Biotech Hangout: Episode 191 - July 31, 2026

Sourced by podcast-ingest on 2026-08-04. Auto-transcribed via AssemblyAI (universal-2, en). Speakers identified by AssemblyAI Speaker Identification using the per-podcast host/regulars hints; the resulting label→name mapping is in the frontmatter. Duration: 1h00m. Episode page: https://podcasters.spotify.com/pod/show/biotechhangout/episodes/Episode-191---July-31--2026-e3mti92. Audio: https://anchor.fm/s/55bdff38/podcast/play/123700962/https%3A%2F%2Fd3ctxlq1ktw2nl.cloudfront.net%2Fstaging%2F2026-7-3%2F429128317-44100-2-73910c94bc5be.m4a.

Show notes (from RSS)

On this week's episode, Graig Suvannavejh, Tim Opler, Yaron Werber, Paul Matteis, and Brian Skorney kicked off with a review of the market, noting pressure in the XBI despite a longer-term bounce-back from trough levels, though they see biotech fundamentals as largely intact. The group also discussed the trend of reverse mergers as an alternative to traditional IPOs, along with AI's expansion and uncertain role in accelerating drug discovery. In regulatory news, the co-hosts welcomed the return of FDA advisory committee meetings, including those for Capricor and Replimune, and highlighted Anthony Fauci's recent Senate testimony on the handling of the COVID-19 pandemic. In deals, J&J struck an in vivo CAR-T partnership with Sail Biomedicines, with potential readthroughs for Legend Biotech, and Argenx is set to acquire Forte Biosciences to bolster its immunology pipeline. The group also highlighted Lilly's recent acquisition of psychedelics company AtaiBeckley, opening a broader discussion on deals in the psychedelics space. The episode concluded with company news including Alnylam shares dropping 30% following disappointing updated guidance, Novo Nordisk’s Phase 3 study for its anti-IL-6 ligand antibody, and MapLight’s Phase 2 schizophrenia readout. *This episode aired on July 31, 2026.

Transcript

Greg Savanovich: You're listening to Biotech Hangout, a live and unedited weekly discussion of all the latest news in our industry with a group of biotech leaders and experts. I'm Greg Savanovich and my co hosts today are Tim Opler, Jeroen Werber, Paul Matias and Brian Scorney. For more information about our hosts and guest speakers, or to listen to the most recent episode, please go to biotechhangout.com so it's great to be back on the show and second quarter Biotech earnings season is in full swing now. Earnings earning season is always somewhat if not very painful for those of us on the sell side and buy side. But in any case, we've got another great program in store for you today. As usual, our show is structured generally the same way. We'll first discuss markets and the macro picture. Next we'll move on to this week's BD deals in biotech, followed by comments on the regulatory landscape and we'll close with notable company specific developments where we try to get through perhaps the more salient news events of the week. But to start off, let's talk about biotech sector performance, especially as we're now firmly past the halfway point of the year. I'd say at a high level it continues to be a bit choppy of late and I'd go even further to say we're seeing some pressure in the sector particularly today. I'm seeing the xpi down about 3.5% and the expire is now trading at sub 1 $150 levels. Recall we crossed the 160 mark at the beginning of the month and even hit the 164 level on July 9th. That said, I think we've come a long way in the bounce back from trough levels of several years back and bigger picture in terms of our sector outlook. And my team and I at MIZU just published our second quarter biotech sector preview earlier today, but I think overall biotech fundamentals appear very much intact. Importantly, I'll call out at least three specific themes that I think could continue to drive sector outperformance. These include and I'm sure there are others as well, but I will highlight previous headwinds at FDA that given high profile turnover and senior leadership at the agency of now, we believe at least have turned into tailwinds for the sector and we'll have more to say on this in terms of what we're seeing at the FDA in a little bit.

Paul: 2.

Greg Savanovich: The Biotech IPO locomotive continues running a full steam ahead. And if I have my numbers right, I think we have about 14 US biotech IPOs year to date and I think that's more than the eight that we saw all of last year and for sure there are several more in the queue. And third, just a continuation of very robust M and A activity where I will remind that over the next decade or so I think there's an estimate out there of over 300 billion in revenue that is at risk due to patent expirations or losses of exclusivity. And that just means that big global pharma companies are going to need to find ways to plug in revenue gaps, gaps or holes and that often means them looking to acquire smaller and mid cap biotech companies. This is all good in my opinion and as I don't see any real big picture macro reasons for near term underperformance, I think this sector continues to rally throughout the balance of the year. In terms of the XBI which we look at as the best, although by no means perfect proxy for the biotech sector. We were seeing 24% year to date performance as of at least yesterday's close. And this compares very favorably against year to date performance for the S&P 500 which stood at a plus 9% year to date, and the NASDAQ Composite which is up 8%. And for additional perspective just in this time versus three months ago, the XBI is gained some 1600 basis points. So meanwhile healthcare more broadly speaking is up only 6% year to date. So again given 24% positive performance for the XPI, biotech continues to be a clear winner. And of course we'd love to see this trend in biotech continue. I'll just briefly comment on the US Biotech IPO market. After seeing Scribe Therapeutics make its public debut last week, this morning or sometime today, I think trading should begin in apnemed. And that is a Cambridge Boston based biotech focused on respiratory or breathing related diseases. And then next on the calendar I think is Braveheart Bio, that's a San Francisco based biotech focused on hypertrophic cardiomyopathy and related conditions. So I think the biotech IPO market is nicely humming along with this in the background just on a macro of where we are in biotech. I'm going to pass things along to Tim who I will consider one of our more senior states persons in our industry. And Tim, I think you want to make some some comments on current trends we are seeing with reverse mergers and pipe financings and then I think separately afterwards you're going to cover the ever evolving and of course, perhaps controversial role of AI and biotech in the life sciences. So, Tim, go ahead and take it away.

Tim Opler: No, thank you, Greg. And you know, just a comment on the market today. It hasn't escaped my attention that like when there's a week where there's not a lot of M and A, the XBI tends to drift down and then like if there's two weeks like that, it drifts down even more. And then the moment someone gets bought, you know, the XBI starts headed in the other direction. And we haven't had too much in the last couple weeks, but you know, it's coming and you, you nailed it, Greg. I mean, there's just so much need for pharma to buy. I think the fundamentals are very much in place and I wouldn't be surprised to see the XBI finish the year closer to like 175, 200 than where it is right now, which is under 150, really for the first time in a while on these reverse mergers. By my count, there's roughly 10 companies that have gone public this year via reverse merger. So that reverse merger mechanism is pretty much as important, if not more important this year than the traditional ipo, which is quite the change. The question is why? I talk to people in funds and I'd love to hear what the rest of you think. What fund managers say is that if you do a pipe deal in the reverse merger, you get to do confidential diligence, which is a little different than an IPO those public sooner. So a lot of people are worried about the midterms for whatever reason. Trump's numbers don't look great. And I think there's just a lot of uncertainty about the complexion of the country around politics. It's not that people are so pessimistic or optimistic. It's rather no one wants to wait around and find out what it's going to be. One of the fascinating things about reverse mergers this year is if you look at the post market performance, these deals have done really well. And so, you know, you get the endorsement of a bunch of funds that have had the opportunity to do confidential diligence. And so people pile on and you have a transaction that's oversubscribed and then the stack does well. This week we saw two of these transactions as an example. I'm going to pause before I jump into AI and just see if anyone else has thoughts on this topic.

Jeroen Werber: Yeah, it's your, I mean, the only

Paul: thing, the only Thing I would just say is, like, on these reverse mergers, I feel like at one point people would ask questions, why did a company go public like that? You know, maybe a company goes public via reverse merger and they're like, no one really knows or most of the market doesn't really know who they are for two years.

Brian Scorney: Right.

Paul: But now it feels like the process has been kind of perfected. You don't really sacrifice syndicate quality. Right. I mean, look at the syndicates of some of these. Right. It's often the who's who. And so I just think in the context of that.

Greg Savanovich: Right.

Paul: I also hear anecdotally, it's cheaper too. It feels like some of the prior disadvantages around perception have waned. What were you going to say? Your own?

Jeroen Werber: Yeah, to your point, I was going to add, it's like what we're hearing, because we've done some of these, is it's just a lot faster. And that's what's critical for the investor base and for the, for the management team. They can get it done really fast. It does take time for the deal to close and I would say that's kind of the Achilles heel, the process. But to your point, they've been very well received.

Tim Opler: Well, thank you both. And no, it's really interesting. We'll see how the rest of the year kind of finishes out. It does feel like IPOs are starting to pick up a little bit more and they were sort of quiet before and it seems like wasn't so long ago that US was bombing Iran all the time. And that was focus and there was a lot of uncertainty in the market and that that uncertainty is perhaps a little bit less today. The other topic I thought would be interesting to touch on is what's going on in AI and specifically Anthropic with their cloud science program's been coming on really strong. There's a lot of speculation last week that, you know, Anthropic could go out and buy a big pharma. Right. They could just snap up Bristol Myers or AbbVie or something. Seems all like a little crazy. I will say that the interest from big pharma and AI because of this move is really strong. And, you know, when we talk about AI in the life sciences, we're often speaking about the idea of using a computer to make molecules. The problem with that idea, even if computers are really good at making molecules, is most of the time costs. And the real cost is actually in the clinical side where AI is helpful but not as helpful. And so, you know, making Molecules with AI doesn't necessarily solve our industry's bottleneck. So what Anthropic is really doing with cloud science is they're using agentic AI to allow scientists to essentially get a lot more leverage. I'm sure we're all trying that. A lot of people are using these various programs, you know, from OpenAI or Cloud or whatever. And I know I use them in my just everyday life as a banker and it's just kind of crazy how much incremental leverage I can get. So that's even bigger on the science side. So there's all sorts of companies out there, cloud being the main one, but others like K Dense that are just so cool and K Dents for example, has added like over 150,000 scientists to their site in just like the last couple months. And so this space is just red hot. My gut instinct is that AI is going to be really transformational to the process of doing science. And I don't think it's so much, you know, making molecules as just being a scientist. Like how am I going to write this protocol? Please design this experiment for me. Here's the results of this experiment. Computer, write up the experiment. Review this article. Do you think the article is well done? No, it's not. Okay, we'll fix the article. So those are all things that you know, used to take scientists weeks and months that like you can do in 10 minutes now. So it's very transformational. Anyway, I just wanted to comment on that. I thought it was some of this kind of breaking right now that probably we should talk about more on biotech hangout. I don't know if any others have thoughts on this kind of trend.

Jeroen Werber: I mean I, I cover some of the areas Tim, that of the, the, the drugs that use informatics to actually design the molecules. And it's been to your point, you know, we've seen sort of this game before that they've been actually fairly successful and I would say really kind of im comes to mind. There's, there's other examples. The challenge to your point is that the platform, and this is sort of even anthropic buying a large pharma, the platform could be, can have unlimited power and limited ability the abilities to then reduce that to practice and, and, and the associated costs associated with it, especially given some of the failures that are inevitably are going to happen. So we think of it as it's going to be a technology that's going to get embedded in everybody's research. So I'm better job with it. Than others. But at the end, I don't know that the technology itself is going to be the sole driver. It's going to be an enabler and everything around it is going to be equally or even more critical.

Tim Opler: Thank you very much Greg, back to you.

Greg Savanovich: Yeah, I mean, I think I'll add this just on AI. I mean I, you know, many of us have been following the biopharma industry for a long time and I've, I've been out there and said in various forums that, you know, it's not as if AI has not been tried to be, you know, worked into making the drug discovery process more efficient and make things less expensive, just overall more productive. I do think we're in a, and we haven't seen much success. I think we're in a newer age now and I, I just recall that, you know, we've got some public traded companies that I don't cover. But I think Recursion and Schrodinger are two companies that have been very levered to AI and I haven't been following them closely but I think, you know, if you look at those stock charts, they haven't really been all that great. But you know, we're hopeful and hopefully we'll get some successes because at the end of the day we just want to newer and hopefully better drugs in the hands of patients and physicians so we can get better health outcomes. It is a fascinating space to follow. I'm not the smartest one on this space, but I feel like every day that things go by, advances continue to be made, that it's hard to keep up with everything. So that being said, let's move on to deals of the week and we have a couple to talk about. And I will start briefly with JJ's new partnership with privately held Sail Biomedicines, which I think I read somewhere as a flagship ventures company. And the deal involves JJ in licensing sales, novel in vivo CAR T platform that is designed to generate CAR T therapies directly within the body. And this move is meant to strengthen JJ's presence in immunology and CAR tank. And in terms of the deal details, JJ is making total initial payments of 785 million. But interestingly, as part of the deal, JJ can also opt in to acquire Sail at some point for an additional 2.6 billion. So I think the deal is interesting for a couple of reasons. First, it's yet another deal in the white hot in Vivo CAR T space. And here I will remind listeners of Eli Lilly's $2.4 billion deal for Orna and its In Vivo platform, Car T In Vivo platform for Ini and then another Lilly deal that it struck in in vivo Car T for Colonia therapeutics more for Hemonc purposes and that was for 7 billion. The second reason I think it's an interesting deal is that there could be some potential read throughs for Legend Biotech and for that I'm going to pass things along to Jeroen who will comment on Legend and also Jeron, if you could follow up that conversation on Legend, on commenting on a deal we saw European biotech company Argenics do. So Jerome, please go ahead.

Jeroen Werber: Yeah, no, absolutely. So Sail is really a terrific company. As Greg has just mentioned. They're really approaching the whole in vivo cartine a very different way. They have essentially a. It's a programmable RNA therapeutics using nanovesicles that are chemically encoded and so they can actually deliver the RNA payload in a very different way. They're moving away from peg. They're going to be using stabilizing lipids. So it's not really the standard lipid nanoparticle and it's not just targeting the hepatocytes. So this is why they are sort of very different. It's called Erna. It's a lot more durable than circular. It's more durable because it's using a circular RNA sort of construct to prevent degradation. But it's also the MRNA kind of maxes out within a day and the cargo is fairly large. So it really has a very kind of broad transduction potential. And to. For jj, this is the second deal that they did. Of course, the first deal was to get a broad collaboration and access to the in vivo CAR T capabilities. That's using a lentivirus from Colonia, which was more for target for oncology, presumably really for hematology. Of course BCMA was not included. As you know, JJ has a deal for the number one selling cell therapy in the world. It's Corvicti. It's an ex vivo. So they actually make the cells as you know, in the factory and give it to the patient. It's not in vivo. And Ying Wang was the CEO of Legend, we all know and respect. Ying Ying just announced literally on Monday that he's going to be stepping down. He accepted a role presumably as a CEO of a new venture backed oncology company that I think is going to be fairly active in business development and other activities. So you know, not, not something you, you want to see your CEO leaving a company legend of course has been a little bit on the crossroads for probably three main reasons. One is Gilead's anidocell. It's their version of an anti bcma. CAR T is expected to get approval in December. It's basically one of the, the key issues with Carvikti is that it does cause some immune related disorders like Parkinsonisms and, and Bell's palsy can cause colitis. It causes cytokine release and that's been the Achilles heel of the drug. Anida Cel does not seem to cause the same AES. It might actually be a smidgen less potent as well. We're waiting for the final data but that competitive overhang is pretty big. That's coming in December. Secondly, they're a little bit of at a standstill. They have a relationship with J and J for Corviki and it's unclear whether JJ is going to opt in to then develop the in vivo CAR T for myeloma. And if they don't do that, neither company can go into myeloma without therapy. And then finally it's a question of how they're going to be broadly developing their in vivo platform. Now that they had some really good lymphoma data, I think there was a lot of hope that JJ will, will buy Legend. I think we've been saying in our reports that we think that's unlikely. Well now they've done two essentially deals that give them a broad in vivo platform so even less of a reason to, to buy their partner. And then secondly, how are they going to ultimately, you know, develop the platform? So clearly there's been probably some strategic sort of misalignment there. So not ideal. The stock reacted. Obviously Corvikti in the meantime is continuing to sell, you know, really well. But that market is getting very, very competitive. For that.

Greg Savanovich: Yeah, yeah.

Jeroen Werber: I think you mentioned the next deal.

Tim Opler: Yeah.

Greg Savanovich: If you want to also comment on Argenics's deal, that would be fantastic.

Jeroen Werber: Yeah, absolutely. So our Genics bought a company called Forte. We have the luck of covering both of them. So it was really fun to kind of see that go to fruition and was kind of very efficient to, to put the models together. The they're, they're under the new CEO, you know, Karen Massey. This is the first deal actually that I believe Organics has ever done in terms of acquisition. It was 2.2 billion. They are absolutely committed to external innovation in addition to their internal innovation. We really have to applaud them for being very early and getting proactive despite their internal Pipeline very much humming and Vivgard, their main drug, doing absolutely well. And they beat another quarter. I think it's their 14th or 15th quarter in a row that they beat. They launched but getting you can never come get too early on bringing in external assets. The key drug is targeting the CD122 receptor, which is where the IL15 cytokine and also IL2 signals through it. They're binding to the receptor. And they've had positive phase 1b data in celiac disease and vitiligo. And we're waiting by the end of this year to get the confirmatory phase 2b celiac study that's randomized and the phase 1b data for alopecia areata. So we're, we've been fairly bullish about this asset. I think it's looked very good so far. We are optimistic that the celiac study will be, will be positive as well and that this area is getting a little bit more competitive. It's getting a lot of attention. So of course you have Teva with Royalty Pharma developing their IL15 antibody. So they're not binding the receptor. They're binding to the cytokine in the blood that binds to the receptor. And they've had positive data in Vitiligo. And I think we're all now anxiously waiting in the second half of their celiac data. And then after that, I think Vitiligo is the lead indication there. And then of course there's another company called First Tracks that has also a CD122 antibody that is going to read out their phase 1a slash, phase 1b data and celiac second half. So this is really, we think, the next area of innovation ini big unmet needs. And great to see Argenics now jumping in as well.

Greg Savanovich: Really interesting deal for Argenics, which has been a remarkable success obviously in biotech in general, but particularly for European biotech. So it's nice to see them with their aspirations. Acquiring Forte. I'm just going to quickly touch upon a deal that was previously announced and then we're going to segue into a broader biotech m and a discussion. But I wanted to mention that we got an update on Eli Lilly's recent acquisition of psychedelics player Atai Beckley, which they yesterday disclosed via an SEC filing some of the play by play of how that deal went down. And I always find the play by plays a very fascinating read. It shows how BD deals get done in the history. But it looks like in this particular case, and again That's a, that's a recent deal that Eli Lilly announced. But it looks like ATAI was approached in December at first by another pharmaceutical company which obviously is unnamed. But that was initially for a co development and co commercialization deal for ATAI, Beckley's lead asset, which is called BPL003, that's for treatment resistant depression. And there was an offer for 125 million upfront for this type of deal. Notably, this approach came one month after ATAI had completed its merger with a company called Beckley scitech. Nothing pretty much happened for a couple of quarters. And then Lilly joined the fray I guess in early June with an initial deal and they ended up maybe a couple of weeks later sweetening its offer June 11 with a $6.75 upfront. But then they tacked on a $1 per share contingent value, right, or CVR, which was tied to potential FDA approval of a compound called VLS01 for treatment resistant depression. And VLS01 is in phase two testing. The back and forth continued for a few more weeks but ultimately Eli Lilly moved up on their CVR to $2.50 and that's what got the deal done. But from an initial BD discussion by another suitor, and again as I mentioned earlier, it seems like Eli Lilly is buying everything, which is very impressive to see what they're doing. But I guess it's with a view that perhaps the obesity related or GLP1 related or triple G related future revenue streams will be there and maybe they won't be there forever. They're certainly being very aggressive with M and A. Paul, let's get you into the conversation because I think you had some thoughts that you wanted to offer to our audience on this idea of when companies that are kind of smaller but then are starting getting bigger, when should they get acquisitive and then maybe we can segue into a broader M and A discussion ahead. Paul?

Paul: No, totally. I want to, I, I want to make this comment and then I'm actually curious from your own like what he heard from people on the organic side. But I think it's like, like our genics is an interesting point to be an acquisitive company. You know, Alam is kind of getting to the point now too where it's like, are they going to do something? I hear people talk about this with like, you know, maybe insmed at some point, like these companies that get into this kind of like mini large cap range, maybe built on, you know, a 1 to 2, you know, really big product franchise. And then it's kind of like they almost become a little bit of a victim of their own success where people start to say what's next? And I think some of the cautionary tales around this one I think was like Alexion, where with Soliris and Ultimaeris they had so much success, but then a competitor to that was even in early mid stage development emerged and then suddenly it became this whole existential threat to the terminal value and where's the pipeline? And you know, they kind of played catch up to backfill the pipeline. You know, I don't know exactly how this is thought about with Argenics, so maybe your own can chime in, but just like on Al Milam, you know, I mean Al Milam had this monster TTR launch and I know we'll probably talk later in this call about their guide this week that disappointed people, but you know, it quickly became a 50 or 60 billion dollars company. And then, you know, they got a couple of shots on goal in the pipeline, but nothing clear cut. And it quickly becomes this what's next conversation. You know, we saw Vertex in this limbo for a couple years until they kind of started to break through with a couple pipeline assets. And now Vertex is, you know, much more comfortable with doing M and A. And so I think it's, I actually thought it was like really cool to see Argenics do this deal because I do think when things are going well and you've got, you know, a drug franchise like Vivgard or you know, like at least before yesterday, where you're beating and things are going well, I think it's easy to kind of be, to be risk averse, right. And to stay focused on what's doing, what's, what's going great. But the market dynamics and investor perception and the multiple that people are willing to put in your business can change quickly, often via factors that are beyond your control. And so I know there's multiple companies in my coverage, like Biomarin is another one, right. Where I think a lot of investors view it as an undervalued stock. But this whole question of what's next, what's my upside variance? And the pipeline continues to loom. And so, yeah, and I think maybe just the last thing I'll say is I've kind of been paying attention to sort of how are the acquirers of companies in the past few months, how's their stock trading, right. And, and I think in general, like we're very rarely seeing big down moves and Sometimes like in the ABV apogee situation, we're seeing, we're seeing up moves. And so outside of the other factors, that favors more M and A, that's probably a tailwind for the space too. But your own. What did you hear on, on the Argenics piece?

Jeroen Werber: Well, I think that this one was a little different for probably a couple of reasons. Number one, Argenics has been very upfront about their bill, their desire to start doing deals for innovative INI assets. So that was expected. Two, they actually invested in back in late April or early May. Right, right.

Paul: In for. In this company. Right.

Jeroen Werber: Part of the recent offering. Exactly. So we sort of knew they were around the hoop and we knew this data is coming. And on the heels, well, we, we knew that Forte released their Vitiligo data, which, which led the stock obviously to go up a lot. And at that point they also pulled forward their guidance that they're going to have data, quote, unquote, soon slash imminently for Celiac before it was 2026. So I think. And then on the, on Thursday, Argenics reported and again reiterated their desire to do M and A. So Forte stock absolutely ripped on Friday and of course it got acquired on Monday. So it was a little bit televised, but it was very well received on both sides.

Greg Savanovich: And then, Paul, since you spend a lot of your time on the neurospace, any thoughts about kind of what that Lilly deal for ATAI might mean for M and A in the psychedelic space or just activity in the psychedelic space?

Paul: No. And you chime into, Greg, especially given your, like, experience doing bd, because I think, I mean, I think, you know, I cover. So I cover Compass, I cover Definium, and I cover GH and obviously pay close attention to all the, all the competing assets. I think one of the questions has really been like, you know, we saw Abby do the Gilgamesh deal. You know, we saw Transcend Theory of Therapeutics get acquired by Otsuka. But those were like relatively smaller M and A transactions. And I think one of the questions with some of, like, the bigger, more established companies in this space is like, you know, is someone is a traditional pharma company that, you know, might care a little bit more about perception or might be a little bit more conservative with how they view perception, are they going to be willing to step in and buy, like, buy a psychedelics company? Right. And, and this was a conversation that was actually really relevant with GW Pharma a number of years ago, right. Who was developing CBD for Orphan Epilepsy and you know, CBD ended up being Schedule 5.

Brian Scorney: Right.

Paul: There's nothing like, you know, stimulants are scheduled too, but, but still, like, I think there was even a Bloomberg article, I want to say like 10 years ago about how, you know, GW Pharma, like the buyer pool might be small for GW Pharma, and then it was eventually bought by Jazz, right. A spec pharma company. So I mean, I think like Lilly, you know, Lilly, probably the most powerful brand in the pharmaceutical space, putting their stamp of approval on, on dmt, right. Which is, you know, a psychedelic compound that has some tremendous efficacy data, but also like, is pretty out there on the psychedelic experience side. I think that's like really, really validating for the space. I mean, people are going to always wonder, well, why did they pick this one, then that one? And it's always like a hard conversation to have, but I think for the other companies that I cover in this area, I think it's validating. I also think, like, it's going to probably help to have someone like Lily, you know, building the, the infrastructure here.

Brian Scorney: Right.

Paul: I mean, I think a number of these companies are going to benefit from what J.J. did with Spravato. So. Yeah. Do you have any other angles, Greg? I mean, in your BD seats and I think you're at AbbVie and maybe somewhere else. How much of that kind of perception angle of this came into play in the conversation?

Greg Savanovich: Yeah, first of all, I thousand percent agree with everything you just said about the psychedelic space. Clearly, given what the current administration is saying and doing about their support for the space, a lot of great tailwinds for those companies. And look, just as I'm sure you have as well, I've met with a bunch of private companies that admittedly have said to me, you know, we're jumping on the bandwagon and there's obviously very interesting science and some admittedly great efficacy data that exists for a lot of these products. And so I do think it's going to be a very, very active space. And Lilly does validate what's happening. And I think that deal does further open the floodgates for more activity. You know, from a BD perspective, I think there's always an element. It's not a thousand percent true, but there is an element of a little fomo, a little kind of, hey, so and so is doing that and we don't want to be left behind, so we better catch up. And I think, you know, obviously given Eli Lilly's market cap, I Think if I'm a CEO of a large pharma company, I'm trying to figure out how do I get there. And if Lilly's making a lot of first moves, then I think the rest of the industry has to at least internally debate whether they feel the need to catch up or not. So obviously every company is different. Not everyone is in the neuro space and certainly not everyone is got a play in psychedelics. There are only a handful of publics and you look at some of the valuations in particular definium, which I think is 5 to 6 billion, and they just reported some really great data. So kudos to them. But that would be a pretty hefty M and a price if someone was looking at definium. I'm not here to say whether it's worth it or not. I don't cover any of the psychedelic companies. And you do see market caps for the other companies. You follow, Paul, in terms of Compass and GH being maybe I don't want to say more reasonable. I'm not going to say that. But you know, lower valuations, at least from a public perspective at 1 to 2 billion. It'll be very interesting to see how this space evolves. Tim or Brian or your own. Any thoughts there?

Tim Opler: Okay,

Greg Savanovich: we are going to move on to regulatory and policy matters and we've got several things to work through. So Brian, I think you had two things, if not maybe three things that you wanted to comment on. So I'll turn it over to you.

Brian Scorney: Oh yeah. So everyone, everyone knows ADCOMs are like one of my favorite parts of the sector and they are back in big fashion and they're. There were two really good ADCOMs this week that look, I think it really embodied all that I appreciate about this process and we can have different opinions on what constitutes substantial evidence. But look, biology and medicine is complicated and not always necessarily straightforward. And look, we were almost always presented with perfect information that comes into play in clinical trials. So look, I think the FDA has a really tough job where they get these imperfect applications and need to balance the responsibilities they've been taking passed with under Cafava Harris, which is the amendment to the Food and Drug and Cosmetic act that makes drug companies prove products are both safe and effective before selling them. But often the process between FDA and companies winds up being very opaque. We really only get insight from what the companies tell us throughout this entire process. But one of the things that I love that really gives us broader public insight is when the agency gets a particularly complicated application and they hold These advisory committee meetings. And again, this embodies sort of the scientific discourse and how can we really achieve and the process of achieving a scientific consensus with imperfect data in really transparent fashion. And, you know, look, one of my biggest beefs that I had with Marty Macri and Vinay Prasad when they're running the FDA the last year and a half before their departures was the decision to kind of stop doing these and really just internalize the process. Right. And you know, there's a number of applications that were rejected or just told not to file. And, you know, companies sort of made pleas to the public that, you know, the FDA just wasn't listening. We just really didn't have great insight into what was going on behind the scenes. So this week we wound up with advisory committees for two pretty controversial applications, Capricorn for DMD and Replamune's RP1 for melanoma. And look, in classic Wall street fashion, critical briefing documents were publicly disseminated a couple days before the ADCOM and the respective stocks got hit pretty hard as the agency really did criticize the data. There were just kind of like a best of all of the different statistical complaints that the FDA could have or nuances around changing data or how to analyze specific pathology. In Capricorn's case, it was really a heavy argument around statistics and how protocol, protocol changes can lead to biased results. A critique that really resonates with me. If you look at my Twitter profile, I have the multiplicity calculation for type 1 error in my headline. So it's one of the things that is a big pet peeve of mine to begin with. In Replamine's case, it was a little more around how to measure intratumoral injection activity versus sort of the way we use rhesus for more of a systemic therapy. And look, I think the FDA made a really good case where they had previously rejected both of these programs and why the applications don't meet the statutory threshold of substantial evidence of effectiveness. But this was also balanced by a decent presentation by both companies. Arguably, probably replimunes was a little more resounding, but also open public hearing portion, which generally does sway in favor of approvals. And then in both cases, look, a really robust and well thought out discussion, I thought, among the panelists who consist of staff statisticians or specialists in the respective fields. And in Capricorn's case, The panel voted 3, 9 against. And in Replimune's case, it was the reverse, basically with a 10, 3 vote in favor. And look, the FDA doesn't always go with the ADCOM votes non binding but they very often do and there's usually a big blowback to the agency when they go the other way. But there's a lot of nuances to the commentary and it was clear in both cases the committee members really couldn't make a very confident decision and what the benefit of either of these drugs is if there is a benefit. And then I think as always it comes down to sort of the subjectivity of substantial evidence and clinically meaningful or in the case of accelerated approval, reasonably likely to predict. But look, I mean I just love that we're seeing it occurring again. We get a lot of transparency. I think deep diving on these things is really educational about all the considerations one has to think about in running clinical trials and then, and then trying to reach a conclusion from clinical data that is imperfect. And maybe just to put a final point on how this impacts the sector, look, I think the FDA for the vast majority of drugs is pretty straightforward not to diminish orphan drugs, but where we often wind up with these sort of highly debatable results just because it's hard to enroll. Very, very clear large studies. But these on the bubble applications are really a very small part of the the sector. So even though some of us view them as kind of the most interesting part of the sector. Look, I don't think FDA being more or less conservative in these situations is as impactful as say drug pricing reform or interest rates. But for those who thought the departure of Marty and Van Eye was a signal of FDA just giving everyone the

Paul: go ahead, I think it was pretty

Brian Scorney: clear from these panels that that's not the case. These may be more one off examples and we'll have to see as we see more of these applications go forward and more ADCOMs go. But, but this FDA was not pulling punches at either of these outcomes and that's love to hear anyone else, did anyone else listen to these ADCOMs?

Paul: I love it.

Brian Scorney: Brian.

Paul: That was like, that was, that was a classic FDA rant. I thought that was, I thought that was like really great. I, I, you know I cover unicure which is completely unrelated to either of these but the stock trades around on just the FDA vibes thermometer, right. And was down on the Capricorn documents and then up last night after replimune. And so I mean that just tells you right that investors are still in these kind of contexts, right where there's an element of subjectivity or flexibility still really taking the temperature of where The FDA is at. And it's a, and it's a touch and go, day by day thing.

Greg Savanovich: I love the fact that ADCOMs are back. You know, again, my sell side colleagues and I have been in the space for quite some time and there were times, I'm sure that some of us, if not all of us have attended an ADCOM in person down in Bethesda and trying to, trying to get some, you know, sense of the body language or even, you know, trying to get an inside read, but they're always just really fascinating. With that said, I mean, other big pieces of news I think from a regulatory and or policy perspective. Brian, I think you want to talk about dying and kind of progress it's making.

Brian Scorney: Yes. Well, I mean, less on the, on the regulatory front, but Dine announced this week that they gotten an. They. They received clearance from the US FDA for its IND application for a phase one study of their drug in fshd. Physioscapulo humeral Muscular dystrophy. And this is something just kind of has been a little long in the tooth for Dyne. I think we've sort of been waiting for this for a while, but as I said last week, it's a company that started really starting to, to kind of move along in a more efficient manner. And you know, it's interesting because as we all know, Avidity got acquired by, by Novartis last year and a big part of Novartis's thesis, at least in their slides, I mean they made a big deal around FSHD and obviously Avidity and Novartis is ahead in fshd. But you know, Dyn and Divinity have sort of been, you know, paralleling each other. They've had very similar platforms in terms of muscle delivery. So I thought this was a nice positive for Dine and I'm just glad to see another program moving into the clinic for fshd.

Greg Savanovich: And then Tim, some of us probably saw the headlines, if not, we're very curious to see about the Senate hearings and I guess Anthony Fauci being put to the stand, so to speak, in the public eye. Comments you want to make on that?

Brian Scorney: Yeah.

Tim Opler: So you know, Tony Fauci is like in his 80s. He got a subpoena. He had to appear before the Senate Homeland Security and Government Affairs Committee and a hearing that was titled Testimony of Anthony Fauci. And you know, this committee's chairman, Rand Paul, who's, you know, a hardcore libertarian, has accused him of misleading Congress about whether or not NIH funded research in wuhan contributed to the pandemic. Sort of little crazy. And, you know, Fauci's denied this. And, you know, Fauci just got up there and had an opening statement where he invoked the Fifth Amendment and he ended up invoking his Fifth Amendment rights more than 100 times through roughly three hours. You know, to make this even more interesting, kind of like talking about ADCOMs, you know, Senator Paul released more than 1100 pages of his 2019-2022 personal, personal diary. And, you know, there was no evidence about Covid's origin and those diaries. But, you know, it's just, I guess, trying to embarrass the man. So this was a game of tactics, I suppose, you know, right wing libertarian types essentially trying to, you know, make Fauci look bad, make it look like there was some type of conspiracy behind the COVID type situation. The Republicans, you know, accused Fauci's silence, his confession. Senator Hawley says no honest person plead the fifth. You know, Senator Tuberville accused him of having something to do with killing 9 million people. Representative Anna Paulina Luna called him Dr. Mengele Fauci. So, you know, very politicized event. Democrats, like, you know, would have nothing of it and said the hearing is actually doing damage. Another person, Senator Blumenthal, likened this to a McCarthy type hearing. You know, think of it what you will. What I would say is the only choice that Senator Paul has to do is to have a vote in the Senate holding for contempt. But that's not likely to take place. And that's only because there's not enough votes for that to go through. I personally thought the most interesting thing about this entire theatrical event was President Trump. He said nothing. He did not participate. When he was asked about it by the media, he just said, I inherited Fauci and said he wasn't big factor for me. So, you know, I think in a funny way, this is a bit of a tempest and a teapot. And, you know, Senator Paul is, you know, trying to appeal to his base, which is, you know, libertarian. So they're, they're trying to create an issue that's my own opinion. You know, others might feel differently. I'd be very curious to hear what others think.

Jeroen Werber: I mean, I think that, you know, look, this is very unfortunate. Political grandstanding is kind of not something that should be ascribed to someone who's been such a public servant and that there's obviously two sides to what's going on. But sadly, this has always been a very political topic. I, I personally just feel Awful for the man given what he's done to us. I don't think he, given, given how much he's contributed, I should say right to medicine in general. General to public health. And to be kind of caught in, in the crosswinds. I'm, I'm not sure what. Clearly you've mentioned it. There's obviously political consideration for this. I guess I just don't see the real point to this. I'm just mostly kind of saddened for him. This is, it's sad that it's actually going to cause a lot of distrust in our public officials on the health side on top of all the distrust that's going on already. And I know this, I know we recently talked about the allowance to compound sort of peptides. It's almost like healthcare is becoming a little bit of a self choice in a way, you know, with what patients are going to take regardless of what FDA's position is. And there's kind of less and less public trust sort of in the agencies at the same time. So it's a little bit of a duel Ed, sort of.

Greg Savanovich: Well said. Your own. We've got some company news in the time that we have left. And Paul, I know we, we highlighted Al Nylam earlier in the, in the show. You want to comment on kind of what we saw about Al Nylam this week?

Paul: Yeah, sure. I can be brief because I know we have a few other things. But you know, essentially Alnylam surprises street this week when they lowered their guidance, you know, on the second quarter call just after issuing it at JP Morgan. This is for their TTR product and Vutra which had this monster launch last year. But, but since then, now this is the second time that they've missed consensus in three quarters. So the stock, I mean really got hit. Right. I think, you know, embedded in that 30% down move is, you know, some meaningful amount of fundamental and some meaningful amount of just, just emotional frustration and kind of like ugh, like how do I even kind of think about the new guide and is there a risk to that? And so you know, outside of around all this like consternation is probably sort of lost in the fact that even in their new guide, second half 26 over second half 25 is still growing at over 50%. But you know, the other wrinkle here too, and I think your own at least covers Ionis, is you know, the Ionis TTR outcome study for their silencer failed seemingly because of a lack of benefit. On top of defamadis, Alnylam's Next gen Silencer, which, you know, essentially would increase the profitability of their TTR franchise by almost double by eradicating the royalty is in a, is in an outcome study that is almost functionally being run as a defamitous combo study. And so, you know, I think part of this sell off too is waiting for ESC to see this full Ionis AZ data. What is Al Malam going to do with their outcomes trial? But you know, it kind of goes back to some of the other sort of discussion we had on Argenics where, you know, I want to say doesn't have a pipeline. They do have a pipeline. They have a couple intriguing shots on goal, but they don't have anything else de risked.

Brian Scorney: Right.

Paul: And, and you know, I do think with the ALNYLAM platform and how productive it was for a long time, you know, I think a lot of investors thought there would be more, you know, meaningful programs and kind of late stage development at this point. And so I think that those are the kinds of pushes and pulls people are grappling with.

Greg Savanovich: Eron, did you want to comment at all given the Ionis situation?

Jeroen Werber: Yeah, I mean, maybe I'll be brief. I mean, I guess what I can really contribute more is what to expect at esc. I mean kind of what we know is that there was no benefit to the combo versus mono. We know that in the patients who got Wayneua mono versus placebo, the hazard ratio was 0.71. So that's a lot more apples to apples to the Imutra Helios B data. The data Ionis believes that the totality of the data at esc, including an independently conducted meta analysis will show that in Vutra is very, very similar to slash identical to to Wainua. And so they believe that ultimately stabilizers did better than they did historically. It's possibly because of the contribution and the amount of patients that were NAD Class 1 where both stabilizers and silencers do extremely well. Because you're moving really early. The big question is did the stabilizer, how did the stabilizer do against the silencer? They don't have that data in house yet. They will apparently have it for esc, but the their belief is that ultimately the silencer and the stabilizer did equally as well.

Tim Opler: So.

Paul: Hey, your own. Can I chime in on this?

Brian Scorney: Yeah, go for it.

Paul: I think this stabilizer silencer comparison is like the dumbest thing ever. Like not saying that Ionis is dumb. Ionis is brilliant. They're great drug developers, but just from like a context perspective like the patients who've been on the stabilizer had been in the stabilizer way longer, anywhere from six months to years. Right. So it's like a delayed start analysis. I don't see like I hear a lot of people comparing the data for this. Right. And again, I don't mean this at all as a shot against Ionis. Like I have have like those guys are so smart and you know, like they're, they're legends, right, in drug development. But I don't see why people are playing this analysis up. I think the issue for Alnylam is like Alnylam has a hypothesis and why their drug is different. I don't see how like ESC is going to really like at best it's going to be hypothesis generating in my opinion. So I still think at the end of the day like they're going to have to do something with their study to rescue people's confidence. But, but these like comparisons on arms and different trials when like the duration of treatment is different and like the timing of treatment and initiation is different and like the demographics are different. Like I don't know, like that almost feels like it's set up to throw. I don't know, I don't get it. Do you disagree?

Jeroen Werber: So let me tell you, the Ionis train in TTR has absolutely left the station and is no longer right. Relevant to the story at all. So this is really being played because of the other companies. Right? It's the Onylum and Bridge Bio. Ionis at this point, honestly is an innocent bystander that has to present this data. I agree with you. From an Ion's perspective, it's irrelevant. It looks like the two drugs are identical which then begs the question who do you start with? Do you start with a cheaper oral or do you go with an expensive, you know, injectable? I think that most people are kind of, that's probably the issue here for Annihilated. Most people believe they'll start with a cheaper oral. Why not?

Paul: Yeah, no, I think that's right. I think, I think that's right.

Tim Opler: Right.

Paul: I mean Alam talked about how like tons of these TTR prescribers haven't written their drug yet. I mean there's, you know, like I, I think the one thing. And we're still like defending Al Nylam. I mean the stock is down so much. But just outside of the stock context, I think the one thing that we got wrong here that I do think is an interesting kind of nuance that can happen when you do diligence on the Wall street side is, you know, I felt like if you talk to a handful of KOLs, more of them believe that the silencer mechanism was more effective. Even after we got the Helios B data.

Brian Scorney: Right.

Paul: That didn't 100% prove that. But I always now kind of wonder, you know, was that really an extrapolatable sample? And to your point, you're on like, you know, you've got this community physician who runs a busy practice, like they might not be mega, mega in the weeds on the data and they're going to, you know, if it's close enough, they might do what's easiest.

Brian Scorney: Right.

Paul: And I think that that's kind of what we've seen play out.

Jeroen Werber: Well, plus there's one more learnings for me and sadly my team and I have kind of been joking internally that we've done a better job dodging the bullets that we were positive on and we were working on a big piece. We never got it out and it blew up. So you want to be lucky all the time as opposed to being smart. It's always, it's a much better, better business plan. And where I'm going with this is we were, we did not get right on the, on the IONA side. But if you actually look and the learning for me is this is one of those cases, when you looked at the original Helios B data, it did show you that combo is not better than mono. It was underpowered and I think there was always a supposition that because it was underpowered and it was small, it was not relevant statistically and it was actually clinically incorrect.

Tim Opler: Correct.

Jeroen Werber: The early data showed you that there was no benefit and that then worked out in the, in the bigger sample too.

Paul: Yeah, it's interesting. I mean, yeah, they, they have this huge reduction in mortality. Some of the other functional secondary endpoints like kccq six minute walk are, you know, are less convincing. Right. I mean, I, I would imagine there probably is some benefit if it's studied in the right context. Right. Or the right population, the right severity. But again, from the Alnalam angle, right, like it's going, I, I think ESC is at best for them gonna be still up to interpretation. And so the question is just how quickly do they move? And you know, how many patients have they already enrolled in their outcomes trial? Like we don't know the answer to that.

Greg Savanovich: Thanks guys. I'm gonna try to squeeze in some data from today, which was Novo Nordisk, whose shares are down almost 10% and that's not a small amount of money on a negative readout from a phase three study called the Zeus Study for its anti IL6 ligand based antibody. Basically that antibody is for cardiovascular diseases. They miss the primary endpoint on a MACE outcome. But there is interestingly some very negative read throughs for a host of companies that are developing this novel class of agents called the LRP3 inhibitors. And we've got several public companies that are down significantly on negative read throughs on what that data means for the space. And we've got a company called Monterosa therapeutics that's down 61% on a read through from the Novo data from today Bio Age down 31% Intraday and Nomura Therapeutics down 9% Intraday. And I think the thought here is that, that people are trying to get a look on whether lowering this cardiovascular biomarker HSCRP and if you could meaningfully impact that could lead to a change or an improvement in cardiovascular outcomes. The Novo data showed that at least using their anti IL6 ligand antibody that is not indeed the case. I do think it's interesting. I don't follow Amontorosa or bioage but on the Nomura side which I do cover, they've got an oral NLRP3 which just had an update earlier this week. There had been a scare or a concern that perhaps there were some adverse events. The company ran a new and separate 13 week rat tox study. There are no adverse events so they're going to move forward with their program. That program differentiates from perhaps the Monterosa in Bio Age programs and that it's highly brain penetrant. They are not going after cardiovascular outcomes in terms of an indication, but they are going after obesity. You know we'll probably get some data early next year but that being said, interesting in terms of what's happening in the NLRP3 space. We might have a minute Paul, if you want to touch upon like some CNS news.

Paul: Oh, sorry, I was on mute.

Brian Scorney: Yeah.

Paul: Really quickly this map like data came out in schizophrenia for their M1 M4 drug. It did not show the same efficacy as Cobenthy. It did not show the efficacy statistically of a QD formulation which I think was a hope for differentiation, tolerability was, was a little bit better, retention was a little bit better. But you know the stock sold off really significantly. It has bounced back some. You know I think it raises an interesting conversation just in CNS in general and like you know, outside of just the whole stock expectations game, like how much, how important is effect size and, and what does drive commercial success? I would argue effect size is not the best correlate of commercial success in almost any neuroscience category like outside of a crevis and Ms. Like just look at psych, look at epilepsy. I honestly look at Ms. Even before a crevice launch. Right. I mean it really wasn't in an efficacy driven market. But for maplite, it's tough when you don't meet expectations. I think the next question going forward for them as they move forward in phase three is how does the Alzheimer's psychosis data look for Cobenfi and for maplite? I think in ADP there's much greater room for Maplite to differentiate given the dosing dynamic with Cobenphy. And I think there's reason to be optimistic, or at least cautiously optimistic that Muscarinics may work in adp. I think a lot of antipsychotics probably do work, right, but are limited in their utility because of the black box for morbidity mortality. But these studies are not without risk. Right. So we'll kind of have to see and we'll get that data from cobenfi. I think Bristol pushed it to next year and then Map Lights next year as well.

Greg Savanovich: And I'll just briefly mention that Nomura Therapies, which I mentioned earlier, does have their own Muscarinic franchise. It's M4PAM based and we are going to get updates later this year. Well, that's all the time we have for today. Thanks again for those who tuned in live and in signing off. My best to everyone on a great summer weekend and my co hosts Tim, your own Paul and Brian and I hope that you'll join us on our next biotech hangout. Thanks everyone.