# Episode 191 - July 31, 2026

An episode of [Biotech Hangout](https://invisiblenetwork.ai/podcast/1568911820), 3 Aug 2026, 1 h 00 min.

Audio: https://anchor.fm/s/55bdff38/podcast/play/123700962/https%3A%2F%2Fd3ctxlq1ktw2nl.cloudfront.net%2Fstaging%2F2026-7-3%2F429128317-44100-2-73910c94bc5be.m4a

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

[0:00] When you're listening to Biotech Hangout, a live and unedited
[0:03] weekly discussion of all the latest news in our industry with
[0:05] a group of biotech leaders and experts.
[0:08] I'm Greg Sivanovich and my Co host today are Tim Opler, your
[0:12] own Werber, Paul Matthias and Brian Scorney.
[0:15] For more information about our hosts and guest speakers or to
[0:18] listen to the most recent episode, please go to
[0:21] biotechhangout.com. So it's great to be back on the
[0:24] show and second quarter biotech earnings season is in full swing
[0:29] now. Earnings season is always
[0:31] somewhat if not very painful for those of us on the sell side and
[0:35] buy side. But in any case, we've got
[0:38] another great program in store for you today.
[0:41] As usual, our show is structured.
[0:43] Generally the same way. We'll first discuss markets in
[0:45] the macro picture. Next, we'll move on to this
[0:48] week's BD deals and biotech, followed by comments on the
[0:51] regulatory landscape. And we'll close with notable
[0:54] company specific developments where we try to get through
[0:58] perhaps the more salient news events of the week.
[1:01] But to start off, let's talk about biotech sector
[1:04] performance, especially as we're now firmly past the halfway
[1:07] point of the year. I'd say at a high level it it
[1:11] continues to be a bit choppy of late and I'd go even further to
[1:16] say we're seeing some pressure in the sector, particularly
[1:20] today. I'm seeing the XBI down about 3
[1:23] 1/2% and the XBI is now trading at sub $150.00 levels.
[1:30] Recall we crossed the 160 mark at the beginning of the month
[1:33] and even hit the 164 level on July 9th.
[1:38] That said, I think we've come a long way in the bounce back from
[1:41] through levels of several years back and bigger picture in terms
[1:45] of our sector outlook. And my team and I at Mizzou just
[1:49] published our second quarter biotech sector preview earlier
[1:52] today. But I think overall biotech
[1:54] fundamentals appear very much intact.
[1:57] Importantly, I'll call out at least three specific themes that
[2:01] I think could continue to drive sector out performance.
[2:04] These include and I'm sure there are others as well, but I will
[2:07] highlight you know previous headwinds at FDA that given high
[2:11] profile turnover and senior leadership at the agency of now
[2:14] we believe at least have turned into tailwinds for the sector.
[2:17] And we'll have more to say on this in terms of what we're
[2:19] seeing at the FDA in a little bit. 2, the biotech IPO
[2:23] locomotive continues running a full steam ahead.
[2:27] And if I have my numbers right, I think we have about 14 US
[2:32] biotech IP OS year to date and I think that's more than the eight
[2:36] that we saw all of last year. And for sure there are, there
[2:38] are several more in the queue. And 3rd, just a continuation of
[2:42] very robust M&A activity where I will remind that over the next
[2:47] decade or so, I think there's an estimate out there of over 300
[2:52] billion in revenue that is at risk due to patent expirations
[2:55] or losses of exclusivity. And that just means that big
[2:58] global pharma companies are going to need to find ways to
[3:02] plug in revenue gaps or holes and that often means them
[3:06] looking to acquire smaller and midcap biotech companies.
[3:11] This is all good in my opinion. And you know, as as I don't see
[3:15] any real big picture macro reasons for near term
[3:19] underperformance. I think this sector continues to
[3:24] rally throughout the the balance of the year.
[3:27] You know, in terms of the XBI, which we look at as the best,
[3:30] although by no means perfect proxy for the biotech sector,
[3:34] we're seeing 24% year to date performance as of at least
[3:39] yesterday's close. And this compares very favorably
[3:43] against year to date performance for the S&P 500, which stood at
[3:48] a + 9% year to date and the NASDAQ Composite, which is up
[3:53] 8%. And for additional perspective,
[3:57] just in this time versus 3 months ago, the XBI has gained
[4:01] some 1600 basis points. So meanwhile, healthcare more
[4:05] broadly speaking, is up only 6% here to date.
[4:08] So again, given 24% positive performance for the XBI, biotech
[4:14] continues to be a clear winner. And of course, we'd love to see
[4:18] this trend in biotech continue. I'll just briefly comment on the
[4:22] US biotech IPO market. After seeing Scribe Therapeutics
[4:25] make its public debut last week, this morning or sometime today,
[4:30] I think trading should begin in apne Med and that is a
[4:34] Cambridge, Boston based biotech focused on respiratory or
[4:37] breathing related diseases. And then next on the calendar I
[4:40] think is Braveheart Bio, that's the San Francisco based biotech
[4:43] focused on hypertrophic cardiomyopathy and related
[4:46] conditions. So I think the biotech IPO
[4:49] market is nicely humming along with this in the background just
[4:55] on a a macro of where we are in biotech.
[4:57] I'm going to pass things along to Tim who I will consider one
[5:01] of our more senior states persons in our industry.
[5:04] And Tim, I think you want to make some comments on current
[5:06] trends we are seeing with reverse mergers and pipe
[5:10] financings. And then I think separately
[5:12] afterwards you're going to cover the ever evolving and of course
[5:15] perhaps controversial role of of AI and biotech and the life
[5:19] sciences. So, Tim, go ahead and take it
[5:21] away. So thank you, Greg.
[5:23] And you know, just a comment on the market today, it hasn't
[5:28] escaped my attention that like when there's a week where
[5:30] there's not a lot of M&A, the XBI tends to drift down.
[5:34] And then like if there's two weeks like that, it drifts down
[5:36] even more. And then the moment you know,
[5:38] someone gets bought, you know, the XBI starts headed in the
[5:41] other direction. And we haven't had too much in
[5:45] the last couple weeks, but you know, it's coming.
[5:48] And you, you nailed it, Craig. I mean, there's just so much
[5:50] need for pharma to buy. I think the fundamentals are
[5:53] very much in place and I wouldn't be surprised to see the
[5:56] XPI finish the year closer to like one 75200 than where it is
[6:01] right now, which is under 150 really for the first time in in
[6:04] a while. You know, on these reverse
[6:07] mergers, by my count, there's roughly 10 companies that have
[6:10] gone public this year via reverse merger.
[6:13] So that reverse merger mechanism is pretty much as important.
[6:17] It's not more important this year than the traditional IPO,
[6:20] which is quite the change. And, you know, the question is
[6:22] why? I talk to people and funds, and
[6:24] I'd love to hear, you know, what the rest of you think.
[6:27] What fund managers say is that if you do a PIPE deal in the
[6:32] reverse merger, you get to do confidential diligence, which is
[6:34] a little different than an IPO. Those public Sooners.
[6:37] So a lot of people are worried about the midterms.
[6:40] You know, for whatever reason, Trump's numbers don't look
[6:42] great. And I think there's just a lot
[6:44] of uncertainty about the complexion of the country around
[6:48] politics is not the people are so pessimistic or optimistic is
[6:52] rather no one wants to wait around and find out what it's
[6:55] going to be. One of the fascinating things
[6:58] about reverse merchants this year is if you look at the post
[7:01] market performance, these deals have done really well.
[7:05] And so, you know, you get the endorsement of a bunch of funds
[7:09] that have had the opportunity to do confidential diligence.
[7:12] And so people pile on and you have a transaction that's
[7:15] oversubscribed and then the stacked as well.
[7:18] This week we saw two of these transactions as an example.
[7:21] I'm going to pause before I jump into AI and just see if anyone
[7:24] else has thoughts on this topic. Yeah, it's, I mean the only.
[7:30] Thing, the only thing I would just say is like on these
[7:33] reverse mergers, I feel like at one point people would ask
[7:37] questions, why did the company go public like that?
[7:40] You know, maybe a company goes public via reverse merger and
[7:43] they're like, no one really knows or most of the market
[7:46] doesn't really know who they are for two years, right?
[7:48] But you know, now it feels like the process has been kind of
[7:51] perfected. You don't really sacrifice
[7:53] syndicate quality, right? I mean, look at the syndicates
[7:56] of some of these, right? It's often the who's who.
[7:58] And so I just think in the context of that, right?
[8:00] I also hear anecdotally it's cheaper too.
[8:03] It feels like some of the prior disadvantages around perception
[8:07] have waned. What were you going to say to
[8:08] your own? Yeah.
[8:09] And to your point, I was going to add, it's, it's like that
[8:12] what we're hearing because we've done some of these is it's just
[8:14] a lot faster. And that's what's critical for
[8:17] the investor base and for the for the management team that
[8:19] they can get it done really fast.
[8:21] It does take time for the deal to close.
[8:23] And I would say that's kind of the the Achilles heel of the
[8:26] process. But to your point, they're
[8:28] they've been very well received. I'll take you both.
[8:33] And no, it's really interesting. We'll see how the rest of the
[8:35] year kind of finishes out. It does feel like IP OS are
[8:38] starting to pick up a little bit more and they they were sort of
[8:40] quiet before. And it seems like wasn't so long
[8:44] ago that US was, you know, bombing Iran all the time.
[8:48] And that was focus and was a lot of uncertainty in the market
[8:52] that that uncertainty is perhaps a little bit less today.
[8:56] The other topic I thought would be interesting to touch on is
[8:59] what's going on in AI and specifically Anthropic with
[9:02] their cloud science programs been coming on really strong.
[9:05] There's a lot of speculation last week that, you know,
[9:08] Anthropic could go out and buy a big pharma, right?
[9:10] They could just snap up Bristol-Myers or Abby or
[9:12] something. Seems all like a little crazy.
[9:15] I will say that the interest from big pharma and AI because
[9:20] of this move is really strong. And you know, when we talk about
[9:26] AI in the life sciences, we're often speaking about the idea of
[9:31] using a computer to make molecules.
[9:33] The the problem with that idea, even if computers are really
[9:36] good at making molecules is most of the time cost.
[9:39] And the real cost is actually in the clinical cyber AI is
[9:42] helpful, but not as helpful. And so, you know, making
[9:46] molecules with AI doesn't necessarily solve our industries
[9:49] bottleneck. So what Anthropic is really
[9:53] doing with cloud science is there using agentic AI to allow
[9:57] scientists to essentially get a lot more leverage.
[9:59] I'm sure we're all trying that. A lot of people are using these
[10:02] various programs, you know, from Open AI or Claude or whatever.
[10:06] And I know I use them in my just everyday life as a banker and
[10:09] it's just kind of crazy how much incremental leverage I can get.
[10:13] So that's even bigger on the science side.
[10:15] So there's all sorts of companies out there, Claude
[10:18] being the main one, but others like Cadence that are just so
[10:21] cool. And you know, Cadence, for
[10:23] example, is added like over 150,000 scientists to their site
[10:28] in just like the last couple months.
[10:31] And so this space is just red hot.
[10:33] My, my gut instinct is that AI is going to be really
[10:38] transformational to the process of doing science.
[10:41] And I don't think it's so much, you know, making molecules as
[10:46] just being a scientist. Like how am I going to write
[10:49] this protocol? Please design this experiment
[10:52] for me. Here's the results of this
[10:53] experiment. Computer write up the
[10:55] experiment, review this article. Do you think the article is well
[10:58] done? No, it's not.
[10:59] OK, we'll fix the article. So those are all things that,
[11:02] you know, used to take scientists weeks and months that
[11:05] like you can do in 10 minutes out.
[11:07] So it's very transformational. Anyway, I just wanted to comment
[11:10] on that. I thought it was some of this
[11:11] kind of breaking right now that probably we should talk about
[11:14] more on biotech hang out. I don't know if any others have
[11:18] thoughts on this kind of trend. I mean, I, I cover some of the
[11:29] areas, Tim, that of the, the, the drugs that use informatics
[11:33] to actually design the molecules.
[11:34] And it's been to your point, you know, we've seen sort of that
[11:38] this game before that they've been actually fairly successful.
[11:41] And I would say really kind of immediately jumps to mind that
[11:44] there's, there's other examples. The, the challenge to your point
[11:47] is that the platform, and this is sort of even Anthropic buying
[11:51] a large pharma, the platform could be, can have unlimited
[11:55] power and limited ability. The abilities to then reduce
[11:59] that to practice and, and, and the associated costs associated
[12:03] with it, especially given some of the failures that aren't
[12:06] inevitably are going to happen. So we, we think of it as it's
[12:09] going to be a, a technology that's going to get embedded in
[12:12] everybody's research. So I'm going to do a better job
[12:15] with it than others. But at the end, I don't know
[12:19] that the technology itself is going to be the sole driver.
[12:23] It's going to be an enabler and everything around it is going to
[12:25] be equally or even more critical.
[12:30] Thank you very much, Greg, back to you.
[12:32] Yeah, I mean, I think I'll add this just on AII mean, I you
[12:36] know, many of us have been following the biopharma industry
[12:39] for a long time. And I I've, I've been out there
[12:42] and, and said in various forums that, you know, it's not as if
[12:48] AI has not been tried to be, you know, worked into making the
[12:53] drug discovery process more efficient and make things less
[12:57] expensive, just overall more more productive.
[13:01] I do think we're in A and we haven't seen much success.
[13:04] I think we're in a newer age now and I, I just recall that, you
[13:09] know, we've got some public traded companies that I don't
[13:12] cover, but I think Recursion and, and Schrodinger are two
[13:18] companies that have been very levered to AI and I haven't been
[13:22] following them closely. But I think, you know, if you
[13:25] look at those stock charts, I haven't really been all that
[13:27] great, But you know, we're hopeful and hopefully we'll get
[13:31] some successes because at the end of the day, we we just want
[13:35] newer and hopefully better drugs in the hands of patients and
[13:39] physicians so we can get better health outcomes.
[13:43] It is a fascinating space to follow.
[13:46] I'm not the smartest one on this space, but I feel like every day
[13:50] that things go by, just advances continue to be made that it's,
[13:54] it's hard to keep up with everything.
[13:56] So that being said, let's move on to deals of the week and we
[14:03] have a couple to talk about. And I will start briefly with
[14:07] J&J's new partnership with privately held Sail
[14:11] Biomedicines, which I think I read somewhere as a flagship
[14:16] ventures company. And the deal involves J&J in
[14:19] licensing sales novel in vivo car T platform that is designed
[14:25] to generate car T therapies directly within the body.
[14:29] And this move is meant to strengthen J&J's presence in
[14:32] immunology and and car T And in terms of the deal details, J&J
[14:38] is making total initial payments of 785,000,000.
[14:43] But interestingly as part of the deal J&J can also opt in to
[14:48] acquire sale at some point for an additional 2.6 billion.
[14:52] So I think the deal is interesting for a couple of
[14:56] reasons. First, it's yet another deal in
[14:59] the white hot in vivo car T space.
[15:01] And here I will remind listeners of Eli Lilly's $2.4 billion deal
[15:08] for Orna and it's in vivo platform, car T, in vivo
[15:12] platform for I and I and then another Lily deal that it struck
[15:17] in in vivo car T for Colonia Therapeutics, more for Hemonc
[15:25] purposes and that was for 7 billion.
[15:28] The second reason I think it's an interesting deal is that
[15:30] there could be some potential read throughs for Legend
[15:33] Biotech. And for that I'm going to pass
[15:36] things along to your own who will comment on Legend and also
[15:42] your own, if you could follow up that conversation on Legend, on
[15:46] commenting on a deal we saw European biotech company
[15:50] Argenics do so your own. Please go ahead.
[15:53] Yeah, no, absolutely. So, So Sale is really a terrific
[15:57] company as as Greg has just mentioned, they're really
[16:01] approaching the whole in vivo carte in a very different way.
[16:05] They have essentially a, it's a programmable RNA therapeutics
[16:10] using nano vesicles that are chemically encoded.
[16:13] And so they can actually deliver the RNA payload in in a very
[16:18] different way. They're moving away from PEG,
[16:20] They're going to be using stabilizing lipids.
[16:23] So it's not really the standard lipid nanoparticle and it's not
[16:27] just targeting the hepatocytes. So This is why they are sort of
[16:32] very different. It's called erna.
[16:34] It's a lot more durable than circular.
[16:36] It's a, it's more durable because it's using a circular
[16:40] RNA sort of construct to prevent degradation, but it's also the
[16:45] mRNA kind of maxes out, it was in a day and the car goes
[16:48] fairly, it's fairly large. So it really has a very kind of
[16:52] broad transduction potential. And to for J&J, this is the
[16:57] second deal that they did. Of course, the first deal was to
[17:00] get a broad collaboration and access to the in vivo corticate
[17:05] abilities. That's using a lentivirus from
[17:08] Colonia, which was more for target for oncology, presumably
[17:12] really for hematology. Of course, BCMA was not
[17:15] included. As you know, J&J has a deal for
[17:19] the number one selling cell therapy in the world.
[17:21] It's called Victi. It's an ex vivo.
[17:23] So they actually make the cells, as you know, in the factory and
[17:26] give it to the patient. It's not in vivo.
[17:28] And Ying Wang was the CEO of Legend.
[17:32] We all know and respect Ying. Ying just announced literally on
[17:36] Monday that he's going to be stepping down.
[17:39] He accepted a role, presumably as the CEO of a new venture
[17:44] backed oncology company that I think is going to be fairly
[17:47] active and come on business development and other
[17:50] activities. So, you know, not, not something
[17:53] you, you want to see your CEO leaving a company.
[17:57] Legend, of course, has been a little bit in a crossroads for
[18:00] probably 3 main reasons. One is Gilead's Anita Cell.
[18:04] It's their version of an anti Bcmacar T is expected to get
[18:08] approval in December. It's basically one of the the
[18:11] key issues with Corvicti is that it does cause some immune
[18:16] related disorders like parkinsonisms and and Bell's
[18:20] palsy. It can cause colitis, it causes
[18:22] a cytokine release and and that's been the Achilles heel.
[18:26] The drug Anita Cell does not seem to cause the same AES.
[18:31] It might actually be a smidgen less potent as well.
[18:34] We're waiting for the final data, but that competitive
[18:37] overhang is pretty big that's coming in December.
[18:40] Secondly, they they're a little bit of A at a standstill their
[18:43] relationship with J&J for Corvicti and it's unclear
[18:47] whether J&J is going to opt in to then develop the in vivo
[18:50] Corti for myeloma. And if they don't do that,
[18:52] neither company can go into myeloma without therapy.
[18:56] And then finally, it's a question of how they're going to
[18:59] be broadly developing their in vivo platform now that they had
[19:02] some really good lymphoma data. I think there's a lot of hope
[19:05] that J&J will, will buy Legend. I think we've been thing in our,
[19:10] in our, in our reports that we think that's unlikely.
[19:13] Well, now they've done 2 essentially deals that give them
[19:16] abroad in vivo platform. So even less of a reason to to
[19:20] buy their partner. And then secondly, how are they
[19:23] going to ultimately, you know, develop the platform?
[19:26] So clearly there's been probably some strategic sort of
[19:29] misalignment there. So not ideal.
[19:32] The stock reacted. Obviously, Kovic in the meantime
[19:35] is continuing to sell, you know, really well, but that market is
[19:39] getting very, very competitive. Yeah, yeah.
[19:47] I think you mentioned the next. Deal.
[19:49] Then if you want to also comment on our Genex's deal, that would
[19:52] be fantastic. Yeah, absolutely.
[19:54] So our Genex bought a company called Forte.
[19:57] We have the lack of covering both of them.
[19:59] So it was really fun to kind of see that going to fruition and
[20:03] it was kind of very efficient to to put the models together.
[20:07] The they're, they're under the new CEO, you know, Karen Massey,
[20:11] this is the first deal actually that I believe or Genics has
[20:13] ever done in terms of acquisition.
[20:15] It was 2.2 billion. They are absolutely committed to
[20:19] external innovation in addition to their internal innovation.
[20:23] We really have to applaud them for being very early and getting
[20:27] proactive despite their internal pipeline very much humming and
[20:32] Vivguard their main drug doing absolutely well and they beat
[20:35] another quarter, I think it's their 14th or 15th quarter in a
[20:38] row that they beat since they launched.
[20:40] But getting you can never come get too early on, on on bringing
[20:44] in external assets. The, the key drug is targeting
[20:48] the the CD 122 receptor, which is where the aisle 15 cytokine
[20:53] and also aisle 2 signals through it.
[20:56] They're biting to the receptor and they've had positive Phase
[20:59] 1B data in celiac disease and vitiligo.
[21:03] And we're waiting by the end of this year to get the
[21:06] confirmatory Phase 2B celiac study that's randomized and the
[21:11] Phase 1B data for alopecia areata.
[21:14] So we're, we've been a fairly bullish about this asset.
[21:17] I think it's looked very good so far.
[21:20] We are optimistic for the, the celiac study will be will be
[21:23] positive as well and that that this area is is getting a little
[21:26] bit more competitive. It's getting a lot of attention.
[21:29] So of course you have Teva with Royalty Pharma developing their
[21:33] Illinois 15 antibody. So they're, they're not binding
[21:36] the receptor, they're biting to the cytokine in the blood that
[21:39] binds to the receptor. And they've had positive data in
[21:42] vitiligo. And I think we're all now
[21:44] anxiously waiting in the second-half of their celiac
[21:47] data. And then after that, I think
[21:50] vitiligo is the lead indication there.
[21:52] And then of course there's another company called First
[21:54] Tracks that has also a City 122 antibody that is going to read
[22:00] out their Phase 1A slash Phase 1B data and celiac second-half.
[22:05] So this is a really we think that the next area of innovation
[22:08] in I9 big unmet needs and great to see Argenix now jumping in as
[22:15] well. Really interesting deal for
[22:16] Argenix, which has been a remarkable success obviously in
[22:20] biotech in general, but particularly for European
[22:23] biotech. So it's nice to see them with
[22:26] their aspirations acquiring Forte.
[22:29] I'm just going to quickly touch upon a deal that's was
[22:33] previously announced and then we're going to segue into a
[22:36] broader biotech in any discussion.
[22:38] But I wanted to mention that we got an update on Eli Lilly's
[22:45] recent acquisition of psychedelics, Blair A Ty
[22:47] Beckley, which they yesterday disclosed via an SEC filing.
[22:53] Some of the play by play of how that deal went down.
[22:56] And I always find the play by plays a very fascinating read.
[23:01] It shows how BD deals get done in the history.
[23:03] But it looks like in this particular case, and again
[23:06] that's a that's a recent deal that Eli Lilly announced.
[23:10] But it looks like a tie was approached in December at first
[23:14] by another pharmaceutical company, which obviously is
[23:18] unnamed. But that was initially for a Co
[23:21] development and Co commercialization deal for a tie
[23:25] Beckley's lead asset, which is called BPL 003.
[23:28] That's for treatment resistant depression and there was an
[23:31] offer for 125 million upfront for this type of deal.
[23:35] Notably, this approach came one month after Etai had completed
[23:40] its merger with a company called Beckley Scitec.
[23:45] Nothing pretty much happened for a couple of quarters and then
[23:49] Lily joined the fray I guess in in early June with an initial
[23:54] deal and they ended up maybe a couple of weeks later sweetening
[24:00] its offer June 11th with a $6.75 upfront.
[24:09] But then they tacked on a $1.00 per share contingent value,
[24:14] right? Or CVR, which was tied to
[24:19] potential FDA approval of a compound called VLSO, one for
[24:25] treatment resistant depression. And VLS 01 is in Phase 2
[24:32] testing. The back and forth continued for
[24:35] a few more weeks, but ultimately Eli Lilly moved up on their CVR
[24:42] to $2.50 and that's what got the deal done.
[24:47] But from an initial BD discussion by another suitor and
[24:52] again as I mentioned earlier, it seems like Eli Lilly is buying
[24:55] everything, which is very impressive to see what they're
[24:58] doing. But I guess it's with a view
[25:00] that perhaps the obesity related or GLP one related or triple G
[25:05] related future revenue streams will be there.
[25:09] And maybe they won't be there forever, but they're certainly
[25:13] being very aggressive with M&A. Paul, let's get you into the
[25:20] conversation because I think you had some thoughts that you
[25:24] wanted to offer to our audience on this idea of when companies
[25:32] that are kind of smaller but then are starting getting
[25:35] bigger, you know when should they get acquisitive and then
[25:40] maybe we can segue into like a broader M and a discussion.
[25:43] Go ahead, Paul. No, totally.
[25:45] I wanna I. Wanna make this comment and then
[25:46] I'm actually curious from your own like what he heard from
[25:49] people on the Argenix side. But I think it's like Argenix is
[25:53] an interesting point to be an acquisitive company.
[25:57] You know, Al Milam is kind of getting to the point now, too.
[26:00] Where it's like. Are they going to do something?
[26:01] I hear people talk about this with like, you know, maybe in
[26:03] SMED at some point, like these companies that get into this
[26:06] kind of like mini large cap range, maybe built on, you know,
[26:10] a one to two, you know, really big product franchise.
[26:13] And then it's kind of like they almost become a little bit of a
[26:16] victim of their own success where where people start to say
[26:18] what's next. And you know, I think some of
[26:20] the cautionary tales around this, you know, one I think was
[26:25] like a Lexion where with Soliris and Altamiris, they had so much
[26:29] success. But then a competitor to that
[26:32] was even an early mid stage development emerged.
[26:35] And then suddenly it became this whole like existential threat to
[26:37] the terminal value and where's the pipeline?
[26:40] And you know, they kind of played catch up to backfill the
[26:42] pipeline. You know, I don't know exactly
[26:44] how this is thought about with Argenix, so maybe your own can
[26:47] chime in. But just like on Al Mylam, you
[26:48] know, I mean Al Mylam had this monster TTR launch and I know
[26:52] we'll probably talk later in this call about their guide this
[26:55] week that disappointed people. But you know, it quickly became
[26:58] A50 or $60 billion company. And then, you know, they got a
[27:01] couple shots on goal in the pipeline, but nothing clear cut.
[27:03] And it quickly becomes this what's next conversation.
[27:06] You know, we saw Vertex in this limbo for a couple years until
[27:09] they kind of started to breakthrough with a couple
[27:11] pipeline assets. And now a Vertex is, you know,
[27:14] much more comfortable with doing M&A.
[27:15] And so I think it's, I actually thought it was like really cool
[27:18] to see our Genex do this because I do think when things are going
[27:23] well and you've got, you know, a drug franchise like Viv guard
[27:26] or, you know, like and Vutra, at least before yesterday, where
[27:30] you're beating and things are going well.
[27:31] I I think it's easy to kind of be, to be risk averse, right?
[27:34] And to stay focused on what's doing what's, what's going
[27:37] great. But you know, the market
[27:39] dynamics and investor perception and the multiple that people are
[27:43] willing to put in your business can, can change quickly, often
[27:45] via factors that are beyond your control.
[27:47] And so, you know, I know there's multiple companies in my
[27:50] coverage, like, you know, Bio Marin is another one, right,
[27:52] where, you know, I think a lot of investors view it as like an
[27:55] undervalued stock, but this whole question of like, what's
[27:57] next? What's my upside variance in the
[28:00] pipeline continues to loom. And so, yeah, you know, and I,
[28:03] and I think maybe just the last thing I'll say is like, I I've
[28:06] kind of been paying attention to sort of how are the acquirers of
[28:08] companies in the past few months, how's their stock
[28:11] trading, right. And and I think in general like
[28:13] we're very rarely seeing big down moves and sometimes like in
[28:17] the ABV Apogee situation we're seeing, we're seeing up moves.
[28:20] And so outside of the other factors that favors more M&A,
[28:22] that's probably a tailwind for the space too.
[28:24] But your own, what did you hear on, on the Argenics piece?
[28:27] Well. I think that this one was a
[28:29] little different for probably a couple of reasons #1 Argenics
[28:33] has been very upfront about their build, their desire to
[28:37] start doing deals for innovative I and I assets.
[28:41] So that was expected. 2 They actually invested in back in
[28:45] late April or early May, right? Right.
[28:48] In this company. Right, part of the recent
[28:50] offering. Exactly.
[28:51] So we sort of knew they're around the hoop and we knew this
[28:54] data is coming. And on the heels, well, we, we
[28:57] knew that Forte released their vitiligo data, which which led
[29:03] the stock obviously to go up a lot.
[29:04] And at that point, they also pulled forward their guidance
[29:08] that they're going to have data quote UN quote soon slash
[29:10] imminently for celiac before it was 2026.
[29:15] So I think and then on the on Thursday, our Genex reported and
[29:19] again reiterated their desire to do MNA.
[29:22] So Forte stock absolutely ripped on Friday and of course, it got
[29:25] acquired on Monday. So it was a little bit
[29:27] televised, but it was very well received on both sides.
[29:36] And then, Paul, since you spend a lot of your time on the Neuro
[29:40] space, any thoughts about kind of what that Lily deal for a tie
[29:45] might mean for M&A in the psychedelic space or just
[29:49] activity in the psychedelic space?
[29:51] No. And and you, you chime into
[29:53] Greg, especially given your like experience doing, doing BD
[29:56] because I think, I mean, I think you know, I cover, so I cover
[30:00] Compass, I cover Difinium and I cover GH and obviously pay close
[30:04] attention to all the, all the competing assets.
[30:07] I think one of the questions has really been like, you know, we
[30:10] saw Abby do the Gilgamesh deal, you know, we saw Transcend
[30:14] Therapeutics get acquired by Otsuka, but those were like
[30:18] relatively smaller M&A transactions.
[30:21] And I think one of the questions was some of like the bigger more
[30:24] established companies in this space is like, you know is
[30:26] someone it is a traditional pharma company that you know
[30:31] might care a little bit more about perception or might be a
[30:34] little bit more conservative with how they view perception.
[30:36] Are they going to be willing to step in and buy like buy a
[30:39] psychedelics company, right? And and this was a conversation
[30:42] that was actually really relevant with GW Pharma a number
[30:45] of years ago, right, who was developing CBD for orphan
[30:47] epilepsy. And you know, CBD ended up being
[30:49] schedule 5, right? There's nothing like, you know,
[30:52] stimulants or schedule 2. But but still, like, I think
[30:54] there was even a Bloomberg article, I want to say like 10
[30:57] years ago about how, you know, GW pharma, like the buyer pool
[30:59] might be small for GW pharma. And then it was eventually
[31:02] bought by Jazz, right, a spec pharma company.
[31:03] So I mean, I think like Lily, you know, Lily, probably the
[31:08] most powerful brand in the pharmaceutical space, putting
[31:11] their stamp of approval on on DMT, right, which is, you know,
[31:15] a psychedelic compound that has some tremendous efficacy data,
[31:20] but also like is pretty out there on the psychedelic
[31:23] experience side. I think that's like really,
[31:26] really validating for the space. I mean, people are going to
[31:29] always wonder, well, why did they pick this one than that
[31:31] one? And it's always like a hard
[31:32] conversation to have. But I think for the other
[31:34] companies that I cover in this area, I, I think it's
[31:37] validating. I also think like it's going to
[31:39] probably help to have someone like Lily, you know, building
[31:43] the, the infrastructure here, right?
[31:45] I mean, I think a number of these companies are going to
[31:46] benefit from what J&J did with Spravato.
[31:48] So, yeah. Do you have any other angles,
[31:50] Greg? I mean, in, in your BD seats and
[31:53] you, I think you're at ABV and maybe somewhere else.
[31:55] Like, how much of that kind of like perception angle of this
[31:59] like came into play in the conversation?
[32:03] Yeah, I mean, there's first of all, 1000% agree with everything
[32:06] you just said about, you know, the psychedelic space clearly,
[32:12] given what the current administration is saying and
[32:16] doing about their support for the space.
[32:20] Lot of great tailwinds for those companies and look, just as I'm
[32:25] sure you have as well, I've met with a bunch of private
[32:28] companies. That admittedly have said to me,
[32:32] you know, we're jumping on the bandwagon and there's obviously
[32:37] very interesting science and and some admittedly great efficacy
[32:41] data that exists for a lot of these products.
[32:44] And so I do think it's going to be a very, very active space and
[32:48] Lily does validate what's happening.
[32:52] And I think that deal does further open the floodgates for
[32:57] more activity. You know, from a BD perspective,
[33:00] I think there's always an element.
[33:03] It's not 1000% true, but there is an element of a little FOMO,
[33:08] a little kind of, hey, so and so is doing that and we don't want
[33:12] to be left behind. So we better catch up.
[33:15] And I think you know, obviously given.
[33:17] Eli Lilly's market cap. I think if I'm ACEO of a large
[33:22] pharma company, I'm trying to figure out, you know, how do I
[33:25] get there? And if Lily's making a lot of
[33:29] first move, first moves? Then I think the rest of the
[33:35] industry has to at least internally debate whether they
[33:38] feel the need to catch up or not.
[33:40] So obviously every company is different, not everyone.
[33:44] Is in the neuro space and certainly not everyone is got to
[33:49] play in psychedelics. There are only a handful of of
[33:52] Publix and you know, you look at some of the valuations in
[33:56] particular Definium, which I think is, you know, 5 to 6
[34:00] billion and they just reported some, some really great data.
[34:04] So kudos to them. But that would be a pretty hefty
[34:08] M&A price if someone was looking at definium.
[34:12] I'm not here to say whether it's worth it or not.
[34:14] I don't I don't cover any of the psychedelic companies and you do
[34:18] see market caps for the other companies.
[34:21] You follow Paul, in terms of Compass and GH being maybe I
[34:26] don't want to say more reasonable, I'm not going to say
[34:28] that, but you know, lower valuations at least from a
[34:31] public perspective that you know, 1 to 2 billion.
[34:35] It'll be very interesting to see how this space evolves.
[34:40] Tim or Brian or your own. Any thoughts there?
[34:46] OK. We are going to move on to
[34:50] regulatory and policy matters and we've got several things to
[34:54] work through. So, Brian, I think you had two
[34:56] things, if not maybe three things that you wanted to
[34:59] comment on. So I'll turn it over to you.
[35:02] So, yeah, so, so everyone, everyone knows adcoms are like
[35:06] one of my favorite parts of the sector and, and they are back
[35:09] in, in big fashion. And there were two really good
[35:12] adcoms this week that that, look, I think it really embodied
[35:15] all that I, I appreciate about this process.
[35:17] And we can have different opinions on what constitutes
[35:19] substantial evidence. But look, biology and medicine
[35:22] is complicated and not always necessarily straightforward.
[35:25] And look, we were almost always presented with him for perfect
[35:28] information that comes into play in clinical trials.
[35:31] So look, I think the FDA has a really tough job where they get
[35:34] these imperfect applications and need to balance the
[35:36] responsibilities they've been tasked with under Cavalra
[35:38] Harris, which is, you know, the amendment to the Food and Drug
[35:41] and Cosmetic Act that makes drug companies prove products are
[35:45] both safe and effective before selling them.
[35:47] But often the process between FDA and companies winds up being
[35:50] very opaque. You know, we really only get
[35:53] insight from what the companies tell us throughout this entire
[35:57] process. But one of the things that I
[36:00] love is that really gives us broad, broader public insight is
[36:03] when the agency gets a particularly complicated
[36:05] application and they hold these advisory committee meetings.
[36:09] And again, this embodies sort of the scientific discourse and how
[36:13] can we really achieve and the process of achieving a
[36:16] scientific consensus with imperfect data in a really
[36:19] transparent fashion. And you know, look, one of my
[36:23] biggest beefs that I had with with Marty Macri and Vinay
[36:26] Prasad when they're running the FDA the last year and a half
[36:29] before their departures was the decision to kind of stop doing
[36:32] these and really just internalize the process, right?
[36:35] And, and, you know, there's a number of applications that were
[36:37] rejected or just told not to file.
[36:40] And, and, you know, companies sort of need pleased to, to the
[36:44] public that, you know, the FDA just wasn't listening.
[36:46] We just really didn't have great insight into what was going on
[36:49] behind the scenes. So this week we wound up with
[36:52] advisory committees for for two pretty controversial
[36:55] applications. Capricorn's Dermi SL for DMD and
[36:57] reply means RP one for for Melanoma.
[37:00] And, and look, in classic Wall Street fashion, critical
[37:03] briefing documents were publicly disseminated a couple of days
[37:05] before the ad come and the respective stocks got, you know,
[37:08] hit pretty hard as the agency, you know, really did criticize
[37:12] the data. They were, you know, just kind
[37:15] of like a best of all of the different statistical complaints
[37:18] that the FDA could have or nuances around changing data or
[37:22] how to analyze specific pathology.
[37:26] In Capricorn's case was really a heavy argument around statistics
[37:29] and how protocol changes can lead to biased results.
[37:32] A critique that really resonates with me.
[37:35] If you look at my Twitter profile, I have the multiplicity
[37:37] calculation for type 1 error in, in, in my headline.
[37:40] So, so you know, I, it's one of the things that is a big pet
[37:43] peeve of mine to begin with. In Repla means case was a little
[37:46] more around how to to measure intratumoral injection activity
[37:51] versus sort of the the way we use recess for more of a
[37:54] systemic therapy. And look, I think the FDA made a
[37:57] really good case where they had previously rejected both of
[38:00] these programs and why the applications don't meet the
[38:01] statutory threshold of substantial evidence of
[38:04] effectiveness. But this was also balanced by by
[38:07] a decent presentation by both, both companies.
[38:09] Arguably probably Repla means was was a little more
[38:12] resounding, but also open public hearing portion, which you know
[38:16] generally does sway in favor of approvals.
[38:19] And then in both cases, look, a really robust and well thought
[38:22] out discussion. And I thought among the
[38:24] panelists who you know, consist of statisticians or specialists
[38:28] and in, in, in the respective fields.
[38:32] And in Capricorn's case, the panel voted 39 against and in
[38:35] reply means case it was the reverse basically with a 10/3
[38:38] vote in favour. And look, the FDA doesn't always
[38:41] go with the Adcom votes non binding, but they very often do.
[38:45] And there's usually a big blowback to the agency when they
[38:47] go the other way. But there's a lot of nuances to
[38:50] the commentary. And it was clear in both cases
[38:52] that committee members really couldn't make a very confident
[38:55] decision and what the benefit of either of these drugs is if
[38:58] there is a benefit. And then I think as always, it
[39:00] comes down to sort of the subjectivity of substantial
[39:03] evidence and clinically meaningful or in the case of
[39:05] accelerated approval, it reasonably likely to predict.
[39:09] But look, I mean, I, I just love that we're seeing it occurring
[39:12] again. We get a lot of transparency.
[39:14] I think deep diving on these things is really educational
[39:17] about all the considerations one has to think about in running
[39:21] clinical trials and then and then trying to reach a
[39:23] conclusion from clinical data that is is imperfect.
[39:27] And maybe just to put a final point on how, how this impacts
[39:30] the sector. Look, I think the FDA for the
[39:32] vast majority of drugs is pretty straightforward not to diminish
[39:36] orphan drugs where we often wind up with these sort of highly
[39:39] debatable results just because it's hard to to enroll very,
[39:43] very clear large studies. But these on the bubble
[39:46] applications are really a very small part of the sector.
[39:49] So even though some of this view them as as kind of most
[39:51] interesting part of the sector, look, I don't think FDA being
[39:54] more or less conservative in these situations is as impactful
[39:58] as say drug pricing reform or interest rates.
[40:01] But for those who thought the departure of Marty and Van I was
[40:04] a signal of FDA just giving everyone the go ahead.
[40:07] I think it was pretty clear from these panels that that's not the
[40:10] case. These may be more one off
[40:13] examples and we'll have to see as we see more of these
[40:15] applications go forward and more ad coms go.
[40:18] But but this FDA was not pulling punches at at either of these ad
[40:22] coms and that's love to hear anyone else did did anyone else
[40:28] listen to these ad coms? I.
[40:29] I love it as much as Brian. That was like, that was, that
[40:32] was a classic FDA ran. I thought that was, I thought
[40:36] that was like really great. I, I, you know, I cover Unicure,
[40:39] which is completely unrelated to either of these, but the stock
[40:46] trades around on just the FDA vibes thermometer, right?
[40:49] And was down on the Capricorn documents and then up last night
[40:53] after Replimune. And so I mean, that just tells
[40:56] you right that investors are still in these kind of contexts,
[40:59] right, where there's an element of subjectivity or flexibility
[41:02] still really taking the temperature of where the FDA is
[41:05] AT and it's A and it's a touch and go day by day thing.
[41:11] I love the fact that Adcoms are back, you know, again, my cell
[41:16] side colleagues and I've been in the space for quite some time.
[41:19] And there were times, I'm sure that some of us, if not all of
[41:24] us have attended an Adcom in person down in Bethesda and
[41:29] trying to trying to get some, you know, sense of the body
[41:33] language or even, you know, trying to get an inside read.
[41:37] But they're always just really fascinating.
[41:41] With that said, I mean other big pieces of news, I think from a
[41:44] regulatory and or policy perspective, Brian, I think you
[41:47] want to talk about dying and kind of progress it's making.
[41:54] Yes, well, I mean, less on the, on the regulatory front, but a
[41:57] Dine announced this week that they gotten an, they, they
[42:01] received clearance from the US FDA for its Ind application for
[42:04] phase one study of, of their drugging FHD, physioscapial
[42:11] flow, humoral muscular dystrophy.
[42:13] And, and, you know, there's something, you know, I just kind
[42:16] of know, you know, has been a little long in the tooth for
[42:19] Dine. I think we've sort of been
[42:21] waiting for this for a while. But you know, as I sort of said
[42:23] last week, umm, you know, it's company that started, you know,
[42:25] really starting to, to kind of move along in a more efficient
[42:29] manner. And, you know, it's interesting
[42:31] because as we all know, Avidity got acquired by, by Novartis
[42:36] last year. And a big part of Novartis is
[42:38] these are at least in their slides.
[42:40] I mean, they made a big deal around FSHD and obviously
[42:42] Avidity's and Novartis is, is ahead in FSHD, but you know,
[42:46] Dine and, and Dividity have sort of been, you know, paralleling
[42:51] each other. They've had very, very similar
[42:54] platforms in terms of muscle delivery.
[42:58] So, you know, I think I thought this was a nice positive for
[43:01] Dine and and you know, I'm just glad to see another program
[43:04] moving into the clinic for FSHD. And then, Tim, some of us
[43:10] probably saw the headlines. If not, we're very curious to
[43:14] see about the Senate hearings and I guess Anthony Fauci being
[43:19] put to the stand, so to speak, in the public eye.
[43:23] Comments you want to make on that?
[43:26] Yeah. So, you know, Tony Fauci is like
[43:28] in his 80s. He got a subpoena.
[43:30] He had to appear before the Senate Homeland Security and
[43:33] Government Affairs Committee and a hearing that was titled
[43:36] Testimony of Anthony Fauci. And, you know, this committee's
[43:41] chairman, Rand Paul, who's, you know, a hardcore libertarian,
[43:45] has accused him of misleading Congress about whether or not
[43:49] NIH funded research in Wuhan contributed to the pandemic.
[43:53] Sort of little crazy. And, you know, Fauci's deny
[43:57] this. And, you know, Fauci just got up
[43:59] there and had an opening statement where he invoked the
[44:02] 5th Amendment and he ended up invoking his Fifth Amendment
[44:06] rights more than 100 times through roughly 3 hours.
[44:09] You know, to make this even more interesting, kind of like talk
[44:12] about adcoms. You know, Senator Paul released
[44:15] more than 1100 pages of his 2019 to 2022 person personal diary.
[44:22] And, you know, there was no evidence about COVID origin and
[44:25] those Diaries. But, you know, it's just, I
[44:27] guess, trying to embarrass the man.
[44:29] So this was a game of tactics, I suppose, you know, right wing
[44:34] libertarian types essentially trying to, you know, make Fauci
[44:41] look bad, make it look like there was some type of
[44:43] conspiracy behind the COVID type situation.
[44:48] The Republicans, you know, accuse Fauci's silence is
[44:53] confession. Senator Holly says no honest
[44:56] person plead that this, you know, Senator Tuberville accused
[45:02] him of having something to do with killing 9 million people.
[45:06] Representative Anna Paulina Luna called him Doctor Mengley Fauci.
[45:09] So, you know, very politicized event.
[45:12] Democrats like you know, would have nothing of it and said the
[45:15] hearings actually doing damage. Another person, Senator
[45:19] Blumenthal, liken this to a McCarthy type hearing.
[45:23] You know, think of it what you will, but I would say is the
[45:26] only choice that Senator Paul has to do is to have a vote in
[45:30] the Senate holding for contempt. But that's not likely to take
[45:35] place. And that's only because there's
[45:38] not enough votes for that to go through.
[45:40] I personally thought the most interesting thing about this
[45:43] entire theatrical event was President Trump.
[45:48] He said nothing. He did not participate when he
[45:53] was asked about it by the media. He just said I inherited Fauci
[45:57] and said he wasn't big factor for me.
[46:01] So, you know, I think in a funny way, this is a bit of a Tempest
[46:06] in a teapot. And, you know, Senator Paul is,
[46:12] you know, trying to appeal to his base, which is, you know,
[46:16] libertarian. So they're, they're trying to
[46:18] create an issue. That's my own opinion.
[46:20] You know, others might feel differently.
[46:22] I'd be very curious to hear what others think.
[46:23] I. Mean, I think that you know that
[46:28] look, this is very unfortunate political grandstanding is kind
[46:32] of not something that should be ascribed to someone who's been
[46:38] such a public servant and that there's obviously two sides to
[46:42] what's going on. But sadly this has always been a
[46:44] very political topic. I I personally just felt awful
[46:47] for the man given what he's done to us.
[46:49] I don't think he given given how much he's contributed, I should
[46:52] say right to medicine in general, to public health and to
[46:56] be kind of caught in, in, in the crosswinds.
[46:59] I'm, I'm not sure what clearly you've mentioned it.
[47:02] There's obviously political consideration for this.
[47:06] I guess I just don't see the real point to this.
[47:11] It's I'm just mostly kind of saddened for him.
[47:13] This is, it's sad that it's actually going to cause a lot of
[47:17] distrust in our public officials on the health side on top of all
[47:21] the distrust that's going on already.
[47:23] And I know this, I know we recently talked about the
[47:26] allowance to compound sort of peptides.
[47:30] It's almost like Healthcare is becoming a little bit of a self
[47:34] choice in a way, you know, with what patients are going to take
[47:36] regardless of what FDA's position is.
[47:39] And there's kind of less and less public trust sort of in in
[47:43] the agencies at the same time. So it's a little bit of a dual
[47:46] Ed sword. Well said your own.
[47:50] We've got some company news in the time that we have left and
[47:53] Paul, I know we we highlighted Alnylam earlier in the in the
[47:58] show. If you want to comment on kind
[48:00] of what we saw out of Al Nilam this week.
[48:04] Yeah, sure. I can be brief because I know we
[48:06] have a few other things. But you know, essentially Al
[48:08] Nilam surprised the Street this week when they lowered their
[48:12] guidance, you know, on the second quarter call just after
[48:15] issuing it at at JP Morgan. This is for their TTR product
[48:19] and Vutra, which had this monster launch last year, but
[48:24] but since then, now this is the second time that they've missed
[48:26] consensus in 3/4. So the stock, I mean, really got
[48:31] hit, right? I think, you know, embedded in
[48:33] that 30% down move is, you know, some meaningful amount of
[48:37] fundamental and some meaningful amount of just emotional
[48:40] frustration and kind of like, oh, like, how do I even kind of
[48:43] think about the new guide? And is there risk to that?
[48:46] And so, you know, outside of around all this like
[48:48] consternation is probably sort of lost in the fact that even in
[48:51] their new guide, second-half 26 over second-half 25 is still
[48:55] growing at over 50%. But you know, the other wrinkle
[48:57] here too, and I think your own at least covers Ionis, is, you
[49:01] know, the Ionis TTR outcome study for their silencer failed
[49:05] seemingly because of a lack of benefit on top of tefamidis.
[49:08] Al Nalam's next Gen. silencer, which you know, essentially
[49:11] would increase the profitability of their TTR franchise by almost
[49:15] double by eradicating the royalty is in a is in an outcome
[49:18] study that is almost functionally being run as a
[49:21] tefamidis combo study. And so, you know, I think part
[49:24] of this sell off too is waiting for ESC to see this full Ionis
[49:27] Arizona data. What is Al Malam going to do
[49:30] with their outcomes trial? But you know, it kind of goes
[49:33] back to some of the other sort of discussion we had on our
[49:35] Genex where, you know, I don't want to say Al Nolam doesn't
[49:37] have a pipeline. They do have a pipeline.
[49:39] They have a couple in intriguing shots on goal, but they don't
[49:41] have anything else de rest, right?
[49:43] And and you know, I do think with the Al Nolam platform and
[49:45] how productive it was for a long time, you know, I think a lot of
[49:49] investors thought there would be more, you know, meaningful
[49:52] programs and kind of late stage development at this point.
[49:55] And so I think that those are the kinds of pushes and pulls
[49:58] people are grappling with. Aron, did you want to comment at
[50:02] all given that Ionis situation? Yeah.
[50:06] I mean, maybe I'll be brief. I mean, I guess what I can
[50:08] really contribute more is what to expect that ESC.
[50:11] I mean kind of what we know is that there was no benefit to the
[50:15] combo versus mono. We know that in the patients who
[50:18] got Wayne knew Amano versus placebo, the hazard ratio was
[50:22] .71. So that's a lot more apples to
[50:25] apples to the Invitra Helios B data.
[50:28] The data Ionis believes that the totality of the data at ESC
[50:33] including an independently conducted meta analysis will
[50:36] show that in Vutra is very, very similar to slash identical to to
[50:42] a newer. And so they believe that
[50:45] ultimately the stabilizers is better than they did
[50:48] historically. It's possibly because of the
[50:51] contribution and the amount of patients that were NAD Class 1.
[50:56] We're both stabilizers and silencers do extremely well
[50:59] because you're moving really early.
[51:01] The big question is did the stabilizer, how did the
[51:04] stabilizer do against the silencer?
[51:07] They don't have that data in house yet.
[51:11] They will apparently have it for ESC, but the but their belief is
[51:15] that ultimately the silencer and the stabilizer did equally as
[51:20] well so. Hey, your own, can I chime in on
[51:22] this? Yeah, go for it.
[51:23] I think this stabilizer silencer comparison is like the dumbest
[51:26] thing ever. Like not saying that Ionis is
[51:28] dumb, Ionis is brilliant, They're great drug developers,
[51:31] but just from like a context perspective, like the patients
[51:35] who've been on the stabilizer have been in the stabilizer way
[51:37] longer, anywhere from six months to years, right.
[51:40] So it's like a it's a late start analysis.
[51:42] I don't see like I hear a lot of people comparing the data for
[51:45] this, right. And again, I don't mean this at
[51:47] all as a shot against Ionis, like I have like those guys are
[51:50] so smart and you know, like they're they're legends, right,
[51:55] and drug development. But I don't see why people are
[51:57] playing this analysis up. I think the issue for Al Mylem
[52:01] is like Al Mylem has a hypothesis and why their drug is
[52:03] different. I don't see how like ESC is
[52:06] going to really like at best it's going to be hypothesis
[52:09] generating in my opinion. So I still think at the end of
[52:11] the day, like they're going to have to do something with their
[52:14] study to rescue people's confidence.
[52:15] But these like comparisons on arms and different trials when
[52:19] like the duration of treatment is different and like the timing
[52:21] of treatment and initiation is different and like the
[52:24] demographics are different. Like, I don't know, like that
[52:27] almost feels like it's set up to throw.
[52:31] I don't know. I don't get it.
[52:32] Do you disagree? I so let me tell you the Ionis
[52:36] train in TTR is absolutely left the station and is no longer
[52:41] relevant to the story at all. So this is really being played
[52:44] because of the other companies right?
[52:46] It's the the obviously on island and bridge bio.
[52:49] I noticed at this point honestly is an innocent bystander that
[52:52] has to present this data. I agree with you, from an
[52:55] owner's perspective it's irrelevant.
[52:57] It looks like the two drugs are identical.
[52:59] Which then begs the question who do you start with?
[53:01] Do you start with a cheaper oral or do you go with an expensive,
[53:05] you know, injectable? I I think that most people are
[53:08] kind of, that's probably the issue here for Anilum.
[53:11] Most people believe they'll start with a cheaper oral.
[53:14] Why not? Yeah, No, I think that's right.
[53:18] I think I think that's right, right.
[53:21] I mean, I talked about how like tons of these TTR prescribers
[53:24] haven't written their drug yet. I mean, there's, you know, like
[53:26] I I think the one thing and and we're still like defending Al
[53:30] Nylum. I mean the stock is down so
[53:32] much, but just outside of the stock context, I think the one
[53:34] thing that we got wrong here that I do think is an
[53:36] interesting kind of nuance that can happen when you do diligence
[53:39] on the Wall Street side is, you know, I felt like if you talk to
[53:42] a handful of Kols, more of them believe that the silencer
[53:46] mechanism was more effective. Even after we got the Helios B
[53:49] data right, that didn't 100% prove that.
[53:52] But I always now kind of wonder, you know, was that really an
[53:55] extrapolatable sample? And to your point, you're on
[53:57] like, you know, you've got this community physician who runs a
[54:01] busy practice like they might not be mega, mega in the weeds
[54:05] on the data and they're going to, you know, if it's close
[54:07] enough, they might do what's. Easiest, right?
[54:09] And I think that that's kind of what we've seen play out.
[54:11] Well, plus there's one more learning for me and, and, and
[54:14] sadly, my, my team and I are kind of been joking internally
[54:17] that we, we've done a better job dodging the bullets that we were
[54:21] positive on and we were working on a big piece.
[54:23] We never got it out and it blew up.
[54:26] So you want to be lucky all the time as opposed to being smart.
[54:29] It's always, it's much, much Better Business plan.
[54:32] And where I'm going with this is we were, we did not get right on
[54:35] the on the side. But if you actually look and the
[54:38] learning for me is this is one of those cases.
[54:41] When you looked at the original Helios B data, it did show you
[54:45] the combo is not better than mono.
[54:47] It was underpowered. And I think there was always a
[54:50] supposition that because it was underpowered and it was small,
[54:54] it was not relevant statistically and it was
[54:56] actually clinically incorrect. The early data showed you that
[55:00] there was no benefit and that then worked out in the in the
[55:02] bigger sample too. Yeah, it's interesting.
[55:05] I mean, yeah, they, they have this huge reduction in
[55:07] mortality. Some of the other functional
[55:09] secondary endpoints like KCCQ, 6 minute walk are, you know, are
[55:14] less convincing, right. I mean, I, I would imagine there
[55:17] probably is some benefit if it's studied in the right context,
[55:21] right, or the right population, the right severity.
[55:25] But again, from the El Malam angle, right, like it's going,
[55:27] I, I think ESC is at best for them going to be still up to
[55:31] interpretation. And so the question is just how
[55:33] quickly do do they move? And you know, how many patients
[55:36] have they already enrolled in their outcomes trial?
[55:38] Like we don't know the answer to that.
[55:41] Thanks guys. I'm going to try to squeeze in
[55:43] some data from today which was Novo Nordisk whose shares are
[55:48] down almost 10%. And that's not a small amount of
[55:50] money on a negative readout from a phase three study called the
[55:55] Zeus study for its anti Illinois 6 ligand based antibody.
[56:01] And there are basically that antibody is for cardiovascular
[56:06] diseases. They missed the primary endpoint
[56:08] on a Mace outcome. But there is interestingly some
[56:13] very negative read throughs for a host of companies that are
[56:17] developing this novel class of agents called the LRP 3
[56:21] inhibitors. And we're we've got several
[56:24] public companies that are down significantly on negative read
[56:30] throughs on what that data means for the space.
[56:32] And we've got a company called Monterosa Therapeutics that's
[56:37] down 61% on a read through from the Novo data from today, Bio
[56:44] Age down 31% intraday and Numura Therapeutics down 9% intraday.
[56:52] And I think the thought here is that people are trying to get a
[56:55] look on whether lowering this cardiovascular biomarker HSCRP
[57:02] and and if you could meaningfully impact that could
[57:05] lead to a change or you know, an improvement in cardiovascular
[57:09] outcomes. The Novo data showed that at
[57:13] least using their anti Illinois 6 ligand antibody that that is
[57:17] not indeed the case. I do think it's interesting.
[57:21] I don't follow a Monterosa or Bio Age, but on the Nomura side,
[57:25] which I do cover, they've got an oral NLNL RP3 which just had an
[57:30] update earlier this week. There had been a scare or a
[57:33] concern that perhaps there were some adverse events.
[57:36] The company ran a separate, a new and separate 13 week rat
[57:40] talk study. There are no adverse events.
[57:43] So they're going to move forward with their program.
[57:44] That program differentiates from perhaps the Monterosa and Bio
[57:48] Age programs and that is highly brain penetrant.
[57:52] They are not going after cardiovascular outcomes in terms
[57:55] of an indication, but they are going after obesity.
[57:58] You know, we'll probably get some data early next year.
[58:01] But that being said, interesting in terms of what's happening in
[58:05] the NLRP 3 space. We might have a minute, Paul, if
[58:08] you want to touch upon like some CNS news.
[58:14] Oh sorry, I was on mute. Yeah, really quickly this map
[58:17] like data came out in schizophrenia for their M1M4
[58:20] drug. It did not show the same
[58:23] efficacy as Cobenthe. It did not show the efficacy
[58:26] statistically of AQD formulation, which I think was a
[58:29] hope for differentiation. Tolerability was was a little
[58:32] bit better, retention was a little bit better.
[58:34] But you know, the stock sold off really significantly.
[58:37] It has bounced back some. You know, I think it raises an
[58:40] interesting conversation just in CNS in general.
[58:43] And like, you know, outside of just the whole stock
[58:45] expectations game, like how much how important is effect size and
[58:49] and what does drive commercial success?
[58:52] I would argue effect size is not the best correlate of commercial
[58:55] success in almost any neuroscience category.
[58:59] Like outside of a crevis and Ms. like just look at psych, look at
[59:02] epilepsy, honestly, look at Ms. even before a crevis launch,
[59:06] right? I mean, it really wasn't an
[59:07] efficacy driven market. But you know, for map light, I
[59:10] mean, it's it's it's tough when you don't meet expectations.
[59:13] You know, I think the next question kind of going forward
[59:15] for them as they move forward in Phase 3 is, you know, how does
[59:17] the Alzheimer's psychosis data look for cobenfi and for
[59:20] Maplite? I think in ADP there's much
[59:22] greater room for Maplite to differentiate given like the
[59:25] dosing dynamic with cobenfi. And I think there's reason to be
[59:28] optimistic. They're at least cautiously
[59:30] optimistic that muscular NX, you know, may work in ADPI.
[59:33] Think a lot of antipsychotics probably do work, right, but are
[59:36] limited in their utility because of the black box from Iridium
[59:39] mortality. But these studies are not
[59:41] without risk, right? So we'll kind of have to see.
[59:43] And we'll get that data from Cobenfi.
[59:45] I think Bristol pushed it to to next year and then map lights
[59:47] next year as well. And I'll just briefly mention
[59:50] that Nomura Therapies, which I mentioned earlier does have
[59:52] their own muscarinic franchise. It's M4 Pam based and we are
[59:56] going to get updates later this year.
[59:59] Well, that's all the time we have for today.
[1:00:02] Thanks again for those who tuned in live and in signing off.
[1:00:05] My best to everyone on a great summer weekend and my cohosts,
[1:00:07] Tim, your own Paul and Brian and I hope that you'll join us on
[1:00:11] our next biotech hangout. Thanks everyone.

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