Ep. 368 - ASCO Preview, China Policy, ADC Linkers

At ASCO among presentations focused on pancreatic cancer innovation beyond KRAS; however, abstracts for the cancer conference also highlight ADCs, bispecifics and diagnostics that are broadening the field’s approach to the cancer. On the latest BioCentury This Week podcast, BioCentury’s analysts discuss Revolution’s daraxonrasib, other readouts to watch for in pancreatic cancer and what else is on BioCentury’s radar at this year’s American Society of Clinical Oncology meeting.

BioCentury’s analysts also discuss a push by China hawks in Congress to get the Trump administration to invoke national security powers to narrow Chinese life sciences companies’ access to U.S. markets, technology and capital; an initiative by Rep. Jake Auchincloss (D-Mass.) that seeks to modernize how clinical trials are conducted in the U.S.; and a BioCentury analysis on new antibody-drug conjugate linker techniques. This episode of the BioCentury podcast is brought to you by Jeito Capital.

View full story: https://www.biocentury.com/article/659581 

#Biopharma #ASCO2026 #PancreaticCancer #ClinicalTrials #ADCInnovation

00:01 - Sponsor Message: Jeito Capital
02:26 - ASCO Preview
14:24 - U.S. China Policy
22:48 - Modernizing U.S. trials
27:17 - Optimizing ADC Linkers

To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.

Transcript

0:00

[Autogenerated Transcript]

Voice Talent: 0:02

BioCentury This Week is brought to you by Jeito Capital, a leading global independent private equity fund with a patient-benefit driven approach, aimed at financing, and accelerating the development of ground-breaking medical innovation. Jeito’s unique investment strategy combines significant capital and collective expertise to support biopharma companies and their management teams-ranging from clinical development to market access for cutting-edge innovations—with one main objective: go faster for the patient. Learn more at jeito.life

Jeff: 0:41

Welcome to the latest BioCentury This Week podcast, where we focus on all things biopharma. This week is ASCO Week, the grand mama of cancer conferences. And this year, we are focusing on pancreatic cancer innovation beyond KRAS, among quite a few other things, but that's what we're gonna talk about today. And we'll also check in with Washington editor Steve Usdin on how the Trump administration is considering restrictions on China deals. And Steve will also give us the word on how Representative Auchincloss is developing a clinical trials package to enhance US competitiveness and why he is currently seeking input from stakeholders. Plus, much of the next wave of ADC innovation is focused on linker and conjugation technologies, with site-specific conjugation a major focus. We'll take a closer look with Dr. Tierney Baum., Joining me on today's podcast are my colleagues

Simone: 1:59

Simone Fishburn, editor-in-chief

Lauren: 2:01

Lauren Martz, executive director of Biopharm Intelligence

. Steve: 2:05

Steve Usdin, Washington editor

Tiereny: 2:07

Tierney Baum, Biopharma Analyst

Jeff: 2:10

All right. Welcome to the show, guys., ASCO week, always a busy week, and right after ASCO is BioCentury Grand Rounds. That'll be in Seattle. We still have room for more delegates. If you are in the Seattle area, why not come over and check us out? Vancouver's just a quick trip down the 99 to the 5. It'll put you right at the intersection of academia venture capital in early-stage biotech. Simone, what are you looking forward to most next week?

Simone: 2:44

Oh, look at you being all local with your knowing the road names, Jeff.

Jeff: 2:49

I put in my time, I have to say, in Vancouver four years, which came in very handy when I went back to my college reunion in New Jersey last weekend and all it did was pour.

Simone: 3:02

And there it is. We thought that only people from Harvard talked about where they're from, but here we go.

Jeff: 3:07

you go.

Simone: 3:08

So

Jeff: 3:09

Well, we from the College of New Jersey are made of tougher stuff

Simone: 3:13

so for those of you not aware, Jeff's talking about Princeton, but right now I wanna hop over to the other side of the Atlantic, go back to the Grand Rounds, meeting, which is really shaping up to be a good one. We do have a few spots left for attendees., I think you can also walk in, like you do some walk-ins, but it's better if you register ahead of time. And if you want reasons to go other than to meet Tierney and myself and Selina and Karen or KTT -- as we call her, and Lindsey Martin, the people you hear on the podcast, we are upstaged by not one, but two Nobel Prize winners, David Baker giving the keynote talk, and Mary Brunkow, a local as well, recent Nobel Prize winner, who is gonna be heading up our Horizon session. And I'm really excited also, I'm gonna do a fireside chat with Chris Arendt, who is the CSO at Takeda, and we are going to be talking about how pharma is taking on AI. Is it like two steps forward and one step back, or the other way around? And then one other panel I just wanna talk about, 'cause this is such a big topic for us this year that I'm excited to moderate, is on first-in-human trials and sort of what needs to happen to break, um, I don't know if I should call it break the logjam. And I think Steve's gonna talk a little bit about regulatory changes being advanced by Jake Auchincloss today So I've got a, a great lineup of panelists where we'll be talking about that, uh, super hot topic. So yeah, come on and join us

Jeff: 4:50

Excellent. Yep. Uh, you can learn more at BioCenturygrandrounds.com. Kicks off June 3rd. That is, uh, not this Wednesday, but next., We hope to see you there. Okay, ASCO, always gets the blood pumping., We're thinking pancreatic. Revolution had those great data that, that caught a lot of folks' attention recently. Uh, Lauren has been following that,, along with many, many other things. Lauren, where do you want to start?

Lauren: 5:20

Thanks, Jeff. Um, yeah, so I think the reason that some of the focus this year is on pancreatic cancer is, of course, the, uh, anticipated Revolution Medicine full data from the Phase III trial. So we already know this was a successful trial., There's a survival advantage in, in the second-line setting that, hasn't really been seen before, at least for a long time. Um, and because of that, I think there's just a lot of positive energy around this indication that's been so challenging to treat. So, um, after the abstracts came out last week, there weren't a ton of big stock moves on, um, from biotechs on the data that came out in the abstracts. But one company that did move throughout the day on Friday after, uh, releasing its, you know, initial data in the abstract was Immuneering, which has a MEK inhibitor, uh, that tested in Phase IIb as a first-line therapy for pancreatic cancer, and, it did show a survival advantage in that indication. Again, this is first line. It wasn't quite as, um, eye-catching as, as what we saw on second line with the Revolution Medicines' KRAS program. But there was, there was a bit of excitement around that, that, trial, and we'll have additional data at the conference when the, the company presents that for more patients. and so we just looked through the abstracts for other pancreatic cancer, innovations and updates, and I was encouraged by what I saw. I think one trend that stood out was antibody drug conjugates that were being applied to this indication. There are none for this, uh, of this modality approved to treat pancreatic cancer, and there was some clinical data for a small group, all against different targets, which I thought was interesting. and, lots of responses of, uh, objective response rates between twenty and thirty-seven percent, I think, across, uh, six programs that we saw. So, that was just a subset of the, the pancreatic cancer innovations I think will be highlighted this week.

Simone: 7:25

So, Lauren, this really has been a theme. I mean, looking back to our AACR coverage, that also was very much highlighting KRAS, I think. and in pancreatic cancer, obviously we've seen like the broader press really pick up on this advance So, you know, is this just pancreatic cancer sort of time? It just took until now for this to happen. Um, have there been sort of signs along the way? Just this has been one of the hardest cancers really to crack, and it just seems that there's bad news for patients, and there has been for a long time.

Lauren: 8:05

Well, I think this is potentially a breakthrough that everyone has been waiting for, and this all started back with the KRAS, the KRAS G12C breakthrough, where, we figure out how to drug that specific mutation, which is more common in non-small cell lung cancer. But that definitely triggered this just big surge in interest in being able to drug KRAS, and KRAS G12D is the one that's more common in pancreatic cancer. But, this Revolution Medicines program is a pan-KRAS inhibitor. And so I think to, to have a breakthrough in drugging a disease driver in a, in a cancer subtype that's really challenging, it's getting a lot of attention because it's just potentially huge for patients. Now, there are some things everyone's watching for. We're watching for what the toxicity will actually look like in the Phase II trial because when you're blocking all of the, um, KRAS mutations, there's the potential for, um, some relatively serious toxins. So you're sort of starting to see innovations break off from that, ways to minimize the toxicity, um, for a mechanism that we already know is effective, so different ways to restrict activity of the, um, pan-KRAS inhibitors, for example. And I think it's just anytime we see this over and over again, anytime you see success in an indication, you see more innovation in that indication where people see that it's possible and, and want to build on that

Simone: 9:29

Right. So that gets into what I was actually gonna follow up and ask, and I think you partly answered it there. So, you know, in some fields like obesity, everybody's on the sidelines. Two companies just kept going, and that broke it open and everybody came in, right? And so here, obviously, RevMed, Revolutionary Medicine, RevMed, have been a, a leader in this and, and they're persisting. But it sounds like what you're saying is that this isn't just everybody waiting for one company or one or two company-- leading companies to read out that there's a, a whole bunch of activity in the space. Is that correct?

Lauren: 10:03

I think so. Yeah. So i- if you look through that abstract, there's a lot of early stage innovation where you're seeing some early signals. And so these are mechanisms that maybe have worked in other, uh, cancers that have some common underlying biology that could apply to pancreatic cancer. But, um, I think in an indication that, that's really challenging to treat, there's potential for lots of different mechanisms, and there's a need for lots of different mechanisms. This-- We're not talking about a cure right now. Um, but we're talking about trying to extend overall survival and progressive free survival

. Jeff: 10:37

All right, Lauren, what else are you looking out for?

Lauren: 10:40

Yes, I think-- So we always look to the late-breaking abstracts and the plenary sessions at the conference to see what the big news will be, and there are a couple that I thought are really-- will be really interesting. one of them is new selpercatinib data from Eli Lilly. This was, um, the RET inhibitor. It was one of those really early precision medicine, precision oncology drugs that got a ton of attention, but then hasn't had a ton of commercial success because of the limited testing that's happened. So this is a Phase III adjuvant setting trial, and we know that the data are positive. We don't have details on the data yet. But I think, you know, depending on how positive, this just builds the case for upfront mutation testing in non-small cell lung cancer patients, which, you know, adds to the case that, um, some other successful adjuvant trials have already started to make., We're also gonna see HARMONY-6 data from Ivonescimab, which is the, , Summit, Akeso, uh, PD-1 /VEGF bispecific that everyone's been watching. And I think that this is a China-only study, but it will be really important because it's first-line combination with chemo against a PD-1 inhibitor. So this was kind of the criticism from that HARMONY-2 data that got all the attention a couple years ago is that they weren't testing it in a chemo combination when it went head-to-head against Keytruda. so that, that's just another one that we'll be watching

Jeff: 12:07

Excellent. And it all kicks off, Friday, in Chicago. Chicago again this year, Lauren?

Lauren: 12:13

Always Chicago, I think

Jeff: 12:15

Always Chicago. All right. Well, sounds good. We're gonna take a quick break and then we'll come back and bring on Mr. Usdin

Voice Talent: 12:24

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. Jeff: 13:31

Okay, we are back. Uh, Steve, uh, more, dare I say, saber-rattling out of, , Congress over China. Uh, what's the latest?

Steve: 13:43

So, uh, last Thursday, Representative John Moolenaar, who's the chairman of the House Select Committee on China, sent the Treasury Secretary, Scott Bessent, a letter. He wants Treasury to designate biotechnology as a prohibited technology under the Comprehensive Outbound Investment National Security Act., Which everybody, for obvious reasons, calls COINS. Moolenaar wants to use COINS as a tool to block US companies from engaging in co-development and commercial collaborations with Chinese biopharma companies. This isn't the first we've heard of this. In February, he, House Foreign Affairs Committee Chairman Brian Mast, sent letters to Bessent that was co-signed by the Republican leaders of intelligence and foreign affairs committees in both chambers, urging addition of biotech to the COINS Act. Those letters identified three buckets, right? Bioweapons, who's gonna be, opposed to controls on bioweapons. Supply chain vulnerabilities, again, I think that's something that there's broad consensus about. And the third, US leadership in biotechnology. Moolenaar's letter last week focused on the US leadership part, and he went further than anyone has in letters in the past or in proposals in the past for COINS, saying that he wants to target the deal structures really that have reshaped drug development. Um, he wants to target US transactions with China involving the licensing of pharmaceutical IP, drug discovery platforms, clinical R&D capabilities, biologics manufacturing, and commercialization know-how. And he cited the recent partnership between BMS and Anrou Pharmaceuticals, the one that we've talked about on the podcast, has a total value of about $15 billion. He cited that as an example of the kind of deal that he believes should be prohibited.

Simone: 15:37

Hey, Steve. I'm sure there's sort of a lot of intricacies in how COINS works. Maybe you'll talk about it, or maybe you'll send people to read it in your article on our website. Um, but I did wanna ask something about this because I know that there are some people inside the industry, and you talked about them in your article, you might outline them, who are broadly in favor of, uh, this kind of legislation. I would go so far as to say they're probably a minority, and a lot of the big voices do not think this is good. And I think the reason for that is that most people sort of understand just the seminal role of deal-making and how China is advancing, and that, um, deal-making is sort of fundamental to how the industry grows. I mean, you talked about the BMS deal, but GSK had a deal with them growing beforehand, -- as we've been covering. So my question to you is this, a little bit of a long question, so bear with me. A while back, Katie Porter, you might remember, kind of also had some statements about against the M&A and our industry as destroying, and it really seemed as if she didn't understand how the industry operates, that the arguments she was making didn't bear through. My question really is, is this an issue where the members of Congress sort of don't actually understand the nuts and bolts of the industry, or do they understand it very well and still wanna keep China out and wanna have this suppress China approach, even if it hurts American industry?

Steve: 17:07

So I think that it's a little bit of both. I think that, uh, Representative Moolenaar and the members of the China Select Committee, their, interest, their really self-identification is as China hawks. They're not experts on life sciences or on the biotech industry. Um, there are other members of Congress who are familiar with the industry, and who are advocating this. But what I would say is that what's interesting is to look at who's, you know, who, who are they listening to, right? And, and so, um, what I point out in the story that probably the loudest, most prominent voice calling for this, you know, explicitly protectionist policy toward the Chinese biopharm, industry is Jason Kelly, the CEO of Ginkgo Bioworks. He was, um, chairman of the National Security Commission on Emerging Biotechnology, a bipartisan congressional advisory body that has recommended, outbound investment controls on, on life sciences investments from the United States to China. company, focuses on synthetic biology. Uh, but he's not the only one. There's, there's also a group of investors, um, around Curie Bio, for example, who are calling for the similar kinds of, protectionist, constraints on, US investment in China. at the same time, y- you know, um, there's some very loud voices who are pushing back the other way. Peter Kolchinsky of RA Capital, has been very eloquent in, pointing out what he believes are the flaws in trying to protect against, China, to have protectionist policies against China. Uh, I spoke with, john Maraganore, the, the founder of Elnilum. He also, spoke out against, erecting walls between the United States and China

Simone: 18:42

Sorry. Can I just-- we go, you know, go a little bit deeper into the people who are advocating. We've covered a lot the reasons not to do this. Certainly happy to talk more about that and write more about that. But I wonder if you could draw a line between, you know, is there a self-interest with Ginkgo and, you know, synthetic biology and the protectionist stance, or is this really purely philosophical?

Steve: 19:06

You know, I, I don't, uh, think that it's, it's fair to i-impugn, uh, you know, people's, people's motives and I, I, I'm not doing that. But of course there are financial, uh, alignment on both sides of the issue, right? So, Ginkgo Biotech, their biggest competition comes from Chinese companies, from BGI and from other Chinese companies. The Chinese government is investing a large amount of money in, um, synthetic biology and, the US government i-is not, matching that. so yeah, there's a, there's an alignment between Jason Kelly's, uh, financial interests and, imposing protectionist controls on China. But on the other side of it, there's also an alignment of, of financial interest. Of course, the big companies that are quietly, pushing Congress, to avoid, a decoupling with China, AstraZeneca, Pfizer, companies like that, of course, they have massive investments in, in China. Uh, Peter Kolchinsky from RA Capital, uh, as I said, has been one of the most public advocates for avoiding, protectionist, measures. Um, he also has, investments in China. So yeah, there, there's, there's an alignment between the financial interests of all the parties, I think, who are making these arguments and arguments. But I, I think there's also kind of a philosophical issue. I think that, the people who are advocating for a, a decoupling believe that the United States market, access to the United States market is a, um, kind of a choke hold, sort of like the straight-up arm moves of biotech, that the Chinese industry can't survive without access, to the US market. I'm not sure that they're right about that, but that's what they think. and they think the United States should, um, exploit that. I think other people think that, it's a far wiser, decision to focus on enhancing, uh, our competitiveness to stop, to stop advancing policies that make it more difficult, to develop drugs in the United States and then to, you know, emulate some of the things that China's done that, um, for example, speed first in human trials. Uh, so that's a kind of a, a philosophical debate. I think also what's happening, there's a little bit people who are familiar with the semiconductor industry, the electric vehicle industry, the solar industry, and they see what's happened in terms of US competition with China in those industries, and they apply what they know or what they think they know about those industries to biopharma without really realizing that those learnings and that experience really isn't applicable to the life sciences. The life sciences are fundamentally different from semiconductors and these other technologies

Simone: 21:48

I think that's very fairly said. Thanks

Jeff: 21:50

All right, Steve, turning to, uh, Jake Auchincloss's, uh, proposal, um, bring us up to speed on the details

Steve: 21:59

So, so I'd say that this is really the starting whistle for FDA reforms, tied to PDUFA reauthorization. For people who aren't familiar with it, uh, every time PDUFA is reauthorized, Congress attaches a whole package of reforms that are intended to change FDA's mission, to change the resources that it has, to change the way that, to, to improve, the way that drugs are developed in the United States, and that's had a whole range of, manifestations from drug safety to biosimilars, to, the, uh, breakthrough designation, things like that. So, um, Representative Auchincloss believes that modernizing how clinical trials are conducted in the United States, is one of the best ways to accelerate innovation and improve competitiveness of the life sciences enterprise, and he's trying to use PDUFA reauthorization as a vehicle for that change. He released a discussion draft of a proposal that aims to facilitate embedding clinical trials directly into routine healthcare delivery and to streamline early stage trials. I spoke with him about it last week. He emphasized that, this is just a starting point, the discussion draft, that he's seeking input from practitioners, that means our listeners, about what should be in this legislation. First about, what they think about the proposals that he's already put forward and more importantly, what else should be in the legislation. I think he's gonna have, hearings and, he's gonna introduce this as standalone legislation, but the intention is to have it incorporated into PDUFA reauthorization that's expected to pass next year. He has a Republican partner, Representative Morgan Griffith of Virginia, who's the chair of the Health Subcommittee of the Energy and Commerce Committee. There's a, you know, there's a pattern for this. Diana DeGette from Colorado, Democrat from, uh, Colorado, teamed up with Fred Upton, Republican from Michigan, to get the 21st Century Cures Act passed, in a previous, uh, PDUFA reauthorization, and I think that that's a model that, Representative Auchincloss and Representative Griffith are hoping to, um, to emulate in this, go round.

Simone: 24:04

So can you talk a little bit about what, the reforms entail, Steve? Because, you know, we have been talking and gonna continue to talk about some of the specifics, regarding, you know, this topic. And obviously, we do believe that making clinical trials, especially first in human ones, uh, more efficient is, uh, not only solving one of the biggest uh, translational blocks in the drug development process, but also an important competitive thing as China has completely raised the bar on that

Steve: 24:34

So, um, the centerpiece of the legislative proposal is the Cures and Care initiative. It would create a network of point-of-care clinical trial platforms, essentially turning hospitals and clinics into ongoing research sites rather than treating clinical trials as a separate standalone event that happens at these sites. FDA Center for Clinical Trial Innovation, that's at CDER, would serve as the coordinating hub. The Advanced Research Projects Agency for Health, ARPA-H, and NIH would be directed to launch at least three platform pilots covering rare diseases, a high-burden chronic condition, and another area of significant unmet need. First in human when we're talking about healthy volunteers is a very different thing when we're talking about patients. In any case, what his proposal is, um, it would establish pilot programs for third-party oversight of lower risk first in human trials modeled on Australia's clinical trial notification scheme, which allows trials to begin faster, uh, and u-under a streamlined, um, review process. He also has proposals for, um, FDA to lead global regulatory alignment initiatives that would leverage existing international forums to harmonize standards, um, for early-stage trials and the creation of point-of-care platforms

Jeff: 25:56

All right. Well, you can check out Steve's story on biocentury.com. I'll also drop a link in the show notes. Okay. Uh, let's turn to ADC linkers. our colleague Tierney had a great piece a, a week or so ago, and well, Tierney, welcome to the show.

Tiereny: 26:18

Thank you

Jeff: 26:19

Excellent. Well, let's, let's talk a little bit about optimizing linker design. You, you really dug into some nitty-gritty here. Why don't we start with that?

Tiereny: 26:30

Yeah. So, as you mentioned at the start of the show, you know, there is more and more evidence that the features built into linker design are really beginning to modulate ADC performance and therapeutic index. And by far the most innovation coming out of ADCs right now is in linker technology. Linker, which is how the payload attaches to the antibody. and so one of a whole toolbox of techniques that includes like modulating hydrophobicity, engineering conditional activation onto your linker. One of those in there is something called site-specific conjugation. and that's just one method in this toolbox that companies are using sometimes multiple of to overall increase their th-therapeutic index. So I kind of was diving into like what, what do we mean when we say site-specific conjugation? Uh, basically, historically, they would use the naturally available lysines or cysteines to antibody to payload, and that just resulted in a very heterogeneous mixture. And so there's been a greater adoption of being able to control where the payload attaches to the antibody through this site-specific conjugation. and it's really not a new idea. It's been around for about twenty years with Genentech's DioMab platform, but has really failed to kind of take off, especially in the clinic. And I think in the last few years, we're starting to see newer, exciting approaches that might really be, the next wave in like pushing the space forward.

Lauren: 28:09

Tierney, before you get into some of the, um, specifics on the types of, uh, site-specific conjugation, I'm wondering, I don't know if you can answer this, but are there examples in the clinic of, site-specific conjugation ADCs having better safety or efficacy than an ADC, using random conjugation, for the same target?

Tiereny: 28:31

Yeah, I think it's, hard to say. Uh, I think that the-- because so many of these companies end up using a number of different linker technologies, so technology, so it's hard to pinpoint that like the better safety is exactly, tied to the site-specific conjugation. But generally, what you're looking for is less free payload. And so a lot of the time, the site-specific conjugation does prevent early release of payload, which mitigates toxicity. So they've seen that across trials that you can have a better toxicity profile if you're able to avoid that, and that is something that they've shown, and better PK overall

Lauren: 29:15

Okay. And then I know your deck gets into a few different ways that companies are doing this site-specific modification. Uh, can you talk about the, um, advantages and disadvantages of each of those approaches?

Tiereny: 29:27

the vast majority use cysteine engineering to attach the payload to specific cysteines. and that has, like I said, been around for a couple decades now, and that, uh, has significant drawbacks because of, uh, something-- parts of the reaction that can lead to premature payload release. That's become widely adopted and we're, we have learned how to scale up that process and manufacture that well, it has significant drawbacks in efficacy. newer approaches include an enzymatic approach where you can either use an amino acid tag or a glycan as a recognition site for an enzyme, and this allows really high chemoselectivity and pairs really well with click chemistry. So it's very versatile. It's very, uh, you know, click chemistry is very fast, reproducible chemical reactions. So, it's a high fidelity thing and, um-

Simone: 30:27

gotta say, you know, click chemistry always a friend of the pod. We love a little click chemistry here and there. Um, I think it's a very in-depth, analysis in a slide deck format for what Jeff likes to call the geeks in our audience, uh, to get their geekdom done. Um, but I really like this evolution. I think a lot of people like me who've been around for a long time are very familiar with, the cysteine handle kind of thing, and that, transition from there to tag-based and glycan-based sort of site-specific strategies, and now then to the engine, sorry, engineering in, enzymatically, like the, the tRNA-based, uh, and the click conjugation, as I just mentioned. So you see this transition, and you kinda see the trade-offs, and it feels like the, the last one that I mentioned, maybe you can talk a little bit about this, is more, uh, early stage, is more, like, where things might go. And did you get a sense when you talk to people that that will become mainstream, or do you think that what's happening is we're just building a bigger and bigger toolbox, and there'll be a place for all of them?

Tiereny: 31:33

Right. Um, so yeah, so I think the, the modality or the strategy you're referring to is kind of the third option in this toolbox, which is insertion of these non-canonical amino acids, and that, offers the absolute highest versatility. You can put these, this amino acid handle anywhere on your antibody. It's the least likely to affect antibody, function because it's genetically encoded. so it's highly modulatable, highly diversifiable, but because of that, it requires intensive engineering. Uh, and so, my sense is that for these approaches is that they're different items in the toolbox, depending on what you're trying to go after. If you're looking for something, if you're trying to attach a payload that requires a more complicated linker where you really need to be able to pick any site on the antibody, then you wanna go with like a non-canonical amino acid approach. Whereas if you want a, a little bit of a quick and dirty approach, you might be fine with cysteine engineering. Um, generally though, I will say, even though cysteine engineering is probably used by about half of companies right now who are in the site-specific conjugation space, the sense I got from, uh, you know, the experts I talked to was that they think in the future that will be phased out, that we are moving away from that. and these more what are currently niche approaches will be more mainstream, but I think, there's still innovation happening across the board, so it's hard to say exactly.

Jeff: 33:09

All right, and, uh, I will drop a link into the show notes for Tierney's, GeekFest deep dive on ADC linkers. And thanks to Tierney, Lauren, Steve, Simone, and our production engineer extraordinaire, Ashton Moraski. Thanks also to Kendall Square Orchestra for doing the music for our podcast.

Voice Talent: 33:35

BioCentury would like to thank Jeito Capital for its continued support of our BioCentury This Week podcast and our 26th annual Bio€quity Europe conference this May in Prague, Czech Republic.