BioCentury This Week

Ep. 337 - FDA’s Moving Goalposts & China’s Innovation Arc

• BioCentury • Season 6 • Episode 337

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A baffling decision by FDA to issue a complete response letter for a pediatric medicine the medical community stood behind is just the latest example raising concerns that the agency is shifting the regulatory goalposts amid a lack of transparency. On the latest BioCentury This Week podcast, Washington Editor Steve Usdin explains how the absence of advisory committee meetings at FDA is in part to blame for a lack of consistency in decision-making and divergence from decisions taken by other global regulatory agencies. VP and Editor-in-Chief Simone Fishburn then discusses the takeaways from Franck Le Deu’s guest commentary on how China’s biotech ecosystem is evolving, and whether government support for the sector is helping or hindering its overall health. BioCentury’s analysts also discuss whether conventional CRISPR therapies will ever be commercially successful, and what’s next for NLRP3 inhibitors to treat obesity following the first set of Phase II data for the class.
We'd also like to invite our listeners to participate in our important survey about their experiences interacting with FDA. To take the survey, please go to BioCentury's FDA Sentiment Survey. This episode of the BioCentury This Week podcast is brought to you by Voyager Therapeutics.

View full story: https://www.biocentury.com/article/657698

#FDARegulation #CRISPRTherapies #NLRP3Inhibitors #ChinaBiotech #DrugApproval

00:01 - Sponsor Message: Voyager Therapeutics
01:31 - FDA Sydnexis CRL
07:36 - CDC Vaccine Claims
09:55 - China’s Innovation Arc
16:49 - CRISPR Commercial Viability 
26:39 - NLRP3 for Obesity

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

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[AI-generated transcript.]

Eric Pierce:

BioCentury This Week is brought to you by Voyager Therapeutics. Voyager Therapeutics is dedicated to leveraging the power of human genetics to modify the course of – and ultimately cure– neurological diseases. Voyager addresses the challenge of delivering novel treatments to the brain through the company's innovative TRACER™ AAV capsid discovery platform, as well as Voyager's NeuroShuttle™, a non-viral delivery platform designed to transport multiple modalities of neurotherapeutics across the blood-brain barrier. The company's programs address diseases with substantial unmet needs, including Alzheimer's disease, Friedrich's ataxia, Parkinson's disease, ALS, and other diseases of the central nervous system.

Stephen Hansen:

The curious case of Sydnexis CRL that is questions about consistency of decision making at FDA. Plus a perspective on the state of play for China's biotech industry. Can CRISPR therapies be commercially successful. And NLRP3 inhibitors in obesity, we'll discuss all of this on today's BioCentury This Week. I'm Stephen Hansen, one of the Directors of Biopharma Intelligence here at BioCentury, and joining me are my colleagues.

Simone Fishburn:

Simone Fishburn, Editor in Chief.

Lauren Martz:

Lauren Martz, Executive Director of Biopharma Intelligence.

Steve Usdin:

And Steve Usdin, Washington Editor.

Stephen Hansen:

Great. So I'm, uh, filling in for Jeff this week. Who is off enjoying, I think the best that the American Midwest has to offer, so we will be kicking off here talking with, Steve. I think you had a story this past week on a surprising FDA decision, regarding a pediatric medicine, can you just fill us in on the context and what it means for how we should be thinking about FDA at this point?

Steve Usdin:

Yeah, so I highlighted the Sydnexis CRL, which didn't get a lot of attention in newspapers or even in publications that cover biopharma because I think it's, one, it's really important to patients, and two, because I think it illustrates the kind of problems that seem to be coming more common at FDA. So Sydnexis had out to solve a very specific problem to create an FDA approved version of low dose atropine and eyedrops to treat myopia in kids. This is in no way a rare condition. In fact, it's a huge problem and it's growing. Myopia that occurs while children are developing often creates lifelong vision problems, even blindness. It's growing as I said, probably at least in part because kids are spending more time with screens that are six inches away from their face and less time outdoors. So you could say, well, kids should just spend less time with screens and more time outdoors. That isn't happening right now, and until it does myopia needs to be treated. Many physicians prescribe low dose atropine drops. There isn't an FDA approved product, so parents purchase compounded drops, but the quality is really variable. It turns out that preventing atropine from degrading in these drops isn't simple, and many compounded drops have subtherapeutic concentrations. They also have a lot of contaminants. So Sydnexis is set out to create an FDA approved product. FDA recommended, or at least signed off on an endpoint for the Sydnexis trial of its drug SYD-101. The company conducted what it says is the largest trial ever conducted pediatric myopia, and it hit the endpoint. EMA approved the drug, so did MHRA in the U.K., but FDA issued a CRL according to Sydnexis. The CRL acknowledged that they hit the primary endpoint, but FDA said it doesn't believe that the company demonstrated efficacy. Physicians who treat pediatric myopia are apoplectic. One of the things they point out is that FDA Center for Devices has approved lenses to treat myopia based on less robust evidence of efficacy than this Sydnexis trial. So normally, FDA would've held an advisory committee meeting to discuss the application. Its thinking would've been made public, and it would've been pressure tested by academic experts. But FDA has sharply curtailed the use of adcoms, and it didn't hold one for Sydnexis' product. Here we have, it looks like we have shifting regulatory goalposts, a divergence between FDA and regulators and other jurisdictions, a lack of transparency, and parents and physicians using a compounded product rather than an FDA approved drug.

Stephen Hansen:

Steve, it seems hard to figure out exactly why FDA reached this decision based on all, you know, the reporting you had from other. the physicians and, and the company itself, and what was in the CRL. So I mean, is there any chance that this is just the FDA being severely short staffed and so they're having to issue CRLs as a way of trying to manage the volume of applications they're reviewing? Uh, I'm just wondering whether the staffing issues that we've already talked about, you know, previously, could in any way be playing into this or is there a way to know that it's not related to staffing issues?

Steve Usdin:

We really don't know. We don't have any insight into why the CRL. was issued. There are issues, you know, I spoke with some physicians. There are issues about the ways that you can measure progression in myopia. There are ways that FDA could look at the data and say, well, you know, we're not convinced about it. The problem, of course, is that regulators in other countries looked exactly the same data and found it persuasive. So you know if FDA has something else that it wants, I think that it has responsibility to the community, both to the parents and to the physicians to do two things. One is to explain what it is that, that this company didn't provide that they think is necessary. And two, to say, well, what would be a path forward? So the parents and kids could have access to an FDA-approved therapy.

Simone Fishburn:

Steve, you talked about FDA, looking at the data differently than the European regulators. Now that's not obviously the first time it's happened. In fact, I think we've generated some data in the past comparing, certainly I think it was in the context of accelerated approvals. How the two agencies look at it. Can you talk a little bit about how different this is from anything else in the past, whether you think that this is prelude or why you think this might be prelude to more discrepancies from other agencies?

Steve Usdin:

Well, actually, I think if you go back and look at it that most of the times when there's been discrepancy between FDA and Europe, it's been because FDA has been more permissive, it's approved things that weren't approved in Europe. Um, this is the opposite obviously. I think also that this isn't a lot of the, the controversies have been around products where there was, uh, where they didn't meet their endpoints or they were very rare conditions where there weren't large trials and there weren't large effect sizes and things like that. That doesn't seem to be the case here. And I would say, really, the core issue is the lack of transparency. You know, in the past we've had advisory committee meetings where these issues come out and we, we know the public knows, the physicians know the patients know where FDA's coming from, why it's made the decisions that it's made. All of those things are a little bit different from what's happened in the past. And then this gets back to what we talked about last week, which is, you know, 'cause this product, by the way, it's at CDER. So this gets back to what we talked about last week, which is what are the kind of changes that we can expect under Rick Pazdur at CDER? One of the things that I think that we can expect is more advisory committee meetings. And this controversy is kind of a poster child for why advisory committee meetings can be really, really important.

Stephen Hansen:

Great. No, I I think you're absolutely right Steve, and know, I also wanted to get your thoughts on, I think everyone's probably aware of the comments from CDC related to vaccines and autism. But I wondered if you could provide some perspective on kind of what you think the implications are for industry, maybe, just beyond you know, these initial comments.

Steve Usdin:

Yeah, so really quickly, CDC posted on its website, a statement that the claim vaccines do not cause autism is not an evidence-based claim. Look quick shout out to B io, they put out a statement this morning saying that, extensive scientific research with dozens of peer-reviewed studies and continuous safety monitoring over decades have consistently shown that vaccines in their ingredients do not cause autism. So here's the forward looking part of it, which is even worse or even more alarming, than what's happened to date, which is that where Secretary Kennedy is going with this is to investigate and to cast out on the safety of vaccines that contain aluminum, which he claims contrary to the evidence causes autism. Polling vaccines with adjuvants containing aluminum would re many essential vaccines, vaccines against polio, against measles, against pertussis. You know, it would have horrific public health consequences. So that's why I think it's, it's important to kind of stay on top of this one. And honestly for people to speak out, speak out publicly to prevent this from going even farther.

Stephen Hansen:

Well, thank you for that, Steve. We will continue this conversation in a moment, but we'll take a quick break and be right back.

Alanna Farro:

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Stephen Hansen:

Welcome back to BioCentury This Week I'd like to now turn to Simone to discuss a very interesting guest commentary we had from Franck Le Deu, Founder and Managing Partner at KerZheng Ventures, and Senior Partner at Emeritus with McKinsey. He highlighted some of the promising aspects of China's burgeoning biotech sector, but he also, you know, I think, shared some concerns. So what were your, what were some of your takeaways from his piece, Simone?

Simone Fishburn:

Yeah, so I strongly encourage people to read this, and I just wanna take a couple of minutes to give some sort of context here. So, Franck Le Deu recently left McKinsey where he'd been, oh, I'm not gonna say how long, but like a very long time. Like over 10 years. I'm not sure if it's 20. Anyway, he'd been there a very long time. He is a very, very knowledgeable and informed observer of the China biotech scene. He's also been involved with BioCentury and our conferences since we've started them 12, 13 years ago. And I think what's interesting is right now, as I've talked about, this is the year the rest of the world woke up to biotech in China. Franck's several steps ahead of everybody, right. So he has some very sophisticated thoughts about how the China ecosystem is working out. And he draws this analogy. I gotta be honest, I'm not a mixed martial arts. expert or even person. So I kind of had to look it up, to be quite honest, don't tell Franck, but anyway, he calls it, you know, is China entering the Oktagon, that's Oktagon with a k, which is a mixed martial arts concept. What he talks about is China being the world's toughest arena for innovation. But he draws some really interesting parallels with electric vehicles, EVs, right. And that was something where the China central government made it a really big priority to create EVs. I think early in the 2010s, you know, that has sort of had this global impact, arguably, he argues leading to Tesla. Many players now, rest of the world, U.S., Europe, Japan, South Korea, playing catch up. What he says is that the industry in inside China has unsustainable economics because it's got a very deep price war, over capacity is rampant and so on, I'm not gonna go into that in too detail. But what he says is, does the China biotech industry, could that go the same way? And he talks about some of the flaws that are reminiscent of these other industries. So I wanna wa just talk through a couple of the ones that he mentions, he talks about over capacity. It's another parallel. Too many companies going off the same target. Too many investors, insufficient capital allocation, insufficient rewards by the local innovation market, which is like China biotech's being driven to price war behaviors, 'cause they've got volume-based procurement of generics, National Reimbursement Drugs List, and it's not all sustainable. Geopolitics as we know, limits the ability to go to the West. So there are a few sort of, headwinds for that market. And then he talks about the ways that these flaws could be addressed and the certain levers, which I think Americans call levers, right? Whatever levers to pull.

Stephen Hansen:

That works.

Simone Fishburn:

And you know, market conditions access conditions could improve and flight to quality and so on. So I think that it's really worth reading. He sort of talks through the prevailing headwinds from inside China that are making that ecosystem. Might say vulnerable to some of the things that you know, other sectors like electric vehicles have experienced.

Steve Usdin:

He mentions also in passing, the possibility of Biosecure passing in the United States. And I would say from what the conversations that I'm having, it seems very likely that Biosecure 2.0 as we're calling it will be part of the National Defense Authorization Act that's likely to pass in December.

Simone Fishburn:

So let's just stay there for a minute, Steve, especially given the 1.0, the 2.0, and I know you've written about this, but let's just remind listeners. What actually remained in this?'cause it wasn't quite as draconian if I understand it as the first version. But what are the actual implications if or when this does get passed?

Steve Usdin:

You know, the, the problem is that we won't really know that for some time. Because the second version gives a lot of discretion to the administration in terms of what companies are swept up into it, and what the implications of it are for the marketplace. Basically, the biggest difference between the second version, the one that's likely to pass now, and the first version is, the first version mentions specific companies that would be subject to the Biosecure Act in particular WuXi AppTec and WuXi Biologics. The second version basically says, well, the, the administration is going to set up a process for figuring out what companies are so-called biotechnology companies of concern, and it creates broad parameters that the administration could use, they could, um, include the two WuXi companies if they wanted to, but they could exclude them if they want them also. So it's not known whether they're gonna be included. And then there's really also a certain amount of ambiguity about what it actually means. It's clear, or it seems to be clear that, for example, companies that use services from biotechnology companies of concern, after a five-year grandfather period, won't be able to sell their products to NIH, to the Veterans Administration, to other defense department programs. What really isn't clear, is the extent to which it would impact, for example, Medicaid, the Medicaid markets, and that again, is going to have to depend on implementation policies from the administration.

Simone Fishburn:

That's very helpful, Steve. So, you know, I just really encourage people to read Franck's commentary, it is in fact in front of the paywall. And I, I think that just gaining really knowledgeable insights from insiders about the opportunities, but also the headwinds for any particular ecosystem. Reminding people we are global at BioCentury. We care about all of it. Who's where and who can be where. Um, and the China ecosystem is obviously a very important one. So I really encourage readers to go to that. And I am sure that our trustee colleague Cole, will put this in our show notes. He's the guy who makes everything happen, just a shout out to Cole. We get a lot of compliments about the podcast, but really it's all Cole.

Stephen Hansen:

That's right. I'm sure he will, that's wonderful. Thanks Simone, and you know, I, I'm also just excited'cause I got to cross off one of the last few squares on my 2025 Bingo card when you talked about MMA, it was one of the few remaining ones. So nice to,

Simone Fishburn:

I am really excited to know what's on the card for next year, so I'll be, uh, yeah,

Stephen Hansen:

Oh, well, we'll, we'll, we'll keep that, we'll keep

Simone Fishburn:

we got the World Cup actually then don't we, we got World Cup coming up.

Stephen Hansen:

Hmmm, yeah. But anyways, let's turn now I would like to turn to Lauren, who herself had a quite an interesting commentary piece, looking at whether conventional CRISPR therapies will ever demonstrate commercial success. So, Lauren, give us a bit of context here, what were your takeaways?

Lauren Martz:

Thanks Stephen, and this is hard to write because I'm gene therapy gene editing's biggest fan. But recently there have been a few events that I think we've all Been following that have contributed to an increasingly negative sentiment around gene editing therapies. You know, this isn't news, but it got me thinking about what that opportunity is for what we would call conventional or traditional CRISPR-Cas9 therapy at this time. And it's crazy that we're even calling it traditional CRISPR-Cas9 because it's such a new technology. So one of the recent events that we may have talked about before on this podcast is the patient death in Intellia's Phase III trial of nex-z, to treat transthyretin amyloidosis. So in that trial, a patient died from liver toxicity, which presented outside of the normal window for lipid nanoparticle related toxicity. You know, this patient was older, had comorbidities. But it still raised the potential for a toxicity that we weren't anticipating, a toxicity that may be related to the target or the to the genetic cargo, or something else. And it, it's just an important reminder I think for investors and for everyone that there's still some uncertainty around the long-term safety of in vivo genetic editing therapies. At the same time that things like this have been happening, we've been watching this incredible rise of the RNA modalities, siRNA, antisense. And there's a lot of overlap in the indications that companies are treating with in vivo gene editing therapies, and with these RNA therapies, you know, transthyretin amyloidosis is an example of one. In both cases you can knock down gene expression. With RNA therapies you can do it pretty durably, these are dosed like every six months now and quite efficiently, during that durability window. So I think what's happening is that the difference in value that you could get from a one-time CRISPR-Cas9 therapy and RNA therapy is really shrinking. The question kind of becomes for patients and physicians, is it worth taking the risks of a one-time gene editing therapy to not have to take an injection, or an infusion every six months.

Steve Usdin:

Are there examples of things that can be done or could be done with CRISPR therapy that really aren't possible with other modalities?

Lauren Martz:

So that's the question that I was thinking about, and there may be. With the knockdown knockout approaches, there's a ton of overlap there. With inducing expression of a gene, this is something that you can't do with those types of RNA modalities. It's something that you may potentially be able to do with a prime editor for example, or some of the newer iterations of the CRISPR technology. But then the question becomes, if those are going to advance through the clinic. And we haven't been able to do that very efficiently with a traditional CRISPR-Cas9. You know, is there, is there an opportunity there either? I think all of this may become more clear as the technology is followed, as we learn more about the safety and efficacy in the long term. And I think there's also an important point to make here, which is that the CRISPR-Cas9 therapies that are in the clinic have been working incredibly well, and they just happen to be overlapping with a lot of other modalities, you know, some other modalities that are in the clinic or in development for the same indications. There are all of these unaddressed indications out there. So, I think that everyone should be spreading out what they're addressing with these newer technologies or with these alternative technologies, and continuing to develop, not abandoning what's effective because in the future there may be something that could be, you know, slightly safer, slightly more effective.

Simone Fishburn:

Yeah. So first of all, again, this won't surprise anybody. I'm gonna encourage you to read the piece. It's really very well written and It's just a very interesting field that we've been watching literally since its birth, we don't often get to do that. And, you know, acknowledging the huge impact. I think there's one point that you've made, Lauren, which is sort of in response to Steve's thing, is like we talked about herding, right, that Franck talked about, but we all see that as going on. And testing these new technologies at this point it really needs to be going into areas where they're not massively covered by something that could frankly just do better than them. But I do wanna ask you one question, you know, half of the premise, your piece say's like half of it is what you just said, which is like actually prime editing and base editing might be better served, we'll find that out, for some of the more specific or advanced mutations that you might want to address in disease. But then the other half of it is that RNAi so siRNA or antisense have really you know taken the business case, let's say, away from some of the CRISPR-Cas9 kind of gene editing. So for prime editing, whatever they came afterwards. But, siRNA and antisense has been around a lot longer than CRISPR. And so we've been writing over the years, like the market would go crazy in CRISPR technologies, even just on a preclinical preprint, it was insane. So what is it that this frenzy is all about? I mean, what I'm trying to say is that, that information was there also five years ago and also 10 years ago, about the potential for RNAi and antisense. And so why is it only now that that argument is coming to the front?

Lauren Martz:

In my opinion, I mean, we've watched these parallel indications advanced through the clinic. And you're seeing knockdown levels of the targets that are not looking very different. And I don't know if that was ever appreciated before. Maybe it was, but it, I I certainly didn't expect that, you know, in the 90s, regardless of what modality you're using. The whole premise of CRISPR-Cas9 was that you could do this so efficiently and you could do it one time. And so I think, there just wasn't a full understanding of how effective the RNA class of therapies could be, and how long lasting, you know, the chemistry has changed from where it started out, the long lasting oligos are, it's kind of a game changer, right? If you can dose it once a year or even.

Simone Fishburn:

Yeah, so what I'm hearing is that actually, antisense technologies have really moved a long way in the last few years. I mean, Stephen, you are nodding, I dunno if you wanna weigh in on that. And so, even though they've been around a long while, they've just got an incredible amount of validation, maybe extra commercial and technical validation in the last few years. Is that how you see it, you guys?

Stephen Hansen:

Yeah, well, well, I was just gonna say, I mean, one of the big game changers for the siRNA sort of modality was the GalNAc stabilization technology, right. When that came in, that really sort of changed things and allowed companies to move past that sort of delivery formulation challenge that they had faced. And, I'm kind of putting you on the spot here line, but I'm, I'm wondering if there's like a, a parallel sort of step change that CRISPR modality would need to see to sort of enable it to be able to have the same impact that we're now seeing from the RNA technologies? technologies

Lauren Martz:

I actually don't have an answer to that. I think as Simone mentioned, the markets have been really tough on the CRISPR gene editing technologies. I mean, the safety efficacy overall is very strong for the programs that we've seen. One thing that I didn't touch on in the perspective is delivery. So I think that back to Steve's original question, this is an opportunity, I think that's kind of still up for grabs, is which modality will get outside of the liver most effectively. There could be some overlap in the types of technologies that ultimately will be used for extra hepatic delivery. But, you know, you could use something different to deliver RNAi very well to, to different tissues. So, those are still just completely open, I think for, for both of these types of technologies.

Stephen Hansen:

I, I, I think just, just also real quickly just to comment on when Simone was mentioning about those, that heyday for CRISPR companies, when they were flying up a 100% on preclinical data, there was probably a real strong under appreciation for the safety issues that they could potentially face, right. And so now that they've gotten further into the clinic and some of those issues, unlike gene therapy have come to the fore, uh, I think there's a better, better maybe appreciation of the, the benefit risk profile that these therapies maybe potentially carry.

Simone Fishburn:

Okay well, I'm gonna jump in here because then shame on the investors, right. Like the, the risk okay of the gene editing technologies was there all the way along and we were writing about it, right. so shame on them if they didn't really have a good understanding of the risk at landscape. doesn't mean you're wrong. I'm just saying that, that investors need to do their homework. Lauren's not agreeing with me.

Lauren Martz:

I don't know. I just think it's been so up and down. You know, you, there may be a slight indication that you could have an off target edit and the stock prices tank. And then there dozens of patients are completely fine after being treated with this and everything seems fine. And then, you know, one liver toxicity, one severe liver toxicity event. It just goes up and down, I think there's been an understanding all along that the stakes are high for a one time therapy when it comes to safety.

Stephen Hansen:

Yeah, maybe one final thing is it's just also a reflection of how fast innovation moves these days, right. I mean, it's only been. 12, 13 years since we had the first CRISPR publication, and it's already potentially becoming obsolete, you know, too strong of a word. But, uh, I think it's just a reflection of how fast things move these days now. Got to stay ahead.

Steve Usdin:

I want to, turn the tables a little bit on Stephen Hansen and ask a question. We've seen the first clinical data on NLRP3 inhibitors in obesity. What do we see?

Stephen Hansen:

Yeah thanks Steve. when I host, don't you? You love turning the tables on me. Um, yeah, so we had the first data come in about a month ago, Phase II data, and uh it wasn't good if you were expecting an NLRP3 inhibitor to show weight loss. So a bit of context here, about 18 months ago, there was some very unexpected preclinical data published by private biotech company NodThera, that showed that an NLRP3 inhibitor can lead to monotherapy, weight loss, and a mouse model. And they also showed additive weight loss when it was combined with a GLP-1. So that basically sent every company that had an NLRP3 inhibitor, scrambling to test their own programs in preclinical models, and quite a few of them then quickly moved into the clinic. The first to do this was Ventyx Biosciences. They had seen decent weight loss, in a DIO mouse model, they showed 9% monotherapy weight loss after 28 days. And then, when they added it to a GLP-1, they saw more than what you got with a GLP-1 alone. So that was enough for them. They moved into a Phase II study, late last year, I think, uh, 175 patients, with their program VTX3232. So that study was the one that just spread out this past, a month ago. And, first glance it seemed pretty clear cut. There was no difference on weight loss from placebo at 12 weeks for the monotherapy arm. And then patients in the combination cohorts, where they had this 3232 program combined with semaglutide. The weight loss was actually numerically worse than the weight loss for semaglutide alone. So it seemed, seemed pretty clear cut. Right? I mean, I, I spoke to Ventyx’s Founder and CEO, Raju Mohan, for him he thought it absolutely was quite clear cut, you know, he basically said, there's no signal here in this Phase II study. there's no solid biological evidence to support the role of NLRP3 in obesity other than this hypothesis around neuroinflammation. So, you know, he thought it was pretty clear cut and dry, we tried it, doesn't work. We're moving on to other things. But as you might suspect you know, not everyone kind of agree with that conclusion. There are other biotechs, such as aforementioned NodThera and Neumora, that are pushing forward, and that is sort of based on their suggestion, their hypothesis that their compounds are either more potent or have a higher level of brain penetration, necessary to hit the target in the hypothalamus. So they're moving forward, they also feel like they showed greater efficacy in preclinical models. Yeah, you know, I guess, we'll wait and see. But, you know, I have to say, it was an interesting, finding when we first wrote about it 18 months ago, I now kind of consider myself, I guess maybe a bit of, a bit of an NLRP3 skeptic when it comes to weight loss and obesity. I'm also of the opinion that. I'm not really sure if it matters a ton because you know what Ventyx did demonstrate and what sent their stock up quite a bit was that NLRP3s, you know, are pretty potent anti-inflammatory molecules and they showed some pretty impressive, like 80 to 90% reduction in inflammatory markers, for CV risk reduction in their obesity trial. And so, I can envision a scenario in which even if you don't show any weight loss whatsoever, you know, you could see a scenario where you could combine an NLRP3 if, obviously if this, you know, anti-inflammatory CV risk reduction were to pan out. You could see this being part of the regimen because, you know, I think we all know obesity patients, you know, have one of the highest elevated levels for CV risk, of other patients with these comorbidities. And right now, you know, on GLP-1s, obesity patients get about a 20% reduction in CV risk, based on the semaglutide CVOT data. So if you can add on NLRP3 and you can dramatically boost or substantially increase that risk reduction level, even if you don't see more weight loss, I think there still could be a role for NLRP3

Steve Usdin:

So,

Stephen Hansen:

in this space.

Steve Usdin:

what would it take to demonstrate that? Because those kind of trials are not short and they're not cheap right?

Stephen Hansen:

That's true, that's true. It would take a, it would take, a CV outcomes trial of its own. So you're right, that is definitely not a space where your typical small biotech would likely be able to run a study. So they'd probably have to do this either with a partner or they'd have to be able to raise a substantial amount of money. That's, I guess, for the investors to try and figure out whether they think it's, it's worth the risk. But this isn't the only setting where they'd have to do that. I think Ventyx is also testing this molecule in a pericarditis, trial. And so that also will potentially require a CV outcome trial too. So these will be big studies. But, for instance if I just throw it a hypothetical. If you can double the risk reduction, I think that very well could be worth it, but we'll see. Well, thank you to my colleagues for joining me today, and thanks to all of you for tuning in this week. Before we go, I would also love for everyone, that is listening, if they could join us and participate in our current survey that we have ongoing about the FDA, there will be a link in the show notes, and I think Simone wants to provide some emphasis as to how important this is to us, so Simone.

Simone Fishburn:

It is important to us, Stephen, because it's important to them, to our audience,

Stephen Hansen:

That too. That's too.

Simone Fishburn:

we live to serve them. Yeah. So the survey link everybody is BioCenturysurvey.com. That's BioCentury survey one word .com. Cole aforementioned Cole. We'll have the link also in the show notes. This is a survey for investors and biotechs, in particular who've been working with FDA or other regulatory agencies, but this is specifically about FDA. We need to know what is working, what isn't working, good, bad. It only takes five minutes. It's an unbiased survey. We are really just taking the temperature. We are trying to get into some of the very specifics of parts of the agency and interactions where sponsors are having productive outcomes or interactions and areas where less so. It's not a superficial survey, but it is a quick one.

Steve Usdin:

I wanna point out that it is anonymous also. Because I've received concerns from some people who were thinking about filling out the survey, and they're concerned about anonymity, it is anonymous.

Simone Fishburn:

Our surveys are always anonymous. Thank you, Steve. That is really important and we will be presenting aggregate data from the survey before the end of the year. If you all do your job and fill it out, then you'll get the answers before the end of the year.

Stephen Hansen:

Great. Thank you Simone. and thank you all for joining us. As I've mentioned before, all of the stories that, uh, we've discussed today, you can find at BioCentury podcast.com. You can also check out our sister podcast The BioCentury Show, where believe the most recent episode featured Steve, in conversation with Elias Zerhouni former NIH Director, and after that Global Head of R&D at Sanofi. Thank you again and we will catch you next week.

Eric Pierce:

BioCentury would like to thank Voyager Therapeutics for supporting the BioCentury This Week podcast. To learn more about Voyager's programs advancing transformative medicines for neurological diseases, visit voyagertherapeutics.com.

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