# Episode 168 - January 9, 2026

An episode of [Biotech Hangout](https://invisiblenetwork.ai/podcast/1568911820), 9 Jan 2026, 1 h 01 min.

Audio: https://anchor.fm/s/55bdff38/podcast/play/113762473/https%3A%2F%2Fd3ctxlq1ktw2nl.cloudfront.net%2Fstaging%2F2026-0-9%2F415821361-44100-2-404d6edf5e356.m4a

On this week’s episode, Sam Fazeli, Paul Matteis, Brian Skorney, and Tess Cameron discuss biotech market sentiment and the sector’s strong momentum heading into JPM and 2026, with expectations for increased M&A activity. They note that companies showing strong fundamentals have been rewarded, while policy uncertainty remains a risk. The group also overviews the HHS decision to revise pediatric vaccine recommendations -- removing 17 of the 11 previously recommended shots -- and its potential impact on public health and the sector. The conversation shifts to the first IPO of 2026: Lilly-backed Aktis Oncology, which raised $318M. The co-hosts then discuss rumors of AbbVie or Merck purchasing Revolution Medicines, with Merck potentially paying $32B -- a positive sign for industry deal-making. On the data front, Zenas Biopharma’s Phase 3 trial of obexelimab for IgG4-RD met its primary endpoint, while Ultragenyx shared updates on setrusumab for Osteogenesis Imperfecta. The group also highlighted Neumora’s Phase 1b Alzheimer’s agitation results, noting cautious optimism. The episode closes with discussion on late-stage success for Alumis’ envudeucitinib in plaque psoriasis and obesity updates, including Novo Nordisk’s oral GLP-1 pill and Arrowhead’s significant raise. *This episode aired January 9, 2026.

## Transcript

[0:00] You're listening to Biotech Hangout, a live and and edited
[0:03] weekly discussion of all the all the we try latest news in our
[0:08] industry with a group of biotech insiders.
[0:11] I'm Sam Fazeli and my Co host today are Brian Scorney, who's
[0:15] here. We are still waiting for Paul
[0:17] Matisse and Tess Cameron. For more information about our
[0:21] hosts and guest speakers or to listen to the most recent
[0:25] episode, please go to biotechhangout.com.
[0:29] And a happy new year to everybody.
[0:31] It is my pleasure to open the first session of the year.
[0:38] So we're looking for, looking forward to enjoying a whole new
[0:44] 2026 full of energy, hopefully the same pace that it started
[0:49] the year. So normally we start with
[0:54] politics, market sentiment, etcetera.
[0:56] So let's just let's just do that exactly that.
[0:59] So XPI is up for the obvious reasons because it's been M&A
[1:05] deals and we've had an IPO that by all the intents and purposes
[1:09] is successful, which is great news.
[1:12] And and we talk about the M&A etcetera.
[1:16] And, and we're on the, I could say the eve of JPM because we
[1:20] won't be from, from a, from a working day perspective, we're
[1:23] close to the on the eve of JPM. So, Brian, did you want to just
[1:28] quickly catch us up on how you feel the year has started off
[1:33] off in terms of your your what, what you've been seeing, the
[1:36] data you've been seeing and the news that you've been seeing?
[1:39] Yeah. So, you know, I think I think it
[1:40] started off a little bit manic as one is kind of used to with
[1:46] the biotech tape. You had some big
[1:49] underperformance days, some really big outperformance days.
[1:53] Yeah, we're one week into the air and, you know, we see some
[1:56] some modest outperformance for the XBI, but you know, could
[2:00] have looked another day and and you would think it's it's a slow
[2:03] start to the year, at least in terms of where where the
[2:06] market's going. You know, I think sentiment is,
[2:08] is is good overall. I mean, we had a, you know,
[2:12] really monster last four or five months to the year.
[2:14] And I think people have a mix of hope and a mix of confidence
[2:20] that we're going to see to some extent continuation there.
[2:23] And I've spoken a lot about this.
[2:24] I'm pretty bullish on 2026 as a whole.
[2:27] I think, you know, the, the sector's certainly not an
[2:32] expensive sector relative to a lot of other parts of the equity
[2:36] markets. And you know, I think we've seen
[2:39] a lot of data catalysts, a lot of MNAA, lot of enthusiasm
[2:43] really play out here. You've talked a lot about drug
[2:45] pricing reform. So, you know, we, we have like
[2:47] our sector preview out today and, and you know, we go through
[2:50] a lot of these things and I think, you know, I know that I
[2:54] particularly have some very unique view, but I think sort
[2:58] sort of my view and, and you know, quote, quote, the, the,
[3:01] the average consensus view among investors as it's, it's going to
[3:05] be a good year for our performance of, of biotech.
[3:08] And look, I mean, we've seen, we've seen a pretty busy week.
[3:11] You know, one of the comments we've sort of had internally is,
[3:14] you know, it seems like things get pulled forward earlier and
[3:17] earlier in the year. Obviously JPM is sort of the,
[3:21] the pilgrimage that we all make to start the year and, and get
[3:26] updates. And you know, it's probably a
[3:27] few years ago where people started announcing things
[3:30] earlier than JPM. But you know, this kind of the
[3:33] first year and, and you know, I haven't put together date on
[3:36] this specifically to say this, but it feels at least from an
[3:41] observer perspective, they've just seen a lot more deals also
[3:44] occur, you know, versus we used to see a lot of follow ONS
[3:48] really get priced after JP Morgan.
[3:50] So you know, maybe in addition to to people feeling that they
[3:54] want to have it be early on the curve on the news, it seems like
[3:58] companies are are also looking to be early on, on the follow on
[4:02] front. Certainly, I imagine we'll,
[4:04] we'll continue to see a lot of deals over the next 2-3 weeks.
[4:07] And you know, at some point they'll probably be a level of
[4:10] investor exhaustion. I know talking the buy side, I
[4:12] think they're, you know, they're pretty much busier this week
[4:15] than maybe they traditionally are.
[4:18] Well, that's great news, I think and you know, as you said, XBI
[4:22] is trading at where are we at now 2125 spot 5/3 on my
[4:28] terminal. And the last time we were around
[4:31] this level was the 10th of November 2021.
[4:35] And that was us coming still coming off the excitement of of
[4:39] COVID and that COVID is going to make everybody really super
[4:43] appreciate the Pharmaceutical industry, which didn't quite
[4:46] happen and it kind of went in the opposite direction.
[4:48] Tess and Paul, very nice to see you here.
[4:50] I was beginning to sweat under the color a little bit.
[4:53] So do you want to guys take turn or ladies first Test and then
[4:59] Paul on in in the general topic about how you're feeling for the
[5:03] year. I mean 9th of January test.
[5:06] Yes, absolutely happy to, you know, I think, I think feeling,
[5:12] you know, feeling relatively positive, you know, I think that
[5:17] we've, we've seen a lot of really strong fundamental
[5:20] progress in 2025 that, you know, that drove valuations.
[5:25] Our team is actually going to be coming out with a, you know,
[5:28] with a report over the next day or two that summarizes some of
[5:31] our, you know, overarching thoughts about the sector.
[5:35] But you know, what you'll see in that report is if we look at the
[5:38] returns for 2025, M&A certainly contributed to returns, but the
[5:45] returns were actually really strong.
[5:46] Even if we take out M&A, which is obviously you know something
[5:51] that's that I think is, is really important and really
[5:53] encouraging is that, you know, companies that made strong
[5:57] fundamental progress were rewarded.
[5:59] And so you know, I'm hopeful that that theme, you know
[6:02] contributes, you know continues this year.
[6:05] Maybe you know, hopeful is a better word than than
[6:08] necessarily optimistic for me. You know, we do have, you know,
[6:14] we do have continued policy overhang, right.
[6:16] We saw the CMS a demo come out with, you know, with MSN.
[6:20] I'm sure, you know, that's probably going to be litigated.
[6:22] We'll we'll likely have to see how how that plays out to see if
[6:26] that you know is, is, you know, introduced and really comes into
[6:29] play as a pricing, you know, as a pricing risk.
[6:33] I think that likely impacts, you know, companies with existing
[6:38] products more than companies that are that are launching new
[6:41] products and and really have yet to make a pricing decision.
[6:44] But I think that is is probably the major, you know, the the
[6:49] major kind of continued unknown variable in in 2026 is is what
[6:54] could kind of pop up from a from a policy standpoint that could
[6:57] that could surprise to the downside I think.
[7:00] You know what's interesting about?
[7:01] Progress is is very encouraging and and companies are really
[7:05] well capitalized to to keep advancing.
[7:07] And what's interesting is that the the stocks stock prices
[7:10] didn't button earlier to that. And you know, I mean, I've, I've
[7:14] gone on record saying that I think the the MFN dust has
[7:18] settled. Maybe that was premature, but
[7:21] they did, you know, no, but not nothing happened.
[7:23] The market just moved on. So that I found.
[7:27] I found that. Interesting.
[7:28] It it really is. And and it makes me maybe other
[7:32] people have different perspectives.
[7:33] I think that could be for one of two reasons.
[7:35] One reason could be that people look at that and they're like,
[7:38] yeah, whatever. It's like, not actually going to
[7:40] happen and not actually going to get implemented, which is a bit
[7:43] like the, the Taco trade, you know, the the Taco trade thesis.
[7:48] And then I think there is another perspective that I don't
[7:53] think is the right perspective, which is like, Oh, well, if this
[7:56] gets implemented, it's not really any problem.
[7:59] Because maybe, you know, companies in the US are just
[8:02] going to, you know, raise their drug prices in the US for to
[8:04] compensate for the fact that they are no longer going to
[8:07] launch in Germany. Because, you know, the German
[8:10] price would, you know, have too much of an adverse impact on
[8:14] their on their price in the USI don't necessarily agree with
[8:17] that perspective. I don't think that any US
[8:20] pharmas or biotechs are really leaving, you know, a lot of
[8:23] pricing room on the table in the USI think they're, you know,
[8:26] trying to price what the, you know, what, what works
[8:29] efficiently from a market, from a market perspective.
[8:32] So I, I think that that has yet to, you know, the, if MFN
[8:36] actually becomes a thing, you know, I think we might see some
[8:41] surprises, but you know, perhaps the lack of market reaction just
[8:45] indicates that there's little expectation that, that that
[8:48] would actually be implemented. Right, Paul, you're have a go at
[8:54] your start of the year, came back with a with a major
[8:59] excitement all around. Yeah, no, great, great week.
[9:03] Hey, good to see everybody. Sorry, I had to re download the
[9:07] X app and then do a forgot password.
[9:09] It's always pleasant to do that at 11:59.
[9:11] So my bad. But yeah, good to see everybody.
[9:14] I mean, I think like it's hard not to feel mostly optimistic
[9:17] for the year, right? It feels like we're in a good
[9:19] place of strength in the sector. Going to see more M and A right.
[9:22] I mean, I you know, I sound like the cliche sell side animals,
[9:25] right, bullish, more M and A but in general, like I really feel
[9:28] that way. I think, Tess, what you're
[9:29] talking about is interesting because I just think at this
[9:32] point, like investors, right or wrong, have become so jaded to
[9:36] drug pricing headline risks that that probably is a real risk to
[9:40] the downside. Because I think it takes a lot
[9:42] now to get people to take something like that seriously,
[9:44] but something significant comes along.
[9:46] I mean, I think that really could take the wind out of our
[9:48] sails. But I mean, separately, like,
[9:50] you know, I feel good about a lot of companies in my coverage.
[9:53] You know, I think we're continuing to see strong, strong
[9:55] commercial watches from the big guys, data sets getting
[9:58] rewarded. So, you know, we'll see how JP
[10:00] Morgan Monday looks. Maybe the Rev Med deal take some
[10:02] pressure off of needing like some big M&A.
[10:05] But but yeah, I mean, I sort of agree with what everyone said.
[10:09] I just wanted to add another, you know, a couple other data
[10:11] points that that are going to be coming out in our in our report.
[10:15] I think something else that's that's really important for the
[10:17] performance in 2025 is that it was not like indiscriminate
[10:22] performance, right? It was not consistent across the
[10:25] whole sector. It was really driven by strong
[10:30] companies. And we will often do this
[10:33] analysis where we compare companies that had specialist
[10:37] investors, you know, versus companies that didn't right.
[10:40] And you assume that maybe there's a bit more, you know,
[10:44] selection, you know, specialists are, you know, doing a lot of
[10:47] fundamental diligence and, and maybe that's a way that you can,
[10:50] you know, have some indicator of quality.
[10:52] Obviously, there's there's some companies without specialist
[10:55] investors that have performed well.
[10:57] But when we look at the performance of those that had
[11:00] specialist investors versus didn't, you know, there was
[11:04] still a lot of like discrimination in the market and
[11:08] there were a lot of companies that like really didn't perform.
[11:11] And you know, fortunately the companies that did perform
[11:14] really drove the outperformance of the sector.
[11:16] But I think that again speaks to, you know, overall, overall
[11:21] sector, sector health. Yeah, of course we'll get to
[11:26] talk about the, the, the, the rooted.
[11:28] I don't want to rumor deals. We, I, I have to choose my words
[11:32] very carefully. Of course, we all do Revolution
[11:36] medicine, Merck, etcetera. So let's just before we go there
[11:39] on the policy side of things, Tess, I think you wanted to
[11:42] raise the subject, which is I'm very passionate about myself.
[11:46] But it gets, you know, you, you start, you start losing the, the
[11:50] will, the energy to keep talking about this.
[11:52] And that's the pediatric vaccines developments in the US.
[11:57] Absolutely. Yeah.
[11:59] So this was an update from the CDC where the CDC removed 6
[12:03] vaccines, you know, from the recommended list.
[12:06] And they did that without any ASIP discussion or
[12:09] recommendation. So that was, you know,
[12:12] rotavirus, COVID vaccine, influenza, meningococcal,
[12:17] hepatitis A, hepatitis B, all of those got removed, HPV down to a
[12:23] single dose. It's kind of like, where did
[12:24] this, you know, where did this come from?
[12:26] And like, is ASIP doing anything?
[12:30] You know, no, no, fortunately, like there's a, there's a couple
[12:33] ways where you could say like, wow, OK, this, you know, it's
[12:35] going to have a negative impact, you know, certainly on just
[12:39] what, you know, what parents are actually seeking for their
[12:43] children. But then also insurance
[12:45] coverage. I think importantly there isn't
[12:48] any change, you know, or at least we don't anticipate any
[12:51] change to insurance coverage for those vaccinations.
[12:56] But this, you know, this could absolutely have an impact on
[13:00] just vaccination rates. And you know what, what what
[13:05] parents are are getting for their kids, as you say.
[13:08] And as you know, as Paul has said, you know, it seems like
[13:11] everyone's just kind of like, Oh my gosh, like, you know,
[13:14] another, you know, another kind of vaccine recommendation that
[13:22] isn't scientifically based. Maybe we're getting, you know,
[13:26] maybe we're getting a bit immune to that.
[13:29] But it, it is like, you know, it does really 'cause me to
[13:33] question like what, what, what does it take for us to remember
[13:37] that these are, these are real risks, right?
[13:39] And these are, these are real risks, you know, not just to our
[13:43] sector, but these are real risks to, you know, to public health.
[13:46] So, you know, yet another, you know, yet another change
[13:50] introduced from a stock standpoint, you know, you saw a
[13:53] backside I think actually go up on the day, you know, because it
[13:56] kind of removed a worst case scenario of pneumococcal, you
[14:00] know, pneumococcal potentially being in that list.
[14:03] You know, that was going to be taken off the, that was going to
[14:05] be taken off the schedule. Yeah.
[14:08] I mean, the, the, the one thing I think is at least worth saying
[14:12] is that it's not the worst set of recommendations in the world.
[14:16] It's pretty much in line. I haven't done a line by line
[14:20] comparison with what what happens in Denmark.
[14:23] So, you know, I don't, I don't, I think that's, but Denmark is a
[14:27] very different type of society to an access to Healthcare is
[14:30] very different to that in the US.
[14:33] So if if that's the intention to try and equalize it relative to
[14:38] that particular country for whatever reason, then I think
[14:41] it's missing out a whole bunch of other aspects that are
[14:44] important from the perspective of of public health and how
[14:47] public health is administered in the different countries.
[14:49] So we will wait and see. And of course the states in the
[14:53] US can have their own rules. And I think there are groups
[14:57] that have taken over like the American Pediatric Association
[15:00] from essentially ASIP, because I think a lot of people feel that
[15:04] ASIP is not at least the physician side of people not
[15:09] delivering what it used to be doing.
[15:10] So let's move on to, unless anybody wants to make another
[15:14] comment here, deals and fundraisings.
[15:17] I'm going to start with the IPO of Actis.
[15:19] I think the folks on this call weren't on the book, so feel
[15:24] free to chip in. What's interesting, of course is
[15:28] that it's a great start to to the year.
[15:31] I was a little bit surprised thinking we've got a company
[15:33] that, that has no clinical data yet.
[15:36] I mean, to have a clinical product testing phase 1B data
[15:40] expected possibly end of this year into 2027, I think is the
[15:43] target. But the Radio Ligen therapies,
[15:47] very novel approach to Radio Ligen therapies.
[15:51] So I was a little bit worried when it was when it was coming
[15:55] up and I thought, do we really want to start with this?
[15:58] Should we not have a company with a bunch of data in hand?
[16:00] But you know, hats off to them. They've done a great job.
[16:03] They they priced at $18.00. The range was 16 to 18.
[16:07] Take #1 take #2 they raised more than they expected $318 million.
[16:12] In the end is is the number I've got at least.
[16:15] And it's opened up. So it opened up at about 27 and
[16:21] it's now setting down around 2223.
[16:24] Remember $18.00 issue, all of that is, is a great sign and the
[16:28] investors are a good set of investors bringing the company
[16:31] to market. And of course, $100 million or
[16:33] so has come from Lily, given that they had a deal with the
[16:36] company. So Lily has a deal with the
[16:38] company and puts money into it. So I think that tells you a lot.
[16:42] Apparently the book was 10 times just very quickly the company's
[16:47] rate. Last raise was in in September,
[16:51] I think 2020, $475 million series BRA Capital RTW, Janice
[16:58] Henderson. And then of course, they were
[17:00] already alongside the OR existing investors 0 Price
[17:04] Avidity and Lily and the Bristol-Myers.
[17:08] So there there's a very good set of investors here, which are
[17:11] including and and also Merck venture fund.
[17:13] So approach is different. It's a radio ligand therapy, but
[17:17] it's not just any radio ligand therapy.
[17:19] They're not using existing known peptides.
[17:24] They're using a mini proteins I think they call them and they
[17:27] have a discovery platform for these mini proteins they had to
[17:31] deal with. Lilly signed on the 21st of May,
[17:33] $60 million upfront, 1.1 billion milestones.
[17:36] And we've seen the split is about 5050 between development
[17:40] milestones and commercial milestones.
[17:42] So that's, that's pretty good. And you know, it's, it's an area
[17:46] where they've shown already that in patients to get the right
[17:48] distribution into the tumors, etcetera.
[17:50] And the first one they've got in the clinic is an Ectin 4, which
[17:54] we know that if you attach a drug to it in the form of
[17:57] Patsev, you got really good quality results in.
[18:01] I mean, it was a revolution essentially in bladder cancer
[18:03] when it first reported out. So everything's good here.
[18:08] Let's just hope that the data continues to be good.
[18:10] One little thing that I've been looking around for, which is
[18:13] anti drug antibodies. These are these are designed
[18:15] proteins, novel proteins, 50 to 75 amino acids apparently.
[18:20] And I couldn't find any information on that.
[18:21] But you know, the banks on the deal.
[18:23] I'm pretty sure I've done the due diligence and we're at least
[18:26] comfortable with what they've seen so far.
[18:27] And given the investors going in, it gives me hope that
[18:30] that's, that's nothing to worry about.
[18:33] So and then of course we have a bunch of MNA.
[18:36] But before I move on, did anybody want to say anything
[18:38] about this IPO? I take silence as a no.
[18:44] I'm going to carry on. And of course we've got the
[18:45] revolution medicine now. It's a company that we've held
[18:51] with high regard at NRBI Research.
[18:55] As you all know, we don't do buy, sell, hold recommendations
[18:58] or any price targets or anything like that.
[19:00] But we've done a very deep analysis of the K Ras data set,
[19:06] Ras data set evolution medicine is is that's their focus and
[19:10] they have a very powerful engine in terms of developing these
[19:12] novel agents. The drugs, theirs and the other
[19:15] drugs that are coming up from Rosh Nilly Merck are potentially
[19:21] better than, well, they are better in terms of the evidence
[19:23] and data that we're seeing, efficacy data and safety profile
[19:27] potentially than the first generation would say from now.
[19:31] Bristol, which was Mirati and Amgen.
[19:36] So the, the news was Avi is looking to buy and I think that
[19:41] was Wall Street Journal a couple nights ago.
[19:43] And remember, I'm in Europe. So things tend to end up being
[19:47] nights for me. And then that came from Wall
[19:52] Street Journal. And I think Bloomberg then
[19:54] phoned them up and, and they said, no, no, we're not in
[19:56] discussions. Those are the phrases.
[19:58] I don't know what that means. And then the next day Financial
[20:03] Times is reported that Merck is in discussion.
[20:06] So, and the price they've mentioned is 28 to $32 billion,
[20:10] which is a pretty hefty price by looking at EV to save multiples
[20:15] of recent deals and oncology deals going back to Aloxo and
[20:20] Array all the time ago. So whatever method you use to
[20:27] compare the valuation, that would be a rich valuation if
[20:30] that ends up being the case. But as as enthusiasts for the
[20:34] biotech sector, if America's prepared to pay that, then
[20:37] that'd be great because there's a pile of cash coming into the
[20:41] sector. And the history and story of
[20:45] Revolution Medicine is interesting because remember
[20:47] there was a, a deal they did, they did with Eco RX where they
[20:52] took the cash from that company emerged and, and, and funded
[20:56] their, their pretty hefty R&D efforts here.
[21:00] So before I move on, does anybody want to comment on that?
[21:05] I think, I think, I can't imagine anybody would, would
[21:08] disagree that this would be good for the sector.
[21:12] No disagreement. No disagreement.
[21:15] That's good. Can we just keep it like this?
[21:18] And what's interesting, of course, is that one of them, I
[21:20] mean, their key asset is a pan Ras inhibitor that they've got
[21:24] their Axon recipe. And then just a couple of week
[21:28] days before or a week before, I can't remember exactly, it's
[21:30] been such a hectic week. AstraZeneca announced they did a
[21:34] deal with the China's Jacob Bio with 100 million upfront and up
[21:38] to close to $2 billion of milestones for a pan Ras
[21:42] inhibitor on which we haven't seen a huge amount of data.
[21:45] It's, but I'm assuming that there's data in house and that's
[21:49] seen just the same as these M&A deals.
[21:52] So that's looking pretty good. And but that then you have to
[21:56] say, OK, well Rev Med's obviously a lot further.
[22:00] They've got products in phase, the drugs in phase three,
[22:02] particularly pancreatic could be on the market in a in a couple
[22:05] of years where there is massive unmet need.
[22:10] So and then of course the last deal that happened was Lily
[22:14] VTYX, which actually happened. So these are the this revolution
[22:18] one is, is a rumor, whereas Lily announced the deal and I guess
[22:24] this goes to what was it, was it Brian or Paul said that things
[22:27] seem to be coming forward. The deal was announced before
[22:29] JPM, but I think that might be because there was some rumors on
[22:33] the market on that. Yeah, I meant more on the
[22:35] secondary offering side. But yeah, I mean the point
[22:37] probably holds on MNA. To yeah, I mean usually they
[22:40] wait for JPM to give it a bit of extra, extra boost, right.
[22:46] Anyway, so, so anything else anyone wants to mention on the
[22:50] deal side? I think there's been quite a lot
[22:51] of follow ONS, as you said, Brian.
[22:55] Is it possible that's going to end up being the the strongest
[22:58] first week of January in follow on land?
[23:00] I don't know. It's a yeah, I mean, it's a it's
[23:03] a lot of money that's got that's gone around and and, you know,
[23:05] it's notable. I think, I think they're all
[23:08] meaningfully up from from price. I mean, I know, you know,
[23:11] looking at the, the names that are on my list that had deals
[23:14] this week, they're all, you know, double digits.
[23:16] I mean, and both and, and all of the names were able to upsize.
[23:20] Imagine the shoes are exercised on all of them.
[23:22] So, so you know, I mean, I think follow on performance is a great
[23:25] indicator for the level of enthusiasm there is out there.
[23:28] Certainly there's capital to get to work.
[23:31] Yeah. So since you've got the mic,
[23:33] we're going to move to data and you've got, I call it kinetics.
[23:37] I don't know if it's Kinetics Pharmaceuticals.
[23:40] Nice share price chart I'm looking at here.
[23:42] A big jump in the new year. Tell us what's going on.
[23:44] There yeah. So I mean I think this is you
[23:46] know one of the interesting case studies to to kind of prove my
[23:50] point that there is both data pulled forward and and the
[23:52] following pull forward. So they you know they early
[23:55] announced the metrics on their Pulsanify launch.
[23:58] This is a new drug that was approved second-half of 2025.
[24:05] This is really the first, first quarter of sales and we had, you
[24:09] know, very, you know, a couple of weeks of data when they
[24:12] announced third quarter. So fourth quarter sales the
[24:14] first quarter and it's you know, really outperformed the
[24:18] consensus number. I think, you know, we we had
[24:20] wrote up probably more important like we think it that really
[24:24] outperformed in terms of the number of enrollment forms that
[24:26] 200 enrollment forms, which is a very robust for, for this size
[24:30] indication right now. You know, and I think it's, you
[24:33] know, you're seeing people revise their models upwards, you
[24:35] know, outperforming launches are always ways for stocks to go up.
[24:39] But you know, they also topped it off that they had some pretty
[24:43] impressive data from an additional cohort of a phase two
[24:45] study they're running in congenital adrenal hyperplasia.
[24:50] You know, the data looked really impressive on both biomarkers
[24:53] and reduction of of glucocorticoids, which are, are
[24:56] the standard of care that, you know, obviously carry a high
[24:58] doses, very significant side effects and you know, part of
[25:01] this disease. The goal is to to get patients
[25:04] to to lower levels of glucocorticoids.
[25:07] You know, I think part of the story here is Neuropran has a
[25:10] drug chronicity that's launched really well in chapter also, you
[25:13] know, I think outperforming expectations by meaningful
[25:16] amount. So you know, people are looking
[25:17] at this data and saying there's really good competitive data in
[25:20] an indication that seems to be larger than than people
[25:23] expected. So, you know, I think chronic X
[25:26] use the opportunity to, to raise additional cash.
[25:30] You know, again, it's right now it's trading about 21% up from
[25:35] the offer price. So you know, in four days time,
[25:38] 3 days time, that's a that's a pretty good response to a follow
[25:42] on. Yeah, well, it's not all been a
[25:46] bed of roses, right? So Tess is going to talk to us
[25:49] about Zenith. And then at the back end of last
[25:55] year we had Ultra Genics. So Zenith is, is is interesting
[25:58] because the the press release had a positive headline and then
[26:03] the share price collapsed. So talk us through that.
[26:07] Absolutely, Yeah. So maybe maybe just starting
[26:10] with, you know, Zenith and a bit of an overview of what they
[26:13] have. So, you know, 'cause there was a
[26:15] lot of excitement, I think coming into the readout that
[26:18] they shared at the beginning of this year, you know, which they
[26:22] have a drug for IgG 4 related, you know, related disease.
[26:29] And this is, you know, essentially a, a CD19, you know,
[26:33] factor 2B, you know, factor 2B drug.
[26:37] And so the, the pitch is that, you know, hey, you're, you're
[26:40] actually targeting, you know, the, the CD9 T cell is the CD
[26:45] 19, you know, expressing plasma cells, but also some of these,
[26:49] you know, some of these earlier, you know, some of these earlier
[26:51] cell types like like plasma blasts.
[26:54] And, you know, the, the pitch was that this Co engagement, you
[26:58] know, could potentially make this drug more potent than, you
[27:03] know, a drug like Upliznet, which is, which is really just
[27:06] focused on CD19. You know, I think the, the cross
[27:10] trial comparison, you know, ended up, you know, ended up not
[27:14] looking as great, right. So when you looked at, you know,
[27:17] flares, which is I think what a lot of people were focused on
[27:21] the zenith, this drug, sorry, I just want to make sure I
[27:28] pronounce it right. Obexelumab.
[27:30] So obexelumab when you looked at their flare reduction, it was
[27:33] about 56%. But then if Blizzna has
[27:38] something closer to 87%. So I think, you know, I think
[27:42] there was, I think that's where a lot of the the disappointment
[27:44] came from was this focus on on flare reduction.
[27:48] And, you know, what does this mean for, you know, from a
[27:53] competitive landscape standpoint?
[27:55] And, you know, I think, you know, once the baseline
[27:58] characteristics came out, there wasn't, you know, anything that
[28:00] really stood out as explaining, you know, why that would be, you
[28:04] know, why that would be, you know, meaningfully different,
[28:07] You know, so they, so the companies, you know, they're
[28:09] moving forward, you know, and they have a filing that's that's
[28:12] actually coming up, you know, they're going to be filing in
[28:16] the, in the USFDA. And, you know, EMA and I think
[28:20] they're, you know, they're excited to, they're excited to
[28:23] bring this forward. And, you know, it'll be a
[28:26] question of, you know, what they point to and, and really how
[28:29] they compete, how they compete in the marketplace.
[28:32] They do have, you know, they they are focused on just, you
[28:38] know, a weekly sub Q dosing and you know, that's, that's
[28:42] certainly a differentiation from from mood plosness.
[28:45] So you know that'll be you know that'll that'll certainly be
[28:49] worth watching. Sorry, couldn't find the mute
[28:54] button. Yeah.
[28:55] So did you want to also just talk about ultra genics?
[28:57] And then I'm going to ask you to talk about some positive stuff.
[29:00] Yes, absolutely. So you know, this, this, you
[29:04] know, probably feels like ages ago for everyone because we had
[29:08] the we had the Christmas break and everything like that.
[29:12] But actually over the with the holidays, ultra Genex, you know,
[29:17] released a very highly anticipated, you know, trial,
[29:21] you know, trial results for cetirizumab, which is their drug
[29:25] for osteogenesis and perfecta. And if you recall their whole
[29:28] thesis, you know, force the Theresa map was there was this,
[29:32] you know, pretty, you know, pretty phenomenal, you know,
[29:36] pretty phenomenal data that they had observed in, you know, I
[29:41] think a phase two study that showed, you know, pretty, pretty
[29:47] awesome fracture risk reduction as well as BMD changes and what
[29:53] was really a surprise from the Citrismab study.
[29:56] So if you recall, this study was structured with a number of
[29:59] interims. And so there was an interim one
[30:01] that you know, was maybe going to read out in the first part of
[30:04] the year. There was an interim 2 that was
[30:06] around mid year. And then this was really the
[30:08] final analysis and they actually had two trials going and it was
[30:13] kind of sequenced depending on, you know, whether he's interim
[30:17] set. And you know, the final analysis
[30:20] in the one trial how they would look at, you know, the the other
[30:23] trial, one being a trial that that compared to placebo and the
[30:27] other being a trial where they were looking, you know, versus
[30:29] bisphosphonates also in, in different, you know, in
[30:32] different osteogenesis and perfecta patient populations.
[30:36] And the, the first interim did not hit the second interim, you
[30:41] know, did not hit either. So, you know, expectations were,
[30:46] were certainly lower going into this result.
[30:48] But, but nonetheless, you know, I think there was, you know,
[30:52] there was a surprise just to see that, you know, the, the
[30:56] endpoints, you know, the, the endpoint on fracture rate did
[31:03] not, you know, did not materialize.
[31:05] So there was not statistical significance.
[31:08] There were secondary endpoint improvements in bone mineral
[31:11] densities and the safety profile looked pretty consistent with
[31:15] what they had before. So, you know, I think it'll be
[31:18] very interesting to better understand, you know, these data
[31:23] and you know, understand what, you know, what the path forward
[31:27] is in terms of, you know, Ultra Genex discussing with the with
[31:31] the FDA. I think we're anticipating, you
[31:34] know, we're hoping for an update around, you know, JP Morgan just
[31:37] to just to get some more details on the potential, on the
[31:40] potential path forward here. And so not now on to something
[31:44] good with the share price direction went in the opposite
[31:46] direction test was obviously Monterosa with their data and
[31:52] one of those followers that Brian was talking about.
[31:55] So do you want to just touch on that before I move on to Paul to
[31:58] talk about Nomura? Yes, absolutely.
[32:02] So I think, you know, the Monterosa came out, Monterosa
[32:06] data came out, they were pursuing a next 7 degrader.
[32:11] And you know, this this was is you know, the the they were,
[32:17] they were looking at this in healthy volunteers.
[32:20] But you know, the potential market opportunity is a pretty,
[32:23] you know, it's a pretty big, you know, market opportunity because
[32:26] it's, you know, it would essentially be going after
[32:28] cardiovascular risk, right? So ASCPD very big market.
[32:32] You can think of this, you know, as a drug that would compete
[32:36] with tourmalines drug, right? The the Illinois 6 Nova Nordisk
[32:41] also has an IO 6. I think we're expecting outcomes
[32:43] data for IO6 coming out around, you know, potentially,
[32:48] potentially later this year from Nova Nordisk.
[32:52] And it was it was really impressive to see, you know,
[32:56] some of the biomarker impacts of their next 7 to greater.
[32:59] So they had a, you know, what's, what's, you know, HSCRP
[33:06] reduction that came in around 85%.
[33:11] And I think the IL 6 were, you know, were, were were something
[33:14] around 65%. So, you know, this was quite
[33:17] interesting. And then we also saw Speaking of
[33:20] Speaking of CRP reductions, Ventex, right, Speaking of CRP
[33:24] reductions and, and Speaking of, you know, deals, we, you know,
[33:30] Ventic, Ventic showed a CRP reduction that, you know, was
[33:33] also in that range. So I think this you know, was
[33:37] obviously a really, you know, big positive for for Monterosa
[33:41] that's, you know, clearly found, you know, really interesting and
[33:45] attractive market for their technology here.
[33:51] Thanks for that. Do we have Paul back on?
[33:55] No, it doesn't sound like it. So I'm going to.
[33:57] I was going to be old nice and not go straight to myself again,
[34:02] but he's not on. Let me just check again.
[34:03] Paulie there. No, he's having trouble with his
[34:06] ex today, so never mind. I'm.
[34:09] Sure. Hey, Stan, can you hear me now?
[34:10] Here you are. Yes, yes, Nemora and GH
[34:13] research. I don't know what the deal is
[34:15] man. OK, thanks.
[34:16] Yeah. Well Nemora had an interesting
[34:18] week because of the Ventex take out and the stock reacted well
[34:22] to that as you would expect because they have an NLRP 3 as
[34:25] well with with some data later this year.
[34:27] But earlier this week, they put out data for their V1 AR program
[34:31] in, in Alzheimer's agitation that from my discussions with
[34:35] investors, I think has been kind of seen from a couple different
[34:38] angles, some that some of you had optimistically, some of you
[34:40] had skeptically. Essentially the study showed a
[34:44] small trend for their drug versus placebo on an agitation
[34:50] scale. Alzheimer's agitation is like a
[34:52] huge unmet medical need probably, which goes goes
[34:55] without saying, super tough to treat, right?
[34:57] Really hard to have a drug that can kind of help patients feel
[35:00] less agitated, but also, you know, sort of thread the needle
[35:02] on like side effects and things like autonomal and sedation,
[35:05] things like that. So the opportunity here, if they
[35:07] can get it right, is enormous. But on the primary sort of
[35:11] outcome, right? And again, this wasn't powered,
[35:13] you know, the effect size wasn't huge.
[35:15] And also like this, the data as it was shown was not totally an
[35:19] intent to treat data set with all patients.
[35:21] They did talk about a subset that they were excited about in
[35:24] patients with elevated levels of anxiety where the effect size is
[35:28] potentially bigger. They talk about that aligning
[35:31] better with the mechanism. I, I would say from being
[35:35] someone who's followed a lot of these psychiatry readouts over
[35:38] the years and has gotten excited about things that look promising
[35:40] early and don't hold up. I almost feel like in neuro
[35:43] psych and I would include agitation in that bucket.
[35:46] Like you kind of want data in a phase 1B study that is super
[35:50] clean because you kind of have to bank on there being, you
[35:53] know, some meaningful level of regression in your effect size
[35:55] in future trials. So our interpretation here was
[35:58] was somewhat more cautious, but you know, I mean, given given
[36:02] the upside opportunity, it's certainly understandable why
[36:05] they try to pursue this signal further.
[36:09] And then, you know, I think the other interesting news this week
[36:11] and you know, I can probably also comment on another
[36:13] psychedelics name as well, came from GH research who has one of
[36:19] the best data sets we've seen for any psychedelic in treatment
[36:22] resistant depression. They are developing A inhaled
[36:25] formulation of five Mio DMT and they put out their data about a
[36:29] year ago that had a 15 point difference between drug and
[36:33] placebo in the Madras. You know, for context, the
[36:35] average drug has about a three-point difference.
[36:38] Certainly that study comes with some caveats.
[36:40] It was not a huge trial. Placebo effects were modest.
[36:43] And I think people wonder with a lot of these psychedelic trials
[36:45] around functional unblinding. But the data looked really,
[36:48] really good. And from an efficacy
[36:49] perspective, it looks fairly de risk.
[36:51] They had run into this very odd situation on an FDA clinical
[36:55] hold where they had already run multiple clinical trials outside
[36:58] of the US, including this large phase 2B that even had an open
[37:01] label extension. And yet the FDA kept holding
[37:04] them up from filing an I and D due to this rat tox issue that
[37:09] there was a lot of precedent that this may have been a rat
[37:12] model specific issue. They did a dog tox model that
[37:15] looked clean. And so they finally got this off
[37:17] hold and are ready to advance into phase three.
[37:21] You know, as if it's not already clear, like we think this is a
[37:23] super promising approach. And I just think broadly
[37:25] speaking for psychedelics, like we're seeing now Spravato from
[37:29] J&J move towards being a three to $4 billion drug in the next
[37:32] handful of years. And I think that really
[37:34] validates the market more broadly.
[37:36] But good setup here for GH to advance into phase three later
[37:39] this year. You know, the next catalyst in
[37:42] this space that we're watching is going to be the Compass data
[37:44] this quarter from their style of cyber product, from their second
[37:48] phase three and also from their long term during study.
[37:53] And that I think that durability piece continues to be one of the
[37:56] biggest questions for these next Gen. psychedelics from 2 angles.
[37:58] You know, one, I think not not to imply that the bar is high,
[38:02] but I still think it's a little bit Gray on exactly how the FDA
[38:07] is going to be interpreting durability data for these drugs.
[38:09] If you look at Spravato, it's given on a fixed interval,
[38:14] right. But these other next generation
[38:16] psychedelics are are trying to explore this idea of like PRN or
[38:19] as needed dosing, right. And I think that gets into a
[38:22] really, really interesting question of from the FDA, like
[38:24] how what what data do you need to see to be comfortable and
[38:27] sort of maintenance of benefit and how open minded are you just
[38:31] totally leave this up to physicians.
[38:32] But, you know, I mean, I think we're positively biased going
[38:34] into this compass data because we already have a decent enough
[38:37] durability evidence for South side.
[38:39] And and I also think in the real world, like a lot of these TRD
[38:42] patients will probably be getting a psychedelic on top of
[38:45] another medication like an SSRI, but certainly a really big year
[38:48] for this space. You know, instead of GH going to
[38:50] the phase three, you've got this compass pastry, you've got my
[38:53] Med phase three readouts, you've got Spravato crushing it.
[38:56] You know, so it's an area where for where for me, like, you
[38:59] know, back when Compass went public and a lot of the data
[39:02] were from these academic studies with poor placebo controls.
[39:05] Just like so many reasons to be skeptical.
[39:08] And I think at the Tide has, I'm not even talking about the kind
[39:12] of RFK bowl case. I mean, I think even outside of
[39:15] that, right, let's just assume these have to go through a psych
[39:17] division that is, you know, stringent to the normal
[39:20] standard. I still think there's a lot of
[39:21] reasons to be optimistic on this category.
[39:24] That's a perfect segue to, to Brian to talk about drug to drug
[39:29] to us. Brian, do you want to go that on
[39:31] that? I mean, I, I just have to say
[39:33] from a ticker perspective, I think it's got the best ticker
[39:35] out there bar DNA, I suppose, Brian.
[39:40] Yeah. So Bright Minds Biosciences,
[39:42] they had a new data in, in 2 two, two different epilepsy
[39:47] indications, absence epilepsy and a sort of a basket study of
[39:53] developmental epilepsies. And it's phase two, it's it's
[39:58] open label. So we're not looking at that
[40:00] placebo-controlled. And you know, I know, I think
[40:02] Paul wants to comment a little bit on, on sort of the
[40:05] consistency of, of open label data in epilepsy and, and
[40:13] decrease in seizures on an open label basis and how, how that
[40:17] corroborates. But you know, I think we thought
[40:19] looked really good. Certainly there's a number of
[40:23] programs that have have gotten approved on open label data on
[40:26] large data sets in, in DE specifically.
[40:30] And you know, we saw a very good mean reductions in the in these
[40:34] DE patients small study, but 63.3% which is certainly you
[40:39] know on the upper end, if not not the highest end of open
[40:42] label seizure reductions that that we've seen.
[40:46] You know, again this is sort of basket of different DE ES.
[40:49] And what's also interesting is we we saw very, very good
[40:53] reductions 73% in, in absence seizures, you know, which really
[40:58] hasn't been an area that that people have been focused on in
[41:01] drug development. You know, it doesn't quite have
[41:05] the same patient numbers or, or patient numbers that are unmet
[41:07] when you talk to docs about it. But you know, these studies seem
[41:10] to enroll pretty quickly. So, so I think given the, the
[41:13] relative dearth of new drugs in absence seizures, you know,
[41:17] they're planning on moving into, into two pivotal programs here.
[41:22] I think it'll be two studies for each of the indications.
[41:24] So probably four phase three studies.
[41:26] But you know, certainly the, the mechanism makes sense.
[41:29] It's another mechanism that's, that has seen recent approvals.
[41:34] We think this looks better than like bexacassarine, which is,
[41:38] you know, the, the most recent one to, to get approved in
[41:42] epileptic seizure indications. And you know, that's been
[41:45] another one. They did a, they did a financing
[41:47] on the back of it and it's sitting here today 37% up from
[41:52] the offering price of of $90.00. So, so was well received and you
[41:56] know continues to be well received in in the market.
[41:59] You know, if Paul wanted to comment a little bit, I know we
[42:01] both follow that seizure space. Yeah, I well, I just, you know,
[42:07] yeah, Brian, you know, this name a lot, a lot better than me.
[42:10] But I know that the drug and like I've been following the
[42:12] category for a while. I just thought it was like
[42:14] interesting. Like, you know, how can everyone
[42:16] hear me by the way? Yeah, you sound brilliant.
[42:19] It's just so annoying. I don't know what's going on I
[42:21] guess, sorry. You're good.
[42:24] Well, now you're not. You were doing so.
[42:27] Well, I mean, I have to say Paul's sound is the best amongst
[42:32] all of us. I need or literally have to turn
[42:34] the volume down when he's speaking.
[42:37] I'm sure he'll be back. But Brian, you've got another
[42:39] one, which is yet another positive news and yet another
[42:43] fundraise. Do you want to talk us through
[42:45] that alumus? Yes.
[42:46] So I mean there's another name like I've been really excited
[42:48] about been talking a lot about it, especially in in well, it
[42:53] was all through last year really.
[42:55] Alumus is a company developing a a novel TIC 2 inhibitor called
[43:01] Envu ducitinib. This has been like a really
[43:04] interesting process to follow through.
[43:07] So Tic two really kind of came into the spotlight from
[43:12] Bristol-Myers. They were developing a drug that
[43:14] is approved now ducravacitinib branded under the name so Tic 2.
[43:20] And it was interesting when Bristol acquired Celgene, they
[43:25] they wound up having to divest Celgene's Otezla and Amgen
[43:29] famously purchased it and Amgen's like really been
[43:33] absolutely smashing it with Otezla in plaque psoriasis.
[43:38] And, and, you know, I think a lot of us thought Otezla would
[43:42] never really be a big drug before it was approved, even in
[43:46] early days in commercial. And it's really done remarkably
[43:49] well for a drug that I would say is is not very effective.
[43:52] It's oral. So it has an advantage over, you
[43:55] know, on a convenience factor over a lot of the other I and I
[43:57] drugs that are used in the space.
[43:59] Biologics are sort of the mainstay of of post oral
[44:02] therapy. Otezla doesn't work anywhere
[44:05] near as well. Bristol chose to to divested,
[44:10] they had to do so on an FTC basis in to focus on so tic 2.
[44:14] Everyone thought so tic 2 was going to be a huge drug because
[44:17] they did head to I think there's a variety of factors there, but
[44:31] it's sort of led to a lot of skepticism about Tic 2
[44:34] inhibition as a class. And you know, I've sort of
[44:38] remained very bullish on the potential as a class and, and
[44:42] thought, you know, there's some liabilities that so Tech 2 has
[44:45] that hopefully second generation tech twos would get.
[44:47] But you know, people really had their doubts and I think these
[44:50] were compounded last year by J&J, which put out really great
[44:55] data for an oral Illinois 23 inhibitor showing efficacy on
[45:01] par with biologics. I mean, injectable aisle 23
[45:05] antibodies are really kind of the mainstay standard of care in
[45:10] psoriasis right now. So J&J putting up this really
[45:13] fantastic phase three data. And what's big selling point in
[45:16] here is sort of the high hurdles of like Pazzi 90, Pazzi 100.
[45:20] You know, you're talking about over half of patients getting to
[45:23] Pazzi 90 on icotrachinra, you know, 30 to 40% of patients
[45:30] getting fully PASI 100 scores, which is really you just really
[45:33] don't see with oral drugs at all.
[45:37] But now we've had two data points from 2 TIC 2 inhibitors
[45:40] over the last two months, both alumnus, which I think was
[45:42] really great data and Takeda with their drug Tech 279 last
[45:48] month, basically showing what I would argue is very much on par
[45:51] with Jay and Jays oral aisle 23. And I think it kind of like just
[45:55] reframes the the whole market opportunity here where we're now
[45:58] seeing, you know, these really potent TIC 2 inhibitors or or
[46:04] oral Illinois 23 inhibitors, which are showing efficacy that
[46:08] that is on par with biologics. And you know, I think that's
[46:12] creating a lot of enthusiasm here.
[46:14] I think one of the additional benefits of of all these
[46:16] mechanisms, you know, these are implicated in a lot of INI
[46:20] diseases and you know, have the potential to expand well beyond
[46:24] just sort of plaque psoriasis, which I think we understand
[46:27] they're very efficacious for now, psoriatic arthritis
[46:31] potentially moving into IBD with like ulcerative colitis.
[46:34] Bristol has phase three data with so Tech 2IN SLE this year.
[46:39] Alumus has phase two data with their Tech 2 Andrew Disit NIB in
[46:44] SLE this year. So this is, you know, really
[46:47] become a story that I think people are starting to get
[46:50] really excited about as we see the, you know, not only that
[46:53] it's matching the potential of these biologics, but really has
[46:57] the opportunity to be classes that have pipeline and a drug
[47:02] more than just the potential. It's, I think it's becoming very
[47:05] clear that they are, you know, going to expand it to multiple
[47:08] indications. Hey, Brian, with these next Gen.
[47:11] tick twos, like is is showing better efficacy enough or like
[47:15] is the problem with this not taking off really more on the
[47:17] safety tolerability side? And Otezla is less efficacious,
[47:22] but it's seen as oral and super safe and the branding is great.
[47:25] Yeah. I mean, I mean, I think there's
[47:27] an element of that. And I guess I would argue that
[47:30] the the efficacy, you know, that's probably what really
[47:33] drowned out. So take two that you just have
[47:36] so much better opportunity to go to high efficacy biologics and
[47:41] you know it. The I think tick 2, certainly
[47:44] from like the historical investor perspective, I guess I
[47:46] would argue less among the treating physician perspective,
[47:49] but sort of has this association with with Jack 2, which has or
[47:54] Jack inhibitors that have had, you know, more significant
[47:57] safety. But look, I mean, as, as we've
[47:59] seen more and more data, not just within like the tic two
[48:01] class, but within the Jack class, right?
[48:02] I mean, I mean, you know, you look at like Pfizer's first
[48:05] generation and the commercial performance there.
[48:08] And you know, you could follow that for years and be like, oh,
[48:10] it's, it's doing terrible. But like now you look at ABV
[48:13] with Rinvoq and I mean, it's like 1 of, you know, one of the
[48:15] biggest oral drugs in the world, right?
[48:16] So, so I think over time the data will has proven out that
[48:20] there there aren't, you know, when you get to more selectivity
[48:23] for, for just tic two, you really do get away from a of
[48:26] these safety issues and and nothing, you know, across the
[48:29] Loomis data or the K to data so far would indicate that there
[48:33] there's some sort of safety issue to really be concerned
[48:36] about. And I think as we get more and
[48:37] more exposure, you know, to that, you'll sort of see that
[48:41] dynamic shift where people will look at the class and say, no,
[48:45] this is like a really, really effective class on the safety is
[48:47] not something to be concerned about with these more selective
[48:51] agents. And pause, now that we got you
[48:56] back, did you want to go back and comment on the epilepsy side
[49:00] or you're good to go? Well, yeah.
[49:01] I mean, yeah. Can you hear me, Sam?
[49:04] Yeah. All right.
[49:06] Sweet. Yeah.
[49:07] I wanted to ask Corny a question just like what he would say to
[49:10] this sort of not push back, but like, you know, so from
[49:14] following some of these open label data sets and epilepsy, I
[49:16] cover GW Zojenex, you know, I cover rapport, I, you know,
[49:21] follow Xenon and people look at the practice as competitive.
[49:24] Like it does seem like open label to placebo-controlled.
[49:28] Depending on the sample size of patients, you can have a pretty
[49:30] big regression in effect size. And I remember Zojenex had this
[49:34] 55% seizure reduction in LGS and a open label study that was like
[49:39] something like 12 patients. And then it was, I think it was
[49:42] like 25% in an RCT. And so I, you know, I understand
[49:46] you have the mechanistic validation, but you know, how do
[49:48] you or how do other investors get comfortable that the drug
[49:51] product is, you know, actually better?
[49:55] Especially something like absence seizures, which are so
[49:57] subjective to codify. Like I don't know how you really
[50:01] can tease that out in a small M like that, but I'm not as close
[50:05] to it as. I look, I mean, I think it's I
[50:09] think taking open label data and then trying to figure out like
[50:13] the point estimate for a placebo adjusted effect size is is
[50:17] really hard. I mean, you know, I guess I
[50:19] would argue if you get into like, you know, very specific
[50:21] subgroups where you have, you know, better historical data on
[50:24] understanding, you know, baseline seizure frequency, what
[50:27] what those patients look like, how many different anti seizure
[50:31] meds they're on, you can get a little more consistent.
[50:33] Which is why I think we've seen more and more focus on sort of
[50:35] not just going after like a broad set of seizures, but like,
[50:38] oh, we're going to go for a CDAL K5, we're going to go for Lennox
[50:41] Casteau, you know, really target this more and more.
[50:45] But certainly I don't, you know, I'm not going to look at, you
[50:49] know, this, this uncontrolled data and say, oh, an absence is
[50:52] 73% seizure reduction. Like that's what the, you know,
[50:56] placebo-controlled is going to be absolutely not.
[50:59] You know, and it's going to be even hard to to look at what you
[51:04] think placebo control will because to your point, there's a
[51:07] lot of subjectivity here. But I guess I kind of look at it
[51:10] and you could say, well, you certainly can predict whether or
[51:15] not it's like efficacious. So like at 73% in, in Opson, 63%
[51:20] in D EE SI mean, this is this is a really high number.
[51:24] And right, you know, we both see this.
[51:27] I I got this to some extent on, on debate on some of the praxis
[51:30] data as well. But it's, it's, it's not a
[51:33] question of like, does it? I think we answer a, a big part
[51:36] of the question of like, does it work?
[51:38] Is it, you know, reasonably probable to hit in a phase three
[51:42] study, you know, what you get into a more nuanced debate
[51:45] around is like how, how robust is it going to be a, you know, a
[51:49] 45% delta between placebo and, and treatment?
[51:54] And yeah, I, I, I don't know that I'd be reasonably
[51:56] comfortable saying that there's going to be a static delta.
[52:00] You know, would you, what would you power for?
[52:02] Would you power for a 30% delta? Maybe probably, you know, I'd
[52:06] probably say be a little more conservative, but I think at
[52:09] this point where you're really looking for is drugs that are,
[52:12] that are safe, that are convenient that that very
[52:14] clearly show efficacy on on top of multiple anti seizure meds.
[52:19] But yeah, I, I hear you. Like I would, you know, I'm a
[52:21] big advocate to for always randomizing placebo patients in
[52:26] every study that one ever does if it's not unethical.
[52:33] I think this conversation that you guys just have proves that
[52:37] is the real reason why we this, this Twitter space is this, this
[52:42] podcast or whatever you want to call it, conversation is still
[52:46] valuable. I mean that that sort of detail
[52:48] that you guys went into is gold dust.
[52:50] So thank you for that. Well done.
[52:52] I didn't want to end the first session of 2026 without a
[52:57] comment on obesity because I think that would be a very, very
[53:02] bad thing to do. We've had the biggest fundraise
[53:05] came from Arrowhead, which had some srna data in the space,
[53:09] early stage data. The drug is Arrow.
[53:12] I don't know how I call it Inhiba E, Inhiba inhiba inhibi,
[53:18] inhibi inhibi. OK, there you go.
[53:20] Inhibi, inhibi, inhibi. Phase 2 is moving into Phase 2
[53:26] and shows some interesting benefits in particularly
[53:30] diabetic obese patients. But the that there was some
[53:36] angles in here that that did make us scratch our heads about
[53:40] how the regulatory pathway would would fall form the drug
[53:47] monotherapy in obese patients didn't do anything.
[53:49] I think that's fair to say that and knock me down if you'd like
[53:53] to, But it worked really well in combination with, I think it
[53:59] was, I can't remember, was it Tanzapatite?
[54:00] It was combination with yes, in the obese diabetics.
[54:06] It was a, it was a brilliant effect and, and, and the data,
[54:13] we've done a full comparison looking at different aspects of,
[54:18] and they showed quite a lot of detail with the visceral adipose
[54:21] tissue, total adipose tissue, liver fat content.
[54:24] I mean, it really did a fantastic job.
[54:26] I'm not going to go into the detail of the mechanism of
[54:28] action because and it's not AGLP 1.
[54:30] So let's put that there similar to what Wave is doing.
[54:35] And I think they, they, they did a pretty good job here.
[54:37] Clearly the market loved it because they they ended up
[54:40] having a upsized raise of a $625 million.
[54:44] So well done to them. And I think it's a very
[54:48] interesting, these are more and more of these novel modalities
[54:51] that are coming along now. I think the maybe the story of
[54:54] GLP ones is last year's story and this year's going to be more
[54:57] about these other ways of either bringing new additional weight
[55:05] loss or helping weight loss in a situation where you want more
[55:08] fat loss versus muscle loss. A lot of these has to be figured
[55:12] out still. But clearly the market size
[55:15] hasn't changed. And of course you've got the
[55:18] other changes in the commercial side with oral, the Govi pricing
[55:23] at apply at a level that that is relatively accessible, etcetera.
[55:28] So that was it, that was a good year start to the year from an
[55:31] obesity perspective. And Tess, did you want to add
[55:35] anything here? You know, I think, I think the
[55:39] only thing I'd add is I absolutely agree with you, Sam,
[55:42] in terms of, you know, some of these, you know, mechanisms that
[55:46] that people have been excited about and are, are awaiting data
[55:49] readouts for. So maybe just adding to
[55:51] Arrowhead, they had the the data for NB and they also have an ALK
[55:57] 7. And these are both, you know,
[56:00] these are essentially both going after that, you know, the same
[56:03] pathway to, you know, with different parts of the, of the
[56:07] same pathway to essentially, you know, help, you know, help obese
[56:11] patients. And they didn't get report data
[56:14] on the ELK 7:00 but that data is, is forthcoming.
[56:19] And I think we have a few other targets like that where, you
[56:22] know, we'll, we'll hope to see, you know, we'll hope to see
[56:24] data, you know, at at some point that's here or maybe next.
[56:29] Yeah, Yeah, I think this is where we're we're looking
[56:31] forward to seeing that particular data on the on the
[56:34] improving life policies from with the Alex 7 target, which is
[56:40] I think really exciting. And and these are you know what
[56:44] one, what we really want to see is, is safety.
[56:46] And so far they seems to have been quite safe.
[56:48] You know, as RNA or or small nucleotide approaches to these
[56:54] things have have do worry you a little bit, especially if
[56:57] they're the the mode of action is the target is deliver itself
[57:01] at some in some of these situations.
[57:03] So I think we can we can end there.
[57:06] Of course, we did have a bad news from Sanofi on their total
[57:10] brutiny, but I don't think we need to particularly go into
[57:12] that. I don't I don't want to end on a
[57:14] negative. I think we're doing very well,
[57:15] ending on a positive. So I was going to just sorry,
[57:17] Sam, I just wanted to jump in it because you brought up the the
[57:20] oral Wagovian. I think, you know, one of the
[57:21] interesting things to just follow on on, on just sort of
[57:23] the politics side is, you know, Orphoglyprin, Lilly's oral GLP
[57:29] one I think is like, you know, they've submitted that for for
[57:32] the commissioners National Priority Review.
[57:36] And you know, I think they've been talking about like approval
[57:38] in January. I think it's really interesting
[57:40] when we look at like the, the initial set of national priority
[57:43] review vouchers under the CNPV, you know, I think a lot of us
[57:46] kind of scratch our heads whether it has any real impact,
[57:49] but this is potentially like a real, real big impact and a
[57:52] real, real big indication. And, and kind of, you know, when
[57:56] I think of all the things that HHS has has done and you know, I
[58:01] think we probably criticize them a lot.
[58:03] I mean, this is actually something that could, you know,
[58:06] meaningfully move up present values on, on things.
[58:09] And if you know, big, big drugs that are of great interest are
[58:15] moving from a 12 month review cycle to a two-month review
[58:18] cycle, that's kind of a big deal.
[58:21] It is, it is the IT, it, it certainly helped the Nova share
[58:24] price which was on a on a One Direction slide for pretty much
[58:28] most of the year. What's interesting of course is
[58:31] going to be interesting to watch the battle between these two
[58:33] orals. You've got we go V with a
[58:36] slightly better weight loss around 14% versus a problem of
[58:42] dosing in terms of needing the scheduling and and when you take
[58:48] the drug versus a 12% weight loss with or for glimepirone.
[58:52] But it's an oral drug. So it's a, it's a real oral
[58:55] drug. And of course supply, you know,
[58:57] there's 10 times more dose in the 25 milligram oral we go V
[59:01] versus 2.4 milligram injectable. So that's kind of interesting to
[59:04] watch. And I have to say, when I saw
[59:06] the the national remind me what it's called again designation
[59:12] for Tekvale in myeloma, I was really excited.
[59:16] I mean, this is something that you would have thought would
[59:18] take another nine months at and you know, OK, it's an already
[59:21] approved drug to get to market for these second line patients
[59:24] in multiple myeloma. And the the results were were
[59:27] spectacular in the in the patient groups that were tested
[59:32] and they've got that. So is it possible that it's
[59:34] going to come in Q1? We'll see.
[59:37] So we're on the hour. Anyone want to close with
[59:40] anything that's positive? No negatives allowed?
[59:46] No, that looks like that's it. So enjoy JP Morgan next week,
[59:50] folks. Do not come back with infections
[59:52] or anything. Hopefully everybody comes back
[59:56] fully charged with lots of excitement for the year.
[59:58] I look forward to speaking. I think we have another session
[1:00:02] next Friday and thank you very much for joining.
[1:00:06] I do have one thing that I have to finish with, of course, and
[1:00:09] that is that if you're heading to JPM next week, Biotic
[1:00:12] Hangouts got an in person networking event on Tuesday,
[1:00:15] January 13th from 7 to 10 PMI wish I was there at Persona is
[1:00:20] the place where it is at, which is the same location as the past
[1:00:23] two years. We hope to see everybody there
[1:00:26] except I won't be there and I'm very sad for a fun night on open
[1:00:30] bar which is dangerous. Thanks to our gold badge
[1:00:34] sponsors, CFGO and Incubate Coalition and our Blue badge
[1:00:38] sponsor sponsors FDI Consulting, Catalytic Agency and Mispro.
[1:00:43] Be sure to RSVP please. The registration link will be re
[1:00:47] shared shortly on the Biotech Hangout social media channel
[1:00:52] January 13th from 7:00 to 10:00 PM on Tuesday.

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