Episode 176 - March 13, 2026

You're listening to Biotech Hangout, Alive and Unedited Weekly Discussion of All the Latest News in our industry. And of course, I say all and that's I don't think we ever managed to get there. But we're a group of biotech leaders experts. I'm Sam Fazilli and my co-hosts today are George Schimmer, Paul Matisse, and Greg Subanavigen. For more information about our hosts and guests, speakers, or to listen to the most recent episodes as I often do when I miss them, please go to biotechhangout.com. Now, we've had a pretty interesting week. Everybody's got there. We were trying to figure out one of the main conversation pieces that we want to look through. So I'm going to start off by getting everyone to talk through their key thing that I think happened from a regulatory basis today this week. But I'm going to come back to that for a minute. But I do recall listening to last week's call, which I felt like was a really nice, bullish, warm, fuzzy feeling for the biotech sector. I don't think any of you guys were there. I think it was just it was your own and Eric and Michael, of course. Now, I don't want to take away from that by definition to be a biotech analyst. I think you need to have a large dose of overexpression of optimism genes in your body, because otherwise, you wouldn't be able to cope. However, I just want to bring one thing to a discussion point. And maybe the others can just talk about it is if you recall, when we were talking about the bad days of biotech, which are years or months or a biotech for the three or four years before the big turn in August, we kept blaming-- one of the things we kept blaming was the high interest rates, which of course kept people away from high risk space. One of that was one of the issues. Now we've got a situation where unfortunately, there's a war raging in more than one area of the world, and the particular one that I'm referring to is the Iran-Israel United States War in the Middle East, which has led to a very sharp rise in oil prices, which doesn't seem to want to go down. I think we're hovering around $100 again. This leads to inflation through many mechanisms. And in this particular case, because it's the area that has been impacted where a large amount of urea fertiliser production comes from, and liquefied natural gas, it's likely to feed through to fertilizers to food production issues and costs, and therefore all of them go up. And of course, this leads to higher interest rates as a result of inflation. So I'm beginning to worry a little bit that if this carries on longer and sticks a bit, then we might get-- as well as the uncertainty that war brings, then we might get some conversation coming back and again saying, well, interest rates are high. We're going back up again. I'm not-- we're going to take a break on the sector. So I want to take-- through this back to the team, you are told worried, obviously, aside from the war directly itself, but through this rate rise issue. If there is a worry, what do you think is going to give first IPOs? I don't even know if there's anyone actively marketing on IPO right now because of the war, et cetera. So I'm going to throw it back to the team, see what your reflections are, or maybe you hate me for being a little bit negative here. And it's such a great time for the sector. And-- or maybe-- Yeah, I don't know. I'll try. I'm like the opposite of an expert on the macro piece. But I mean, I think this was a good week for the sector in the sense that we saw data readouts get really rewarded and end up in big fundraising. And there was also-- even outside of Smith Cap, right, like a large cap data readout for vertex that was really rewarded even of the data weren't even the bulk case. And I guess on the rate side, I'd be curious. Is that how Bloomberg is forecasting things? Because my sort of thought-- and this might be super ignorant-- was that if the war in the Middle East drags on, and we actually start getting some recessionary indicators, maybe that actually attenuates the risk of a rate increase, right? If anything, maybe there's pressure going the opposite direction. So by no means saying that the sector is immune from some of this stuff, I mean, I think the biggest real issue for biotech is just it's super high data. And it's a risk off sector. But it does feel like maybe more uncorrelated. I'm having a harder time seeing the rate risk unless I'm missing something. How are you guys thinking about it? Josh? Greg? Yeah, I mean, I'm not that macroeconomist. I'd personally be a little surprised if high oil prices drove so much inflation that culminated in a rate hike, as opposed to just stabilization of rates. The good thing about biotech is that fundamentally, it's insulated from all of this. It's insulated from oil prices. It's insulated from what's going on in the AI and software world. So it kind of becomes still a somewhat defensive sector. And by the way, biotech isn't what it used to be. But biotech is no longer the casino type speculative sector with all the value really coming from products that aren't going to be on the market until 10 years from now. It's a much more mature sector. I had personalized respect. It will be proved to be much more insulated against all of this than folks might believe because it's a sector that's becoming a cashflow positive sector. And a way that we've never seen before. So it's just less speculative, more mature, and more garpy. Great last word. Yeah, sure. What I'll add is I would agree with what we said. I do think it's a very different sector. And I also think, importantly, that I think we still have at the biotech company level, provided if funding is available for them. But they're still innovating. They're still an opportunity for investors to make money and for companies to raise capital on good data. And so, yes, while in the near term, we've got market volatility. But there's always market volatility. And obviously, we can't predict what's going to happen geopolitically, particularly as it relates to what's happening in the Middle East and having forbid things spread somewhere else. But I do think that, even with oil prices and gas prices rising, I do think that biotech, as Josh mentioned, is fairly insulated. And you could argue that stocks always go down and as they go up. But I like what we're seeing in biotech. I don't know how the IPO pipeline is going to get impacted. But I do think that it's going to be on balance. Again, not knowing what the future is going to have. The store for us on a macro stage. But I think it's still going to be a pretty good year for a biotech. Well, that's great to hear. Because at the end of the day, as Paul said, is that what Blumog is forecasting? I mean, it's so difficult to forecast that. You can build so many different scenarios based on the duration of this conflict based on whether, after even if the US or Israel or somebody declares victory and the immediate hostilities against each other stops, what is that then resulting in terms of does the straight of homeless open or doesn't open is the risky place. So it's very difficult to tell. But I'm really happy to hear that you're all still seeing a positive momentum in the sector, especially as Paul highlighted with the deals this week. And of course, one other thing that-- I mean, I've always thought this was a hindrance of the sector is a positive. It is the news that WinnepearSide is departing from the FDA from April. We've had several discussions and conversations about whether WinnepearSide is a good thing or a bad thing or a one person at the FDA is a good thing or a bad thing for the sector. And of course, once this news came out, I don't particularly recall a major bounce in the sector. Because I think the first time that that, when Dr. Pissade left, there was a bounce in the stocks. But I'm just wondering whether everyone's kind of got used to the ups and downs on the FDA and they're just getting on with it. But did you guys have a particular feel for whether it's going to be a positive? Is it-- do we have a blue as to who's going to be taking over whether that person is going to be positive or negative for the sector? Just wanted to just touch on that before we move on. No clue who's taking over. I think the angle that I would maybe point people to is just let's see how some of the next events play out in the rare disease FDA flexibility arena. We've got a pedufa for Denali in Hunter Syndrome on April 5th. That's for a blood-brain barrier. area enzyme product that has outstanding data, but open label data on biomarkers, right? We always thought that that was one of the better data sets across kind of the rare flexibility realm, but still it's the next test of FDA flexibility. We won't know what would happen if than I was still at the FDA, but I think that that's important. I think the other question too is like what happens with the unicorn here? Is this kind of lead them to have some sort of dialogue and a path to refiling? So I mean, I think we're going to learn over the next year or next, sorry, not if next season, like the next three to four months, right? Sort of like, even just is there a new equilibrium before we get someone at seabird? You know, Josh, I think I saw like a, maybe a Bloomberg headline or something you wrote about arguing for someone at the FDA that was, you know, maybe more intermediate versus Peter Marks or Van Eyme, am I putting words in your mouth? I thought that was kind of like an interesting comment. I got him forest and it flagged that and just kind of agree with the view that I think many of us felt that, you know, Peter Marks, who really did have patients best interest at heart, but might have been a little too lenient in terms of the requirements for drug approvals going through seabird. I think many feel that Van Eyme, Prasad was too stringent. I think that's actually a debatable point and a very interesting debatable point. You know, we had our own kind of recent debate whether Van Eyme, Prasad was a good regulator versus a good leader. He seemed to fail as a leader at the agency and, and Moralid really deteriorated, at least based on many of the reports that came out of the great work from the stat news group and that perhaps more than anything might have cost him his role there. But the regulatory decisions and the bar that he was placing for approvals was defensible. It was always going to be controversial. Right? Peter Marks was controversial in his way with being lenient and Van Ey was controversial in his way with being stringent, but there was a case to be made for his views. So it's a regulator. And by the way, he was incredibly astute and sharp and like he sees through all of the games that get played by companies from, so from that regard, he was a very competent regulator, but not necessarily the most appropriate leader for the organization. Well, a lot of debate to have. It's in all in the past now the question is who's going to come in and fill that role. What are the implications going to be for where that bar gets set? Are drugs that Van Eyme, Prasad had felt were below that line now going to be viewed as above the line? I don't think we have any good sense right now, as to what those answers are until we find out who's going to be heading up, heading up seabird. Yeah, I'll keep my comments relatively short. I don't have insight as to who might be coming next and sometimes it's better to have a devil, you know, versus a devil, you don't know, but I'm hopeful and optimistic that we have someone who perhaps brings some stability to the FDA where industry and feel that there is more predictability and reliability, but that is a TBD and we'll just see how, as Paul mentioned, we'll see how the next few months plays out. I mean, I always thought maybe I'll be very naive here. Of course, the two characters individuals that you spoke to Peter Marx and Van Eyme, Prasad, did not kind of underscore this thought that I had, that the FDA employed experts and reviewers and scientists and clinicians to review data sets and safety and efficacy of products that came along, take it to a committee of experts often, not always, in outcome ways, and that the director was there to make sure that they were not making, that they were doing their job correctly, not to intervene and say, "All that work you've done, I disagree with," or an positive or negative way. Maybe I was being naive, but that's what I thought the regulators supposed to be, what other was, what is the point of having all those people in place doing all that review work? So, that's the bit that really got me a little bit about, perhaps both, right? Josh, I mean, I remember all the discussions we had about the approval of the AMD drug. So, look, it's happened now and we'll find out, as Paul said, we have a few events coming up to see whether the FDA is genuinely putting its money where it's mouth is with regards to all the positive commentary about rare diseases and we want to get drugs for rare diseases. Let's see how this comes out. Of course, any cause one is a data set that's going to be reviewed and maybe there's something else they found in the find in there, but we keep our fingers crossed. Any other comments on that before I move on to the next FDA discussion point that I think you're not sure how, what does this mean for us, but any other comments? Okay, so this is one that Greg Broder has a possible discussion. I don't know what it means in terms of how we do our job, which is the FDA merging the adverse events trackers into one database so that the verse one is coming into the drug one. Does this make any difference? Is it just a formality that they're going through? Do you have any insight into that? Any of you guys, Greg? Well, maybe I'll just recap the news first and we can all pine on it, but earlier this week, the FDA did announce that it was launching a new adverse event reporting system. That's going to be, it's technically called the FDA adverse event monitoring system, so the acronym is AEMS. And I think it's what's notable here is what they're doing is they're basically combining three databases. Basically, many of us in the investment world have particularly keen to looking at the fares safety database, which contains reports for drugs and biologics, but there's also a veyers database, which is really more related to vaccines. And then there's another database that relates to animal drugs and animal foods. So these three are legacy systems that are being combined and will now be under this new AEMS system. The FDA and its official pressure list did mention that the three different platforms cost about $37 million a year to operate and give an expected efficiency. The FDA does expect to save over the next five years about 120 million. So I could see just from efficiency perspective, it makes sense. I'm not quite sure necessarily how it impacts the industry. I think the view is that it will actually make finding information much more seamless and perhaps this is a positive development, whereas I think many times we're thinking that news from the FDA is creating headaches. You want to talk about it? How did we find that it is the 50th anniversary of the biotech industry? You want to talk to us about that? I think this is on the back of John Crowley, he features in our discussions sometimes on the biotech hangout. Instead, I'm curious to have him read it, to be honest with you. What did he think of the sector? What he would look like in the next 50 years? I mean, that's one hell of a crystal ball. Yeah. It was an opinion piece that John Crowley, who had a bio, the trade organization, authored. He did a line on that 50 years, Sam, just so you know, he correlated the 50 years with the year where Genentech was founded. So that was his definition on why we're at the 50 year mark. And I think what he tried to do at the very nicely articulated piece was to try to talk about all of the accomplishments that have been achieved by the biotech industry, throughout stats in terms of what percent of drugs have been approved here in the U.S. I think he says that between the years 2012 to 2021, obviously there might be a little cherry picking there, but about, you know, a large percentage of drugs come from particularly U.S. biotech. He also talks about all the jobs that have been created. I mean, he talks about there being $3.2 trillion in economic activity that's been generated from the U.S. biotech industry. But I think where he's going with this is really he's talking about what does the future have in store and he doesn't really make predictions per se, but where he goes with this opinion piece is it's really about pricing and this idea that as we're now in an era where the current administration would like pray. in the US to more mirror prices that are seen outside the US, what he tries to do, John Crowley is highlight that this is not necessarily a good thing and we need to continue to protect US biotech and US pharmaceutical pricing. I don't think he necessarily defends high pricing, but he talks about where there's the role of PBMs, the middlemen, so to speak and the rebates there. This is really about not prognosticating what the next 50 years, what we're going to see, but really trying to identify some of the challenges that we're facing here in the US and pricing does have an impact on the viability of the industry because if we can't find ways to recoup the investment that does spell or create some challenges for the industry. That was basically the piece there. I don't know if anyone else has a view around making predictions about the next 50 years, that could be interesting, but I just wanted to highlight the pricing. We didn't really go into foreign competition. I know everyone is maybe worried, so to speak about the potential role of, for example, say China biotech, but this article did not specifically go there. That's an interesting segue, actually, Greg, and I'm pretty sure you meant it because I've just come back from China for days there, meeting many companies and a couple of events and discussions, etc. But I mean, no company going to China for over 20 years now visiting companies. When I first went in 2005, I think it was, there were probably one or two or three companies that were that you could label as drug development companies. One of them we did develop a relationship with when I was at Pype Jaffee those days called Hutchmet, which of course is well known now, and it's probably one of the two, what you could call a multinational corporation by the fact that they've got assets and drugs that they're directly selling themselves in different regions, and the other one, of course, being B1. And these 20 years I'll be watching the sector evolve, and in the past five to 10 years, it's completely taken off. And there are many correlates as to why that happened, and a large part of it is the management who had been trained by either multinational corporations in the West or by a tax going back to running companies within China. So the point about pricing, however, is an interesting one. It's something that I'm itching to do with my colleagues at Bloomberg if I have a bit of time to sit down and talk through it is we need to consider how AI plays into this. If as many industries expect to increase productivity, that productivity automatically should walk through to the bottom line, and if that's the case, then maybe the companies can start not increasing prices and drugs. I mean, in fact, so the new drugs that come to market maybe can be lower priced. Of course, that really upsets the cart when it comes to what about the old drugs that are on the market at a higher price for that same indication, etc. But it's something that I think is worth talking, thinking about. I've just put out a podcast with Mark Tassielovine, I'm sure you all know him, was now CEO of Zera. And we did talk about what he believes could happen to the time he takes to develop a drug. If you could take down that time that takes to develop a drug, which equals cost, then maybe there is an opportunity to reduce prices and keep your profitability high. So that's something that's interesting to talk about as time goes on. But if nobody wants to make any further comments on this, we can move on to a couple of deals that we've had this week. All, Josh, am I good to go to deals? Right, couple of deals. We haven't had a couple of deals. We've had one deal, and another one that was a regular rumor that seems to come up, I don't know, I haven't quite measured this catastrophe, it's not the first time. But the deal was a survey, a private French farmer company. And this is not perhaps on too many people's radar, but it's a company's got a annual revenue around 7 billion euros. So multiply that by something in the original 1.3 and you get to about eight and a half billion dollars. They say it all depends how you measure it. They're the 35th largest farmer company. But anyway, they bought day one. I don't think any of you guys covered day one. I did have a look. Is that right? Dawn. No. So, a $2.5 billion payment here. And what they've bought is a oncology business that fits very nicely to serve you as oncology business themselves. It's rare diseases. So the agenda, which is a topper-affinib, a class of drugs that are already relatively well known. But it's the first FDA approved and they went after a pretty rare cancer in terms of pediatric log-rate gliomas. It's the first FDA approved drug for these real relapse, relapse, reflector patients who have the B-Raff fusion or rearrangement, the 600 mutation, etc. So that's approved. It's growing. I think the last number that they reported was $155 million for the year 2025. Guidance between 2025 and $250 million. So it's a good deal to see. What's interesting is that the drug outside the US is a prove is licensed to another French company called Ipsin. So of course, Serbia appears to have perhaps bigger firepower or whatever reason Ipsin didn't feel like it wanted the broader indication. So that's good to see another M&A deal. But it's not the multi-billion dollar one we're all looking for. Which of course, if you guys, you may or may not have seen it a couple of days ago, Bloomberg interviewed Eric Tokat and on about M&A in the sector. He was saying there's lots of M&A coming. $20 billion plus is still expected. So I'm assuming we're all keeping our fingers crossed because that is a good positive thing in our sector when the cash comes back to play. So did any of you want to comment on the dawn acquisition? I just point out that it was Serbia that acquired the Agios oncology assets about half a decade ago or so with that included Veranago, I guess, for another brain tumor. So probably some synergies that they saw with the day one acquisition, the launch of Veranago has actually gone quite well, by according to to at least some of some of the reports, but Serbia doesn't break out their own individual product sales. Also about the IDH world has become a lot more exciting as well in the glioma space. So I think that makes a very nice package, as you're right to say Josh. And of course the other one was the rumor. I have to say I chuckle every time I see these things. Abvy Vax, French company that has had some exciting data in alternative collitis, I think, if I'm not wrong. Back in August, when the share price went absolutely ballistic. And there's been several all rumored by the same journal, I think, a journal in France called Lalette. And this time it was apparently they had given AstraZeneca this amount of time for exclusive access to the data after which they would go and seek other or continue to talk to other threshold buyers. And it turned out the company itself turned around and said, that's not true. So I don't really know what's going on here, but this is made around several times. So any of you guys think that one day we'll wake up and actually see a deal for Abvy Vax? Where am I pushing too far over the line from speculating? Well, I think I'll just chime in. I think Abvy Vax plays in the Sinai space, which just, you know, the pipeline and the product potential just seems, you know, just very tantalizing for an acquirer. And so whether, you know, whether Abvy Vax actually gets taken out, I don't know. But I certainly think that for the data that they've presented and for the profile of a type of a company that it is, I wouldn't put it past anyone where this might not be taken out at some point, whether it's this year or next year, I'm not quite sure. I don't know when the next clinical data are, but it certainly falls within kind of the sweet spot, I think, for where the larger CAP farmers, which again are facing, I don't know the numbers, whether 150 billion or 200 billion in potential revenue that's at risk over the next five years. They're going to have to solve for that. And I think many of us think it's probably going to be primarily through what we call external sources of revenue or innovation. Yeah. But Greg, you've got the mic. So do you want to talk to us about idea? They've got some data coming up that looks-- we like the drug and Bruno Moulin intelligence. But talk us through that, please. Yeah, sure. So they're a really interesting company based in California called Idea Biosciences. It's a company that I cover. But they have a small molecule called Derrova Certib. It's an oral PKC inhibitor. And they've got top line data coming out at the end of this month. It will be phase two/three data in nature. And it is-- or an efficacy endpoint, which will be median progression for a survival or PFS. And the drug is in combination with another EKI, Krizotnib. And the view is there is going to be potential utility in UVal melanoma. And we don't have too many drugs for UVal melanoma. Many people know about skin or cutaneous melanoma. And I would say that there are certainly a lot of drugs already for skin or cutaneous melanoma. And many more that are in the pipeline. But here, the current-- well, there's only one approved drug right now. And that's a Kim track, which is what was the very first TCR-based therapeutic ever approved. And that is a drug by immunocore. There is another company that we cover. And Kim track has done very well as a drug. It is probably in his fifth year of being on the market. It is annualizing at about 400 million. And patients-- interestingly, patients who are on Kim track, they may actually not have very high response rates. Medium PFS may not be great, but at the same time, there is a proven overall survival benefit. And patients are staying on the drug, even though their tumors may be progressing. But it's been a very nice drug. The limitation of Kim track is for the type of therapy that it is, the TCR-based therapeutics is that they are restricted by HLA status. And so this is not a drug that would be amenable to all patients with UVal melanoma. And therein lies a potential opportunity for other companies. So here we have idea with its Derova Surtib. They've got data coming. Phase one, two data showed a seven-month benefit. We're talking about patients with existing other standards of care. Again, in a non-HLA-restricted setting, only getting two to three months. Checkpoint inhibitors don't work here, although they do work well in skin melanoma. And so anything above two to three months, obviously, would be tremendous for patients. As I mentioned, we did see seven months before in an earlier study. And these data are coming at the end of this month. And I think that what we're looking for is anything better than perhaps five and a half months with seven months seeing in a prior clinical trial. So anticipated that these data will come at the end of the month. And this is a big event for today, which has a very broad and diverse pipeline. They're really focused more broadly on synthetic lethality, so very novel mechanisms of action. They're well-funded. But this is the first real big, I would call it, chunky, late-stage data event for the company. And we just actually did a call for clients earlier this morning. And I K.O.L. that we spoke with predicted that perhaps there could be as high as an 80% probability of success. We're at, I think, 65 or so. But this would be a very welcome addition for patients who have UVal melanoma patients sometimes need to get their eye removed and no one wants to lose an eye, literally. So something that we're all looking forward to. And Greg, is it approvable? Is it a submittable data set on a PFS number? Yes, I think, obviously, the proof will be in the strength of the data. But the company idea has suggested that if they do see the results that they want to see, there is an accelerated approval pathway that they would pursue. And with that in mind, I think that we could see the struggle potentially on the market next year if these data were indeed positive. And then just lastly, if you had a situation with KymTrack, which was kind of the opposite, the PFS wasn't that great. And then OS turned out to be a lot better. And of course, there's been lots of discussions about that, so in the past, could you see a situation, you ever worry about the reverse situation here? You get a decent PFS, but doesn't translate to a big OS signal. I'm not suggesting anything. I'm just actually asking, given that we lived through this with KymTrack in your opposite direction. Yeah, I mean, I think we'll have to see what the data are. There is a secondary endpoint in the study that would be an OS endpoint. And I guess that would provide for a full approval. And I think it is something that, at least based on the conversations that we've had with KOLs, is that because there is really nothing else out there, the bar is very low. And so with that in mind, could you see perhaps not a great OS benefit, even if you see a very good PFS benefit? Anything is possible. But I don't think necessarily that given that there is nothing approved for HLA negative patients, that the drug won't have utility or fine utility. Yeah, so I think we would agree with all of that. We've got a pretty deep research in melanoma. So that's a cool one now. Talking about data, I think we need-- we want to talk about the opposite, the negative data that came out of the Russia's trial press of Vera. Greg, did you want to take that? And then I'm going to ask Josh to comment as well. Yeah, I'll just quickly comment here. So Roche reported what I thought were pretty highly anticipated data for an oral selective estrogen receptor degrade or Sird, which is called geridescent. And this was a phase three study. This was looking in first line estrogen receptor positive, her two negative metastatic breast cancer patients. And this is one of several trials that Roche is running for geridescent. The results, unfortunately, were negative. And I do think that this may take a little bit of the luster on geridescent off a little bit. But that being said, there are re-thrues for several companies. And with that said, I do cover one company called Lyona Bio. It's an interesting one where they previously were a CNS company, but then brought in breast cancer asset just late last year. Their drug is in phase three. And that's the old SIRM for osteoporosis. Many people may remember lesophaxapine. And lesophaxapine is being evaluated in a phase three study. It's called the Elaine three study in a second line setting. But the view was that right now we're seeing more patients with a certain type of mutation. And the view was that if the geridescent results were positive, this might shrink the opportunity for lesophaxapine because it is believed that use of aromatase inhibitors continued use will increase the number of patients with a certain mutation. And perhaps geridescent if the data were positive might reduce potential use of aromatase inhibitors. But we don't have to worry about that right now, unfortunate for patients. But it does look like that from a Lyona Bio perspective, their market is still a good market opportunity. Their view is it didn't really make a difference anyway because aromatase inhibitors are so ingrained and very effective, especially when you combine them with other drugs. So with that said, it's unfortunate result for patients. Obviously the breast cancer market is a very large one. I believe the number that's thrown out there is about 55 billion is the size of the breast cancer therapeutics market. But with that said, maybe I'll stop here and pass it along to Josh. Yeah, Josh? Yeah, I mean, I guess I just point out that the Lidera study in the adjuvant setting did show a benefit for geridescent. And the oral serds have generally struggled in the first line setting. They do seem to work in the refractory setting in the ESR. mutant patient population. But I think the signal here that we're seeing is one that suggests that it kind of becomes more of an either/or with the CDK46 inhibitors, because Lidera was not on a CDK46 background and so it beat placebo. Whereas Persevera was on top of, I believe, the public cycle. And it did not show an incremental benefit there. So I think that's kind of the challenge. It now sets up for trying to figure out how to carve out space in earlier line settings where CDK46 inhibitors are not used, because they are used in certain adjuvant settings. Now there may be some safety advantages to using an oral serred over CDK46 in some of those patients. So it'll be a different interesting battle in the adjuvant setting, but obviously not necessarily one in the first line, kind of an unusual setup. I don't think that's why Russia's share price reacted so much, because everybody, after having seen the adjuvant data in Lidera had come to the, including K.O.S.A. as always, spoke to had come to the conclusion that it's going to work. So that surprised everybody. So Josh, once you've got the mic there, and it just pulls, sorry, just to be sure, do you want to make any comments on what we've just talked about before I asked Josh to talk about a couple of stories. - No. - Okay, cool. Josh, do you want to take it away on GSK and the other topics you wanted to pick up on? - Sure, yeah. So GSK has a late-stage Ibat inhibitor for PBC, Linerix Abat, that I think we had heard they were looking to out license and they found a partner, Alpha Sigma, who's acquired the drug for around 300 million upfront, bunch of bio-bucks as well and royalties. Not a huge sum, given the size of the PBC market, which I think is interesting. What's also interesting though is, if Alpha Sigma is a familiar name, it's because it was the company that acquired Intercept, picked up Ocaliva before Ocaliva was ultimately pulled from the market for not having a favorable risk benefit profile with subsequent data. So at least they do have some familiarity with the PBC community. It's relevant for a company I cover Mirum 'cause Mirum is developing their own Ibat inhibitor. They're trailing, particularly for the PBC indication they're trailing a couple years behind, but I think between choosing between commercial rival of Alpha Sigma and GSK, one might feel that Mirum's got a little bit more breathing room relative to Alpha Sigma and Mirum's drug potentially where as we await full data sets for it, it actually have been dosed at a higher relative exposure level and so may actually have greater efficacy. There are actually some signals that that might be the case. So an interesting update in a somewhat competitive space. - Yeah, and you got two other companies, Benetek and Marva, that actually, couple of other data. - Looking at the share price charts, they're completely contrasting stories. So focus through those things. - Happy to cover those. Benetek's a really interesting company in part because the CEO is a former investor on the West Coast, Gerald Banks, just an absolutely wonderful individual. And one of those circumstances where essentially one individual came into a company and really turned it around and got it on track just to Yomans work by Jurel to get this program moving forward. And what it is is an AMV gene therapy, local injection into throat muscles for patients with the Orofair and Geo muscular dystrophy. They've been providing regular data updates and they give us another data update. Now, two years of follow up for patients in the Lodosurm and they continue to look actually quite good in terms of improvement in swallow function. Gerald put just put a ton of effort in terms of figuring out like, how do you actually measure swallowing for regulatory purposes, lots and lots of work done there. And then they dose one patient with the high dose and that patient's done very well also. Very important on MetNeed for patients. So really, it's an exciting story. In part, very important on MetNeed and in part just kind of seeing this one wonderful individual with hands of this program. He's now got a full team with him to do all this, but it's nice to see that going and happy for Jurel for the success that they've had thus far. Obviously, still a ways to go before this is a drug with a clearly improvable profile, but they seem to be well on their way. And then, Ramada, an interesting update, the NMIBC non-muscle invasive bladder cancer space is starting to get quite competitive. A number of late stage programs, Ramada's not one of the later stage programs, but they're moving into pivotal trials. They're phase two data for their combination, kind of gel therapy, of that incorporates gem-side-of-been-it and dose-at-taxal combination. These are two drugs that are often used for NMIBC, kind of on a more ad hoc basis. They're not approved for this type of use. And so it can be a little bit difficult to procure these drugs and administer them. So basically, Ramada's licensed from a company in Israel, a unique formulation of these two drugs that you can deliver simultaneously and move into a more proper development path. And so they presented some data update that showed the one year complete response for that combination in high-risk NMIBC is close to 80%. Small data set, but it still looks like it's meaningfully above where some of the other competitors are that are further ahead and that includes immunity, bio-J&J, CG oncology, CG is the name that we do cover. Wood note though that CG is working on its own combination product. It has an on-calytic virus that they're in the midst of rolling BLA, for approval for high-risk NMIBC, but they're also now combining with gem-cytebene. So I think what we're seeing potentially is kind of a shift already in this very early evolving NMIBC market away from monotherapy options, potentially to double it. So that's kind of a common theme that you see in oncology, double it's triplets often do better than monoparopeia. And so, we're watching all of these programs as they evolve a lot of different nuances to the space, but it was a good week for Romada, stocks up about, I think, 40% or so over the last week, and more notably over the last year. And this is what you got to love about biotech, because in biotech this happens on a not too infrequent basis, but Romada is up like 2,200% over the last year. Obviously started a very, very small-markie cap. 25 cents, 25 cents was a short piece. - Yeah. - And licensed this product. And they've had so far good success creating value for investors. - Josh, is it the same team that was doing, trying to thread the needle on this whole opioid, non-opioid, and depression? - They had a depression program, I forget exactly what the nature of it was, but yeah, I think it's still-- - Oh, I think it's still Sergio. - It's the same team. - It is Sergio. - Yeah. - So Josh, look, we cover the MIVC and NMIVC market, really in depth, and we've been looking at this data equally, equally like it. The question that we keep going around in our heads is CG oncology, them, et cetera. That somebody's got to be partnering with them. Do you think they can go up against G&J in the EROG G market on their own? - Yeah, I don't see what I can. To their credit, CG has terrific relationships in this space. The CEO Arthur Cwan is, it's actually ironic that we're just talking about Ben and Tak and what Drill, thanks has done for that company essentially Arthur Cwan has done exactly the same for CG oncology. He came in when the company was really floundering. Believe it's been like a decade and honed it on this asset and advancing it specifically for NMIVC and he's really been able to develop deep relationships in the EROG community, which tends to be dominated by these lug pods, these very large centers. And so there aren't that many of them and so you can actually be very influential and have a significant reach as a small company. And then they brought in Amba Billette, who's also just, it's a wonderful management team and Amba also has very deep relationships as a previous EROG just as well. And then most importantly, it all comes down to product profile and differentiation and then J&J product and the credo product are very, very different in terms of how they're administered, the side effect profile, et cetera, et cetera. And then I guess the last point to make is that, when you look at the 12 month complete response rate, at least for the monotherapy, it does change when you get to the combos. But for monotherapy, your 12 month CR rates like 50%, which means half your patients after a year are gonna need something else. So whether you're after BCG, if you're frontline, if you're second line, even if you're third line, there's still gonna be multiple lines of therapies for this patient population to create. that creates very sizable and mathematical need. And it means that multiple companies can coexist and have very important products for patients. It's not an idea or. - J and J has set up a very healthy price with Alexa. So that I'm sure is gonna help these companies be able to get some pretty good profitable businesses. - Yeah, that's it. - Yeah, and if you've been watching this space, it's been a very interesting one to watch because you have. You know, there are more entrants now, such as Ramada and NGN and Protering in this space, immunity biobit. But for a period of time, it was kind of like J and J and C.G. on Colergy as the two later horses in this race to watch it. And Chene J would just really go after C.G. on Colergy or any chance they had and with not so favorable commentary about their competitors in a way that, just kind of knowing J and J and their general credo and how they're supposed to be behaving. - Yeah, a little bit uncomfortable. A little uncomfortable. And by the way, like a lot of the things that J and J was claiming early on about having a major advantage over C.G. on Colergy in terms of data set, completely fizzled. A very unusual situation to see this galaeth of a firma company almost going after a very small emerging biotech company and not only going after them, but being wrong. - Well, I mean, trying to second-guess data and clinical data biology often trumps the cells. Now Paul's got his own fair share of wonderful Lucky Share price charts in Dianna, St. Zenund. Do you want to talk to us about those, Paul? - Sure, yeah. Maybe I'll actually start with vertex. I think the vertex data, Zenund, Dan, this, I mean, these were some of the biggest, I we did a lot of farm in this call, but these were the big biotech news items of the week. I mean, I think with vertex, to be interesting to hear others views, 'cause I'm sure Josh and Greg might cover some of the stuff in the IGAN space, but basically vertex had interim data for Povac has to set. Their April Baff antibody for IGAN, which showed a highly static change in proton area. The interesting thing though, and I think like this kind of raises a question of just sort of where sentiment is at in the sector, and is there just kind of a general appetite to own more high quality biotech companies? Broadly speaking is because, you know, these data were probably not as good as some people expected. I think the hope was that the April Baff dual combination could generate maybe a greater efficacy punch than what we've seen from Otsuka and Barrow with the anti-April antibodies. And yet they really didn't see much differentiation. Safety seems clean, right, which I think was kind of good to see, but the stock had a very big move for a large cabin. It was up at 10% at one point in the day, which for a company with over a hundred billion on news that was quote unquote expected, that was a big deal. I think the other just kind of interesting off-shoot on the IGAN conversation that I'd be interested in hearing others sort of think about is that, you know, this is a category that I think the street has become more bullish on over time for a couple reasons, one, because the physician feedback on these biologics has been good, and applies widespread use. But the other reason is just that Otsuka, who's first here with this class priced at maybe twice as high as expectations. And, you know, I feel like one thing we haven't complained about a lot in this column the past year is drug pricing. We're seeing a lot of just price to the upside trades and not a lot of pushback on it. And so it would just be curious if many others have thoughts on vertex, IGAN, or this whole kind of pricing thing, which, you know, again, I really feel like maybe doubled the tam here versus what people were thinking a year ago. - Well, I don't have big exposure to the kidney space, but that being said, there is a lot of interest given still high on the medical need. As far as drug pricing, I do think that, as I talk to more companies, it does seem that they're getting perhaps, I don't wanna say more aggressive with pricing, but I think they feel that they have the flexibility to price higher. And some of that is, it's interesting. I think some of that reflects perhaps what's happening more globally where some companies feel that perhaps their desire to launch XUS is getting smaller and smaller and that perhaps given the system where it is today, still in place they feel that there is room for them to perhaps take pricing higher than we might have expected. - Paul, do you want to carry on talking about? - Yeah, sure, I think we only have a minute or two left. On Xenon, so they had their face-free data for Zetu Calnare. It was an interesting data set because I think the context was that there was a lot of discussion and debate around what the effect size needed to be for this drug. Our view was always that if you look at the biggest anti-platform, the Olympic drugs, efficacy is a weak correlate of commercial success. Vimpats, the last big drug in this category. I used to joke with people that if Xenon had the Vimpat effect size, the market cap would be cut in half. And yet if Xenon has the Vimpat commercial outcome, that would be a great outcome because it was a couple billion dollar drug. Nonetheless, Xenon's efficacy data actually was better in face-free than face-2, which is extremely rare in CNS, but kind of an artifact of how an epilepsy drug arms often hold up if you run a good study. And maybe you can get a little lucky with placebo or a better managed placebo, which is what they did in face-3. I mean, the long story short is they raised over $700 million, which again, going back to our original conversation, I think shows that this is still a healthy market where companies can raise a lot of capital and great data and investors can get rewarded. Similar deal with diethyst, they had some interim data in CI/DK. Obviously, a really big eye-knife market, crowded, but a big tan, and they also were able to finance and raise $700 million and had a nice stock reaction on their data. So if anyone else wants to comment on these, happy to discuss. Josh? No specific on this one from-- I mean, look, the-- well, it is to the point that we started with, i.e., is there a risk for the sector given all the stuff that's going on around the world? And as Paul highlighted, the share price reactions to these data releases and the fund raises that come behind them are clearly indications of a very positive environment for this for the sector. So I'm really glad that we're finishing on this. Paul, you also wanted to touch on the lookover in FDA news. We have a bit of time. So did you want to do that? Sure. I mean, I think just shows that the FDA still, kind of in an odd, unpredictable place, right? I mean, I feel like every other week I've come on here and kind of hammer the FDA. Maybe I've been more-- more like even though I understand, like, Josh, I think makes the good point that maybe Vinai Prasad is an extremely intelligent regulator and makes good data-driven points about a lot of these drugs. I've still been maybe more bummed out on just a lot of the flip flops and kind of a few of the products are things that I've covered that I really do believe in. So I think this one is just kind of weird, right? I mean, did the long story is this is something that seems to have some political pressure by getting an approval for autism? It's like very limited data, right? I mean, I think maybe the risk-- you know what, I'm not even a super expert in the data, but I think the perceived risk with this drug by those who are around it is not very high. So maybe that's the feeling or part of the risk benefit calculus. But it's strange to me that something like this could happen and some of these rare disease products couldn't even get their own fair share of her review. Yeah, I mean, I don't see the logic in it. So I don't know, Josh, did you want to comment on that? Or we can move on? I think we're close to the end. We are close to the end. As you look, there isn't a week that something happened in biotech that doesn't have to do with obesity. And this week was no different than no time left to go through them, but just to make sure that folks know that we've noticed them. The Roche-Zeland data was quite an interesting setup. Which I have to say was to getting back to the point that's beginning to continue to wind me up personally is these percentages, percentages weight loss here, where you don't have the details. So the share price of Zeeland was significantly impacted. And maybe for the right reasons or not, but you don't know how many women were in the control in terms of gender balance. Women tend to femyth, tend to respond better to drugs, et cetera. We don't know about the background PMIs where there's a lot of data that's needed here. And I think we've had this data. We had the Avie-Gurber data. We've had some data from China, et cetera. So there's plenty of data coming out that's showing that the space is getting super competitive. But of course, the ones who are currently on the market and taking the whole share are continuing to be lily-in. and Nova, and it'd be very interesting to see when these others come to market, where the pricing in this market is. So, and we also had some news from Biontech, which was called People by a little bit of a surprise, which was the management moving on. So, I'm gonna pack up there. I think we are one minute over. So thank you very much for joining us again. All the details are on the biotecanc.com. [BLANK_AUDIO]