing number of antibody drug conjugate entering the clinic. And you think why. Why?
if the success rate is so great, why they keep entering the clinic. Because what we noticed is that the anti-body especially antibody drug conjugates. Have undergone. There's been a lot of research on antibody drug conjugates and they found a way to implement them. And reduce toxicity especially varying the type of payload.
What we noticed is that there's been an increase lately in antibody drug with the different types of payloads compared to first generation antibody drug conjugates. And we haven't shown it here, but our preliminary analysis, because the numbers are still very little, we see that the success rates of antibodies with that type of payload, which is topoisomerase one inhibitors, is much, much higher than the classic payloads like tubulin inhibitors and DNA binding payloads.
And so we do expect the success rate of ADCs to improve in time, because we do see an increased number, especially of these ADCs with the top inhibitor, which in our preliminary analysis is showing such a very nice success rate. And also I want to say something about the antibodies for radioimmunotherapy. So here I'm showing a success rate of 0. But as I explained before, this is only because we are considering antibodies entering the clinic between 2000 and 2019.
Now we do see antibody which are already conjugates. And in clinical studies we do see them is the pink bar. And what we've noticed is that again like for ADCs the payload has changed. So now the majority of conjugates entering the clinic have an isotope, which is an alpha emitter which apparently shows a lower tissue penetration.
And it seems that is causing less damage to the surrounding tissue. So it should cause less toxicity and more be able to target the tumor better. So the numbers are still very, very low. So we hope we might see a decrease in the success rate for these type of molecules as well. Fantastic and does the antibody society track the model or method that the proteins are made for instance mouse strains or dromedary type for example.
Yes, we definitely have that information for some. So bear in mind that the overall data set that we have exceeds 2900. And the origin of the molecules is not always revealed immediately. It can take quite some time to find that information in the public domain. So I would say of the antibodies in the late stage development through to approval.
We may have the majority of that information, but for antibodies that, well, certainly antibodies that are preclinical, forget about it. You probably do not know. Potentially, though, people do like to mention when they're so so maybe for those we have a comprehensive list and certainly ones in phase one, just the information is not available. So we're not able to do analysis that we have confidence in the origin, but we do have the information for at least some of the molecules.
Fantastic and sorry what are your data sources as well. Oh well we do have lots. We do not rely. In fact, I don't believe that there is a single source you could go to and just say, Oh, well, I'll just go and find all this information. It'll be so easy. And no, I've been collecting this kind of data for well over 10 years.
I feel like I'm a little like a little bird, a little magpie that goes around and collects up little shiny bits of information. And then I tuck them into my data set, and that's what we use for the analysis. But the data comes from all over the place. We do want to rely on sources that are reliable. And that would include the company first and foremost. What are they saying in their press releases.
What are they saying in their presentations. What are they presenting in abstracts at various meetings. So we would start with the company. And then of course, you also have other reliable sources such as the World Health Organization. When they're finally given an in. Then there's a lot of information embedded in the information the WHO puts out, of course, regulatory agencies for anything that may be in review, or certainly those that are approved.
Ema does put out very nicely a monthly list of what's undergoing regulatory review. So we do look at that every month. FDA is not quite so accommodating. They do not have a similar list. So we can't say with FDA. It's only if the company chooses to disclose the information that we would know. There are also some public databases that we like to use.
And that would include imgt as well as their sabdam, of course, also published literature. So anything that appears in papers, we would look at that also very definitely the clinical trials registries, but of course, not just clinicaltrials.gov. We're looking at registries that are in China where you look at the Australia New Zealand registry. We look at the Japan registry. So we're looking through all of that data cells.
We do not like to rely on a second or secondary source for key information that we really need to. We need to verify everything that we see we like to verify it with, with, like I said, a trusted source, such as the company, regulatory agencies or the clinical trials registries. And do you have data or an idea on how long the phase transition and approval have changed throughout the years.
Well, I mean, certainly it's easy to point out where things started to change. And that was with the immune checkpoint modulators. It was very common for clinical studies to take anywhere from 8 to 10 years. But the immune checkpoint modulators came through much faster. I mean, as quick as 4 or 4 and a half years for some of those molecules.
And then also as we get additional antibodies that target well validated antigens, I think there's a chance there to speed up the clinical studies, because you have data from previously approved molecules is something as a guide, you can't copy what was done before. It's not ever going to be exactly the same. These are not biosimilars. They are unique molecules.
But it does. The previous knowledge does help in the clinical trials process. Also, the additional experience gained by the regulatory agencies also help because of course, companies don't just go off and run their clinical studies without extensive consultation with the various regulatory authorities. So I think things have moved forward such that the clinical trials can take less time, certainly for the antibodies that are against well validated targets.
You may still be going at a somewhat slower pace than for antibodies against novel targets or with unique, truly unique mechanisms of action. And so you mentioned biosimilars there. Do you also study the rates of approval for biosimilars for those molecules. We do not. We do not. Biosimilars are specifically excluded from our analysis.
Not that we don't like them or think there's no value in them. Quite the opposite. There's a lot of value in them. And I still am super impressed by celltrion's approval of the first biosimilar. They always get a shout out from me for going that route and really doing what people did not think could be done before. It was astounding. Really, really amazing.
Good job. So of course that was some time ago. But in any event, the reason, of course, is because they do have that benefit of being the same as something that was approved before. So you do have an abundance of knowledge about how clinical studies were done before the expected results of the clinical studies. And so I do think that helps shorten the clinical trials process.
You can go immediately from a phase one to a phase three. You normally aren't doing that with an innovative molecule. And so there is a big difference there. And and so we exclude them to keep them separate from the innovative molecules. But there's so many innovative molecules, we don't really have the time to track the biosimilars. Somebody else is doing that though, so we don't have to. Fantastic And what is it that causes some of the biologics license applications to be delayed.
Sylvia, you looked at that comment. Let me let me again. We have a slide I can show you. So this was published in our paper. So basically what we did is that here in this graph we plotted the number of antibodies approved by the FDA and those in review.
And we stratified the molecules according to whether they were approved after one cycle or review or they are still in the first cycle of review or they have a complete response letter. And also we annotated whether the complete response vector was due to CMC issues or other. So as you can see here, we start to see first of all, an increase in the antibodies approved by having received a complete response letter since 2019.
We start to see them. And since 2022 we really see an increase. And also what we see is that the majority of these complete response letters seem to be due to manufacturing issues, and this is the same for the antibodies that are currently. Well, they were very relevant to review as of December 31, 2024 because now the situation has changed. It's just one month.
So you see half of the antibodies in review by the FDA have received a complete response letter, and the complete response letter can delay. So they issue a complete response letter when they have a concern about the marketing application. And this can delay the approval by six months or more. So Yeah, this is what is causing this delay. And so we, we, we really recommend the companies to make sure they manufacture inside comply with the, the FDA standards for manufacturing and CMC.
Fantastic well thank you very much, Janice and Sylvia for answering all of our audience questions. I'm afraid that's all we've got time for today, but if there are any others that we haven't managed to get around to, we'll address them offline. If you do have any other questions for Janice and Sylvia, please feel free to send them across to client projects at UK.
And I would now like to once again thank our wonderful presenters Janice and Sylvia, as well as you, our listeners for your time and questions. If you, you'll receive an email with how to watch this webinar on demand shortly. And don't forget to visit us at ww.com for more webinars. Thank you again for attending everyone and goodbye. Thank you. Thank you.
Bye bye.
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