Ep. 362 - AACR: Data and de-risking

WEBVTT

00:00:00.000 --> 00:00:02.769
[AI-generated transcript.]

00:00:02.769 --> 00:00:06.072
<v Voice Talent>BioCentury This Week is brought to you by IQVIA Biotech.

00:00:06.405 --> 00:00:09.476
<v Voice Talent>A full-service CRO right sized for biotech.

00:00:09.743 --> 00:00:18.150
<v Voice Talent>Dedicated to helping biotech leaders close unproductive gaps in clinical development so they can protect timelines, preserve capital and stay ahead of risk.

00:00:23.922 --> 00:00:28.728
<v Jeff Cranmer>Welcome to a special edition of the BioCentury This week podcast.

00:00:29.028 --> 00:00:32.899
<v Jeff Cranmer>With AACR here and ASCO on the horizon.

00:00:32.899 --> 00:00:40.707
<v Jeff Cranmer>We have the good fortune to be joined by the CMO of this month's BioCentury This Week podcast sponsor.

00:00:40.840 --> 00:00:47.213
<v Jeff Cranmer>He's Dr. James Kyle Bryan, he is the CMO of IQVIA biotech.

00:00:47.981 --> 00:00:56.655
<v Jeff Cranmer>Kyle also serves as global head of the IQVIA Hematology Oncology Center of Excellence.

00:00:57.156 --> 00:01:08.567
<v Jeff Cranmer>Now at IQVIA, Kyle's focused on drug discovery and development in the biopharma industry with an eye on helping his clients' de-risk their clinical programs.

00:01:08.902 --> 00:01:15.641
<v Jeff Cranmer>That, plus his oncology focus comes in handy for us as like some of our listeners out there.

00:01:16.009 --> 00:01:24.183
<v Jeff Cranmer>We are knee deep in the stream of readouts from the American Association for Cancer Research Meeting in San Diego.

00:01:24.384 --> 00:01:35.495
<v Jeff Cranmer>Joining me today are my BioCentury colleagues  Selina Koch my fellow Executive Editor and Lauren Martz, Executive Director of Biopharma Intelligence here at BioCentury.

00:01:36.728 --> 00:01:44.370
<v Jeff Cranmer>I am Jeff Cranmer, your host, and I'd like to bring Kyle right on in and, and say, Kyle, welcome to the program.

00:01:44.370 --> 00:01:45.737
<v Jeff Cranmer>It's great to have you on first time.

00:01:46.539 --> 00:01:47.239
<v James Kyle Bryan>Thank you.

00:01:47.239 --> 00:01:53.480
<v James Kyle Bryan>I appreciate the welcome and I appreciate the opportunity to talk with you guys and talk with your listeners.

00:01:53.712 --> 00:02:01.254
<v James Kyle Bryan>I find that I'm very much of a uh a little bit of a geek when it comes to biotech and biopharm and drug development.

00:02:01.287 --> 00:02:08.328
<v James Kyle Bryan>You know, my, my pedigree goes back to very small biotechs that got bigger and then got smaller.

00:02:08.760 --> 00:02:11.063
<v James Kyle Bryan>Worked in the CRO world for a while.

00:02:11.463 --> 00:02:15.367
<v James Kyle Bryan>I just find the whole experience is just endlessly fascinating.

00:02:15.901 --> 00:02:18.371
<v Jeff Cranmer>Well, welcome to the Geek Club Kyle.

00:02:18.371 --> 00:02:21.441
<v Jeff Cranmer>You are in very good company with my colleagues Lauren and Selina.

00:02:22.040 --> 00:02:34.554
<v Jeff Cranmer>We like to get deep into the weeds on topics such as AACR, and I'd like to caution our listeners not to be too fooled by Kyle's Louisiana accent.

00:02:34.987 --> 00:02:41.227
<v Jeff Cranmer>He's actually a doctor up in the PNW, where our production engineer Cole Travis hangs out.

00:02:41.227 --> 00:02:47.866
<v Jeff Cranmer>Now, Kyle, I know you've got a man on the ground at AACR down in sunny, hopefully sunny SoCal.

00:02:48.100 --> 00:02:51.871
<v Jeff Cranmer>and you've been uh riffing with him on topics of interest.

00:02:51.871 --> 00:02:56.209
<v Jeff Cranmer>I, I wonder what most immediately has caught your attention from what you're hearing.

00:02:57.242 --> 00:02:57.676
<v James Kyle Bryan>Thank you.

00:02:57.743 --> 00:03:06.853
<v James Kyle Bryan>Yeah, we do Have one of my colleagues from the Center of Excellence down in San Diego at AACR, and I'll just say he is definitely getting his steps in.

00:03:07.319 --> 00:03:13.825
<v James Kyle Bryan>He's visiting posters all over the place and tracking people down and listening to conversations.

00:03:14.092 --> 00:03:19.799
<v James Kyle Bryan>I talked with him a little bit last night and said, you know, Jeff, what's, what's at the top of your mind?

00:03:19.799 --> 00:03:24.270
<v James Kyle Bryan>What, what's your impression at the end of a long day when you're relaxing and.

00:03:24.503 --> 00:03:26.939
<v James Kyle Bryan>Thinking about a beer or something like that.

00:03:27.139 --> 00:03:39.384
<v James Kyle Bryan>And he was sharing with me that, you know both the targets and the, the agents that we're accustomed to seeing the immune checkpoint inhibitors, you know, that era of the checkpoint inhibitors is far from being over.

00:03:39.718 --> 00:03:47.794
<v James Kyle Bryan>There's tons of abstracts that are focused on both the familiar targets, you know, pembrolizumab and the PD-1s.

00:03:48.228 --> 00:04:02.609
<v James Kyle Bryan>But also some targets that we sort of in the past had maybe underperformed in some late phase studies, but are now resurrecting either in combinations or in niche indications, things like LAG3 and TIGIT.

00:04:03.042 --> 00:04:20.593
<v James Kyle Bryan>There's been a lot of talk about CTLA-4 kind of new generation CTLA-4 agents with maybe novel mechanisms or different ways of trying to attenuate that toxicity profile, that sort of dampened what we were able to do therapeutically with those guys.

00:04:20.959 --> 00:04:37.476
<v James Kyle Bryan>You know, novel linkers, novel payloads, novel strategies for getting our drugs where they need to be, releasing them at the right time, in the right concentration, and, and getting a really kind of a controlled payload release in the ADCs.

00:04:37.910 --> 00:04:44.449
<v James Kyle Bryan>Obviously bispecific antibodies and both single target and bispecific ADCs.

00:04:44.449 --> 00:04:49.622
<v James Kyle Bryan>And then the dual payload ADCs are very big and all over the place.

00:04:50.055 --> 00:04:51.524
<v Jeff Cranmer>Kyle, let me jump in here.

00:04:51.524 --> 00:04:55.728
<v Jeff Cranmer>I, we, we are gonna dig deep into the ADC dual payloads.

00:04:56.062 --> 00:05:02.201
<v Jeff Cranmer>Lauren just did a big piece on that for us in BioCentury, but I'm intrigued about what you're saying about TIGIT.

00:05:02.267 --> 00:05:06.105
<v Jeff Cranmer>I, I, I had kinda left that by the road side a little while ago, so I'm.

00:05:06.505 --> 00:05:08.307
<v Jeff Cranmer>I know Lauren's written a lot about this.

00:05:08.307 --> 00:05:15.882
<v Jeff Cranmer>Lauren uh I'm curious uh are you surprised to hear what Kyle's saying there about LAG3 uh TIGIT and the like?

00:05:16.882 --> 00:05:18.951
<v Lauren Martz>So uh I'm not surprised.

00:05:18.951 --> 00:05:26.625
<v Lauren Martz>And I think the thread that's underlying a lot of what you've picked out and what your colleague has picked out at AACR is, is antibody innovation.

00:05:26.625 --> 00:05:28.827
<v Lauren Martz>You know, the bispecifics and the ADCs.

00:05:28.827 --> 00:05:28.927
<v Lauren Martz>So.

00:05:29.329 --> 00:05:40.206
<v Lauren Martz>We're talking about giving new life to some targets like TIGIT that haven't necessarily seen a lot of clinical success, especially the, the high profile late stage failures that we've seen for TIGIT.

00:05:41.074 --> 00:05:59.858
<v Lauren Martz>I think that's where antibody innovation comes into play, and specifically for that target, I think there is, or at least a few abstracts and, and we've been seeing this ramp up over the years that are sort of dual checkpoint inhibitors, you know, bispecific antibodies, targeting maybe CTLA-4 and TIGIT.

00:06:00.192 --> 00:06:14.439
<v Lauren Martz>The idea there being that you could knock down two pathways, two pathways that are controlling the or restricting the anti-tumor immune response and, you know, potentially making that CTLA-4 side of the equation safer.

00:06:14.439 --> 00:06:19.478
<v Lauren Martz>So I think that's definitely something that we've seen cropping up and, and something that.

00:06:19.978 --> 00:06:24.983
<v Lauren Martz>We'll continue to see more of at meetings like this that are very focused on the innovative side of, the science.

00:06:26.185 --> 00:06:27.519
<v Selina Koch>On that safety side.

00:06:27.653 --> 00:06:31.391
<v Selina Koch>CTLA-4 I think is, you know, known for having some, some tox.

00:06:32.225 --> 00:06:34.160
<v Selina Koch>What's promising to make a difference there?

00:06:34.160 --> 00:06:37.096
<v Selina Koch>Is it masking pH sensitivity?

00:06:37.396 --> 00:06:39.165
<v Selina Koch>Either of you have thoughts on that.

00:06:39.699 --> 00:06:41.834
<v Lauren Martz>I think all of the above.

00:06:41.867 --> 00:06:45.637
<v Lauren Martz>we're seeing some masking technologies to improve safety.

00:06:45.637 --> 00:06:56.581
<v Lauren Martz>And there's also Fc engineering, Fc tuning to, to try to control the ADCC and enhance the Treg depletion.

00:06:56.581 --> 00:07:02.454
<v Lauren Martz>So I think there are several different strategies in development to improve the safety of the CTLA-4 mabs.

00:07:02.954 --> 00:07:11.062
<v James Kyle Bryan>You know, speaking of, of safety, the, the other thing that is showing up are other modifications to make our ADC safer.

00:07:11.363 --> 00:07:20.939
<v James Kyle Bryan>novel linkers trying to look at how to do the structure so that you get better stability of the ADC, you get a more controlled payload release.

00:07:21.307 --> 00:07:29.449
<v James Kyle Bryan>I think the tandem-cleave linkers are a really interesting part there, where you've got, it takes two steps to release the payload.

00:07:29.449 --> 00:07:42.427
<v James Kyle Bryan>So you need a, a cleaving that takes place at the tumor with the internalization, but this extra stabilization as the drug is circulating it really, I, think the greatest benefit there.

00:07:43.062 --> 00:07:44.262
<v James Kyle Bryan>I, I won't say greatest.

00:07:44.430 --> 00:07:49.000
<v James Kyle Bryan>You're, you're letting me get too excited there, but a solid benefit there.

00:07:49.367 --> 00:08:00.045
<v James Kyle Bryan>You have to remember, I'm a hematologist and oncologist, so blood always gets me in a positive mindset, but it's reducing the hematologic toxicity because it's not.

00:08:00.278 --> 00:08:11.389
<v James Kyle Bryan>having that risk of payload loss in the wrong place, the payload uncoupling is happening where it should be, and that gets you a better therapeutic index and improves your overall window.

00:08:12.391 --> 00:08:19.665
<v Selina Koch>What controls the two phases of the cleavage, is there like a kind of a finite number of different ways that's accomplished?

00:08:20.800 --> 00:08:27.507
<v James Kyle Bryan>I hesitate to say finite just because I feel like  you know, the only thing we're limited by is our imagination.

00:08:27.939 --> 00:08:48.793
<v James Kyle Bryan>But some of the same techniques that are being used in masking where they take advantage of the fact that you know, there are differing enzyme levels at the tumor microenvironment compared to what you're experiencing in the circulation and utilizing that as that initial cleave taking place when you're entering in the tumor microenvironment.

00:08:49.128 --> 00:08:57.503
<v James Kyle Bryan>And then whether it's the target or the payload being freed up, then to go through that second cleaving after it gets internalized.

00:08:58.504 --> 00:09:10.316
<v Selina Koch>I mean, ADCs are so interesting and their complexity, you know, the modularity of it you can do all kinds of uh antibody engineering as Lauren was talking about, on the antibody end multiple specificities, whatever.

00:09:10.750 --> 00:09:14.653
<v Selina Koch>Then there's the linker, which sounds like those are getting more complex as well.

00:09:14.653 --> 00:09:16.688
<v Selina Koch>And then there's the payload.

00:09:16.688 --> 00:09:20.960
<v Selina Koch>There's a, like any number of cytotoxins, but there's radioisotopes on and on.

00:09:21.326 --> 00:09:23.863
<v Selina Koch>Now there's also this dual payload approach, right.

00:09:24.096 --> 00:09:29.568
<v Selina Koch>Maybe we should talk a little bit about the increase in abstracts this year and what we're seeing for, for dual payloads at AACR.

00:09:30.503 --> 00:09:31.971
<v Jeff Cranmer>Yeah, that's a, that's a good call there.

00:09:31.971 --> 00:09:33.272
<v Jeff Cranmer>Lauren just wrote about that.

00:09:33.272 --> 00:09:34.472
<v Jeff Cranmer>Lauren, why don't you jump in here?

00:09:35.106 --> 00:09:35.374
<v Lauren Martz>Sure.

00:09:35.374 --> 00:09:36.042
<v Lauren Martz>Thanks Jeff.

00:09:36.042 --> 00:09:42.315
<v Lauren Martz>So  the dual payload ADCs is one thing that we've picked out as a trend in the abstracts from this year.

00:09:42.581 --> 00:09:49.822
<v Lauren Martz>There were, I think, more than 40 abstracts that discussed this idea which is something that we've heard a bit about.

00:09:49.822 --> 00:09:53.125
<v Lauren Martz>But again, really taking off in this crop of abstract.

00:09:53.859 --> 00:10:04.070
<v Lauren Martz>These were broken down by uh or we broke these down by dual payload ADCs that are delivering two cytotoxic chemotherapy payloads.

00:10:04.636 --> 00:10:11.777
<v Lauren Martz>and some that are delivering, you know, one of the standard cytotoxics plus a targeted therapy or something else like a degrader.

00:10:12.110 --> 00:10:21.988
<v Lauren Martz>I think both of those were, were really interesting approaches because the two cytotoxic chemotherapies, a lot of times it's combining the standard therapies that ADCs deliver.

00:10:22.221 --> 00:10:30.028
<v Lauren Martz>And the idea is that you could overcome resistance that that ultimately develops with most of the ADC treatment, even though these are really potent therapies.

00:10:30.663 --> 00:10:37.035
<v Lauren Martz>It's still a chemotherapy and tumors can still sort of evolve resistance to, to get around them.

00:10:37.436 --> 00:10:50.282
<v Lauren Martz>And then I thought the chemo targeted therapy combinations were really interesting because, it just offers one more way to, first of all to combine two things and, and avoid resistance, but also to localize.

00:10:50.682 --> 00:10:52.518
<v Lauren Martz>The effects of the targeted therapy.

00:10:52.784 --> 00:11:00.993
<v Lauren Martz>In the news last week, we saw the Re volution Medicine data for their pan-RAS inhibitor, that was just phenomenal data.

00:11:00.993 --> 00:11:02.727
<v Lauren Martz>But we do know that there are some side effects.

00:11:02.727 --> 00:11:16.708
<v Lauren Martz>So, you know, one of the abstracts that we saw in this crop this year um from Affinity Biopharma, delivers a pan-RAS inhibitor and you think, well, maybe this is a way to sort of better localize that pan-RAS e ffect and, and avoid some of the side effects We don't know yet.

00:11:16.741 --> 00:11:20.046
<v Lauren Martz>This is all preclinical but just a really interesting crop of abstracts.

00:11:20.846 --> 00:11:21.147
<v James Kyle Bryan>Yeah.

00:11:21.413 --> 00:11:22.648
<v James Kyle Bryan>those are really good points.

00:11:22.648 --> 00:11:27.952
<v James Kyle Bryan>I mean, one of the things I think that's really interesting about the dual payload ADCs is.

00:11:28.421 --> 00:11:36.128
<v James Kyle Bryan>Sort of the steps that you have to take through in the development as you look at this, because again, the, the concept is really strong.

00:11:36.128 --> 00:11:53.211
<v James Kyle Bryan>I love the concept behind, for example, if you're using a DNA damaging agent along with a DNA repair inhibitor and that gets to the whole idea that the reason the ADC fails or the treatment fails is payload resistance.

00:11:53.211 --> 00:12:01.854
<v James Kyle Bryan>It isn't actually loss of target, which all of us that have worked in the antibody world are always, you know, what happens to the expression of my target over time?

00:12:01.854 --> 00:12:02.922
<v James Kyle Bryan>Is that changing?

00:12:03.188 --> 00:12:06.225
<v James Kyle Bryan>Is this why my agent isn't becoming as effective?

00:12:06.625 --> 00:12:16.434
<v James Kyle Bryan>But when you're looking at two payloads, you, you've got to think about the individual toxicities of the agents and the risk of overlapping toxicity of the agents.

00:12:16.836 --> 00:12:30.883
<v James Kyle Bryan>But then the, the extra wrinkle is, well, what if there's a new synergistic toxicity that I don't see with A, and I don't see with B, but when I put A and B together, I now get C, which I wasn't expecting.

00:12:31.317 --> 00:12:44.830
<v James Kyle Bryan>So as I work through, you know, the dose escalation and the dose finding and dose optimization aspect of it, it just becomes one of those things where we need to keep our eyes wide open looking for those safety signals.

00:12:45.965 --> 00:12:52.804
<v Lauren Martz>that brings up another point that I heard in the reporting for this story, which is, yes, the combinations we have to assess the safety.

00:12:52.804 --> 00:13:02.114
<v Lauren Martz>But even once you figure out the right combinations and the right doses, actually creating an ADC that is able to deliver the right ratio of these payloads is really challenging.

00:13:02.114 --> 00:13:10.655
<v Lauren Martz>You know,  depending on which type of linker you use, whether both payloads are on the same linker, you know, it, it's a, it's a heavy lift and, and a really interesting challenge.

00:13:11.557 --> 00:13:12.158
<v Selina Koch>more of these?

00:13:12.158 --> 00:13:12.490
<v Selina Koch>Um.

00:13:12.725 --> 00:13:18.730
<v Selina Koch>Abstracts that you're seeing at AACR have branched linkers or do they connecting them up separately,

00:13:19.565 --> 00:13:21.734
<v Lauren Martz>That ha that's not disclosed in all of these.

00:13:21.801 --> 00:13:22.500
<v Selina Koch>Often not disclosed?

00:13:22.967 --> 00:13:23.001
<v Selina Koch>Yeah.

00:13:23.501 --> 00:13:26.772
<v Lauren Martz>I hear that a lot of them are separate linkers, but I can't confirm that.

00:13:27.139 --> 00:13:27.572
<v Selina Koch>Yeah.

00:13:28.307 --> 00:13:39.684
<v James Kyle Bryan>Yeah, there's not a lot  that they've talked about yet, about for example, the DAR on these agents and, you know, what's the DAR of this payload and what's the DAR of that one?

00:13:39.684 --> 00:13:41.320
<v James Kyle Bryan>It is one impacting the other.

00:13:41.320 --> 00:13:43.556
<v James Kyle Bryan>So there's a lot for us still to learn.

00:13:43.556 --> 00:13:45.924
<v James Kyle Bryan>And again, the, the engineers are kept very busy.

00:13:47.125 --> 00:13:53.932
<v Selina Koch>I think the segue is really nice into a, a topic that I know is um on your mind lately de-risking.

00:13:53.932 --> 00:14:01.774
<v Selina Koch>So we have like like I was saying, this complex modular modality where all, you can tweak any piece of it in lots of different ways.

00:14:01.774 --> 00:14:05.811
<v Selina Koch>Like yeah, the human imagination can do almost anything there, right.

00:14:05.811 --> 00:14:08.980
<v Selina Koch>The combinations are staggering, the possibilities.

00:14:09.280 --> 00:14:12.717
<v Selina Koch>Um, but how do you think about smart de-risking?

00:14:13.719 --> 00:14:26.030
<v James Kyle Bryan>The way I tend to think about it is, is like this, I think when it comes to drug development, and particularly my, my pedigree is in the biotech world and sometimes in the very small biotech world.

00:14:26.264 --> 00:14:42.648
<v James Kyle Bryan>Where when it comes to evaluating a an agent or an antibody or a compound or any investigational product, you have to be a little bit careful of being more paternal than professional in your evaluation of it.

00:14:42.847 --> 00:14:47.219
<v James Kyle Bryan>You do get this feeling it's your baby, but, just recognizing that, you know.

00:14:47.986 --> 00:15:02.100
<v James Kyle Bryan>It may be a, a smarter thing to think of it like um when you're making breakfast, you know how the first pancake never turns out all that great and you may need to toss that one away and, and focus on the rest of the batch, that's kind of the thing.

00:15:02.100 --> 00:15:09.642
<v James Kyle Bryan>So I would say that one of the bits of advice that we give our biotech clients is, again, look at it professionally.

00:15:09.841 --> 00:15:16.649
<v James Kyle Bryan>Consider like a stage gate analysis where you're really looking at, at every step in this development.

00:15:17.349 --> 00:15:24.355
<v James Kyle Bryan>And setting parameters for what you're going to do if you see this, or what you're going to do if you see that.

00:15:24.722 --> 00:15:30.361
<v James Kyle Bryan>As opposed to well, let me see what happens, and then I'll think about what my decisions want to be.

00:15:30.796 --> 00:15:34.166
<v James Kyle Bryan>Because you, you've gotta be looking at is the science credible?

00:15:34.166 --> 00:15:39.038
<v James Kyle Bryan>So what's the science and the tech readiness of this is one point.

00:15:39.337 --> 00:15:41.039
<v James Kyle Bryan>Is the risk acceptable?

00:15:41.240 --> 00:15:46.278
<v James Kyle Bryan>Company wide, the risk to a patient, the risk benefit aspect of it.

00:15:46.611 --> 00:15:54.787
<v James Kyle Bryan>And to do a, a real risk assessment that you're then going to apply to your decision making at each stage as you go along here.

00:15:54.986 --> 00:15:56.154
<v James Kyle Bryan>What's the investment?

00:15:56.154 --> 00:15:59.424
<v James Kyle Bryan>Is the value there, do the economics work for me?

00:15:59.991 --> 00:16:06.865
<v James Kyle Bryan>And then finally, you, you can't forget, is this a strategic fit for my company, for my group that are developing it?

00:16:07.499 --> 00:16:28.620
<v James Kyle Bryan>You may see something really interesting that can carry a, an exciting new direction, but if the strengths of your team aren't in that kind of development, then you're either gonna need to bring in new team members, or you're gonna need to think about, well, maybe this is something that I hand over to someone else to develop at this point.

00:16:28.620 --> 00:16:32.890
<v James Kyle Bryan>Or I look for a different kind of partner, a different kind of engagement.

00:16:33.292 --> 00:16:35.126
<v James Kyle Bryan>To take it to the next phase.

00:16:35.594 --> 00:17:02.620
<v James Kyle Bryan>I think that too often, especially in our, smaller biotechs, that you can get in a more of a state that where your, your overview of the program, it looks more like a project review or an operational review where you're tracking progress as opposed to having a real decision driving mindset at these strategic discussions of shall we continue or not continue.

00:17:02.821 --> 00:17:05.590
<v James Kyle Bryan>As opposed to making the little tweaks around the edge.

00:17:06.025 --> 00:17:12.631
<v James Kyle Bryan>So that, I guess would be my, my broad approach to how you de-risk and think about this.

00:17:12.964 --> 00:17:18.237
<v James Kyle Bryan>Ultimately, you know, we, we want people to focus on trying to eliminate the white space.

00:17:18.237 --> 00:17:33.085
<v James Kyle Bryan>A lot of the unproductive part of drug development comes from not the time to get to a milestone, but getting to a milestone and then the delay in coming to a decision or deciding what you're gonna do with the information that you've received.

00:17:33.551 --> 00:17:58.911
<v James Kyle Bryan>And I think that again, it's a place where it's important to look at your team, look at your advisory persons, whether it's your board or your scientific advisory board, and kind of build in that sort of upfront planning smart decisions about your protocol to keep it in scope with what you can accomplish and really use the data and, and kind of cross-functional alignment to get to a good decision point.

00:17:59.711 --> 00:18:02.047
<v Jeff Cranmer>Some good practical advice there from Kyle.

00:18:02.047 --> 00:18:06.884
<v Jeff Cranmer>We're gonna take a quick break and then we're gonna come back and look ahead to ASCO.

00:18:07.185 --> 00:18:12.458
<v Voice Talent>BioCentury This Week is brought to you by the 26th Bio€quity Europe in Prague, Czech Republic.

00:18:14.292 --> 00:18:19.364
<v Voice Talent>Innovators everywhere are seeing speed as the driver of investment, partnering in success.

00:18:19.798 --> 00:18:20.898
<v Voice Talent>Speed to the clinic.

00:18:21.365 --> 00:18:22.934
<v Voice Talent>Speed to early human data.

00:18:23.469 --> 00:18:25.269
<v Voice Talent>Speed to de-risk assets.

00:18:25.804 --> 00:18:35.047
<v Voice Talent>The question for European biotechs is clear: How do you compete in this arena facing new momentum from Asia, and an unpredictable landscape in the U.S.?

00:18:35.580 --> 00:18:36.848
<v Voice Talent>The science in Europe is there.

00:18:37.449 --> 00:18:39.518
<v Voice Talent>There are more experienced operators.

00:18:40.419 --> 00:18:42.287
<v Voice Talent>An investor sentiment, finally, is turning.

00:18:43.087 --> 00:18:44.655
<v Voice Talent>What's needed now is speed.

00:18:45.324 --> 00:18:59.738
<v Voice Talent>In its 26th edition, Bio€quity Europe travels to central and Eastern Europe for the first time — to explore emerging opportunities in the region and debate how European biotech can accelerate to compete — and lead — in today's world.

00:19:00.271 --> 00:19:05.877
<v Voice Talent>Join us in Prague, May 4 to 6 for this destination event for investors and biopharma leaders.

00:19:06.444 --> 00:19:10.348
<v Voice Talent>Register at BioEquityEurope.com Bio€quity Europe.

00:19:11.083 --> 00:19:12.683
<v Voice Talent>Where Europe accelerates to compete.

00:19:14.786 --> 00:19:15.354
<v Jeff Cranmer>Okay.

00:19:15.354 --> 00:19:20.259
<v Jeff Cranmer>We are back on the BioCentury This Week podcast, it's a Special Edition.

00:19:20.858 --> 00:19:30.169
<v Jeff Cranmer>And we are joined by Dr. James Kyle Bryan, who is the CMO of our sponsor, IQVIA Biotech.

00:19:30.501 --> 00:19:40.979
<v Jeff Cranmer>we're gonna get Kyle's thoughts in a moment on how he's getting ready or thinking about ASCO which is, you know, it's next month, so it's not too far away.

00:19:40.979 --> 00:19:49.688
<v Jeff Cranmer>You know, AACR just runs into ASCO, though you do get that little uh digestive disease week apéritif in between.

00:19:49.954 --> 00:19:56.627
<v Jeff Cranmer>Lauren uh before we get there, do you want to um just give us a few takeaways just wrapping up the ADC thoughts.

00:19:57.195 --> 00:19:57.528
<v Lauren Martz>Sure.

00:19:57.528 --> 00:19:57.863
<v Lauren Martz>Yeah.

00:19:57.863 --> 00:20:10.342
<v Lauren Martz>Just to, to wrap up what we talked about, we've, we've gone through the, the dual payload ADCs is, actually the bispecific dual payload ADCs are sort of the tip of innovation right now at AACR.

00:20:10.342 --> 00:20:14.579
<v Lauren Martz>Uh we found 44 abstracts that cover dual payload ADCs.

00:20:14.579 --> 00:20:16.114
<v Lauren Martz>A lot of them are bispecifics.

00:20:16.615 --> 00:20:23.221
<v Lauren Martz>and just looking more broadly, because Kyle has a focus on antibody innovation in his past.

00:20:23.387 --> 00:20:25.324
<v Lauren Martz>There's a lot more in those abstracts.

00:20:25.324 --> 00:20:37.435
<v Lauren Martz>There are trispecific specific ADCs and masked biologics and, and all kinds of really interesting ways to innovate and take different approaches to risk as Kyle has talked about.

00:20:37.435 --> 00:20:39.503
<v Lauren Martz>You know, with, with these dual payload ADCs.

00:20:40.172 --> 00:20:45.243
<v Lauren Martz>It's a lot of the same targets that we've seen for the approved ADCs when you're talking about the tumor antigen.

00:20:45.576 --> 00:20:48.779
<v Lauren Martz>It's a lot of the same payloads, but just combinations of payloads.

00:20:48.779 --> 00:20:58.056
<v Lauren Martz>So you can see companies and institutions, although most of these are from companies thinking about where they're going to apply that risk um which is it really the technology.

00:20:58.522 --> 00:21:02.661
<v Selina Koch>um, is anyone going out on a limb there and kind of stacking up a little bit of risk?

00:21:02.693 --> 00:21:06.064
<v Selina Koch>Say putting a new target on with a dual payload or...

00:21:06.731 --> 00:21:08.767
<v Lauren Martz>That's a great question.

00:21:09.268 --> 00:21:12.471
<v Lauren Martz>There, there are quite a few new targets and by new.

00:21:13.404 --> 00:21:21.346
<v Lauren Martz>Not new to us as people who are looking at the innovative edge of everything, but new as in no ADCs approved against this target.

00:21:21.613 --> 00:21:29.554
<v Lauren Martz>Certainly a lot of new tumor antigens that are in the list, really a lot of the same cytotoxic payloads that we've seen, but there is some innovation.

00:21:29.887 --> 00:21:36.994
<v Lauren Martz>For example, a company called Baylink has a dual payload ADC targeting GPC3.

00:21:37.296 --> 00:21:39.330
<v Lauren Martz>And one of the payloads is a protein degrader.

00:21:39.498 --> 00:21:43.701
<v Lauren Martz>So lots of risk in that one, but huge potential reward, I guess, if it works well.

00:21:44.303 --> 00:21:48.140
<v Jeff Cranmer>And you can check out Lauren's article on BioCentury.com.

00:21:48.839 --> 00:21:50.675
<v Jeff Cranmer>I'll drop a link in the show notes.

00:21:50.976 --> 00:21:52.376
<v Jeff Cranmer>Wanna bring Kyle back in here.

00:21:52.376 --> 00:21:56.882
<v Jeff Cranmer>Kyle uh how are you thinking about ASCO from where you sit at this time of year?

00:21:57.648 --> 00:22:02.453
<v James Kyle Bryan>Well, you can't really be at AACR without thinking about ASCO.

00:22:02.887 --> 00:22:12.096
<v James Kyle Bryan>In my mind, the way I think about is that AACR is, has always been about the strategic direction of cancer research, where are we going strategically?

00:22:12.564 --> 00:22:17.269
<v James Kyle Bryan>ASCO has traditionally been about clinical practice.

00:22:17.435 --> 00:22:19.837
<v James Kyle Bryan>What are we doing directly for patients?

00:22:19.837 --> 00:22:22.874
<v James Kyle Bryan>You know, is this going to change clinical practice?

00:22:23.075 --> 00:22:35.220
<v James Kyle Bryan>Not that we don't see preclinical data at ASCO because we do, but that sort of what I call the pull through the AACR to ASCO pull through and what likely to happen.

00:22:35.586 --> 00:22:47.365
<v James Kyle Bryan>So I, I really think for this year's ASCO, we're gonna see more about the dual payload ADCs some of the early clinical proofs or at least early discussion on this.

00:22:47.699 --> 00:22:55.740
<v James Kyle Bryan>I think again, this narrative of where the ADC resistance originates that narrative, I think is gonna be picked up.

00:22:55.740 --> 00:22:59.544
<v James Kyle Bryan>And we may see some additional interesting discussion around that.

00:23:00.077 --> 00:23:04.182
<v James Kyle Bryan>Ultimately, you know, we're, we need to see the Phase I expansion data.

00:23:04.548 --> 00:23:11.556
<v James Kyle Bryan>And it's possible we'll have some of that more likely, we're talking about pull through for 2027 ASCO.

00:23:11.722 --> 00:23:14.893
<v James Kyle Bryan>But it's a, just a, a really interesting period there.

00:23:15.192 --> 00:23:24.135
<v James Kyle Bryan>I think looking at other combinations whether it's with checkpoint inhibitors or whether it's with chemotherapy, I think those are gonna be there.

00:23:24.435 --> 00:23:32.943
<v James Kyle Bryan>You know, there's a couple of things that we didn't really even touch on today, that will probably be featured when we're looking at the data at ASCO.

00:23:33.111 --> 00:23:44.722
<v James Kyle Bryan>We didn't even get a chance to talk about the mRNA cancer vaccines or talking about maybe the AI derived biomarkers and what's happening in that space.

00:23:44.955 --> 00:23:58.036
<v James Kyle Bryan>We'll have an exciting ASCO, the amount of data there is way more than you can consume in four or five days, so that's why we all end up reviewing the abstracts and watching the virtual meeting for months to come.

00:23:58.403 --> 00:24:03.442
<v James Kyle Bryan>But  it's really been an exciting AACR so far, and it's not over yet.

00:24:04.241 --> 00:24:05.176
<v Jeff Cranmer>Excellent, Kyle.

00:24:05.176 --> 00:24:07.077
<v Jeff Cranmer>Well, thank you for sharing your thoughts.

00:24:07.311 --> 00:24:12.750
<v Jeff Cranmer>would love to reconnect with you after ASCO just to see what the big takeaways were for you uh there.

00:24:12.951 --> 00:24:20.592
<v Jeff Cranmer>And,   Always grateful to IQVIA Biotech for sponsoring the BioCentury This Week podcast.

00:24:20.925 --> 00:24:26.964
<v Jeff Cranmer>Kyle and Lauren and Selina's, thanks so much for sharing your thoughts on AACR and Kyle.

00:24:27.132 --> 00:24:29.567
<v Jeff Cranmer>Looking ahead for us to ASCO.

00:24:30.268 --> 00:24:31.702
<v James Kyle Bryan>it was wonderful, Jeff.

00:24:31.702 --> 00:24:37.541
<v James Kyle Bryan>I really enjoyed talking with you and with Selina and Lauren, I'll look forward to connecting with you again soon.

00:24:38.143 --> 00:24:50.821
<v Jeff Cranmer>Okay, you've been listening to the BioCentury This Week Podcast Special Edition here with Dr.

00:24:42.380 --> 00:24:50.821
<v Jeff Cranmer>James Kyle Bryan, CMO of IQVIA Biotech.

00:24:52.356 --> 00:24:57.828
<v Voice Talent>BioCentury would like to thank IQVIA Biotech for supporting the BioCentury This Week podcast.

00:24:58.296 --> 00:25:05.170
<v Voice Talent>To learn more about how IQVIA Biotech’s dedicated teams deliver support from innovation to impact, visit IQVIABiotech.com