Ep. 375 - Novartis' ADC gambit & regulation as catalyst for U.K. biotech

Novartis is deepening its antibody-drug conjugate capabilities with its $1.1 billion acquisition of U.K. biotech Myricx Pharma. On the latest episode of the BioCentury This Week podcast, BioCentury’s analysts discuss how the deal fits with the Swiss pharma’s cancer toolkit.
The analysts then discuss MHRA CEO Lawrence Tallon’s Guest Commentary in BioCentury on making regulation a catalyst for U.K. life sciences and why the primary defeat of Rep. Diana DeGette (D-Colo.) is a setback for FDA reforms. They also assess how single-cell Parkinson’s atlases reveal neuronal and glial disruptions in specific regions and stages, and the thin evidence underpinning Congress’ probe of China trial consent. This episode of the BioCentury This Week podcast has been brought to you by CBRE.

View full story: https://www.biocentury.com/article/660033

#ADC #BiotechMA #ParkinsonsDisease #FDA #ChinaBiotech

00:01 - Sponsor Message: CBRE
01:15 - Novartis Buying Myricx
08:01 - U.K. Regulation
14:44 - DeGette & FDA Reform
21:51 - Parkinson's Atlas Insights
29:39 - China Trials Probe

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

Transcript

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[Auto-generated Transcript]

Voice Talent: 0:01

BioCentury This Week is brought to you by CBRE.

Jeff Cranmer: 0:06

Novartis deepens its ADC capabilities with the billion-dollar acquisition of UK biotech Myricx. Making regulation a catalyst for UK life sciences. We'll discuss MHRA CEO Lawrence Tallon's guest commentary from last week in BioCentury on this week's BioCentury This Week. Plus, why a primary loss for a Colorado lawmaker is a blow to FDA reforms. I'm Jeff Cranmer, host of the BioCentury This Week podcast. Joining me today, Editor-in-Chief Simone Fishburn, Washington Editor Steve Usdin, our colleagues Danielle Golovin and Paul Bonanos. We'll also discuss how a House committee is reviving its probe into US drug makers' clinical trials in China, and the latest from our Atlas Insights series, which assesses targetable directions in Parkinson's disease. Okay, let's get to it. Novartis announced Monday morning that it would acquire private UK biotech Myricx, focused on antibody drug conjugates, or ADCs. The Swiss pharma is paying $1.1 billion up front, with the potential for $400 million in milestones. Paul, you took a look at the deal. What did you learn?

Paul Bonanos: 1:37

Yes. So, as you say uh Myricx uh it's in the U.K. It's a spin out from Imperial College London and the Francis Crick Institute. They are working on ADCs, antibody drug conjugates um but with a different payload than other companies. A-an awful lot of ADCs out there use TOPO1. There are a couple of other payloads. Myricx is the only company using NMT payloads that we're aware of. NMT, that's a mouthful, N-myristoyltransferase inhibitors. Suffice to say, some cancer cells rely on a myst- myristoylated protein, there I said it um and inhibiting NMT can result in anti-tumor activity. Um, I think some of us have actually worked on that in the past. Yes,

Simone Fishburn: 2:21

Oh, yeah. I'm, I'm so jumping in on this one on so many fronts. So first of all, I'm very excited because, yes, when I did my postdoc, I actually worked on lipid modifications, including n-myristoylation, Paul, very easily said, myristoylation and palmitoylation. And as I'm sure many people know, these are post-translational modifications that add a lipid moiety um at least they used to be, like, several decades ago, to uh proteins that can direct where they go and what they interact with. And certainly have been implicated in, in cancer. And just want to say a couple of things about this technology and this deal. We actually haven't seen a ton on lipid modifications in this area, and I spoke to Jonathan Tobin from Brandon Capital several years ago When they were just investing a seed round in this technology and, it was quite forward-thinking at the time. I think it still is, is the idea of using different kinds of payloads on ADCs. It actually had been… I think you were gonna tell us about this, Paul. This was a pivot from a small molecule play, right?

Paul Bonanos: 3:27

That's right, yes. they had been looking at small molecules addressing NMT and they found that there was a narrow therapeutic window, some worries about toxicity, but then pivoted to adding NMT as a payload as part of an ADC, which allowed them to reduce the dosage to a manageable range, and at least in preclinical models, they've generated some compelling results

Simone Fishburn: 3:49

Right. And I think, you know just on another issue, I was in touch with a couple of people at Novartis. I think they are very excited about this acquisition. and I think it's generally, um … I've been having a bunch of phone calls this morning on various things, but they've converged on this very nice deal because it's a very nice proof of principle, I think, for Brandon Capital and the early investors who sort of found this technology and thought it would go somewhere. I think for Novartis, you might talk more about this, Paul, but it plays into their strengths they've been building up. Obviously, they're leaders in radioligand therapies, but, you know, ADCs is a natural kissing cousin of that, and I think they are, acquiring a lot of you know, pipeline assets and, and building maybe internally in that vein as well. And maybe we'll get this, to this afterwards, but a couple of people I've spoken to have also talked about this as, you know, really good for U.K. life sciences, 'cause this came out of, as you pointed out, the Crick, you know, that capital gets recycled into that ecosystem, and so kind of a lot of people for different reasons that have been hailing this particular deal

Paul Bonanos: 4:57

Yes, I, I think we'll touch on a lot of that in the story today. you mentioned for Novartis, they've obviously had the strength in cancer in small molecules and more recently in radiotherapy, have done a lot of deals in radiotherapy. I did find uh a quote from Vas, the CEO, at this year's J.P. Morgan conference, where he said he thought ADCs and bispecifics were op-opportunities to build in oncology. Novartis has not done a lot of deals uh in oncology for the past couple of years. They've been doing-- They, they've been more active in other areas, neuroscience and such cardiovascular as well. Well, th-this is an opportunity to build. Um, so it's uh $1.1 billion up front for a preclinical company. That's quite a bit. More upside for shareholders, as you said, $400 million in milestones. Brandon and Sofinnova Partners, we should mention, was the other seed investor. A handsome return for both of them, I'm certain

Simone Fishburn: 5:51

I, I know that Abingworth was in there as well. There was a, a whole bunch of people who saw this on its way

Paul Bonanos: 5:56

there, there was a Series A Novo Holdings and Abingworth were the leaders, I believe, and um that really, once they had solidified their pivot, that's who moved it forward. And so you mentioned Jonathan Tobin. I spoke with him a little while ago. he said that they were actually struggling at one point trying to raise cash during the pandemic around the NMT small molecule idea. And once they made the pivot, you know, I, I, I liked what he said. He said, I'll, I'll read you the quote,"Really the bet was in 2023 that people would shift their attention from linkers and targets to the payloads." Right? So, and in Novartis, Novartis' case, yes, they're coming in a little late to ADCs, but the way he saw it, it's as if they've leapfrogged the competition in a way. He, he called it the second bounce of the ball was toward payloads. So we'll have to see how it plays out, but um certainly a good deal for Brandon and um the other investors we'll see what happens once they get into the clinic too

Jeff Cranmer: 6:53

Surely not a tennis reference there, I hope

Simone Fishburn: 6:56

Yes, I was thinking just the same, Jeff. Um, one quick note, Paul. I know that Jonathan Tobin also said this was the biggest upfront for a preclinical asset in an acquisition. well done to them if, if that's correct. Or in all events well done to them, I guess

Danielle Golovin: 7:14

Yeah. Maybe for Paul or Simone might, you might know, is this payload particularly suited to a specific target or cancer type, or is it pretty ubiquitous?

Paul Bonanos: 7:22

Yeah, I, I, I think Myricx uh saw the NMT inhibitors as an opportunity to create a pipeline with other antibodies. their preclinical assets target B7H3 and HER2. I know that there's a poster where they describe an NMT payload affixed to trastuzumab that they've circulated as evidence of-- It's some of their preclinical evidence. I don't know if they would actually use the same antibody going forward in the clinic.

Jeff Cranmer: 7:50

All right, thanks for that, Paul. Look forward to reading your story, which will be on biocentury.com. Also, drop a link into the show notes. Simone, quite the past few days for England. A win by the Three Lions at the Azteca, Wimbledon in full swing, and Laurence Tallon penning a guest commentary in BioCentury. Where to begin?

Simone Fishburn: 8:16

You know, I really thought we were just gonna talk about Cape Verde on the call today and that we weren't really gonna do anything else because I think Steve would appreciate this as well. Steve, I, I was really thinking that we should be looking at biotech in Cape Verde and going out there to investigate, and maybe our next Grand Rounds should be there. I, I don't know if you've got thoughts on that

Steve Usdin: 8:38

I'm ready to go. Ready to go

Simone Fishburn: 8:39

Okay, so I feel like there's a burgeoning biotech sector there. But I gotta tell you, yeah, the,

Jeff Cranmer: 8:46

gonna be a, a year-long uh party uh hosted by Vozinha no doubt

Simone Fishburn: 8:52

Yeah. Vozinha, yeah. And then I

Steve Usdin: 8:55

the music scene there is great also

Simone Fishburn: 8:57

What is that? What is great, though, sorry?

Steve Usdin: 8:59

Uh, the music scene there is great also, so there we go

Simone Fishburn: 9:02

There we go. And then I had somebody tell me that it, the podcast had to be all about Harry Kane, or Sir Harry Kane as he became for a few hours last week. Uh, but now most of us are still in recovery from an extraordinary showing at the Azteca. But really I feel like we need a whole separate podcast for that Jeff. I, you know, I can't do it justice, but,

Jeff Cranmer: 9:22

Simone in blazer

Simone Fishburn: 9:24

Yeah. It's, um … Anyway, anyway, so that's a good one. Like uh England fans will understand if uh nobody wants to jinx anything here and say anything else. Um, they'll also understand the agony that uh those of us who, who really support the team went through yesterday and every damn day they play. but anyway, Lawrence Tallon is not causing such angst. He is the CEO of MHRA and reached out to us with a really compelling uh op-ed, a commentary by him. I think what is important about this is it's from him, and He is saying regulation needs to help lead rather than follow innovation. Regulation needs to be a catalyst, not a ba- barrier for UK life sciences. And he says the MHRA is rethinking how we regulate for the greatest benefit to patients. And behind that is, a series of, some are policy changes and some are sort of, I don't know, Steve, you might help me with the words, like shifts in mood or vibe or strategy or whatever, where I think he wants inside the agency to rebalance the way they view risk you know, versus the advantage of innovation

Steve Usdin: 10:46

Yeah, so I, I, I spoke with him s- a little while ago also, and the expression I think they used was something about proportionate regulation, that, regulation should be proportionate to the risks and the benefits, and I thought that was a good way to think about it. I found his, essay, really interesting. you know, he says it's too easy for regulators in any sector, not just healthcare, to be overly cautious in decision-making. He said he, he saw it himself as a hospital executive. and so he's, he's basically talking about recalibrating the way that the UK thinks about risk and putting that into practice in his regulation. It's something that has been on a lot of people's minds around the world in the context of therapies for rare diseases, and I think that it's going to be on people's minds a lot more when they're thinking about how to, for example, reduce the time that's required to launch first in-patient trials

Simone Fishburn: 11:39

One of the things that Lawrence Tallon also talks about is the same sort of strategy in terms of personalized medicine, in particular AI. I think a lot of people are wondering what is the role of AI, but the question I wanted to ask you based on FDA and what they've done is, is this something that you sort of have to inculcate throughout the agency at the sort of level of reviewers? Is it a culture change as much as policy change? And, you know, how do you go about doing that?

Steve Usdin: 12:08

Well, it absolutely is. it has to be. Some of the m- the kind of, well, mess um that we've seen at FDA over the last 16 months is a result of a disconnect between the people who are at the top and reviewers. I've talked a lot over the years about this with with FDA commissioners and with um center directors and they all say that the only way that you can really get these kind of fundamental changes to happen is if you work with and you bring the review staff, the scientists at the, at the agency along with you, that you can't just dictate these things from the top. And, and the way to start that, the way to start that conversation is to lay out a vision, and that seems to be what Lawrence Tallon is doing

Simone Fishburn: 12:51

Yeah, I think, I think you're right, and it's certainly one to watch. I can tell you I've been in touch for various reasons with people in the U.K. sector, and there's tremendous support and, you know, belief that Tallon could be a guy to really make a difference for MHRA, which would be important for the sector. So he is quite positively viewed by, you know, the sector, which is not always the case for regulators um heads of regulatory agencies, we might say

Steve Usdin: 13:21

And, and you know, one of the things that's, that's really interesting also is the very beginning of his essay points to the major difference between MHRA and FDA, which is he says, you know, "We're in an interregnum now between governments in the UK," which was kind of a delicate way to put it. But um but the point is that that he's staying, right? He was there before. He's expects to be there for the next one, and most likely for the next one and the next one. So he, he's civil service, he's nonpolitical, and that allows for a continuity and it allows for a, a kind of separation between the regulators and political actors that I think is, is a real strength um for the UK. And it's something that in the long run, the United States, I think, and I've written about this, should aspire to. We should aspire to having FDA run by someone who's nonpolitical and who's expected to endure throughout, through more than one uh presidential administration. You know, the idea that, that the FDA commissioner is a highly politicized job and that it changes with every president is not a strength

Simone Fishburn: 14:24

Yeah, I, I totally agree with you, Steve, but I also want to just add that at the rate at which the U.K. changes prime ministers, it would be highly problematic if it had to change FDA commissioner or MHRA leaders each time as well. But uh you know, therein lies the, the, the strength of the administrative state, so yes

Jeff Cranmer: 14:44

Well, on that note uh let's take a look at what is going on in the US. Colorado lawmaker Diana DeGette has been defeated in a Democratic House primary and that ends the legislative career of a politician who built bipartisan support for FDA reforms for quite some time now. Steve thoughts here

Steve Usdin: 15:10

Yeah. So Representative DeGette as you said, she lost her Democratic primary on July the 1st to Melat Kiros, a 29-year-old attorney and PhD student who's running on a democratic socialist platform. the district that Diana DeGette represents, the first district um it's Denver, it's heavily Democratic, so Kiros is expected to win in November. DeGette had been ranking member of the Energy and Commerce Committee's health subcommittee, and she was positioned to chair it if Democrats um retook the House. She was also building support for a bill, the 21st Century Cures Act 2.0, that was aimed at further speeding drug development. You know, what I wrote is that this is really a, is a major setback for the bipartisan industry collaborative approach to FDA reform that's been the norm for the last couple of decades, really, at least for the last decade. DeGette co-authored the 21st Century Cures Act which was passed in 2016, with Representative Fred Upton. They were a really close partnership. it was really fun to see them. They would go around the country and do um town hall meetings and roundtables and things together, and it was, you know, it was a Democrat and Republican literally um arm in arm trying to come up with policies that would make the FDA better and that would make it better for patients. 21st Century Cures Act modernized evidence standards for drug approval. It created the RMAT designation, kind of equivalent to breakthrough for uh biologics, and it enabled tools um that are now considered routine: the use of real-world evidence, external control arms wider use of surrogate and interim endpoints. The uh 21st Century Cures Act wasn't the only thing that she did. Actually, she started much earlier u- under um the George W. Bush administration authoring the Stem Cell Research Enhancement Act that was vetoed twice by Bush, and then Obama incorporated it into an executive order. she worked very closely with patient advocacy groups. Uh, I spoke with Ellen Sigal, the founder of Friends of Cancer Research, who called DeGette's loss devastating. She says it's a devastating blow. She talked about how DeGette had gone out of her way to understand the science and to build consensus.

Simone Fishburn: 17:26

Steve, um, let me jump in and just ask a, a question or two. So, you know, I think that her legacy certainly, you know, speaks well to the model that you talk about. What I do wanna say and ask is, you know, w- we've looked at the negative side, what we're losing. It's very clear that the sector is losing somebody that was an asset really in Congress. I wanna know whether you see anyone stepping into those shoes and, or whether her replacement you know, I guess it would be the Democratic candidate now for that seat offers anything, you know, that will affect life sciences, or is that largely irrelevant?

Steve Usdin: 18:04

You know, there are other members of Congress who kind of represent that that style. Um, I've spoken, I, I've done interviews BioCentury podcasts and written about Representative Jake Auchincloss from Massachusetts. he's working on a, package now clinical trial reforms that he hopes will be attached to the next PDUFA reauthorization. And when I spoke with him, I asked him specifically, and he's, he's doing it along with Morgan Griffith, a Republican. I said, "Well, really, is this like Diana DeGette and Fred Upton and 21st Century Cures?" And he said, "Well, it, it is." And he, and he hopes that it's as successful as they were. As far as Kiros, the, the candidate who defeated DeGette one of the reasons, one of the things that she campaigned on was DeGette's acceptance of campaign donations from the pharmaceutical industry. She tied that to a broader democratic socialist critique of what they call industry capture of regulators. You know, I think that Kiros and other candidates who she's politically aligned with, other politicians she's aligned with there's a deep divide between them and mainstream Democrats like DeGette on FDA issues. DeGette has treated the pharma industry as a partner to regulate and incentivize. The Democratic Socialist Bloc officially, if you look at their, their platforms, they favor public manufacturing of drugs, limits on profits, IP curbs, and they have a deep skepticism toward loosening what they consider loosening evidentiary standards at FDA What I said in my story is that really the a- advocates who are hoping to extend the kind of reforms that were in 21st Century Cures need to build a new bipartisan coalition, and it's gonna be very difficult now because the environment is far less hospitable to the brand of consensus politics that DeGette exemplified. And, you know, and I guess one other final thing, I think there's some in the industry who would um take issue with me saying that DeGette was an ally of the industry because she also was a firm proponent a champion of the Medicare drug price negotiation provisions and the IRA and other things that were opposed by the pharma industry. So it's not like she was the pharma industry's or the biotech industry's puppet

Simone Fishburn: 20:15

no shill for the industry kind of

Steve Usdin: 20:17

No, she wasn't at all. But, but

Simone Fishburn: 20:19

I think that

Steve Usdin: 20:20

but, but to the extent that what the biotech industry and what the pharma industry are doing is aligned with and must be aligned with public health benefits and with what's really important to patients, I think that DeGette really should be considered to be you know, a champion and a hero

Jeff Cranmer: 20:36

We'll take a quick break, and we'll be back to discuss the latest in our Atlas Insights series.

Voice Talent: 20:44

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Jeff Cranmer: 21:51

We are back on the BioCentury This Week podcast We're gonna bring in uh our colleague Danielle Golovin now, or bring her back in. Uh, she leads our Atlas Insights series. and atlases, what are they for the UN initiative? Well, our weekly literature scans frequently identify papers that function as disease atlases, observational patient studies, typically involving large scale molecular profiling that seek to capture the underlying biology in heterogeneity of disease. Danielle you followed up our colleague Lindsay Martin's epic Parkinson's piece with the Parkinson's Atlas.

Danielle Golovin: 22:40

Yeah, big, big shoes to fill there. Uh, it was, it was a big one. It was a, a me- uh, what was it? A mega chonker? Or what, what's on the scale

Jeff Cranmer: 22:49

yeah, on the uh the cat scale uh from fine boy to a hefty chonker, I think it was a hefty chonk. Um uh for, for dog people, that just means uh something very big and uh potent. so what did you find when you looked at the atlases for Parkinson's?

Danielle Golovin: 23:08

Yeah. So last week you heard Lindsay walk through how the Parkinson's pipeline is finally moving beyond dopamine replacement, towards disease modifying strategies. So her examples were cell therapies, alpha-synuclein programs, and targeting genetic drivers like LRRK2 and GCase. I would say my analysis of these six new single cell multi-omic atlases of human Parkinson's tissue largely validates those targets. But what it does is add a layer of complexity, and that is in which cells and at what stages are those pathways actually lit up. So as we know, Parkinson's disease isn't a single fixed state, it's a trajectory. And if we look at the classic Braak staging scheme Lewy body pathology appears first in lower brainstem nuclei, climbs through the midbrain structures like the substantia nigra, and only later reaches like cortical regions. this means at any given time, different brain areas in a patient sit at different points along the Parkinson's timeline, and this is important for drug development. The implication is that a single disease modifying label can have different biological requirements, you know, at different stages in the disease and even in different parts of the brain. So this obviously matters for which therapies are likely to show benefit

Simone Fishburn: 24:23

Danielle, fill us in a little bit on what you found across the brain regions

Danielle Golovin: 24:28

Yeah, so these atlases kind of span all those regions, which is really nice. So this is not longitudinal data on a single patient, but it gives us sort of a picture of along the trajectory, what kind of things are going on in the different regions. So in the substantia nigra atlas, which is the classic region for dopaminergic neuron loss early on in Parkinson's, it revealed a concentrated inflammatory hotspot there. These were immune cells clustering around the stressed support cells that carry a marker called CD44. And the scientists actually did an experiment and dialed down CD44 in models, and that calmed down the hotspot. For me, that begged the question, what does this mean for the cell therapies that Lindsay highlighted in her deck? The cell therapies that are in the clinic, companies are implanting dopaminergic precursor cells into the putamen and expecting them to migrate to the substantia nigra to restore dopaminergic signaling. And I'm like, what happens when the cells arrive to this inflamed pocket, if you will? Do we just hope the new dopamine cells can cope with that environment, or does it affect them at all? Do we eventually pair the cell therapies with something that can cool down the hotspot? Like, maybe we need to add a CD44-targeted drug with the implantation of those neurons. I, I don't know if that's known, but that's what came into my head when connecting, you know, those two stories. And by the time the pathology reaches the temporal cortex, so this is sort of early cortical involvement the neurons there aren't dead or gone yet. They're just rewired. So the standout there was an excitatory glutamatergic subset, which showed robust alpha-synuclein overexpression and a concurrent 4,000 differentially expressed genes, even though the-- So the neurons are still there, right? The, the cyto architecture is preserved, so it looks kind of like a stressed or maybe a circuit remodeling picture maybe before the neuron loss. And then when we look late in the disease, so the prefrontal cortex, typically a late disease stage, we find glia and resident immune cells dominate, and the neuronal stress response and protein folding pathways are dialed down, so you just get this massive proteostasis failure I would say overall, you see a common thread of lysosomal stress, inflammation weaving through the different stages. And one of the most interesting signals that seems to run across the stages is a protein called galectin-3. And this brings us back to one of the big themes last week from Lindsay's analysis of lysosomal dysfunction and neuroinflammation as the next frontier beyond dopamine. And genetic and protein data point to higher galectin-3 as increasing Parkinson's risk. And interestingly, lab work, like prior lab work, suggests that it helps to leak alpha-synuclein out of damaged lysosomes. And once those are out, it revs up the microglia. I see this as a potential, like, knob you could mess with for synuclein-driven inflammation. And interestingly, when I went to BCIQ, I saw that there is one company testing an antibody against galectin-3 in Parkinson's. So this company, TrueBinding, has the only galectin-3 targeted therapy in development for Parkinson's. It's called TB006, and it's in Phase II

Simone Fishburn: 27:42

Two things I would say. One is the moral of the story is always go to BCIQ.

Danielle Golovin: 27:47

Yeah, exactly

Jeff Cranmer: 27:49

And, and BCIQ, of course BioCentury's database, hundreds of companies, thousands and thousands of targets uh thousands of programs, great for drug hunters

Simone Fishburn: 28:01

And financing and all the rest of it, you're right, Jeff. And so a- actually that's sort of the other thing I wanted to say is that for me, you know, I started out very early on in the, you know, my PhDs in dopamine receptors and some of the questions you raised, Danielle, have been around for a long time when they've for a long time wanted to do implants and the question was, "Well, what happens when they get there? Will they know when to stop growing, and will they connect?" but it really does seem like even though the questions have been around a long time, it really seems to be that the biology is now unfolding to answer them at a completely different pace. And so things like these atlases turn out to be incredibly powerful for both uncovering mechanisms and pathways, finding synergies and like you talked about, like making sense, like you talked about the lysosomal deg- degration. So sort of basically making sense of some of the observations that people have had over these years. Seems to be a very exciting time in translation in Parkinson's

Danielle Golovin: 28:57

Totally agree. It's like, well, we know all these targets, so why do we need these atlases? Like, even if we know the targets already, well, this is giving us information beyond that. And as Lindsay said in the, in the back end of her deck, like, biomarkers are gonna be very important to stratify patients.

Simone Fishburn: 29:11

Tune in for the next deck kind of thing. Yes.

Danielle Golovin: 29:14

And she mentioned this group of patients that, you know, look like LRRK2 patients, but they don't have the LRRK2 variants. I think just the moral of this atlas story is that future biomarkers will need to go beyond genetics and not just do you have this variant or not, but capture whether these pathways are switched on in the vulnerable cell types at the stage of disease that the patient is at

Simone Fishburn: 29:36

Totally

Jeff Cranmer: 29:37

All right. Thanks for that, Danielle. let's turn back to Washington, where the House Select Committee on China has revived and expanded its probe into US drug makers' clinical trials in China. It's a move that's consistent with broader congressional concern about Chinese clinical trials. Steve, you've been following all of these moves that we've been seeing in Congress. what's your thoughts on this one?

Steve Usdin: 30:08

Yeah, so this was a letter. It was sent to AbbVie, to Bristol Myers Squibb, Eli Lilly, Merck, and Pfizer. it repeated the concerns that the committee expressed in, in prior letters to those companies about trials conducted at PLA hospitals in China and Xinjiang, but it added a new concern. It talked about informed consent and made allegations that informed consent in China doesn't meet US standards or global standards. The letters asked the companies for their due diligence policies for all the uh data on all the trials that they've conducted in China since twenty fifteen, site inspection reports IP protection processes all kinds of, all kinds of other data that they're trying to get from them. But the thing is that the allegations about informed consent were really based, I think, on a very thin substrate. And I think this is important. So the committee's suggesting that policies that would have an enormous impact on patients in the US, basically what they're, they're trying to support, I think is what other congressional committees have advocated and what some prominent VCs have advocated, which is that FDA wouldn't accept Chinese clinical data to support IND applications. They're trying to do that based on very, as I said, a very thin uh dataset. So the data that's in the letter comes from a, a review article that discusses one survey of a hundred and seventy patients at a single Chinese hospital. And the review article which is about Chinese informed consent practices warns against generalizing from that study. And it also concludes that most of the documented problems of what's called therapeutic misconception, that's the confidence that patients have that an experimental treatment will be effective, poor understanding of alternatives to trial participation, that these issues mirror well-established shortcomings in Western clinical trials. They're not unique to China, and in fact, even the magnitude that was found in this study of a hundred and seventy patients at a single Chinese hospital matches pretty well the results when um the same kind of issues have been looked at in much bigger studies in the United States and Western Europe

Jeff Cranmer: 32:23

Steve obviously uh some big companies here from AbbVie to Merck, Lilly. Uh, what have they been saying about this?

Steve Usdin: 32:33

I contacted all of them. I reached out to them. I only heard back from a couple of them. Merck commented and said it, holds all of its trials around the world to the same ethical standards, that it follows ICH and PhRMA guidelines regardless of location. the committee's letter to Pfizer noted that the company has already made a commitment to no longer sponsor trials in Xinjiang or at uh military hospitals in China. Other companies basically sent me um no comment comments

Jeff Cranmer: 33:05

Alright well we'll continue to follow this uh along with other initiatives out of US and China. and you can read Steve's story by clicking the link in the show notes. If you like what you've been hearing uh subscribe to the BioCentury This Week podcast. And coming up this week on our sister podcast, we will have the CEO of Roivant in conversation with our colleague Lindsay Martin. thanks for tuning in, and thanks to Kendall Square Orchestra for providing the music for our podcast

Voice Talent: 33:39

BioCentury This Week is brought to you by CBRE.