Episode 189 - July 17, 2026

you're listening to Biotech Hangout, a live and unedited weekly discussion of all the newest and best in our industry with a group of biotech leaders and experts. I'm your own Werber with my co-host today, John Morganore, who's gonna join in a minute, Sam Fasselli and Matt Glign, for more information about our hosts and guest speaker or to listen to the most recent episode, please go to biotechhangout.com. So we have literally an action-packed agenda, and I think we're gonna be remiss if we're not gonna start off by talking about the most important news in the world, in the opinion of N of one myself, when that's the upcoming third and fourth place for the men's World Cup, "Socre Final" tomorrow, and then of course the World Cup, "Socre Final" on Sunday. And we have with us today, we're very lucky to have Sam, who is very close to both England and France. And so Sam, what's your prediction first of all for that game, and I don't know if you wanna share with us who you're actually rooting for? - Yeah, well, remember your own, I'm kind of perfectly hedged here, because I love both countries very much and I live in both countries. So I can't lose, however, I think if England play the same way they've played with the Argentina game, then I don't think they have much of a chance in surviving this particular one tomorrow night. But it could be close because France did and do that well against Spain either. I mean, there was a pretty, pretty abysmal performance with Spain being really solid and tight, so it's very hard to call. I don't know. You probably, I don't know, I really can't tell. And to be honest with you, a hell of a whole bunch of people are saying, what's the point? Who cares? Right? - Well, I got, that's my family members, my daughter and was asking you, what's the point of the game? And I was like, well, you clearly don't live in the UK or France. I mean, this is still a very important game. And Tim Matt, what do you think? I don't know if you have a view. UK or France? - We have a close family friend who's Senegalese and rooted in order for Senegal and then France and then England. And so a Vestor who to bet against on the basis that maybe I can make some money that way? I don't have an axe in the England vs. France game. My son, who's four, has decided he's for Argentina. I'm not sure why, but I guess I'll support his judgments. - Yeah, he's a very smart, he's a very, he's gonna be an amazing biotech investor if he's supporting Argentina. - I like that. - As with any biotech investor, is it lighted on the right answer at random? - John, what do you think? Who is the easier for the three versus four? I think it's gonna be France. I think they've just got, I think they've got a stronger team. Although I'm sure England wants to do it more than France. And I think Argentina's gonna take it three to two on Sunday. That's my prediction. - I love the accuracy there. Well, John, this is why you have a successful CEO. We're still here judging biotech competition. - Sam, what do you think of precision? Not accuracy, precision. - A precision. - Yes, sorry, because accuracy is only post, post-avent, right? - Exactly. So three, two, and is it going overtime? Or not going overtime? - Oh yeah, overtime for sure. Oh yeah, yeah, yeah, totally. But overtime, three, two, Sam, what do you think for the final? - I do fancy Argentina. But then my close colleague, Heavier is from Spain. So I'm gonna have, and we have a Spanish flag hanging off his back of his chair next to me. So I have to bear that in mind if I want to my life to be worth living for the next year. - And Matt, what are you picking for the final? - Well, like I said, I've got to follow my sunset. So I'm for Argentina and have no idea of the score. - Yeah, so I'm, okay, I'm going, I'm taking France. They've looked way too good. I don't know if you saw the statistics, I mean, we probably all watched the games. For the last 20 minutes, 21 minutes of the Argentina against the UK game. Literally, there were H-shots and goal from Argentina. They controlled 93% of the possession. They completed like 180 passes versus seven for England. I mean, it's mind-boggling. How well they did. I think it's not the function of the strategy for the UK. - Yeah. Can you bet on the games through a Calche as well? - I, I'm, I'm, I'm better than you can. - Well, I'm, I'm bad enough doing my day job and I don't bet on anything. - No, not you specifically, but through that. 'Cause that's the topic that I think I might touch on later. - Yeah. Anyway. - Anyway, I'm, I'm, I'm picking Argentina 2-1 and I'm, I'm worried about, I'm a little worried about that game. I think Spain looked extremely good. Yeah. Okay, well, let's now shift over. And let's not kind of, we're going to do macro. We're going to stop from the top and kind of dive in. Matt, maybe give us a little bit of a sense. Kind of what, what are you saying? There's been a lot of volatility in biotech. What kind of questions are you getting from investors? And obviously you're running a pretty stable promising company at this point. So the, the, the whims of the markets are a little bit less important to you right now. But how does that impact your ability to execute? - I think your stability is all relative. I am, I was, you know, sitting around last Friday and you know, you're CEO, you check the market at some point and you realize your stocks down four or five percent. Your first thought is like, shoot, what did I say? And then, and then you realize that what did a competitor do or something like what happened that I'm missing? And then you realize that the index is down, everyone's down, you're like, okay, so like, this is a Hillary Clinton tweet situation, like some public official said something, let him offend pricing or, or, or whatever. And then, and then that's not true. And you're like, okay, it must be the Fed or interest rates. And that's not true. And finally, you throw up your hands and you call an investment bank and you're like, what's happening? And they say, oh, it's factor driven. And you know, so this, this happened to me on Friday. And I was like, well, what does that mean? And they were like, it's James Street, lame James Street. So I called my friend at James Street and he was like, it's not us. And I was led to believe that, and this is like an interesting lesson about the markets at this stage. Like, I think I am probably or like me and my team or the people who know the most about the trading dynamics and Roman stock, we talked to all the investors, et cetera. I think it's just impossible to know some days. And I found that like an almost zen thought as I went around my job. So that's been sort of my experience the last week. And investors all have Pat explanations like SpaceX is down or whatever. But I think the honest answer is, sometimes you just gotta throw up your hands. - Yeah, so much of it is the momentum in RSI indicators, right? Four percent is like nothing these days obviously. - Any, but any, you know, in general, are you seeing anything in the macro environment that you're spending time on, the board is thinking about? - That's not really. Honestly, for us, I think our view is, we've been on a good run and have a lot to do and I think mostly we're focused on stuff that's specific to us. I'm interested in like whether the market dynamic around companies like ours is gonna change at some point and that could have sort of read through effects strategy, but there's not much for us to do about it in advance. - Okay, make sense. We'll come back to you because you're uniquely suited. You're hopefully not gonna what should be launching a drug pretty soon over literally the next two months, two and a half months or so. So I'll come back to you in a minute. Maybe, John, let me go to you next. So we're gonna shift over and talk about Lily is continuing. It's, I'm gonna misspelled. I'm gonna miss pronounce it, the Amazonification of Pharma, acquiring a variety of different companies. They just literally bought a tie-backly for 2.8 million up front plus the 1 billion CVR. That's a psychedelic company. And then in general, there's also an economist article where Lily's not really reinventing the pharma business. What do you thoughts on that? - Yeah, no, I think, look, Lily is just a fascinating story right now and we've heard a lot from Dave Ricks on a number of podcasts that he's done and so forth. And I mean, they're really paving completely new territory as our industry's first trillion dollar business. So it's just fascinating to watch what they're doing. I thought the economist article that came out this week was really interesting. It was about Lily reinventing the pharma business was I think the title of the article. And it talks about Dave's real conviction to remake Lily, go from something that's a traditional drug maker to something that's frankly closer to a tech company at some level. And a big part of that is their shift to focusing on prevention of disease as opposed to treatment of disease, which I think is absolutely the right direction to travel for them to make and others to make as well. And they're barring a lot of playbook ideas from Silicon Valley, which I think is super interesting as well. I mean, one dimension of this, of course, is they're getting a lot closer to the patient and the consumer and they've launched a really interesting effort for commercializing their medicines with Lily Direct, which integrates telehealth and direct to consumer. based strategy effectively going around the PBMs in that regard. And it just shows how they're thinking about digital in building their business. So that was the one thing that one article this week that I thought was super interesting. People should take a close read. But the news this week for Lily was around the tie acquisition. Again, a $3.8 billion acquisition, $2.8 billion upfront and $1 billion linked to a CVR. And a tie is one of these psychedelics companies. They've sort of been arguably on the fringe of some of what we all think is biotech because it's psychedelics. But of course, it's a category that is proving to be pretty important for people with treatment resistant depression, which is a major, major, major, major problem. And the lead asset here is a nasally administered treatment for depression. It's currently in pivotals. So they're buying ahead of the readout, which is a strong and aggressive bet on their part. But arguably, is the right way to do it if they have conviction in the mechanism and the pathway. The other thing about the deal that I sort of find interesting because I know her personally is one of the first deals under Carol Ho's leadership of Lily's neuroscience franchise. Carol is a terrific physician scientist leader. And somebody that Lily poached out of Denali, where she was the chief medical officer. I believe was earlier this year. But anyway, it's good to see Lily continuing their remarkable transformation. They're continued buying spree in the industry, looking for innovation consistently in many different places. And at a personal level, it's great to see Carol taking the lead on this acquisition here from Lily. But Lily is-- I'm sure going to be a frequent topic for this hangout. Yeah. Sam, what do you think? Yes, so that Amazonification comment can partly from me. And I think the reason I use that is that they seem to be going in every possible area of farmer. Now, I'm pretty sure they're not in every single therapeutic category. But if you remember a couple months ago, they did three deals almost back to back in infectious diseases. And then here, this is their third DNS type disease that's outside of-- let's call it the neurodegeneration. I think it speaks volumes to how they're thinking about the future, which will inevitably include some kind of plateau or pressure on their obesity franchise. Plateau, if they continue to keep innovating and replacing, or pressure, if someone else gets a meaningful position in here and at some point, there's some patent-experi or something that puts-- and I'm talking 10 years down the road here, right? So I think the more I see this and John's comments for really fantastic on this, particularly his insight on who's in charge in the neuroscience parts of Lillie. So that's the way I see Lillie going. And I think probably is the only way to be managing such a massive future dilemma that will come. I don't know what else to call it about potential risk that will come up. So over here. What I love is that they're just being so proactive about it. I mean, a lot of companies would say, we've got 10 years of amazing growth in front of us, and we can let it ride and take our time and being urgent about it. But boy, they're just showing nothing less than incredible urgency around that future build and the future product opportunities that they need to have to be able to bridge the gap of just the ginormous amounts of revenues. And that's smart. It's just so smart. And the proactivity is just remarkable. So kudos to that team for doing what they're doing. Yeah, absolutely. Let's move over to-- Biocentric-- by centuries actually had a very nice article yesterday reporting that 40% of Newco's originating from China are now first in class, which is actually the departure from last year. I think this year there's been 14 or 15 newcoves. I think it's more or less in line with last year. But of course, four of them are-- I think it's like four out of the 14 or so. It's about 36 to 40% are now novel. Matt, maybe-- I know your team is constantly on the hunt for assets. What's changing in China? Yeah, I mean, I'm on the record in a bunch of different settings as saying, I think that China is a little bit of a smoke train or a red herring for other dynamics that are changing pretty quickly on the technology side around the commodification of anybody development, around certain kinds of even small molecule chemistry, either with or without AI, getting easier and more reproducible. And about that stuff getting pushed to places that can do it cheaper places that can do it faster, obviously, China-- the current leader there, although I think to the question of politically-- what would happen if we closed off innovation from China? I think it would just happen somewhere else. But I think it's pretty remarkable the speed with which we can now move things-- we collectively globally can move things from an idea to an experiment. And I think it's a great thing that there's more novel targets coming, more-- I don't particularly bias toward the novel targets-- more drugs of any kind coming through the pipeline ready to be tried. And some of the best drugs we have are sixth generation on the same target. And some of the best drugs we have are the first of their kind. And I think they're all great. I do think we, like everybody else, look to China among many other places for new assets. And I'll say, if you compare the sort of surface area of where you find things now to 10 years ago, it is radically different in that-- I think like whatever. There's been a lot less in licensing deals by US companies from Japan, for example. And obviously, just like way, way, way more from China. The one thing that we still have going for us as an industry in the US is what does everyone who invents a new drug anywhere in the world want for that drug? They want it to be studied in late-stage trials in the US and approved for use here. And to be honest, a lot of it has to do with our high pricing for drugs. But nonetheless, it means that innovation around the world winds up benefiting us. And so I think it's a pretty exciting moment. Yeah, I completely agree with Matt on this issue. As you guys probably know, I think it's, I think, for patients and for what our industry really focuses on, which is bringing medicines to patients, having the sparks or the initial sparks of that innovation coming out of anywhere in the world is great. And ultimately, we bring it here to this population and this market because it is the greatest place for reward of that innovation. And that's what attracts it all here at the end of the day. So the American patient does benefit enormously. I thought the bio-century article was interesting. I mean, it wasn't. They called it the Asia to West Newcastle, and it turns out that they include Japanese, a couple of Japanese assets out of the 14 or 15 that they were that they studied. So it wasn't only just China, per se, but I do think that it probably reflects the Matt's comments about just forgetting the exact word to use map at the sort of the breadth of where things are coming from. And obviously more and more coming from China, which is an opportunity. And so, anyway, something to watch in the big China debate, which of course is a bit of a polarizing topic for people, but one to continue to reflect on. Is the data by and large completely reliable now from China? Right? Five to 10 years ago, there was a sentiment that it's not reliable. I think now it's a lot more reliable. But we still hear from bigger companies that are very active in that area, and are actively licensing. So they're there and they're believers, but they're very much saying that not all data are created equal, not all data are trustworthy. Any thoughts about that? I think that's true. By the way, I think that's true. It was a big study recently, John, you might know. The study testing Kichuta, whether you gave Kichuta in the morning, whether you gave it at night. Yeah, right. And did up the amount. The bank, yeah. Yeah, yeah, totally. Yeah, no, look, I think there's still, you know, I mean, there's still gaps in quality of data from different groups. And I think it is a bit of a wild west. And so you have to be super careful about understanding the quality of anything that's true here too. But I think it's because of the volume, and sort of the speed aspect of things in China, which is a positive feature in some ways, but also a negative feature when people are kind of in corners to try to get things done quickly. So it's just, you know, you have to take all these things in balance and buyer beware or people should be diligent, need to be diligent to make sure that they're getting quality at the end of the day. Well, man, what do you think on that? Look, I. I often think these sweeping statements about the data is good or bad from X-place or X-people are good or bad at respecting IP or whatever are mostly. You got to look at the person saying it, but I think they have other incentives behind them in almost every instance. But I do think like there will in life be trade-offs between regulatory speed and clinical trial speed and manufacturing speed and cost and quality. The thing you hope is that you can advance along that curve, so it's what was possible in six months at low quality before is now possible in six months at high quality and whatever. But those trade-offs are going to exist and some of the very same things that make China faster are probably also things that would contribute towards a little more variability. And you just like, if you run a big study, you're going to get less variability through your own small study at some level. And so I think all that's going to obtain. My personal view is, look, I think the proofs in the pudding, there's lots of great drugs invented in China, studied in China, they're now being studied in large studies here. And first of all, in many cases, the data has panned out in second of all. It doesn't really matter because the phase three study is going to be the answer that goes on the label. >> Yeah, bet. Maybe let's tuck in. We have a regulatory and policy section later on, but I think this would be a good tuck in here. I mean, we could be brief about it just given how much we got. There's a company out of China was advised by FDA, not to file because the drug is manufactured in China. >> I'll pitch into that because that's what I heard. And obviously, I can't tell you what the company was. But it was a very, I double checked the fact and that's exactly what it was. So I don't know if how new this is. This is not about data. The data's been generated in the US. It's not even some of the patients are in the US. The US trial being conducted. So the question ends up being, why would manufactured product in China not be acceptable? Is this a completely new thing? Have you guys heard this before or how does this fit with what you know and what you think? >> Well, Sam, I wondered, I don't know any of the details here whatsoever, but it's not unusual that a given site in a given country or state or whatever as a manufacturer does not meet FDA standards. And that would lead to a, you know, could lead to an RTF at the FDA is a wear of an advance of a filing or could lead to a CRL that happens all the time, right? But I don't know the specifics in this case. >> Dozens of approved drugs in the US are manufactured in part in China. So it's certainly not the case that the current view of the US regulators is that drugs that are manufactured in China are not eligible for sale in the US. Beyond that, I think it's just like really hard to interpret without more detail. And this could be as extreme as a strong political commentary by political point D's at HHS that could have drastic implications or it could be that simply a specific manufacturing site wasn't up to snuff. And for various reasons, people are choosing to describe that as an anti-China stance in order to achieve some objective. >> So something to watch? >> Yeah. But I agree with Matt, I don't think there's any reason to think there's a broader theme here, given just the larger numbers of drug products that are manufactured in China. >> Okay. I'd perfect. Matt, let me maybe put you here on the spot and then John would love for you to comment as well. Just given your extensive experience kind of launching drugs. So Matt, your Reuvans is expected and we're certainly expecting Breprositney to get approved for their monomyocytis, for the audience. Many of you know the drug. It's a Jack one/tick-to oral inhibitors that showed very, very nice positive valor phase three data. Our consultants and all our work suggest this is going to be one of the best launches in the sector. The Padufa is coming up. The guidance is to launch in September. So in the next two and a half, one and a half, two and a half months. And we're modeling several billions, I think we've been consistently saying we think this is between six and 12 billion dollar product. So it's got four different indications now in pivotal testing. The next one we'll expect in nine infectious UVI just two phase three data by the end of this year. And we should be positive on the heels of the positive phase two data. So this is going to be probably the next big launch in biotech. What's interesting is about 20 to 40% of patients are taking Jack inhibitors off label. So there's our physicians are already warehousing. Physicians want to switch. And there's obviously a high-med need because currently stem of the care is IVIG, which is extremely inconvenient. So the question is this is going to be, this is not the first drug that Roivin is going to launch, right? You've launched another drug in the past. But I think this is certainly going to be the biggest. So one question is how do you price IVIG's one barometer, 225 grand. The next drug that's going to have data is Vivgard. Vivgard on a gross basis with weekly dosing is 870 before gross to net. So maybe how do you position Roivin to launch? How do you think about pricing with the first launch, first indication and three more to come? Yeah, thanks. Thanks for your own. We've said lots of times we're not going to give much in the way of like specific launch guidance because you all are mean to companies that do. But look, I think you gave two bookends on pricing. I think we've basically said those are our bookends as well and that will be somewhere in that range. Probably frames the way you just framed it closer to the lower end of that range and the top end of that range. But that still leaves a pretty broad range. You know, when we've talked about Vivgard pricing in the past, it's been more of a sort of a $5,600,000 number and I think we'll fall between those bookends. I think it's a privilege to launch a drug with great data. It's privileged to launch a drug that doctors care about and that we think patients will care about. Obviously, you know, I made a comment earlier about how sometimes the best drugs available are, you know, late in class or not the first in class, obviously, Jack inhibitors have been around in different forms for different purposes for a while. And I think Breppesitna is a phenomenal example of a sort of current or next generation Jack inhibitor. And I'm really excited. The last drug we launched was a topical in psoriasis. And I think our experience there among other things convinced us that we want to launch a lot more drugs like Breppesitna. But the other thing I'll say is we're coming in a moment where we get to watch or have gotten the privilege of watching a number of other companies, including El Nilem, on-sterox, extremely successfully, especially in this kind of orphan zone. And so I think we're trying to soak that all up, learn every lesson that we possibly can and stand on the shoulders of giants, so to speak. Yeah, no, super, super interesting. And of course, that's the, you know, as you think even launching a drug these days in terms of getting formula replacement, getting on guidelines, how are things maybe different now? And John Chiamin, then they were they were 10 years ago. I'm happy to speak and then John can speak for you. Yeah, you start, Matt. I think, first of all, to all of the payers listening, I'll remind you, dramatic I said, this is not a large patient population. This is not going to be a huge budget impact. Look, this is an orphan disease. This is a relatively small number of patients and the grand scheme of things. These are patients with a high M that need high medical burden. And I think access, with every one of these launches, what every company in our position says and what I think the industry is largely delivering on at this moment in time is every patient that needs this drug should have access to it. We are committed to that. And our job is to get drug to patients and then work with them to navigate the US healthcare system to get it paid for. And the honest answer is in these markets, in orphan, in orphanage indications with high morbidity in general, that seems to work. And it's not, look, I think payers have a job to do in that job is to make sure that these patients need drug. And I think, you know, we have to work with them to make sure they're doing that job effectively. But in general, I think what the world will find is that these patients need this drug and they're going to be able to get access to it. So I think a lot of techniques have arisen in the past half decade to make this work. I think these are not generally, when they're not sort of by definition, not highly competitive markets. It's not like there's four big pharma companies competing with rebates in this demand by satisfactory space. And so I think these are generally not rebate intensive markets. And what you wind up doing is you have good bridge programs and great patient support people and you work with the payers to get it done. You know, the one thing, the one thing that I think, you know, we experienced it in launching many of our drugs, all our drugs, was working very proactively with payers and even setting up, you know, pro value based agreements at the beginning. And that turned out to be really positive in terms of reducing, you know, what ordinarily could be headwinds. But, you know, one of the reasons we were able to do this, we had a standing data like Matt does as well, which is really important. And then on top of it, you know, we had a way that we could engage with the payer in a setting where the budget impact was not going to be enormous for them, right? that helps as well as one of the better. benefits in the rare disease space in some ways. So I'm sure, you know, Matt and his team are doing those type of things, but those are changes in the system that are, I think, positive and do enable smaller companies to be very successful in doing launches, which is great. - All right, well, fantastic. All right, John, let's last stay with you. Can you talk about buyers' response to the OMB proposal regarding to the political influence on federal grants and kind of what's the latest there? - Yeah, look, I was really happy to see bio come out with a statement on the issue. You know, I think we've all heard of, you know, the proposal to have political decision, political operatives make decisions around either continuing a grant funding or authorizing a new grant to be funded. And, you know, I think all of us have been hoping that the industry associations would make some statement around this, 'cause nobody finds it as being good policy. Bio's response was a pretty sharp review of the OMB proposal, you know, stating amongst other things that, you know, it would destabilize the research ecosystem that it would weaken merit-based funding decisions that would weaken US competitiveness undermine US whole security among other concerns. And it's just great to see our industry association making comments in defense of our academic research enterprise, which again is the top of the funnel for biomedical innovation and so important, as well as the top of the funnel for training of our future scientists. And it is important that that gets done in a merit-based manner like it has traditionally and that political influence is not a part of that, part of that picture. It is also a reminder that, you know, we all need to be vocal on some of the administration policies for any administration, not just this one, but, you know, previous ones that can weaken innovation and we must all be, you know, part of the process of making sure that, you know, we defend our industry and defend what's important for getting medicine to patients. - Okay. Well, let's go to next into a very juicy topic and Sam, I'm gonna maybe call on you first. Kalshi is recently announced literally in the last two days that they're going to be opening a new venue to bet on clinical trials, outcomes, and regulatory approvals. They are going to put guardrails to make sure preclude any inside trading, preclude anybody with non-public information from participating - Teleprompter. - Teleprompter people. (laughing) - Teleprompter people. (laughing) It's gonna be later stage clinical studies. It's gonna be restricted to companies with market cap about 500 million. And this led to a lot of questions, both frankly supporting it and also on the negative side. Some of the supporters said that this is a free market. These are gonna be a great way to play clinical studies and not play stocks. Maybe it's gonna lead to less volatility in stocks. Some people even thought that potentially based on this, patients will be able to kind of look at what clinical studies are given a high chance success. And you know, on the personal basis, might one enroll in those studies and opposed to the other ones that are less likely to work. Of course, the drawback to all of this is then had you enroll the other clinical studies if that becomes norm concerns about integrity of data, concerns about more volatility in the stock market and obvious ethical issues, it's in regulatory issues, et cetera. So Sam, maybe with you, one of the companies that is a partner is applied Excel, which obviously in Bloomberg, you guys have had a relationship with what's your thoughts about all of this? - Yeah, so just for this closure, we do have a partnership with applied Excel. They are an excellent team with whom we're doing some exciting stuff. So I mean, all the things that you've just listed, are all, I would say, fair, the criticisms and the positives. And I think it's something that this market needs to figure out as it happens. Because unless the regulator's getting the way in terms of stopping it from happening, then I think it's going to be something that will become part of our lives. We have to see how big a driver it becomes, you know, for it to become a way for patients to decide which trials to go to. I mean, this is going to have to become a very major source of information flow with regards to the numbers of bits that are put on, if you want to call it that, or the number of positions that are taken for against the trial, et cetera. And so I think that, a lot of times I say to my team, and I think we will, let's have those problems when they occur. I mean, of course, you have to be in front of them and be prepared for them. I think the company, Kelshie, has put quite a lot of restrictions on the types of people who complain in it. In the list that I saw, I don't think I saw patients particularly necessarily in there. But, but, you know, I mean, what I'm looking forward to is being able to get some kind of prediction over time statistical analysis of whether it's a pretty, if they actually do predict the outcome of the trials. Because that could be an interesting way of using probability of bringing another new probability of success into our calculations. So I'm sorry, I'm being very academic about it here. But in all I can tell you is that the group that we work with are sound and solid and very ethical. So how this pans out, I think time will tell. So I can't judge it more than that, to be honest, over. - I agree with you Sam. I think it, look, I think there are concerns that should be discussed and they are being discussed. And I think that's good that they're out there. It's interesting to be that there's selecting companies, larger companies where, you know, ordinarily one can't really generate, you know, a bet, you know, if you wanted to look at the buying stock of Santa Fear, Gilead, for example, which are two of the companies that are apparently FH3 trials that are being considered, you can't necessarily enjoy the benefits of a prediction, you know, based on, you know, just the size of those market caps and so forth. And this does allow you to sort of parse out the, you know, the specific trial that's being investigated for that purpose. So that does have an interesting, you know, flavor to how they're doing it. So we'll have to say, but I do tend to agree that let's, it might be worth, instead of worrying about something and not allowing it to happen or permitting it, might be worth seeing how it goes first. - I mean, honestly, we do have much bigger problems, potentially brewing with regards to AI and jobs and security and all that. So nobody seems to be putting a block in that and we're worried about one thing here. Of course, that's our job, right? But let's see, let's see what happens. I might give you a new, - What? - But it's a success measure, you know. - One one fun thing is you can bet on the approval of a brevacitant of uncalty now. It's one of the contracts. So there's about $3,000. Yeah, it is. According to CalChi, we have an 81% chance of getting approved by the end of this year. So. - Oh, that's good, right? - I like the one percent in that. - Well, that's, well, the bid offers, it's 81 to 26. And I think, yeah, so it's, so, it looks like 81 to 74 is like really where the order book is. And it looks like there's about $3,000 stake down inside. We had a brief debate inside the company. Yesterday, but whether our insider trading policy forbade employees from participating in this market. So, you know, I think that's your disadvantage. - I forgot to forbid it. - We haven't issued a formal decree yet, but I would not be happy to find out that my employees were running on trading on CalChi. Is the honest answer to that question, although I have no insights, the truth is I have no insight in information as to whether brevacitant will be approved. And really it's the FDA that should be making these rules. I, it's a, to me, it's mostly an entertaining curiosity. I will say this to Sam's comment about probabilities of success. My prediction is it is a long time before anyone does a proper statistical analysis of whether this is a good or bad predictor. And frankly, it would take a lot of, whatever the thing you're betting on is, it would take a lot of ends to actually answer that question. So I'm not, I'm not that optimistic that we're, we're gonna know for a while as to whether this is a good or bad tool from that perspective. - The math I intend to be doing an analysis to the front of the 20 years. Hopefully it can get some answer by then. In 20 years, it's gonna be all like clawed betting against anthropic on the, or clawed betting against open AI on these things, right? We're not doing enough to do it. We're just gonna watch the robots talk to each other about it. - That's a scary, scary thought. - They're gonna write the analysis reports too or so. - Exactly. We're still waiting for that to happen. The look, I think conceptually, this is absolutely a need. So why not have this tool? It's just a question, I'm more concerned on the regulatory side to be honest. This would not be good if you're having physicians, betting on the top. or nurses even in big open label studies, you know, or even in, you know, the regulatory element is I think is the stickler for me. Okay, let's move to another one, exciting news. John, gonna maybe call you on this one. Yeah, this is so close to your heart. Mark's lip fendera, it's the oral PCS-K9 drug was just approved. It's the first one. That one does have good data, almost almost kind of antibody like PCS-K9 reduction. I might butcher this one, but this one does have the food effect and AstraZeneca, I believe, does not come you right behind it. Thoughts about is this going to be a revolutionary drug? They have great data, but they don't have outcomes yet. Our outcomes important, or at this point, we know that the lower the better on LVL, that's no longer questionable, and do you really need outcomes? And then I'd love to, if you can comment, about the exciting work that Corsero is doing too. Yeah, no, no, absolutely. Look, I think it's fantastic. It's great, great to see this approval. You know, PCS-K9 was one of the poster child undruggable targets for long time, and you know, Merck succeeded in, you know, as easy as following with a macroscopic peptide that binds to PCS-K9 and inhibits interaction with the LDL receptors. So it's really an exciting piece of science for starters. And, you know, it is going to enter a market with PCS-K9 inhibitors that is now, you know, multi-billion dollar market with Amgen and Repath and Leid on that side of it, you know, second in the mix is Novartis and Elmylems drug, let Fio, which was fun to bring to market along with the medicine's company. I think it's going to be wonderful to have another option for patients out there. It is priced. It's interestingly priced under the price of the antibodies. So $3,800 per year, compared to roughly, you know, $5,000 to $6,000 per year for the antibodies and the SRNA products that are currently on the market. And now, you know, of course, with older rebateology, I don't really know what that means at a net basis. But it's interesting that that's where they landed on the pricing. And it's also interesting that this was a drug approved under Marty, Marty's CNPV program that he brought forward. So I'm excited to see how it launches. I'm going to predict that it will do well. But let's see if Calci agrees with my prediction, ultimately. On a personal note, it's obviously an area of interest because we're developing it. Of course, Sarah, one of my, one of the companies I'm building, you know, a PCS K9 and Andrew Tencinogen, SRNA, given once a year for prevention, which is a different market than different population than where this drug is approved. I still think that in the setting of prevention, especially primordial prevention, that lowering the disutility of these type of therapies with once a year administration, compared to a daily pill, is going to be important because the adherence issues are really prominent and problematic, you know, with statin-based drugs. So anyway, it'll be great to see it and follow it. I'm really excited to see a come to market. So John, quick question for you. The question with Coursera is path to market. And I know this is something that you're, you know, you're in cloud, obviously, very much pioneering with the team. Any updates there? And I'm not sure if that's suitable for you. Yeah, I know it's fine. I mean, I can tell you what we tell everybody, which is we expect to run to studies for approval, one biomarker based and the other outcomes based. And so there will be an outcome study. They'll need to be, I don't think the outcomes data will be an impediment for the fendrous initial launch. Obviously, it'll be supportive when the data mature enough to be made available. The same will apply with what we're doing. So now our outcome study will have to be much larger because of the fact that it is a primordial population with the event rate being lower. But, you know, there are ways of enriching populations to make that more tractable and doing clinical studies with reduced costs, which is what we aim to do. Yeah. A what point outcome study is not going to be required. I mean, we know, right? The lower the better, even a 20 20 makes a best a leader conferred. This is back to one babes of born, right? Yeah, confers. Yeah. Well, they're not they're not required. They're not required for approval. I mean, they've nothing required for approval for a while, which is, which is good. I think everybody believes that, you know, they they are helpful in supporting the business case, right? So I, I, you know, and I think that's why they continue to get done at some level, you know, especially in unique populations. I mean, you know, our population has not actually really been studied, you know, because we're talking primordial primordial prevention, which is, you know, much, much earlier in people that are predicted to have a high lifetime risk of developing a CBD and and artifacts and strokes. So it's a bit it's a bit of a unique population. But, you know, we do think approval can still be done with biomarkers at the end. Yeah. And so the natural question is, is, you know, do you have a sort of a target LDL level? Because you can go, it depends on the risk patient. And obviously, based on characteristic family history, do you go to 70, do you go to 40? Do you just go below 100? Yeah. Yeah. I mean, you know, again, we're we're going to we're going to target primordial prevention. So that doesn't need that to be, you know, over the guideline limits of what currently is indicated for treatment of hypercholestrolemia. And also in a younger population. But that's based on the the belief that we can predict lifetime risk using an AI and able tool, right? So that's the key, that's the key of what we're doing in our approach at the end of the day. Yeah. Yeah. Okay. Terrific. You know, I'm just one last thing to add here that that Astra's master's ambitions is to do a combination with their oral obesity drug. That's what they've talked about. Whether there's a fixed dose combination or not, I don't know, but that's one of their ambitions over. And what's your thoughts about that? I mean, there's so much going on these days in longevity. I don't know. Yeah. And then I don't know if you need that. If if John's successful with an annual drug, which is priced more achievably, then what do you need that? Right? Yeah. Okay. Let's, John, let's stay in and we do want to talk about M&A, but I think one of the, we also have a data section to talk about. Biogen, along with ionists just unveiled two days ago, their face to Deeranursan. This was a injectable towel that goes in shallothically. It's an ASO, targeting towel. This was a randomized study, three different arms placebo against a low dose versus high dose. Dozing either every 12 weeks or every 24 weeks for the audience with the ASO. Primary endpoint was at 76 weeks. They were looking at that this was a significance of the higher dose versus placebo. They didn't compare the low dose versus placebo on an atus cog essentially city or sum of boxes for Alzheimer's. And technically the study failed because the primary endpoint was the high dose. I did not do as well against the low dose, by the way, in the 76 week study looked better, which is actually consistent with the phase 1b data. And based on all of that, which was reduction in phosphorylated towel, reduction in towel imaging, there was also a slowdown of deterioration over a this cog and also city or sum of boxes 0.5 0.5 four points, which is considered clinically meaningful by FDA. The buggy was 0.5. So based on that, biogen is going to go into phase 3. But this is fairly controversial. Biogen stock was down from an ionist perspective. People were looking at that and thinking it's interthinkable. Arrowhead is a S I R N A that's IV or sub Q that's going to be easier and that's behind. So maybe thoughts about this data and the overall technology. Yeah, I mean, look, I think obviously it's a bit of a confusing data set. I'm overall net encouraged by this for as it relates to Tau as a as a target in Alzheimer's. And I think we all have to be mindful that this is a super tough disease. But the Wall Street reaction was mixed and part of it was the inverted dose response. And also the view that the level of efficacy that was achieved was really no better than current anti-amuloid drugs like Leccanby and Kisuna. So I think that's the real nature, the real crux of the response. I think what has got to be considered here is that the nature of this inverted dose response is due once again to the poor, poor tolerability that one sees with a ASOs versus other technologies. And that's why Arrowhead with what they're doing and also while Nilem has a program targeting Tau, which is interethical Arrowhead's program is a trans BVB shuttle. Those programs I'm excited to see where those go. But the ASO story in the CNS of course has been complicated and just to that point last week, we saw Rose terminating their Tome Nurson at another ASO program in Huntington's. And we also notably saw the Eplenturicent Fail in Cardiantress Form last week, which again, a reminder, ASOs have tolerability issues and they could be contributing to mixed interpretations of overall results. So I'm, I'm net, you know, encouraged by this as it relates to Tau. I think a lot of the complexity around the results could be mostly tolerability and ASO related just like we've seen time and time again. So we'll see how it plays out longer term with other approaches that Tau. But I don't think we should dam the target just because of the ASO. - Yeah, I mean, to your point, the higher those did have more AEs and lower those. - Yes. - Density than that lower does. - Yes, exactly. - Can I just ask quickly there in terms of these are, these are not targeting an offending form of Tau necessarily. They're targeting Tau production, right? So what do you think is the risk that if you're actually reducing, I mean, the protein has a function in general. So you're not, you're not, so what do you think about the fact that you're reducing Tau levels? Is there a balance between between the two? Because that was one of the conversations that I heard that you played out. - What do you think? - Well, I mean, I think that's always, so the off target or the on target rather pharmacology being, you know, with higher doses being problematic. I, you know, I don't know if there's enough support for that based on the biomarker data that had been published from the study, which wouldn't support that. - That's true. - That's true, because actually when you look at that Tau leveled those response, I mean, unfortunately, I'm not looking at that chart with the reductions in Tau, saying, oh, look, there's those response here that the high doses in reducing Tau as much as low dose. If all those over error bars were overlapping, et cetera. So, but there is a point here in that, this is a difficult subject. And biogen pays the price for trying something at the, at the, you know, at the edge of our understanding of biology here. And I find that a bit tough to swallow a little bit. I'm not supporting, you know, I'm not saying the share price direction was wrong, or not, but somebody has to do this and figure it out as the time passes. So, absolutely. And have the courage to do it as well. - Absolutely. - Yeah, with absolutely, with look, I have a mother that's got all the time or has been following this very closely. And obviously, follow my honest. The challenge with the antibodies is that there were always, you know, putting a little bit of a cork and into a, you know, a huge kind of fire hydrant. There were too late. So you need to go early. So we're always very interested in the modality of actually going and preventing the propagation. You know, some of the challenges again, having a family member and you got to decide do you treat someone or not, the complexity of the therapy, the issue with, with RIA with the antibodies is monitoring was extremely difficult. Even if you live in New York City and you have good access to care. And the benefits were modest. And the benefits are maybe a little bit better here. But it really is preventing deterioration with a very little city or some of boxers cognitive benefits. It's always the challenge, you know? - But the lack of RIA's signal so far is encouraging your own. - Big deal. - That's a big deal because, you know, the big challenge with the anti-ameloid antibodies, of course, is that risk that factors into it. And, you know, if there's only potential, not that any drug is without its toxin's colorability issues, but if there's only potential upside, then it changes the equation a little bit, doesn't it? - Yeah. And if the member, when you have this disorder a lot of times you don't want to be reminded of it over and over again. And going in to get monitored over and over again is not exactly easy in terms of, even convincing the patient themselves to do this, you know? - Yeah. - Okay, Sam, we have, I think about two and a half minutes left and we have three topics. So I think we're going to cut it down to two. And M&A, let's start with the more interesting one, the AstraZeneca, the D cell deal for EGFR X-1020. AstraZeneca is, you know, is marketing to Grisau, the EGFR inhibitor, there are the 800 pound gorilla, sales are over seven billion or so. And so they're now licensing another one. And X-1020 has been, this has been a well-known class, kind of mixed results in many ways. What do you think of this deal? - Yeah, so I mean, remember AstraZeneca investment in this election, so, but what was interesting is that we were wondering why it took them so long. 600 million dollars upfront, up to 900 million dollar development milestones, et cetera. I mean, the data that we've been looking at all along, we think that as an inhibitor, soon dessert in April, which is the drug that's not approved anywhere outside of China, does stack up, I'm looking at them, are charts looking at it compared to Collinant, to Arievin's data, to Hanzo's data. And also, of course, you've got Rieberband out there, which is John Selling Johnson's EGFR met by specific inhibitors. So the data stacks up and the side effect profile looks easier to manage. And I think AstraZeneca is the ideal partner here to be selling this, given that they have the broader EGFR space. Now, this is a small indication, but it's one that needs the drug. So we're positive on the diesel product, and we'll see, it's marketed in China and it's doing a relatively well over. - Okay, and maybe in the last 30 seconds, Yraska had data relating to RAS, and then they did a 500 million dollar raise, thoughts about the data. - Yeah, I mean, you know, you're on, there are a lot of people who skeptical about Yraska, and in terms of where the drug came from, I think Revolution Medicine helps fan that conversation that are some legal discussions. I don't wanna say, I don't think they've actually taken them to court yet, but about where the, whether the drug infringes the Revolution's IP, but I mean, the 500 million raised, which was up, upsized to about 600 something, and which is quite a tick in the box, in a market that was looking a bit dodgy in the past week, as we just talked about at the beginning of the conversation. So, to me, that sounds like a sign of somebody believes in this, with the data improved relative to the, with an addition of four more patients, and a month more of follow-up, which is always a nice thing to see, because we used to the opposite most of the time, where the data deteriorates, you know, and the ORR is beginning to get very meaningfully in the range that you see from Revolution, and also, I'm slightly thinking about Lucidbit, but it does make me wonder sometimes, with the regards to drugs which show a lower AE thing, anything, well, how do you manage that? So, of course, they have explanations for. So, looks decent for now, and we have a whole bunch more catalysts coming in the next few months. So, it's gonna be fun watching this in pancreatic cancer. - Yeah, well terrific. Well, amazing, thank you, John Madden Sam, for a very insightful episode. To everybody, hope you're watching the games, hope you enjoy them, and please join all of us at Hangout again, next week, same place, same time.