Episode 177 - March 27, 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 enthusiasts. I'm Grace Colón and my co-host today are Josh Zimmer, Eric Schmidt and Brian Cshorney. For more information about our hosts and guest speakers or to listen to the most recent episode, please go to biotechhangout.com. As usual, we've got a packed episode today. Lots of things going on, M&A deals, policy issues, regulatory developments, data readouts, conferences, upcoming and so forth. So we're going to jump right in. As usual, let's start a little bit with the broader macro backdrop. There was an interesting fierce pharma piece this year, this week highlighting that large pharma reduced headcount last year by over 22,000, which should actually be no surprise. But it was quite a large number when you added it all up. We saw the news over the year of bits and pieces of layouts, but that's what it totaled. And it was really interesting because we have that as a backdrop, but then we also have a tremendous amount of capital being deployed in new assets and new companies. And obviously we're talking about that $300 billion patent cliff for a while now, but it's really real now. And we're really seeing the impact. But of course, this is all happening with a backdrop of financial distress in the markets and other things. And I know last week, we highlighted how biotech is somewhat removed from some of this. But curious what the sentiment is this week around the table, given everything going on in some of the big murders that were announced this week. What is going on this week with love to hear sentiments around the room? Eric, you want to start? Sure, Grace, I'll give it a start. I'm not sure that much has changed in the past week. You mentioned some M&A. And we actually did have four deals, but it wasn't quote the right kind of M&A from a market sentiment standpoint, right? Three of the four deals were private company targets. And the fourth, as I know we're going to talk about later in the show, the fourth one for a very Paul Tree premium. So if anything, the M&A was kind of a little bit lackluster and maybe for public market investors, even a little bit maddening. But from where we said, yeah, the macro is still kind of driving the bus. I think, or Josh and I were discussing this this morning, actually, I think that people still want to own biotech. I think they're looking for reasons to increase their positions. I think they certainly still care about the industry. But when you have such a potentially clouded macro economic backdrop, including the war, the economy, interest rates, gas prices, et cetera, it's a little bit hard to reach through your computer and actually put in bi-orders. And I think that we're being somewhat steamy in our bullish optimism toward the sector because of the macro. So I'll pause with Brian and Josh trying to in here. - Yeah, so I'll say it's been a really interesting week and I've had this conversation several times with my team and our healthcare position trader on, there's just for the week, it's pretty sleepy, but there's pretty substantial outperformance. XBI is basically flat on the week when we have S&P down over 2% right now. And we've had a couple of really big outperforming days. Like Wednesday, the entire market was up, but I think the XBI was almost, was more than four X, what the S&P was on the day. And yesterday we had kind of a global equities down day, but XBI was down much less. So despite sort of what you would think of, risk off yesterday, biotech was still kind of the least negatively impacted. And maybe a risk on day on Wednesday, you saw even more outsized performance. So you definitely still have the dynamic out there. That's clear just in the trading and the performance. This week of your right, people seem to still want to be involved in biotech. It is not getting sold more than other equities and days when equities are getting bought. It seems to be getting bought more. You know, is there a great explanation for that? I guess, you know, other than, I think what we've all said time and time again, we think the relative underperformance over multiple years, it was probably unwarranted and poised for a balance. It's hard to identify anything specific. Like this week to be like, oh, yeah, this was the catalyst of why we should have XBI performance and why people should be buying in an upmarket or a downmarket. - I guess I would just add that, you know, in biotech, probably like every other sector, you gotta get the sector called right. And that's what's challenging in the moment, given all the other issues happening around the world and the XBI keeps getting dragged back down, you know, for every day that's, that it's up one or two percent, typically followed by a day where it's down, one or two percent. So we're going from bullish days to bearish days, the bullish days to bearish days trying to figure out, you know, are we gonna break out? If so, are we gonna break out to the upside or are we gonna see more weakness? There was a day that the XBI was below 120. And once it kind of breaks 120, you wanna wear the next level of support might be, on a fundamental basis, as we've talked about in the past, the industry is maturing and it is becoming increasingly a cash flow generating profitable, garpy type industry, but it's not there yet. It's kind of in its adolescent years, I guess, or young adult years because it's just moving to ramp up profitability. If you play this out a few more years, the sector overall, again, looks very attractive from a garp perspective, but not necessarily this year, right? And so I think that's why some of the macro dynamics may disproportionately hit biotech, which is still kind of a view as a more of a risky sector. But again, that's changing as companies turn into real cash flow generating businesses that have more optionality than they do risk. - Yeah, that's a really good point. I mean, we've had a significant number of companies, sort of the mid-stage companies that are commercial, they might be focused in one or two franchise areas. You know, they're probably a bit more vulnerable to everything that's going on, but at the same time, we're seeing more and more of them, we're seeing them get to the big leagues. So it is reflective of that advanced maturity of the industry. But on the other hand, right, there's a lot of pull for new innovation with all the layoffs in far more and kind of seem to be cutting down in many ways on their internal R&D engines and really depending on external innovation. So there's kind of interesting things at play here. And yeah, it's definitely not going to be a boring year. But with that, I think that's probably a really good save way into some of the M&A that we saw this week. And I think Eric, you were going to cover the Gilead deal. - Yeah, I can start there. Maybe just one last comment on the market. Biotech still up a couple percent year to date is Brian mentioned. And the S&P 500's down five, six percent now. So that spread of seven, eight percent relative outperformance versus the S&P, that's very, very substantial for three months into the year here, right? That's a big year of outperformance if this continues to try to that trajectory. So just want to throw that out there for those of us who are inclined on the bullish side that seems like people really want to own this space still. We'll see if that continues. Yeah, so onto some of the M&A Gilead buying ORO. This is one of the three private company targets that was acquired this week. We can talk about some of the others. I think in total, there's about $10 billion of M&A activity this week, which is certainly meaningful. And the Gilead ORO acquisition was for about 1.7 billion up front with another 500 to $1 million on the back end. ORO is an interesting company. They've got a BCMA CD3 by specific or T-cell Engager. It's in Phase 1, 2 trials. And while these by specifics directed at BCMA, seem like they're a dime a dozen, the ORO guys have done something different, which is really tailored and target their development programs toward the hemolytic anemia, this autoimmune amoeuble and an amoeuble is an amoeuble. And they seem to be generating some really good data. I don't think the company had much of a presence with investors. So I think a lot of Gilead analysts are kind of scratching their heads and wondering why the company may have paid this much for what's essentially a kind of competitive and generalized space. But I think the data here is what really creates a lot of value potentially for ORO and Gilead in the future of being first in these rare hemolytic anemias. The other thing that's kind of interesting about this deal is that Gilead seems like it wants to cut in its former partner Galapagos into the transaction. Galapagos has essentially been sitting on a ton of cash with little, really progress or a lot of money. or strategic trajectory and Gilead's willing to allow them to buy into this transaction, share the asset in some ways operationalize the asset and share in the economics. And Gilead's hardly short on cash flow, so I'm not quite sure what the rationale for this is. I'm not quite sure I've seen anything like it before. Maybe the others have views on sort of the uniqueness of this strategy and what Gilead might be thinking. Brian, Josh, you guys wanna comment? - Yes. - Nothing to add on my thesis. - Yeah, no, I think Eric had a good run down there. - Great. And I think next we will go, so thanks Eric for that one. And I think you were also gonna cover, I mean, the turns story is really a remarkable one when we think about the turnaround since CEO Amy Burrow stepped in just a couple of years ago and made a decisive pivot away from its metabolic portfolio and towards oncology. And really that story of that asset and the company has really been remarkable when we saw the data coming out of Ash. Do you wanna talk about that one? - Yeah, thanks Grace. I think it's even less than two years that she's been in the CEO seat. So, wonderful outcome for her and her team and threats to them. This just a year ago was a $3 stock and they're gonna be acquired for about 20 times that. It's about a $6 billion deal. I don't think this one surprised anyone. Mark from their standpoint is known to have kind of rightful shot interest in what they perceive is excellent drugs. And it certainly seems like turn 701, which is a drug for CML patients, essentially a bio better version of Novartis' semplix. Looks like it has all the properties of the best in class drug. Many of us think that semplix is gonna be a $3 or $4 billion drug and it would seem that turn 701 has that opportunity as well. So, from a Merck standpoint, I think many analysts, including our analyst here, Carter Gold, who covers Merck thinks this is a nice acquisition. I guess if there's anything debate or discuss here, it's why turn would take such a modest premium. This deal is done at only a 6% premium to market. Yes, turn is up big time in the past year or so, but that's really irrelevant to an investment decision. Obviously turn is up because they've had great data and what turn was trading at six or 12 months ago is I don't think relevant to a board's decision to sell. So I sense a lot of frustration on the part of investors. And honestly, if I were an investor in turn, I would be a little bit frustrated also that the board decided to sell the company for such a modest premium. And I guess to try and put our listeners into the mentality of an investor, you could sell turn yesterday if you wanted to at essentially market price. And the board's decision to sell here essentially takes that optionality away from investors and forces them to sell by essentially selling the company out from under you. So as an investor, if you thought turn was going to continue to have great success and have a three or four billion dollar drug, you're probably a little bit angry that the board took that decision out of your hands. I know I would be. I'm always skeptical when groups, including boards, tell me that the market price is essentially something that they don't have confidence in or the market's decision to continue to own a stock is something that they feel strongly differs in their views. So kind of second guessing where the market is and saying, oh, the market's already got this right or the market's already priced in the maximum upside and taking investment decision out of investors' hands is something that bothers me a little bit. So maybe I'll throw that out to Brian and Josh and see if I can or yourself grace and see if I can get someone to take the other side of this. Yeah, I mean, it'd be wonderful to be in those boardrooms and hear the discussion and obviously we can't. But you make an interesting point. I mean, I'd love to hear what Brian and Josh think about it as well. I guess you're coming from the premise that we have access to full information and where the one's making or investors, I should say, the one's making the right decision about where the value should be. We don't know what we don't know and it's plausible that there are aspects to either the data set or the setup or something here that maybe investors were missing that might have made it hard for the company to find an alternative acquire. I mean, they use both Jeffries and Center View. You'd imagine they tried to uncover any possible buyer. I mean, there's only a certain number of companies who can afford $6 billion or $5 billion type acquisition. So I'm guessing everyone who might have had interest got a look at it. And then why did everyone else pass? I guess is the key question that we just don't have inside into. I mean, I think-- Right. I mean, my view looking at it and I'm not by any means very close to the story. I mean, CMS is a pretty competitive disease area, particularly in oncology. And it's been dominated by Novartis and maybe to a lesser extent Bristol. So I just wonder if part of the dynamic here is this is not an indication that's particularly favorable, even though it's in oncology for a company to launch itself. And do you really need a firepower of a large flana company that is heavily involved in the oncology space or even more specifically in CNA to really be the driver here? Yeah, well, thank you for your comments. And as always, it's important to come back, at least for me, to talk about the patients. I mean, I really do think that data coming out was viewed as pretty disruptive for patients. So regardless of the market and the acquisition, let's just hope that this new treatment can make it out there to the patients who need it. And hopefully there'll be companies that take these brave pivots into areas where they think they can really be disruptive. And you can do good and do well, hopefully. So let's move on. I think there was another one or two acquisitions. I know there was the Novartis acquisition of the allergy asset, the IgE, and I was wondering if anybody wanted to cover that or we can comment a little bit about it. I mean, this is really interesting. The Novartis needs to really make up for Zolaire and this particular asset, even though it's early stage, seems to have a lot of promise in broad areas in the allergy space. Anybody wanted to, is anybody covering that or would like to comment on that? Josh, you want to take it? Yeah, I mean, not super close to the space, but they paid quite a significant amount for a high affinity half-life extended IG and to your point with the loss of exclusivity of Zolaire and mechanism seeming to be relevant for patients with asthma, food allergies and CSU. All of which have some competitive dynamics in the space. I guess to me, it's a reminder of how hard it is to anticipate what pharma companies are going to buy, what they're looking for, how much they're looking to spend. It's also a good reminder of how many really exciting and promising private biotech companies there are. I mean, dozens and dozens of just stellar private companies in addition to exalergy, Transcend was acquired this morning by Otsuka, another private company for 700 million upfront and nearly half a billion in bio-bucks, they're developing a neuroplaced inage in for PTSD. And again, I mean, what's happening in the private biotech world is really exciting. And I think maybe to some extent these acquisitions highlight that good reminder for that. You know, the other thing that highlights is the trajectory of Zolaire. I mean, this is a drug that's been around for probably almost as long as Brian Scorney, not quite as long as me, but as long as he is. And it went kind of for nowhere for a long time. And it was sort of the forgotten asset within genetic erosion. And it never really got developed in indications outside of asthma, UE. And then finally, they developed it for peanut allergy, about 20 plus years after they launched this thing. And it's taken off. So very, very late in the product cycle, it's having complete rejuvenation. And it's become one of the biggest growth products they have. And I can understand why this is something that they want to continue to invest in. - Yeah, it's interesting. And obviously, very early stage, right? So a lot remains to be seen. So it was a very surprising number, the $2 billion value if I'm not mistaken. I think any more M&A or other deals before we jump to some other topics. Anybody want to cover anything or shall we do? jump into an O'Brien, you want to talk a little bit about regulatory? Yeah, that'd be great. So yeah, I'd love to just move to some regulatory stuff. Obviously, it's like one of my favorite topics to talk about on this. So we look following the second departure of our favorite controversial seabird director of an IPRSAD. There's been a lot of discussion among investors about like, you know, what, what's next now? And there have actually been a few regulatory decisions this week that, and you know, these are pretty small and but seem like maybe there is relative softening compared to the presod days. So one notable decision that I would highlight is the FDA approval of Denali's hunter syndrome treatment now branded as Avala. I think it's notable in that this is a the first approval of a TFR mediated therapy in the US. So this is essentially a transport vehicle to get larger molecules across the blood brain barrier to get CNS exposure. And this is kind of what the core technology at Denali is. But I think from a regulatory perspective, the other notable thing here is that this approval comes a bit over a month after regen X got a CRL rejection from the FDA for their hunter gene therapy. And you know, I think both are effectively probably doing something very similar. Now, I don't want to over read into it because there are differences here. Avlay is the is the missing enzyme in these patients. I donate to sulfate fused to the transport vehicle. RGX121 is an AV gene therapy that produces I2, I2S, the gene IDS that makes I2S. And the biomarker Avlay, I was approved on was CSF heparin sulfate. And the biomarker that's used in the Rigenix pivotal was CFS heparin sulfate D2S6, which is a sugar metabolite of heparin sulfate. So now, now I don't want to go into the specifics of what the assays here. But Joe Moonser is one of the experts on these things and hunter says that when you're measuring HS, you're actually measuring a number of different metabolites, one of which is D2S6. So, you know, unclear how different these measurements really are. But this seems to be one of the key issues that was cited in the Rigenix CRL. It's a numerously brought up in the complete response letter. As we don't know what this means, you know, this is not a validated surrogate. So of course, from a broader regulatory perspective, one of the key differences here is Denali's application was reviewed by Cedar in the Office of Neuroscience. And Rigenix's was reviewed by CBER. And Denali's application was approved after, you know, seemingly the end of the NIS reign at FDA. And Rigenix was rejected earlier. And May or May not have had something to do with his departure. Interestingly, we had an investor event earlier this week with Kim Hunt. Tim is the CEO of the Alliance for Regenerative Medicine. I think we pointed this out at the time. He wrote an opinion article in the New York Post titled, "How Trump's FDA is Breaking His Promise to America's Patients." And Denali's point said, "I didn't leave the NIE was gone the next week." So, you know, we had a lot of discussion at this investor meeting about what is next at FDA. And it does still seem like there's a lot of uncertainty. Right? McCarrie feels like he's kind of on the hot seat now. He was really VNI's biggest advocate. And, you know, we heard was effectively the person who got him brought back when he may remain and have not gotten fired over the summer. And although VNI has gone ahead of Cedar's Tracy Bethhogue who was for a period VNI student. So, there's a lot of question as to even if VNI has gone, how much of his impact remains, and will there be a change as long as RFK is in place as the secretary of HHS? And, you know, I've sort of recommended to some companies with more controversial regulatory applications or accelerated approval applications that may want to wait until after the midterms to file, as it does seem like some of that magma-ma-ha marriage is rather tenuous. So, one of the things we also talked about at the Investor lunch was really how much of a positive surprise Mehmet Oz has been. Of course, you know, we could probably say the relative hurdles pretty low here. But all the interactions we've heard about with him have been really positive. And it also seems like the administration has now been promoting Chris Klomp, who's Oz is right-hand guy at CMS, and feedback on him has also been really good too. So, I think there's kind of this, you know, tenuous hope out there that if RFK were to move on after midterms, this team could get promoted up in HHS. It's probably one of the best shots the Trump administration would maybe have at a Senate confirmation. That would also potentially allow for some downstream calming of the chaos that we're seeing at the FDA. But I would also note, in addition to the Danali approval, which the head of Cedar actually did a little video on X talking about the approval. But we also saw approvals of rockets gene therapy, Chris Loddy for LAD-1. And even though he's on his way out, then I was actually quoted in the PR as this was a Cedar application. And course, I've received approval for Lathurally in Ovarian, Fallopian, Tuber, or Paratineal Cancer. And look, I don't think under a presod threshold hold of approvability, any of these applications are clear layups. So, at least this week, I would say it does seem like the FDA has already been exercising a little more flexibility than they were a month ago. But, you know, would love to hear any perspectives that the rest of the team has on. Yeah, I guess I've been following Danali and rocket. And maybe from my perspective, not so surprising at the FDA, next the Rigenics drug, but approved the Danali drug. There are a number of key differences in the data sets. And obviously, the mode of administration, which at least in my mind pointed to a much stronger, product profile for Danali. So, not necessarily a surprise. And when you read the CRL of the Rigenics program, again, kind of outlying the FDA is thinking and, you know, can agree or disagree, but I think there is always going to be a subject development in terms of where that bar is set for approval in that. That obviously shifted with the exit of Peter Marx and then with the van Aper side coming in. And now we're going to have to figure out if the bar is going to shift from where it is now, depending on the new head of CBR. And then from the rocket perspective, again, not particularly surprising, the FDA, even van Aper side noted that they would have regulatory flexibility for ultra rare diseases such as this. The data set looked fine. The Ahmed Eid is for the very small patients, a number of patients with LAD1 seems to confer very meaningful benefit to those patients. So, I'm not sure from my perspective, anything meaningful you change this week, but, you know, we're constantly learning and a way to see who's going to come in and run the show, going forward. Sounds like it's a very difficult job and role to fail, given the hierarchy and leadership of the FDA and in CHHS. We'll see if that shifts further as well. Yeah, I have to say, I like Brian's thinking here that, you know, the FDA being under pressure, maybe driving some of these, maybe in some cases more rapid decisions. Some of these decisions happen a little bit ahead of their pedophadates. And we have heard that Dr. McCarrie is under some pressure, right? There was even a Washington Times article this week that was scorching, and its review of him as commissioner. Washington Times is known to be a pretty conservative newspaper, so for them to take on a Republican-appointed head of agency like this is a little unusual. And we've all heard from other sources, you know, that the administration isn't really thrilled with the direction that the FDA has gone. So if I'm commissioner, and I guess it's baseball season, so I can use this analogy now, if I'm commissioner, I'm coaching third base, I'm just weaving in these drugs. I'm making sure that anything that has a pedophadate the next month or two is going to get through. Otherwise, I know that the conservative arm of the patient right advocacy groups out there, the right to try folks are going to be telling me how dare you turn down a rare or from disease drug. So I'm not so sure it is just a coincidence. I mean, it's somewhat coincidental that all these pedophadates are happening. But I kind of like Brian's thinking that it may be a little bit more than a coincidence that we've got these two drugs approved this week. Just last week we had the GSK drug approved for PBC and other rare disease. So there may be something to this. And if I were an orphan drug company with an upcoming pedophadate, I'd feel a hell of a lot better than I felt just a month or two ago. Well, that's a great take everybody and we definitely need new hope for orphan drugs. It's been a rocky couple of years in terms of policy as well. So this is probably a good segue to a topic that I know you wanted to cover Eric, which is CDC. Just given all the transitions, and we had Dr. Monarez who was confirmed, but then removed just a few weeks later. And that's sort of been in limbo. We had a gym on yellow, the interim role. And now this morning, I think it was announced that we're delaying once again, finding a permanent director would love your thoughts on all of this. Yeah, I kind of ties into Brian's comment on the administration and how hard it is under RFK, junior to find adequate, capable people to serve, especially to serve and roll like CDC head, which is obviously not just heavily science oriented, but heavily geared toward the public health and of course the public need for vaccination. So what happened this week was that the deadline ended. Your right grace. that Susan Dr. Monter is was the only confirmed CDC director under the Trump administration. And she lasted, I think about a month or so. And with her departure, a deadline was put in place to nominate by the Trump administration a new CDC permanent director that deadline came and went on Wednesday, actually. So without that deadline, we can no longer as per procedures in the US government even have an acting CDC director. The acting CDC director had been Jay Botticaria, who's also head of the NIH. And unfortunately, I don't think Jay Botticaria has protected the public health to the extent he should have. His acting director, a lot of these changes, these anti-vaccine movement directives have been kind of put in place on ACIP and other organizations. So Dr. Botticaria, I think, has been the negligent, and at least in my opinion, in his duties. He's no longer going to be acting commissioner, but there isn't going to be a newly appointed director. And we'll just have to see. I mean, this is still tenuous times. I'd like to believe what Brian said is true. And that maybe at some point RFK will be departing to run his own presidential campaign and do his own thing. And we'll leave the CDC and other important bodies alone. But I think we're still hanging very much in the balance with regard to allowing this agency to perform the very important science and public health directives that it has on its agenda. Yeah, thank you for that. And obviously, there's been a lot of noise in the news as well about the vaccine task force and continued. Members quitting and a number of things going on, a lot of uncertainty. I mean, we have a temporary hold on some of the recommendations with regards to childhood vaccination. But it's a very interesting time for vaccine companies right now. I mean, next week is the World Vaccine Congress. I'll happen to be attending that. It'll be very interesting to see the mood. It's at Congress and the discussions there. So why don't we move into data? And I think there's a lot to go through today. And I think Brian, you wanted to start with Syrefta and Arrowhead. Yeah, so let's talk Syrefta. It will be a totally different conversation than I'm used to having on Syrefta as a hot DMD related. So we saw the first clinical data coming from their Arrowhead partnership this week. And these early data sets are in DM1 and FSHD. When this deal was done, this was really kind of viewed by people as potentially the next leg of Syrefta growth over the last year or so with the safety issues surrounding 11S and the failure of the essence study with Syrefta's PMOs and DMD. I get this question more from investors is are these programs going to be able to save them? So look, these programs you use out of the data six-integrate targeting ligand to deliver SIRNA to muscle. The PR was pretty much the void of any data, but they had a fairly comprehensive slide deck and conference call. And bottom line, what it looks like for us both programs is they didn't get very good drug concentrations in muscle. But what was really probably the money slide in the deck was the Ducks4 reductions in FSHD, which showed 90% plus reductions depending on which Ducks4 associated gene you were looking at. And I think it's fair to say that there's substantially better in terms of reductions than we've seen from other programs. As an example, a VITITY was about 50% in their phase 1, 2, 4 to 2 study. I do think there was maybe a little disappointment we didn't get any splice correction data from the DM1 results. Sir, I have to say we'll get that later this year. But I think there was hope that maybe a conmatch or exceed results seen by VITITY or DINE, even match those that we've seen from PEPCHEN. But maybe not that much disappointment, because the stock was up about 30% on the day. But now it's given about half of that back. So it's sort of been a little bit of warning trend. I'd love to hear if anyone else has perspectives on this. But it seems like there's been a number of recent data points where there's a big move up on a new data set. And then it kind of gets mostly stalled off in subsequent days, thinking like maybe Vertex's data from a couple of weeks ago in their nephrology program. Zeno hasn't pulled back that much. But it certainly has pulled back a little bit more than I would have expected from their focal onset. C# data, which I thought was a tremendous data set. But I think Sirrepta potential turnaround story is still evolving. We'll have to see how these drugs continue to perform as they see some additional patients. And we get more biomarker data. So I don't know if anyone else had wanted to comment on the Sirrepta parahead data. Yeah, Brian, I'm curious. I heard a lot of nitpicking at the data. Love your take. Some of the criticism's being that a lot of patients who were treated were withdrawn from the analysis of data specifically. I think about it half as many patients as was treated. We're shown in those ducts for reduction slides. And then I think the ducts for reductions were normalized versus placebo as opposed to normalized versus baseline. I'm not sure even what that means. But just wondering what you might have thought of some of those criticisms. Yeah, I think the valid criticisms. And I think that's part of the pullback. Again, this is like a very small and data set. We're sort of seeing the best foot forward. I think it's hard to imagine that these reductions, even if you're only taking completers analysis, don't have a meaningful implication. But how safe, how broad this winds up looking in larger studies is fully up for debate. And I think it's really too little to take to say, this is the turnaround story. But I think it's at least somewhat promising that there's something to look at here. And could wind up completely blowing up on the next readout, of course, those are we've seen so many small data sets and phase one move up and have disappointment. So look, I hear the nitpicks. I think they're reasonably fair criticisms. I don't think it really detracts from the idea that these mechanisms, these drugs are getting muscle concentration and at least in sort of a completers analysis are showing pretty substantial ducts or any changes. To your, to your Prouder point though, it certainly feels like there's a bearish element to the tape, even though the XBI itself is flat. Ish for the year, the way stocks are reacting to these binary updates, not full on bearish tape, but certainly some signs which kind of gets back to the earlier discussion about risk and where we are in the current tape. So yeah, totally. And now I guess I would also argue, right? Some of these moves are a little bit of a head scratch and in terms of the magnitude of the move on the upside to the gen lets. I also got a little bit of a fade. It's a little bit of a strange tape right now. But maybe moving on, another data point I'll talk on is May's Therapeutics' update for MZ-829. So I don't follow this one directly, but I sort of do through my coverage of vertex because it's a direct competitor to one of what I've kind of viewed is one of vertexes more interesting potential growth programs. So most of you know I'm probably one of more bearish people out there on vertexes prospects for sort of justifying their growth premium. But they're drug enacts a plan, which is an April 1 inhibitor currently in a phase three study, four patients with April 1 mediated kidney disease. I think this is a very interesting, if not the most interesting drug in their pipeline. And this is potentially first in class, genetically targeted drug that can address up to 250,000 patients in the UX. Vertex has this in a phase three study right now. We may get an interim update around the end of this year early next year from that phase three study to full two years endpoint won't be read out until probably late 2027 or 2028. And May's has a drug that is really positioned as a fast-- as potentially a fast follow, we're also inhibiting April 1. So May's stock really got crushed on this update, about 40% on the week. And it seems like there's a lot of nuances here. So one of the factors that play is that vertex really isn't provided any results for an explanet out of a relatively small data set. They have a few important exclusion criteria. But in that data set, the data looks great. I mean, they have very, very significant and quick reductions in proton area. Of course, having April 1 to April 1 or 1 of the aliels is the absolute mandatory criteria for all of these studies. But vertex study also only looked at patients with focal segmental glomerular, sclerosis, or FSGS. May's study expanded this criteria to look at all EpoL1 patients, including diabetics. And I think that was really where they were hoping on differentiating a little bit to show that they do have broad activity across EpoL1 patients and could move into about diabetics as well. Look, I think the broad top line takeaways are the compare and contrast the vertex data and the maze data on an apples to apples basis. One could say the maze data looks pretty good. E and FSGS patients, the benefits on EpoL1 are a little better than vertex. But again, we're talking very, very small numbers. But I think what the drawback is from this data set is it seems like most of the effect is really driven by the outskirts. FSGS patients. So on the back of the people have really questioned, okay, does this work in broad APL-1 patients? Or is there something about the biology where like this really works well in FSGS patients with two APL-1 alleles, but when you sort of expand the outside of FSGS, you know, then do the nature of the impact from the various factors driving the kidney disease over while I'm just purely like the APL-1 underlying genetics. Because again, if you look at the main data in non-FSGS patients or, you know, even more specifically in diabetic patients, it's unclear that there's really a response anywhere on par as what you're seeing in the FSGS patients. So I think that's sort of been the pushback that I've heard on Naze and even on like the vertex programming does this have a read through to sort of the size of the potential address able market because if it's just FSGS, that's a much, much, much smaller segment of patients than that 250,000. I think Josh, you were going to cover that as well. You had some comments on that one as well. No, actually, I think friends are as decoy love. Okay, great. Thanks. So, Eric, let's move on to beam and it's alpha-1 antitripsin data update. Yeah, beam also had a fairly substantial update this week. They now reported on about 29 patients in their phase one, two study of beam 302 for alpha-1 antitripsin deficiency or AATD. This is a pretty large, but still rare disease, but within the rare disease space, it's about 100,000 patients. So probably one of the bigger commercial opportunities, certainly an opportunity and need of innovation. And that's definitely what what beam is bringing to the equation here, the kind of the leading most advanced genetic therapy. They have a base editing approach toward correcting the underlying genetic affection or the form mutation in AATD. So, really cool, really amazing modern day medicine, personalized medicine, of course. And it's working. I think the main take home message from the 29 patients up from about nine a year ago is that it's safe and effective efficacious in doing almost exactly what you would hope it is doing. Stock market reaction to the data wasn't so hot. The stock's actually down about 10%. And I think here a few grumblings around the margin as to why that might be. We can address that if you'd like. But you know, I really want to focus on just how good a therapy this is. This is essentially taking patients who have in some cases a very, very high risk of dying due to lung disease or in some cases due to liver disease. And potentially normalizing their genetic condition entirely. One of the most exciting things about the data set this week was that we saw a patient who went through the genetic correction procedure and who subsequently had an infection and during periods of infection. That's when your lungs and liver is most vulnerable to harm through the genetic deficiency. And as you would expect from a base-setting therapy that completely corrects the genetic condition when the patient went through this period of stress and infection, the patient's natural, inducible, genetic elements that were restored through the beam procedure increased the amount of healthy protein that was made and protective of the lungs and livers and decreased the amount of harmful protein that was being made as well. So a wonderful end of one, but certainly a wonderful illustration of just how powerful this technology could be. There are others in the space that are also advancing gene editing and genetic therapy type opportunities here, but the Emo start pivotal study toward the middle of the year and I think it's going to have a very big product on that sense. It's very exciting given how much the industry, you know, patients have been depending on replacement therapies. And so to now have a new modality that could permanently address that, that would be amazing. And yeah, it'll be interesting to see how that evolves. I also noticed that the stock drop, but nothing, a lot of these things don't seem to make sense on the surface. I mean, we just talked about the May situation. So why don't we move to Josh and we will talk about the Pfizer's Lyme disease vaccine. Yep. So there's there is still some vaccine innovation going on despite some anti vaccine perspectives at HHS and Pfizer and their partner Valneva reported phase three data for their Lyme disease vaccine. Mostly positive, the little next efficacy vaccine efficacy was around 70 75 percent for a four dose regimen. It's a bit of a cumbersome regimen for for for any vaccine. And then one of the free specified analysis missed the lower bound of efficacy of 20 percent. That was the analysis from 28 days after the final vaccine, whereas the efficacy from day one after the final vaccine cleared that 20 percent lower bound confidence interval threshold. Pfizer sounds like they're confident that this is a product that can still gain FDA approval. Probably does depend who at the FDA is making decisions for these things. But historically, unfortunately, Lyme vaccine adoption has been fairly minimal despite the fact that Lyme disease itself can really be a disabling and crippling event for those who are unlucky enough to be chronically infected with Lyme. So another name that Valneva was down 40 percent this week on on the state update. So not the best moment in time for binary events or certainly ones that that fall a little bit short of where expectations might have been. Great. Anybody else have comments on that? Okay. And I think we had another topic on sort of negative market reaction. But I think we covered that unless there was anything else. I think there was a couple of other names in there and you were going to cover those as well. I think it was Karao Farm where there were a couple of others where there was surprising negative market reactions. Yeah, perhaps one of the the bigger surprises wave covered at Canterbyer or a wonderful full-call week Steve Seathouse who reported an update on there in Hiibi all ago for obesity. The stock nearly got cut in half on on this update. Not dramatically different from from the prior update at a at their 280 milligrams dose. I believe now they've added a 400 milligrams dose. Some of the areas of concern have been no obvious dose response between sorry 240 and 400. But that might have been a result of some baseline imbalances across trial arms and another major concern that some of our articulated is the fact that it's benefit. The drug's benefit appears to be primarily reflected in visceral fat mass and not overall body weight which didn't really seem seem to move for not entirely sure why that's such a huge deal for investors. Visceral fat mass is probably the most closely correlated to outcomes with obesity compared to body weight. And in this context with the wave drug there was a little bit of an increase in lean mass. And if you just consider the ratio of the amount of lean mass compared to visceral fat mass that there is in any individual a small increase in lean mass can more than offset a much more meaningful decrease in visceral fat mass. And so at the end of the day I mean there certainly seems to be the making of some very important cardiovascular benefit for this mechanism in terms of reducing visceral fat mass maybe not as aesthetically pleasing as seeing dramatic amounts of body weight. But when that body weight includes meaningful loss of lean muscle mass that's not necessarily a good thing either. So this is a lot of controversy around this one will continue to watch this field and this class of drugs but at least on the sentiment perspective they took a significant hit this week. Carrier farm also covered a counter by another one of our wonderful colleagues had their phase three data for expo vio in mylofibrosis. And that was also a mixed data set. Hit the primary endpoint of spleen size reduction didn't really seem to do much in terms of symptomatology when added to to rectal it for MF. But there was a pretty interesting overall survival benefit trend that they did see. So a little bit of a controversial data set that one also did trade down this week. Again anything falling a little short of perfection doesn't seem to be getting much appreciation. And now the company is going to have a readout for the same drug expo vio for a subset of patients with endometrial cancer later this year. So another kick at a binary outcome can down the road that later this year for Carrier. Great thanks and let's I think you also were to touch upon apigee and that's an example I think of a positive market reaction. Yeah not super close to this one. So if anyone has other thoughts on it please chime in that they provide. either there are 52 week data update for their long acting, half-life extended aisle 13 antibody. Looks have very good effect in a topic dermatitis as this is one of the companies that Paragon is spun out, developing kind of half-life extended antibodies across various autoimmune diseases, others being Aruka, Jade, Eric helped me a debt. Demore I think was the other one and inspire as well. - Yeah, inspire. - Yeah, in a very strong reaction in this case for apogee. So it's not all bearish in terms of the tape, but certainly some bearish leaning signals. - Great, well while we're on the topic of dermatology, it's a great segue to the upcoming AAD conference where there's a lot of expectations, a lot of data coming from Lumaist, Keta, J&J, the psoriasis wars, really moving towards some exciting new therapies here. So who would like to jump in on this one? I think Eric, you were gonna start. - Yeah, I'll start. Maybe I'll just pick up a minute where Josh left off. I mean, it's almost like the theme of this podcast today that the market is leaning bearish on these data sets. And I don't know, I just feel differently than that. I think some of the data we had this week was just kind of next. I would have even thrown maybe the data that Brian referenced on Syrupta and the kind of lukewarm category and yet they're for some pretty big moves. So I'm not sure why I'm seeing the glasses have full and you guys are maybe Josh is seeing it as half empty, but I don't think we're in a bearish market for biotech. I do think we're in a bearish market for the overall economy and global security. But those are things we just discussed earlier. Anyway, let's look to AED where there's an amazing amazing innovation going on and it happens to come in the field of psoriasis. We've had some very, very good psoriasis drugs for a long time that are injectable and that provide very high skin clearance for patients, very high pausy 7590. In some cases, even pausy 100 scores. So there isn't a whole lot of unmet medical need left in psoriasis and many, I think of the higher end physicians, dermatologists treat this disease are probably gonna stick with those biologics because they're tried and tested have such great long term results and also have impact on the underlying inflammation, systemic inflammation, not just the skin manifestations in the disease, but what's happening with the approval, I guess just last week of J&J's Icatide and now two data sets that are coming out at AAD1 from Alumas and one from Takeda is that we are for the first time, I believe, gonna have really good oral therapies, convenient once and twice daily therapies that can treat, I think a much, much broader swap the patients today. The only two oral therapies of substance, one is Otesla from Amgen, the other is Citic2 from Bristol, neither of them works very well at all. Otesla at least is a good track record of safety but it comes with, I'd say, meaningful tolerability issues in terms of GI upset and irritability and Citic2 has been really a dud commercially because I think it was potentially over-promised in terms of the efficacy that it does get. So what we'll see, I think at two rate breaker presentations, one from Alumas and one from Takeda is data that comes close to the injectables in terms of its ability to improve skin mass festations of the disease, maybe not quite as good. Certainly the Icatide data from J&J that supported the approval of that drug is also in a similar ballpark as Takeda and Alumas and I think what you're gonna see, certainly this weekend is a lot of comparing and contrasting, a lot of people looking at different data cuts and different results and trying to figure out which of these three oral opportunities might become the most commonly used. But in my opinion, this isn't about market share, this is really about a size of the pie. There are literally millions of people in the US with psoriasis and many of them are still using topicals that are difficult to apply and greasy that aren't comfortable. Some of them are very small percent are using those high-end biologics but there is a huge swatht in the population that has not chosen to use something in the middle, an oral therapy that's safe and highly effective and that's what we're finally gonna get for the first time in a year. So I'm excited about this market. I think it's going to be explosives, rice is already in terms of branded drug sales, one of the larger markets we have and we could go from 20 to 30 billion in sales up to 40 plus billion in sales quite quickly here. - Great, sounds like it's gonna be an exciting week and the follow on from all these great new therapies so please making it to the finish line. Okay, I think we're, we've covered all the topics for once we're sort of right on time. Anybody have any other thoughts on the market, on policy, on anything else going on on your weekend plans or if that might be more exciting? - Nope, people are anxious to get out of here for the weekend. So with that, I'd like to thank my co-host, Josh, Eric and Brian and thank you all for listening.