Episode 179 - April 10, 2026

You're listening to Biotech Hangout, a live and unedited weekly discussion of all the latest news in our industry with a group of biotech leaders and experts. I'm Greg Savanovetsch and my co-host today are a fellow cell-side biotech colleagues Josh Schimmer and your own Werber. We've got Sam Fizzelli and also a special guest today, Oliver Barnes, who's joining us for first time, so welcome Oliver. For more information about our hosts and guest speakers or to listen to the most recent episode, please go to biotechhangout.com. So happy Friday everyone. The sun is out, but there's a slight chill in the air still where I am in New York City, but it's great to be back again as a host on the biotech hangout. We had a really fun session last week. I hope many of you joined and I want to thank my co-host from last week, my key in our Schmidt for their always insightful and amazing contributions. Today, I'd like to start with some high-level comments on where we are in the biotech market. So from a public market perspective for the week starting Monday and through at least yesterday's close using the XBI, which is an ETF as a proxy biotech is up 2%. Now this compares to the S&P 500 and NASDAQ both being up 4% for the week, so that is relative under performance. But with that said, bigger picture when looking at the XBI, it's now up 8% year to date. And that's strong out performance versus the S&P 500, which is essentially flat for the year and up only 0.3%. And that's even stronger out performance for the XBI when comparing versus the NASDAQ, which is down 2% year to date. In addition, importantly, with the XBI closing yesterday near the 132 level, this encouragingly marks a new 52 week high. From my perspective, this reflects just an incredible comeback for biotech, especially if we were to look back at this time last year. When the markets were just reeling from the aftershocks of so-called liberation day with the current US administration's announcement of new tariff policy. For context a year ago today, the XBI stood at 71 in change. That's the exact 52 week low level. And for numbers, geeks and perhaps stock nerds out there like me, that is a very nifty and healthy 84% positive return. That compares with a plus 30% return for the S&P 500 and a plus 39% return for the NASDAQ. And while those numbers certainly reflect truly great returns over the past year, a public equity investor would have more than doubled her or his goal. And he would have doubled her or his money investing a year ago had they invested in biotech using again the XBI as a proxy. So just an opening statement on the biotech market that I thought was very worth sharing with you all today. And then in terms of the financing environment, I'd like to highlight just a few things. The S1 filing for Avalon pharma that took place this week for that Boston based company to go public for some background. Avalon pharma was found in 2011. It is working on it and inhaled formulations of two approved and the most established oral drugs for idiopathic pulmonary fibrosis or IPF with those drugs being Ezbria and O5. While terms have not been disclosed yet in its S1 filing, the company is looking to raise $100 million to fund an ongoing phase 2b study for its lead candidate, which is an inhaled version of Ezbria and also to fund an ongoing phase 2 study for a second drug, which is an inhaled version of O5. The IPO plans come after the company successfully raised $100 million in a series of deep financing last July. They were also able to raise $175 million in a sea round in 2023 and 36 million in a B round in 2020. So this S1 filing comes on the heels of a S1 filing for a calerath therapeutics, which is an obesity focused biotech from a few weeks back. And so overall when keeping in mind, six or so, I biotech IPO as we've seen year to date, while we would always like to see more. I think this continues a very healthy trend for US public biotechs and finally with a number of US public and private financings that took place this week, including a $345 million equity raise for publicly traded cell decks therapeutics from the European biotech perspective. So I wanted to flag the successful close of a new 1 billion euro fund by Paris based J to capital. And then I get that right is a J to and then OK, thanks. And then at 1 billion euro or roughly 1.2 billion US dollars according to the company, that marks the largest raise ever achieved by a fully independent European fund dedicated to biofarma. So I think relatively speaking, we're in a very decent, if not a very good place in biotech, although sometimes it doesn't always feel that way. Against this backdrop, I want to turn things over to Sam Fizzelli and Josh Schimmer, who will walk us through a host of health care policy and FDA regulatory news matters. Let's first start with Sam. Sam, go ahead and please take it away. Sure, thanks Greg. So we had a few things administration wise and Josh and Greg is jumping and he runs there too. So jumping when you feel like it. Let's start with the 100% tariffs that the president started talking about for some farmer companies when he start digging into it, you think, wait a minute, didn't be already do this with regards to. The most favored nation about a year ago, roughly, I mean, I've got to remember now there's so many things that happened that it plays havoc with my memory. So here we are thinking that we've settled all these tariff things and this announcement comes out. And then of course, you dig into it and it's much more about. I believe over substance. So it excludes a whole, but first of all, 16 out of the 17 largest companies have already done deals with the US. They've gone and the some most of them have been through the. The overall office for the photo opportunities, etc. And that has required them to pledge to bring manufacturing back to the US, of course, I'm sure we're all going to be out there with our drones and whatever other method we can use to see how that manufacturing build out's going on. But we have one company that hadn't signed yet or has been or they've done to have an announced it and that's regenerant out of the top 17 big companies. And here this 100% tariff applies to I really can't figure out who directly applies to maybe applies to regenerant maybe applies to companies like Mercage EA. And the whole deal is essentially trying to get them to come and sit at the table and and do some, you know, at least some of the MFN agreements with regards to Medicaid, etc. And talk about bringing manufacturing back to the US. It doesn't include generics for obvious reasons because you can't if you tariff generics is finished. There's no market left. By similar, it doesn't include or for drugs and it doesn't include rare diseases. So quite a lot of the little biotechs who do have drugs for these indicates types of indications would be excluded automatically. And so this is the way that I've been seeing it. I don't know if anybody else has a slightly different take on it or I mean the market hardly blinked, although it came in the middle of the world window of the Iran conflict. So I don't know if anyone else wants to chime in on that on this particular one. If not, I'll go to the next one quickly great. And that's the nice news, something that I think we had been expecting, although I'm still trying to also understand the substance and what exactly it means. Create a new clinical trial notification pathway to serve as an alternative to the burdensome existing in investigation on the drug pathway to accelerate drug development time like to make America healthy again. What's the point of this? Well, a lot of people are blaming or at least pointing to for one of the reasons why there have been increasing deals with China biotechs. Is the fact that it's much easier to get into first in human trials in China in terms of speed and regulatory elements than it is an Australia than it is in the US, probably Europe if anybody regulates things it's going to have to be Europe first right they always win on regulation. And so here I think the discussion is mean can we speed this up at least get rid of that relative competitive advantage that China has and this is what it's aimed to do. But then when I read the little detail in the revised the FDA regulatory framework to create an optional risk based expert on the IMD pathway optional is number one right pathway to serve for certain phase one clinical trials. What are they I don't know where there is existing pre clinical data so is that mice rat. Where does that stop? Can I not have to worry about dogs and non-human primates, probably because one of the key things that it does go on to say is that the things that can be, should satisfy the regulatory standard, the validated and NAMS methods, which is the non-animal kind of tests. So it's got to be interesting to see whether this is the way that, if this all of this is essentially suggesting that you don't have to go through the entire process of mice and then whatever other models you use and then dogs and then the non-human primates in some circumstances before you get into the trials. So that's the way I've been, I'm trying to get my head around this. I don't know how many pathways this impacts, but I'm assuming it's going to be a positive thing managed to do it. So anyone else wants to chime in on that? I think it's clearly, I think, obvious to most of us and the listeners that at least in the US as a tries to stay competitive globally, particularly with China biotech. I think it's a positive thing to see at least some initial movement, particularly perhaps coming out of the FDA, but I guess we'll just see how this all plays out over the next bit. Yeah, so what we do need to do is to speed things up. That is for sure how it's actually done and how quickly we can speed, you can have that speed, quickly we can get there to actually make a difference in the next six to 12 to 18 months or time will tell. But if you talk to all the good and the great in biotech that we all do talk to, they all want to see this, this process to be simplified, but not cutting corners, not risking people's lives. So, and I'm pretty sure we can get there. The last thing I was going to just talk about from an administration perspective, if you all, I'm sure, followed on the vaccine world, what I'm understanding is that first the HHS has been kind of directed to, I mean, this is a rumor, I don't know how much factor is in there, to calm it down a little bit on the vaccine, anti-vaccine comments, etc. So, that's at least from the public front side. But one of the significant changes that have happened in the vaccine approval or review process is the complete revamp of the ACIP, which is the advisory committee for immunization practices that is run by the part of the CDC, part of the Health and Human Services Division area. So, what this group had been doing for the past, not as long as I've been around, is reviewing vaccines data and making recommendations about, it's not FDA, right? The FDA approves things as they do. ACIP was telling people how to vaccinate, who to vaccinate, when to vaccinate. And sometimes they would make decisions that was quite consequential on the potential revenues of the vaccine, because they limited to 65 plus, etc. So, what happened with Secretary Kennedy, who came in ahead of the HHS, is that the ACIP was completely gutted. The 17 members were pretty much removed, a bunch of new folks were put in. And some of us viewed those people as not necessarily being the types of experts that they should be. Then we had a court ruling, which essentially said that all these changes were against the charter of how the ACIP should be appointed. So, and put a hold on it, and pretty much was suggesting that they to be reversed. What seems to have happened now, is that there seems to be some changes to that charter itself to essentially make it easier for these changes to stick. Now, what does this mean in the end for vaccines? We all know the vaccines have been under pressure. I think we generally believe, I'm not going to speak for everyone, that they are one of the best things that science ever developed in terms of its value to society and prevention of disease. However, this is the direction that has been going, is to try and prevent or reduce as much vaccine access or public trust in vaccines. And that's where we are, and that we have to see whether this change that's going to potentially come to the charter, will eventually make it easier to just keep the ACIP as it is now, which is essentially people that I frankly would not trust to make a decision on how to vaccinate or whether to vaccinate and who to vaccinate. And the reality is that most states have essentially moved to doing their own thing and the American pediatric association is making recommendations now. So I don't know if I'll be watching ACIP meetings anymore when I used to watch them religiously. So that's where we're at, Greg. Thank you so much, Sam, for those comments. Josh, you're on, I think, if you could provide some comments on a press conference by FDA Commissioner Marty McCarry, that would be great. Yeah, it was an interesting press conference that Dr. McCarry hosted to have the progress that the FDA has made under his leadership ranging from, you know, the food additive stuff that they've addressed and approved by some others. Some of the ACIP had I did reviews that they've completed and that generally true to form is perhaps more of a politician than anything else. It's very, everything is awesome. Things are going great and for the things that didn't, I don't think going great don't blame us, blame prior leadership kind of discussion, perhaps an effort to solidify his role as head of FDA and considering he's also come up to a fair amount of fire for some of the turmoil that we've seen coming out of the aging significance. I'll agree that. Separately, this will be really interesting, and Eric, Jr. is going to start his own podcast where he will be talking about issues that he says will be uncomfortable for folks to potentially hear about. We'll have his Ray and guest speakers will be fascinating to see what he covers on that podcast. I'm sure will give us plenty of fodder for some really interesting discussion here on Hingel based on whatever it is he's going to come up with to talk about, but I think we can all confidently say whatever it is will probably be issues and items that many of us are likely to not agree with. The saga continues for now. Thanks Josh for that. It will be interesting to see what happens on that podcast. We'll shift now to this section of our podcast where we highlight notable deals of the week and we're actually going to start today with a discussion of what I would describe as a highly controversial M&A deal that was actually announced a few weeks ago. That was Merck's proposed $6.7 billion acquisition of publicly traded turns pharmaceuticals a company that I was involved with when it went public via any IPO back in February 2021. Turns out some of you may recall initially was focused on advancing a pipeline of multiple assets delivered to the liver disease Nash. After positive phase two data and when no one came to the table for an out licensing deal for what I thought then was a very good THR beta asset for Nash or Nash as we call it. Now the company then pivoted to obesity and oncology. The shares actually hit a low of $2 last year after the liberation day related weakness in the markets. And then last fall after its oral GLP one drug ultimately proved uncompetitive it pivoted to being an oncology only focused company with a very novel allosteric tyrosine kinase inhibitor for treating chronic myologinous leukemia or CML with what then was considered truly spectacular efficacy data that were announced at the ash meeting last December. The company was able to raise almost $750 million in an equity raise at $40 a share only to then be the subject of Merck's M&A bid at $53 per share that was announced on March 25th. So now the really interesting aspect of that offer was at $53 per share that only reflected a 6% premium versus the last prior days closing price for terms shares. And trust me as I cover turns I heard from many disgruntled investors and I think your own covers turns as well. He probably heard the same thing. But in particular given street views on how exciting and compelling the prospects were for turns as a TKI for CML. And this comes in direct contrast to the 6 billion or so deal we saw last week with many of you were calling from our podcast last week when we discussed biogen acquisition of a palace pharmaceuticals company also cover with biogen offering a 140% premium over a palace's a prior day closing stock price. In that case a palace or at least biogen seemed to be overreaching with perhaps a surprisingly large if not outsized premium for a company that features an emerging orphan kidney disease drug. at the same time a flagship drug and cyphery for geographic atrophy with much greater potential revenue that had previously shown pretty slow if not flat growth over the past year. So getting back to terms, the SEC filing that details how the deal went down became available this week. And I encourage you for entertainment to go to that SEC filing. And wow, did we see many twists and dare I say turns when it comes to the play by play on how that deal um, find the came to fruition. I'll summarize and maybe at the end I'll have your own address comments, but how the M&A discussions went down with something like this in late December after turns had announced uh, earlier in the month, um, it's ash data where we saw a 64% six month major molecular major molecular response or MMR rate in initial ongoing phase one, two study versus an abstract that was initially made earlier in November. So later in in December an unnamed party in in the filing that party is known as party C, which was not Merck initially came in with a $58 per share unsolicited offer. That then kicked off an M&A process that led to other parties and including obviously Merck getting involved in M&A discussions. That party C, that other party increased its bid to $61 per share with an additional $9 CVR. And then Merck came in and on its own offered initially $61 per share. Now the really interesting twist here is that parties went under a confidentiality and got access to a data room. And what the companies ended up seeing in that data room was the most updated data cut from the phase one two study, it's called the Cardinal study. And the efficacy signal, though not made public, had in fact degraded from that original 64% six month MMR. And that led to reassessment of deal offers. In fact, party C ended up dropping out altogether and Merck ended up lowering its offer to $50 per share. And again, ultimately Merck and turns agreed to $53 per share. So it's really interesting. I think it's interesting that the public gets a look at what happens behind the scenes in that SEC filing. We also see what turns initial projections were for peak sales for its TKI. And I was about $5 billion. And perhaps in retrospect, we get to come to a conclusion whether right or wrong the 6% premium, which was not well received by investors that we saw turns ultimately get from Merck. Does it represent a fair deal or not? And the last thing that I will say is if turns had remained independent, if there was never an M&A offer, then if you imagine that sometime later this year, we're to have to update the market on what the efficacy for its TKI might have degraded down to. And in the SEC filing, there is a statement that goes something to the effect of that it would have fallen to the low end of the range that turns was projecting. This could have been potentially catastrophic for the stock and of course, shareholders. So really interesting what happened in the turns and Merck deal that's been proposed. Your own, if you're on, would you like to add maybe some other comments? Yeah, absolutely Greg. So thanks for a really, really nice summary. So there's a couple of things that are in there that in the SEC filing. And that is that the the response was potentially dropped to still within the range, but just at the lower end of the range, but because of inclusion of patients that failed semilix in the past, semilix is the varities drug, as you mentioned, that is also stamp inhibitor. They are the same mechanism, the better exposure based on PK and looks to be a little bit safer so they can get to the right dose. Again, the data has been early. Recall, the varities ultimately was using a lower dose because they did get into some kind of an AES at the third dose. And of course, if you're going to go with the same mechanism of action again, and what was very intriguing and important here is that their drug was very active still in a patient that was experienced to semilix. But of course, if you're going to add those patients saying your response rate is going to come down. And that's probably why Merck again, we don't know some of you say are hypothesizing, but Merck ultimately did stay. They did trim, but they did also say that it still is within the range. I'm just to give you the what we're talking about in response rate that is dramatically higher than what Novartis showed in the past. Novartis was at a 26% response rate. The data was early, but the data was between 64 and 75. So even if you go to the lower end of the range, you're still in the 40s versus Novartis at 26. So definitely interesting. We agreed to stop probably what had gotten down because there's a competitor from Enlive Ends, which is sort of an ATP inhibitor that's the older sort of receptor binding. But interesting, but look, we do have to remember the stock was up like since fall, if not more, from the bottom, much more than sevenfold. And from pre-ash to MNA, it was stocked great. So investors did get re-nominated overall. Yeah, I would add that going back to that December, almost $750 million equity raise that the company did. That deal was priced at $40. And so for even new investors who came in at $40 in December and then to be able to get a return where you're getting $53 less than three months later, or about three months later, or I guess obviously the deal has to close, but that's still a really good return, I think, for investors. So again, we wrote a fair amount on that deal. And with that said, I think it will end up being a very interesting case study for MNA deals. But speaking of perhaps MNA deals and some more recent MNA deals, we did see two deals this past week. We're going to start off with Gilead's acquisition of tubulus, which is a German domiciled company working on ADCs. Sam, I believe you're going to comment on this. Yeah, yeah, thanks Greg. So this is a company that I've seen present two or three times as a good to some of the VC type conferences in Europe. So metrics first, Gilead's paying $3.15 billion up front. This is the third deal this year. So there's 3.15 plus 5.36 upfront for our selects and 1.6 something for euros. So that comes up to about a $10 billion cash spree in the first quarter of this year. Or does that count? Okay, so far this year. And what's interesting is that this company, Gilead already had a deal with them. So to a degree, you could say it's like our selects. I mean, the woman with our selects was much more advanced. And you know, the deal that the drug that they bought with our selects for multiple myeloma was, you know, potentially going to be approved this year, whereas this is a lot earlier. But the access that Gilead had through their deal that they signed in December of 4, sorry, where the upfront payment was only $20 million, right? Clearly had given Gilead sufficient understanding and knowledge about the differentiated potential differentiated methodology that or product development approach that a tremendous has in its ADC program. That's what they do. They call themselves a differentiated C platform. It gave Gilead sufficient knowledge and confidence to go and do this deal. So a couple of things that are particularly like about this. It comes with a couple of assets. The data for those assets are interesting. And there's opportunity there. But I think Gilead's done this to access the platform. Having got into the ADC world through their acquisition of immunovetics back in, I think it was 2000 to 2020 ish timeframe and which gave them the top two ADC, Trudellevi. So first of all, I kept seeing these guys thinking, okay, that's great. This is an ADC company, but most deals for ADCs are going to China. A lot of China companies are doing differentiated different approaches, etc., etc. ADCs. And it's really good to see that just because of the volume more forcefully than China when somebody has it. differentiated approach somewhere else. People don't just keep going to China, which I'm a fan of, but because of what we think is cheaper, cheaper, cheaper. I don't think that's necessarily the case, but in any case here, for ADCs, having kind of made up my mind that the world's going to go to China for any ADC they want, here's one that sort of surprised me a little bit. And of course, it's really good for the European sector, or the VCs that were in it. The company had just raised in October 25 about one of the largest series that I've come across at least for Europe, over just over 400 million dollars. And of course, this being a private company and I'm not saying anything specific here, but it's possible that the investors had a good feel for how that relationship between Gilead and Tuberlis was going. It's a massive raise when their previous raise about a year and a half before was $138 million. And especially when you're in the world of ADCs where again, you have that worry that everything ADC is going to come out of China, like everything GLP was going to come out of China. So that was a very interesting raise and clearly positioned the company to be able to develop its assets by itself. And of course, Gilead decided that it's going to take care of bring them in-house. I don't know what will happen with regards to the organization, etc. I'm assuming a lot of the science, etc. will stay in Germany. But it's good for the European sector. And it's interesting for Gilead also that it's a platform that they bought rather than assets, which is what they did with Oro and Arcelix. I'll stop there and guess there's any, I don't know if there's any questions. Over. Okay. Thank you so much for that, Sam. We also had another very interesting deal earlier this week from Nurecran, which for almost $3 billion acquired an orphan disease company called Salino, I believe it's Salino therapeutics. Josh, I don't know if you cover the company or Nurecran, you may have some comments and then I'd also like to add Oliver to come in again for the first time, welcome Oliver for any comments he might have as well. Yeah, so I think we've all been wondering what Nurecran was going to do with her growing cash position. They definitely committed to being prudent in terms of their capital allocation and they seem to accomplish that. Modest premium for Salino company that's selling Vycat XR for a treatment of Preder Willis syndrome. It's off to a pretty good launch already annualizing north of 400 million. It seems to be on pace to become a blockbuster north of the billion, maybe even a couple of billion assuming that there are no new safety signals that come up. There have been a couple related to hyperglycemia, diabetic ketoacidosis, a couple of patient deaths potentially not related to drug, although it can always be hard to know for sure. As long as safety remains consistent with what we've seen so far, the product should be a meaningful bottom line contributor to Nurecran giving them a third leg to their stool to complement ingreza and kinesity, kinesity having a pretty good launch as well. And some synergies, perhaps more complementarianous, as opposed to true operational synergies between Salino and Nurecran. Not an expensive price to pay at all. Again, assuming that there are no new safety issues to emerge that would change by KedoxR's trajectory, it also, a couple of other things that the deal accomplishes. One is it does take some of the pressure off of Nurecran's later stage neurology pipeline, which I think many of us views a little bit higher risk. And so it gives us a fully de-risk, essentially, commercial stage asset into that mix, so a nice balance for them. And the other thing that is noteworthy is that it keeps these companies in the XBI. And one thing that has been helping biotech lately is this increasing trend of companies to transition to profitability and bottom line growth and really meaningful cash flows that we're starting to see emerge throughout the industry as a whole. And that's in contrast to many years that the industry spend essentially not returning cash, not generating cash, really guzzling cash, and being an industry that can be very hard for generalist investors to wrap their head around because how do you invest in an industry if it doesn't it doesn't make money. So we're starting to see this trend within the XBI within biotech and being able to maintain strong cash flows within the XBI instead of transferring them to Pharma, my mind is actually very very powerful and a potential force to continue to draw generalist interest into our space. And at the end of the day, generalist interest in biotech is going to have a much more meaningful impact on the sector and its valuations than Pharma M&A. And there have been circumstances where we've seen a fairly dramatic transfer of value essentially from the biotech sector to the Pharma sector as a result of M&A. And so as the biotech sector continues to mature and continues to look quite investable for those who are attracted to things like cash flow, cash flow at reasonable valuations. These trends are important, noteworthy, and I think are going to prove to continue to be very powerful for the biotech sector. Greg, as you talked about earlier on, it's been a little up and down lately. I think we agree there's a rosy outlook, but lately we keep getting dragged back into that 120 to 130 range. The hope, though, is that the fundamentals of this industry as we play them out over the next couple of years are really going to create a strong sector breakout. Yeah, thanks for that, Josh. Oliver, welcome to the podcast. You want to add some additional color? Yeah. Well, Josh said, kind of encapsulated it really neatly and thanks for having me, guys. But the other thing, the neuro print transaction, which I think is interesting, is all these mid-sized we may have lost Oliver, but this can actually come here and be there. Okay. Hopefully, it's not better. Yeah, that is better, Oliver, who are you now? We can hear them. Perfect. So what I was saying was one of the things that's interesting about these ideal neurocreme buying Soleno is that now there's more like mid-sized. He's gone again. I think we may have lost Oliver again. Hopefully we'll get him back in. But in the meantime, there's one other deal that we're going to talk about. We'll shift things back to Josh on a deal where a Sergio was acquired by Garda Therapeutics. Interesting, smaller deal. But Josh, do you want to go ahead? Yeah, much smaller potatoes, but still some interesting potatoes on this one. So a Sergio used to be called "Depo Man". I don't remember. I know. It was just starting off. Yeah, I think in the end, in part, maybe to shed some of the I wonder whether this is Twitter that's playing us. That's trouble. Oh, no, sorry. Yeah, somehow it just went back on mute. All right. You're good. So hear me? Yes, we can hear you. Yeah, so it's the old, it's the old depo-med name change presumably to shed some of the opioid baggage that people might got cut up and not nearly as much as some of the other opioid players. It is Twitter. I'll bet you. Yeah, it keeps muting me. It's really weird. I don't know what's happening. I think it's all the same. My joy. So I'm taking complete blame for this. But we can hear you now. So that's good. Yes, exactly. I've got to watch my mute button and make sure it's not changing. Just changing that again. So it's certainly acquired spectrum a few years ago to bring involved down, which is basically like a brand-inversion of new last uh to compete in a kind of a biosimilar heavy space by offering some of the more more meaningful ASP plus 6% economics to certain centers. Turned out like right after that acquisition of what like and by the way, there were rolled rolled on launch for spectrum, what to be going exceptionally well. Arguably too good to be true. It looked like there was a little bit of chip that impacted the trajectory of that asset after assertio acquired it. But now this company Garda, there have appeared something many of us have heard of Garda before. Put a bit to acquire assertio for basically half the price assertio, half the price assertio paid for for spectrum. And what's also interesting about this one is that there's a shopping window where a certain can continue to solicit higher bids from other companies before closing the transaction. So I think this is deal number 11 for public biotech companies year to date. So up to another good start in terms of at least deal number, the dollar volume, that has been more of an average year for M&A. Maybe I could take this short respite from technical issues to chip in too to come back to the the Selano thing. I was just going to say one of the super interesting trends we're seeing a lot of is like these mid-sized drug makers transacting and that's going to be good for the sector, right? That means more people, more buyers, right? More bidders and we've sort of with the neurocreen during the Selano deal. We sort of would survey a buying day one last year by Marin to the $5 billion deal. And the market seems to be reacting well to these deals, right? They like the fact that these mid-sized drug makers are bulking up for size. And I think that means a lot of these processes are going to be a lot more competitive. And I think there's another takeaway too from the Selano transaction, which is bullish too, which is often we heard on earnings calls from some of the CEOs and large cap farmer who were looking to buy biotechs that one of their issues was there was a bid asked spread, right? A lot of the sellers wanted a high premium off all time highs. And you look at a company like Selano and the journey that it's been on, it's sold for around $3 billion. At one point it was valued north of $4 billion after its launch got started in March last year and it was doing gangbusters in terms of scripts. And then the market cooled a bit on it. And then the fact that the board and management were willing to transact at a lower price, it shows that right now we've got this very right market where there are lots of active buyers, there are mid-sized drug makers, there are also large cap stealing with these patent cliffs. And then on the other side, we've got sellers not necessarily looking for unreasonable premiums. And I think that's why what we've seen Q1, which was a really good quarter for M&A, I think we're probably slightly to be replicated for the rest of the year. Go to willing. Okay, Oliver, thanks for that. I'm glad we, I think hopefully have gotten through our technical difficulties. I'll just add a very very brief comment on depot that I remember currently not company in 2001, 2002. And that was a company focused on #. It's happening to you, Greg. Oh, okay. Yes, it's happening to everybody. I was just commenting on depot med and how it's evolved over the years and interesting. Sometimes biotech has nine lives. I'll save my comments for another day on depot med. And I'm still here. I'm here. Okay. I'm going to check my, my intervals too. The story, but the moral of the story is that you need to change your name and you need to have a good name. Like a thirdio is a really good name. Deepa magic sounds like a restaurant, you know, placed by pan. But your own turns didn't change their name. Well, that's a great name. It is. I think Greg, maybe, yeah, let's let's maybe we should have today and then be sure I to explore what time. Oh, man, you're wrong. Why don't you start with the ascendist data? Yeah. And by the way, it is happy to all of us. I'm keep on saying. Yeah. Apologize to all of our listeners. It's not our fault. Okay. So I'll speak very quickly while I'm actually can hear me. So I'll send this release there 52 week data. Just keep an eye on your mute button. There you go. Yep. And I can have muted again. So a conjure pleasure is for patients for people with little stature and the forks fashions are so safe. They already have a proved drug. It's called UV well. It just got approved about a month ago, launched launched last week. It's actually it's a weekly version, essentially, in a better data than by morons daily, which is called. So go both of them are CNP hormone. They basically do a very nice, especially fixing the biology. So to speak of a country pleasure or correct, correcting the biology. They then tested it in combination with their weekly growth hormone. And we've seen 26 week data and that data was incredible. The the CNP drugs alone kind of boost your growth rate to 50% of normal and the count to 97% of normal. I mean, that's fantastic. We've seen the 26 week data. And now this was the 52 week data. And what's really important is they're not only just boosting growth, which they call. But as you know, when you're looking at someone who's who's little, they're they have a body disproportionality. So they're looking proportional. The data now at a year actually showed an improvement in proportionality. If you're really meaningful, this is this data is really a bill. They're now in phase three. They just launched the three study. It also comes at a perfect time because in the meantime, Bridge Bio has now released their data with the oral drug called InfraGratnib that looked very good. It's an FGF R3 inhibitor. So they're going to file this year. They'll be on a kid next year. But now so the market's going to become a lot more competitive with the weekly option from Ascendus and oral option coming next year from Bridge Bio. But then probably in two years, we're going to have the combination from Ascendus, which all our KOOs are saying they really believe is going to become a core of the stand of the kid. So really, we're seeing really great innovation here on the metabolic orphan sign. So it's really great to say. Thanks, Jerome, for that. I'm going to briefly comment on some negative data that we saw from insmed, insmed is a respiratory disease company had a tremendous year last year in terms of stock performance. It had some negative phase two data from what's called the Cedar study. It was evaluating. It's what I would call it now flagship drug, which is called Brin's Supri. Brin's Supri was approved last summer. It is approved as a DPP one inhibitor that's approved for bronchiectasis and out of the gate, the launch of that drug has been amazing. In fact, just if you think about this in its first full quarter of sales, which were for the fourth quarter of last year, they reported, I believe, about 146 million in revenue and guidance for this year in its first full year of launch is according to management at least one billion. Again, this is bronchiectasis, which is a very serious coughing type of a condition due to infection. And Brin's Supri represents the very first product ever approved by the FDA for bronchiectasis. And with that said, they had been insmed that has had been exploring potential use in two additional indications. They had some negative data late last year in a condition called CRSSNP that came as a little bit of a surprise in a disappointment. And if you look at the stock chart for insmed, you'll see a little bit of a cliff that happened in probably the middle of December. And then we were waiting for data from this same drug, Brin's Supri in a skin condition called Hydrodenita Superativa. And there are several drugs that are approved, but not all that many. And while there are no good preclinical models for HS, as I will call it for short, in perhaps what wasn't a surprise, bronchi, Brin's Supri did not achieve the primary endpoint of this kind of signal seeking study. So with that being said, we've seen unfortunately two setbacks for potential label expansion for insmed's Brin's Supri, but that being said again, with first full year sales of at least one billion guided in 2026. And we've got peak sales of almost nine billion. It does not mean that the prospects of Brin's Supri are not very compelling and very exciting. And that's something that is what's driven the tremendous stock appreciation in insmed. With that said, I think I would like to maybe pivot to some breaking news. It wasn't part of our original program, but we saw today some breaking news that was regulatory in nature. And that is a yet unfortunately for Replumune, a second complete response letter from the FDA. I don't follow the story all that closely, but for context, this is a drug that was being developed for advanced melanoma, it had been submitted to the FDA. Last year, or maybe in late 2024, there was a first complete response letter. that came out, I believe, in July of last year. And then after some, after follow-up meetings with the FDA, the FDA allowed them to resubmit. And if you look at the stock chart for Replumune, you can see the highs and lows that correlate nicely with the rejection at first and then the resubmission. But unfortunately, the negative outcome that was just announced mid-morning today, the FDA did reject the drug again a second time. And I think it does ask some questions around how we as an industry should think about, perhaps, what's happening at FDA or maybe not. And with that in mind, I'd like to open it up to see if Sam, whether you've got a view on it and whether others have a view on it. - Yeah, well, look, so Greg, I've just asked a resident expert in melanoma, Max Nisim, for his views, and he's given me a whole huge stuff about the data and how it would it does. So bottom line, I think, if I can dissect all the things that he says and put them into one piece, is response rates are seem okay. There's some interesting angle with regards to whether the patients had had AP or NIVO before or not. And bottom line is that the efficacy is okay. The patient population that it's gone into does need the therapy for this for which melanoma, as you might be saying. Scientific profile is pretty decent. So on a risk-benefit profile seems to have been and let's not forget that this is really a, what do you call it, a viral, a replication-competent virus in terms of, but potentially treating and directing the immune response to the tumor. And there has been some talk of abscopole effect in terms of maybe you can set off the immune reaction to other tumors where you haven't injected them, et cetera. But all of it seems to come down to the fact that it was an uncontrolled study, right? So it was single-arm study. And the data seemed to be fine. As I just said with efficacy versus scientific profile, what I'm a bit confused about is that if the FDA, I mean, they didn't do another trial. I mean, the FDA saying you should have done a properly controlled, a random as controlled trial, if I'm for it it correctly. As you said, it's breaking, right? This is what I'm understanding. But then that, I mean, they couldn't have done that for the versus the last CRM, which was in July. And so I'm a bit confused here. Initially, I thought, no, this is just a good response to a trial that wasn't maybe could have been done at a higher standard as the FDA says apparently. So what I'm confused about is, how could this company have been allowed to refile if this is what the FDA was going to say? So is it pointing to mess at the FDA in inverted commas or not? It's up for debate. Yeah, I'm just going to quickly offer that it's unfortunate in retrospect now. Again, I don't cover Reppelmewn. I don't know the story all that well. But for the FDA to have allowed them to resubmit for approval and then to put them through, I don't know, the ringer of sorts only to reject them a second time just seems a bit cruel and harsh. I don't know, you know, the asset and the clinical trial data well enough to be an authority but it's really not a great sign for industry, I think. Yeah, it's possible that what companies often do is get no, no, we're going to go and do a whole bunch of data analysis here, approved to you that even though it's a single arm study that we merit approval and maybe get, I don't know, I don't know what else you they do in these kind of interactions. So, but you're right. I mean, it's just, it's just something doesn't, doesn't out of it. If they were going to do this, you should have just said, no, don't come back, go and do it. Control trial and come back. So, correct. Josh, are you around any comments there? Yeah, I just said that given some of the turmoil the FDA and what seemed like everything is awesome. Let me keep my job speaking to our friend, the ferry that they would have approved this one. Yeah, I kind of agree with Sam. Like, looks like an active drug recently well tolerated. There is a subjective component to interpreting the data because there's no obvious survival attention at this point of the, the rest of you should be at the asset. So that one, that one agree is a head scratcher. Disappointing because I think we thought that this would be a good test case to show for the FDA to show that they're back open for business and it just means that we're still trying to figure out exactly where the bar is set on a case by case basis. Thanks for that, Josh. We've got five minutes left and we're going to go to some obesity market related news. Certainly can't get through a biotech hangout without talking about the obesity market. And Sam, I think you're going to comment on some approvals that we saw this week. Yeah, I'm going to, Greg, I'm going to try and do two things here. I want to talk about this nature paper, you know, as you know, I love reading these scientific articles. It's my upbringing. So, but but related to the news that we've had. So we had some data, some approvals, the novel, high dose, we go V7.2 milligrams. Remember, the usual dose that people end up on is 2.4. This was launched on April the seventh price that $399 per month for self pay patients, which is the prices is a bit lower than what's up bound was is going out, which is between 499 and 699. Although these prices seem to be changing on a daily basis, almost at the same pace as we get obesity data. So, high dose, we go V, showed what about 21% weight loss at 72 weeks in the stuff of obesity trial and zip bound had about 22%. So this is no vote getting its drug to the level of efficacy that we've seen with zip bound. Remembering zip bound's got two mechanisms of action, right? GLP1, GIP. The other approval we saw was Lily's found aio. I'm going to pronounce it like that or for glipron, which is the true small molecule oral GLP1 mimic or act agonist. So here is going to be it has been available since the 9th of April. So from next week, I'm all excited about looking at the prescription data as they come out. Foundaio starting doses at $149 per month for self pay patients and you go up with the higher doses at 1, 9, 9, 2, 3, 4, 9, compressed to $149 per month of the regovie pill. And weight loss and tolerability, perhaps looks better for regovie definitely on the wet light weight loss basis. But of course, regovie pill does have strict dosing requirements. The reason I said I'm going to link it to this nature paper that was published recently is that we're saying here that this drug has the higher efficacy in the other drug. So what this paper did is actually a lot of it's based out of 23 and me data. 25, 60,000 subjects that were surveyed to find out if they were taking GLP1s or not, GLP1s and then to zip it out, et cetera. Had had a good look at that data and tried to figure out what are the characteristics that might drive higher efficacy in some one page, some patients versus the others. So the study says they identify the misense variant in the GLP1 receptor that is associated to stick to quote significantly with increased efficacy of GLP1 medications with an additional just under a kilo weight loss copy of the effect. They also found an impact on side effect profile and related in a nausea vomiting, et cetera. So that was quite interesting. And of course, they showed again the same bias to women having better weight loss, et cetera. So what I'm trying to say is that all these studies that we look at and we compare data, we really need to think about what the composition of these subjects are, et cetera, within these trials. And as you know, I've always set up my store saying I really don't want a comparison. It's getting all with these things, especially across trials. But the market will continue to do that. And I'm sure that's your point and we'll go up and down on the back of that. But so that's, so that was quite an interesting week, particularly with this paper. I'm assuming we'll get even more studies done like this, trying to dissect out whether patients have a higher propensity or not to respond to GLP1s. Over. Fascinating stuff. Sam, thanks so much for that. Well, that's all the time we have for today. My thanks, my friends and colleagues, Joshua, Ronan and Sam and my new friend and then colleague Oliver Barnes from the Financial Times. And of course, thank you all in the audience for joining and see you on the next episode of The Biotech Hangout.