# Episode 182 - May 8, 2026

An episode of [Biotech Hangout](https://invisiblenetwork.ai/podcast/1568911820), 8 May 2026, 1 h 00 min.

Audio: https://anchor.fm/s/55bdff38/podcast/play/119711830/https%3A%2F%2Fd3ctxlq1ktw2nl.cloudfront.net%2Fstaging%2F2026-4-8%2F423781293-44100-2-6ab3fe18cdd98.m4a

On this week’s episode, Josh Schimmer, Paul Matteis, Eric Schmidt, Yaron Werber, and special guest STAT’s Allison DeAngelis open with what they describe as “a bananas week for biotech,” highlighting strong substantial secondary offerings, including Cytokinetics and Avalo Therapeutics. The conversation then turns to M&A, with multiple new deals announced in Q1 and continued activity this week, including UCB’s acquisition of Candid Therapeutics for up to $2.2B, Angelini’s $4.1B purchase of Catalyst Pharmaceuticals, and Bayer’s acquisition of Perfuse for up to $2.45B. The group also reflects on what feels like the year of developmental-stage biotech, highlighting investor focus on companies with pipeline events such as Vertex and Biogen, while commercial-stage companies have lagged. In regulatory news, the co-hosts discuss Sanofi’s decision to withdraw diabetes drug, teplizumab, from the Commissioner’s National Priority Review program, broader concerns about shifting goalposts and political influence, and contradicting outcomes including Replimune’s rejection versus Atara’s reversal. On the data front, the hosts discuss Cytokinetics’ Phase 3 results and subsequent $650M raise, as well as encouraging autoimmune data from Artiva Biotherapeutics. They also overview neurofilament as a biomarker following Clene’s data, and J&J’s decision to advance its DUET program despite failing to meet its primary endpoint in IBD. *This episode aired on May 8, 2026.

## Transcript

[0:00] You're listening to Biotech Hangout, a live and unedited
[0:02] weekly discussion of all the latest news in our industry with
[0:05] a group of biotech leaders and experts and the rest of us.
[0:09] I'm Josh Schumer. My coach today are Paul Mattias,
[0:12] Eric Schmidt, your own Orber, and special guest Allison
[0:15] Deangelis. For more information about our
[0:18] hosts and guest speakers, we'll listen to the most recent
[0:20] episode. Please go to biotechhangout.com.
[0:22] And Please note that any commentary we have should not be
[0:25] construed as investment advice because as we all know,
[0:28] investing in biotech is very, very difficult, even for the
[0:31] experts and very tricky. This week, it was a bananas
[0:34] week. Holy smoke.
[0:35] I am literally still clearing out emails from earlier in the
[0:38] week because we had so much going on Earnings, earnings,
[0:41] earnings M and A data analyst events, etcetera.
[0:46] Let's let's dig in maybe on the on the markets, Eric, we'll,
[0:51] we'll start with you. We have a number of pretty big
[0:55] secondary raises. And I guess the question is, is
[0:58] too much capital being infused at once?
[1:01] You know, you know the the lore that the the best way to kill a
[1:04] biotech rally is by bankers just printing, printing too much,
[1:10] printing too many new issuances. Are are we in danger of that?
[1:15] Yeah, I'd love to start this discussion off.
[1:17] Thank you, Josh. Thanks everyone.
[1:19] Great to participate with you all again this week.
[1:23] So, you know, let's put a little bit of context around it.
[1:26] Another very, very substantial week of secondary offerings.
[1:29] Many of the companies that were raising hundreds of millions of
[1:32] dollars, Cytokinetics, Avalo today, Joshua or Tiva, these are
[1:36] just names that are coming to mind.
[1:38] I, I haven't done the math or done the statistics on it, but
[1:41] but these are all companies that are having good data and are
[1:44] deserving to raise capital. It seems like we've now reached
[1:50] the point where it's an automatic raise and a very large
[1:54] raise for anyone who has good results in this space.
[1:58] Q1, as we've heard from others on this show was a record year
[2:02] for biotech secondaries. Let me say that again, Q1 was a
[2:05] record year for about a record quarter for biotech secondaries.
[2:08] That's, that was an amazing statistic to me and, and one
[2:11] that was surprising given how much money was raised in.
[2:21] Well, did I? Is it just me who's lost Eric or
[2:24] am I the one? Who's no?
[2:25] I lost Eric too. I lost Eric.
[2:28] Yep, I lost him as well. He went ahead and went on he he
[2:31] called it a Friday early. Alright, well, I'll, I'll take
[2:35] over. He's in the office next to me,
[2:37] but maybe to kind of carry on that the discussion of of just
[2:41] this. Incredible amount of of
[2:42] secondary offerings it it's context dependent right?
[2:46] Like when when generalists are coming into the sector, they
[2:49] they dwarf everyone and provide more than enough capital to both
[2:54] fund the companies and contain that the momentum of the sector.
[2:57] But when we don't have enough generalist interests like we've
[3:01] we've started to generate, the question is can we keep it?
[3:04] And maybe that will be our next discussion topic.
[3:07] If we don't have enough generalist interest, then yeah,
[3:09] paper can can kill biotech. Rally in my view, but I'd love
[3:13] to hear. From others perspective.
[3:16] So I'm just going to wander into Eric's office and see if he's
[3:18] still talking. I'll.
[3:19] I'll chime in for a second and then we can hear from others
[3:22] too. I mean, I think there's a couple
[3:24] dynamics in play like 1 is, you know, there's just been a lot of
[3:27] M&A. So I think that a number of the
[3:29] specialist funds and long only's have cash to deploy.
[3:33] And you know, maybe that's I mean, I guess it's case
[3:36] dependent, but you know, people are just putting more money into
[3:39] the next thing because they can. I mean, theoretically that's not
[3:42] a good thing. But I also think we are
[3:44] acknowledging here too that a lot of these mega raises are
[3:46] coming off of data that's really good and better than expected.
[3:49] And so it doesn't feel like we're seeing big time
[3:54] opportunistic raises for like no reason, right?
[3:57] I think that's where maybe things get a little bit like
[4:01] FOMO ish, you know, and I don't think we've seen all that much
[4:05] of that. So, and I guess the last thing
[4:07] I'll say and Josh, you know, it'd be interesting maybe if we
[4:09] revisit kind of our conversation we had a while ago about IP OS
[4:12] and stuff because it's looking more and more like you could be
[4:15] right on the number this year. But I mean, I do think that, you
[4:18] know, there are, we've had some M&A and I think there's, I think
[4:22] investors I talked to are ready to like kind of they're ready
[4:25] for new ideas, right. So stuff that gets de risked
[4:29] like I think they're expanding their investor bases.
[4:32] I guess what I'm trying to say is, Long story short, I don't
[4:34] feel like anything like that unhealthy is happening yet this
[4:37] does not feel at all like 2020. Maybe it's the best way to say
[4:40] it. Agreed Duran.
[4:43] Yeah. I mean to to me, you know,
[4:44] we've, we've all seen these cycles.
[4:46] This is continue to be healthy early cycle sort of biotech
[4:50] recovery, good, good data gets renumerated with new interest
[4:55] and they capture kind of a lion's share of the interest.
[4:57] But but the stocks are doing well and they're carrying
[5:00] through. So I don't think it's drying out
[5:02] the demand and I think there is a lot of capital, you know, and
[5:06] investors, even generalists are kind of willing to go a little
[5:09] bit, you know, down into kind of midcap biotech land in the the,
[5:15] the sort of platform companies like an Insmet or we'll talk
[5:18] about that. I'm like Roy Vent like like an
[5:21] Ionis, you know, Arrowhead. So I think there's a healthy
[5:24] amount of interest. I actually think it's still very
[5:26] good. You're on, let me ask to you,
[5:29] he's a former operator, what the impact of raising a lot of
[5:32] capital is on a company. Do you think it changes the way
[5:35] they act and perceive or to redeploy capital?
[5:38] Is that a risk that we need to be mindful of?
[5:41] I. Mean you, you to be honest,
[5:42] Eric, you, you would know more than me in in that sense, the I
[5:47] think it really depends on the plan, on the size of the
[5:50] ambition, whether it's a platform or not, how much of is
[5:54] going to be committed capital to manufacturing.
[5:56] That's when things can really get obviously get pretty risky.
[5:59] You're really much better at to answer that because you raise
[6:03] substantial capital in that sense really depends on on how
[6:08] focused on the scope of the studies.
[6:10] I mean, if it's really too, you know, power up studies based on
[6:14] good biology, that's one thing. But if it's kind of carte
[6:16] blanche to go broader and pretty ambitious and ahead of yourself,
[6:19] probably not. Why?
[6:23] Don't we bring Allison into the conversation now and talk a
[6:27] little bit about some of the M&A updates.
[6:30] And you know, I'm always a little ambivalent about M&A
[6:34] being a headwind or a tailwind for a sector, especially when we
[6:37] pull out companies that have really strong long term
[6:41] prospects or. We pull out companies that are
[6:44] generating cash flow because amazingly, cash generation
[6:48] actually matters as we think about valuations.
[6:50] Also catch up some for this week.
[6:54] Oh well, as the startups person, I'm always really paying
[6:56] attention to M&A because I mean it's, it's one of the only ways
[7:00] that you see money really flow out of this sector for young
[7:05] biotechs and go kind of back into the hands in terms of
[7:09] financial returns of venture capitalists and LP's and then
[7:13] get recycled back into our ecosystem.
[7:15] So you know everybody that I've talked to is on the private side
[7:19] is very pleased with the amount of M&A that we're seeing.
[7:23] Q1 was very healthy and this week we got three more deals
[7:27] added to the roster. Angelina Pharma is acquiring
[7:30] rare disease drug maker Catalyst Pharmaceuticals for $4.1
[7:34] billion. Bayer is doing a little bit of a
[7:37] smaller deal they're buying for Fuse Therapeutics and it's
[7:40] pipeline of ocular disease programs.
[7:43] That's about 300 million upfront.
[7:45] And then we've got, you know, 2 point close to 2.5 in bio box.
[7:50] And the one that really caught my attention and made me chuckle
[7:53] this week was UCB buying Candid Therapeutics for $2 billion
[7:59] upfront. Candid is working on T cell
[8:01] engagers. And this is just the, the second
[8:05] time that Ken Song has tried to be CEO of like a public biotech
[8:09] company and it, it, the universe just won't allow it.
[8:14] The first company obviously was acquired, raised bio something
[8:18] like two or three months after its IPO and then Candid had been
[8:23] planning to do a reverse merger and that's now off because it's
[8:27] getting acquired. So, you know, one day, one day
[8:31] we'll see Ken as a public company CEO, but not not today.
[8:35] I, I've known Ken for, for some time and I was kind of early
[8:39] meeting with him just when raised was getting off the
[8:42] ground early meeting with him just when candid was getting off
[8:45] the ground. And he is phenomenal.
[8:48] Like his ability to, to dive into a new field, size it up, go
[8:53] deep, see the big picture. I can't wait to see what he's
[8:57] got planned for us next. So Congrats to, to Ken.
[9:00] Congrats to Irvind as well and the, and the candid team that
[9:03] that turned around quickly. And by the way, assets pulled
[9:07] out of out of China, maybe you know a theme to quickly touch
[9:12] upon. I don't think it was kind of
[9:14] necessarily part of the intended schedule, but it's hard to talk.
[9:16] About candid in this rapid success without acknowledging
[9:19] that. You know, they, they got some
[9:21] very compelling cheap assets out of China and they quickly turned
[9:25] it into a a huge payday. So not sure how others are are
[9:29] thinking about China innovation. I know it's come up fairly often
[9:32] on hangout in the past, but boy, this is it's all coming on
[9:35] coming on pretty strong and, and and fast.
[9:37] We I was with my colleague a couple.
[9:40] Of weeks ago on a on a China biotech pastor Lee Watsek, who
[9:44] who hosted it. And it was so eye opening.
[9:47] So eye opening for me. This is a really interesting
[9:51] point of conversation and one that I spend a lot of time on
[9:55] these days. I would be curious, I mean,
[9:57] candid was kind of part of this early wave of licensing drug
[10:03] candidates out of China and form a new company around them from
[10:07] what I gather. I mean the premiums that
[10:11] companies, you know, whether it's venture capital companies
[10:13] or kind of new codes are paying for assets out of China has has
[10:18] risen. So like, I wonder how some of
[10:21] the companies that are being formed today, you know, how
[10:24] their kind of financials looked look compared to say, a candid
[10:28] therapeutics. And you know, it's it's an area
[10:33] where they're certainly from what I gather, a lot of
[10:36] offerings. But you know, there's the kind
[10:39] of the eternal debate of are you getting the best things first?
[10:45] Who's able to get in and really get on the ground?
[10:47] You really have to kind of do a lot of work to look under the
[10:50] hood of these companies to find the best and and brightest
[10:54] things. And I yeah, I hear some inklings
[10:56] from venture capitalists who are on the ground that, you know,
[10:59] there's a concern that there are there are still assets around
[11:05] there that are not kind of up to snuff.
[11:09] And that, that the one challenge that the Chinese ecosystem will
[11:12] face over the coming years is that the the incentive structure
[11:18] there is to do a lot and produce a lot.
[11:20] And will they kill bad programs? Will they show things that are
[11:26] not working? Are we, you know, will the
[11:29] quality continue to be, you know, robust in China?
[11:34] Is is a outline question? Yeah.
[11:36] My, my sense of it is that the innovation there is almost too
[11:39] fast, right? Because of, I would say you're
[11:41] kind of hinted at this, like, OK, you go to China, you, you
[11:44] may think you're pulling out the, the best looking asset, but
[11:48] there's so much innovation so quick, so fast that the next
[11:51] day, the next week, the next year, there might be something
[11:54] better that someone else pulls out.
[11:56] And then how on earth do you invest when you're not quite
[11:59] sure what you know, how that landscape is, is evolving like,
[12:03] like there, there should be a natural healthy cadence to
[12:06] innovation. And if you if you accelerate it,
[12:09] investors don't know what to do with that and that that can be a
[12:13] little bit dangerous. So what we'll see how it all all
[12:15] evolves. Maybe moving on to to another
[12:18] topic. Number of commercial stage
[12:20] biotechs reporting earnings this week, Paul, and give us your
[12:24] sense in terms of investor interest and appetite in in in
[12:28] investing in these names? Yeah, I, I would love to hear
[12:32] everyone else's perspective here too, because my, my, I mean,
[12:36] look like a company like a rhythm that's, you know, doing
[12:39] their sort of big drug launch and it's just taking off.
[12:43] I mean, certainly there's interest there.
[12:44] But I mean, taking a step back, it feels like 2025 was the
[12:48] commercial biotech year, right? When you look at the leading
[12:52] companies like on Mylan and Insmed and R Genics and Verona
[12:56] and you know, this year, a number of those names have been
[12:59] laggards and it feels like it's been the year of developmental
[13:02] stage biotech, right. And I even was go as far to say
[13:05] is when we went, when we entered this year, you know, I cover
[13:08] some large caps, but not all of them.
[13:10] The two that people were the most interested in were Vertex
[13:13] and Biogen, two companies that couldn't have commercial
[13:16] businesses that are really any more different.
[13:18] But the reason why they were in favor is because they both had
[13:20] pipeline events. So I think in the context of
[13:22] that, like I do wonder if we start to see some rotation back
[13:27] into some of the commercial biotechs that are more value Y.
[13:30] Like you saw a really good quarter from Neurocrine where in
[13:34] the backdrop of kind of lower expectations.
[13:37] But you know, I think the interest from investors is still
[13:39] pretty mixed, right? Like I cover bio Marin.
[13:41] I think there's you know, a real case that bio Marin on an actual
[13:45] like conservative value elevation methodology is not
[13:49] expensive. And yet because there isn't sort
[13:51] of this immediate golden pipeline ticket, I think the
[13:54] investor interest there is a lot more muted.
[13:56] You know, and I've been having conversations with more people
[13:59] and sort of could something could something flip this,
[14:01] right? I mean, maybe it would take like
[14:03] a sort of big old school type M&A like an Alexion type
[14:07] acquisition where a strategic is like, hey, this just got too
[14:10] cheap and then maybe people start extrapolating that.
[14:12] But yeah, I mean, earnings this week I thought was good for a
[14:16] number of our companies, but the investor receptivity to these
[14:19] types of stories still feels very, very hit or miss.
[14:21] Do you guys agree? Eric, you're on.
[14:26] Yeah, maybe let's. Well, I actually I would agree.
[14:29] I mean, I just throw in another name.
[14:31] I have Agios that's launching a drug for thalassemia.
[14:34] This, these guys actually reported last week, not this,
[14:37] but the launch could not be going better.
[14:39] They crushed expectations. My guess is that consensus
[14:44] estimates for this drug in 2026 are probably going to be about
[14:48] threefold too low relative to where it ends up.
[14:51] And stock was up like $2.00. So they've got some other issues
[14:55] at the company. But but yeah, that that's a
[14:57] launch that seems to be falling on deaf ears.
[14:59] There are a couple others that come to mind too.
[15:01] I'm sure you guys can all chime in.
[15:03] So I think you're right, Paul, we're in a bit of a buy the
[15:06] dream phase with regard to developmental stage biotechs and
[15:10] everyone wants that open-ended 5 to 10 bagger upside associated
[15:15] with a readout pipeline event as opposed to hey, let's cry entire
[15:19] with 20% earnings upward revisions.
[15:22] Yeah, your own question for you. You know the general is happy.
[15:27] Yeah, hopefully you can hear me. I think I'm.
[15:29] I'm glitching. I might be glitching a little
[15:31] bit. So I think it's Paul.
[15:33] It's very interesting what you said.
[15:35] And sometimes I kind of zoom out and whether a drug beats are not
[15:41] really a function of the quality of the data.
[15:43] Obviously competitive positioning, formula
[15:44] replacement, obviously the price of the drug, we'll come back to
[15:49] that in a second. But really investor expectations
[15:51] slash sell side expectations, which I think a lot of times
[15:55] emanate from the actual market cap of the company when it's
[15:58] numbers are low, when it goes high, you know, numbers get
[16:01] revised upwards. And so you're right, I think
[16:04] we're seeing this year a catch up effect of the of the great
[16:09] launches from last year now getting revised upwards also,
[16:13] you know, having a hard time, you know, beating estimates
[16:16] because of that. And that's kind of giving it a
[16:18] little bit of the chilling effect.
[16:20] We're also definitely seeing AQ one effect that is very real.
[16:24] The, the, you know, we're definitely seeing, seeing
[16:26] seasonality and that usually now a big sort of bounce back in Q2.
[16:32] So I think that's kind of been giving some of these stocks
[16:35] pauses and a lot of them have really had, you know, fairly
[16:39] dramatic moves down downwards into the Q1 print, you know, for
[16:43] even starting in January in anticipation of kind of weak
[16:47] prints. But I think that these companies
[16:50] are, are still very healthy. It is, I think, jolting the
[16:54] generalists who've gone into like the on islands ends meds,
[16:57] you know, argenics is Ucbs, even a little bit Ucbs that you can
[17:01] argue there were there already, but I think that's giving it
[17:05] probably fueling a lot of the pronounced volatility in the
[17:08] stocks they're they're in and they're like, what the hell did
[17:10] we just buy? And why is this down 15%, you
[17:12] know, in the last two weeks? So I think there's an element of
[17:15] that, but you know, it's not fully kind of start moving
[17:19] downstream. And what's really amazing is,
[17:22] you know, two years ago, I didn't think we're going to have
[17:24] a huge innovation cycle now and that was clearly wrong.
[17:27] We've flipped a lot of positive data cards like, you know,
[17:31] again, you know, kind of things that come to mind bridge by or
[17:35] even immediately ascend this. But also these launches are not
[17:39] doing really well and we think we'll continue to do well
[17:42] because drug pricing gone up so much.
[17:46] These launches are now becoming fairly meaningful drugs a lot
[17:48] faster than when we all started kind of growing up, you know?
[17:52] I would just, I would just add many biotech companies still run
[17:55] their companies for specialists and the more companies run their
[18:00] companies for generalists, the better the sector is going to
[18:03] do. All right, let's move on to
[18:06] regulatory updates. Allison, trying to wrap my head
[18:10] around what happened with this tablizumab commissioner voucher
[18:15] withdrawal from Sanofi, maybe catch us up on what what's
[18:19] what's going on there and then what the implications are?
[18:22] Yeah, it's, there's still some information to be learned here.
[18:26] But what we know is what my colleague Lizzie Lawrence
[18:29] reported this week that Santa Fe has asked the FDA to pull its
[18:34] type 1 diabetes drug, tuplizumab, out of the
[18:38] commissioner's voucher program. It had been accepted into the
[18:41] program and the agency was supposed to deliver a decision
[18:45] on the drug by April 21st that that date has obviously come and
[18:50] gone. The what Lizzie has heard is
[18:55] that the move comes after Tracy Death Hoag, who is now the
[18:59] acting head of of Cedar, disagreed with a staff decision
[19:05] to approve the drug. And now this decision date has
[19:10] has passed. So it seems like Santa Fe might
[19:14] be waiting on its enthusiasm for for this commissioners program.
[19:20] And look, it kind of speaks to some of the larger issues that
[19:25] are percolating both around this program, which, you know,
[19:29] sources have told Lizzie and other folks at staff at the
[19:32] drugs in this program are vulnerable to political
[19:36] influence. And just kind of within some
[19:38] different areas of the FDA that the, you know, the question of
[19:43] how drug makers kind of work through the agency right now in
[19:47] certain sectors of the agency here is really challenging.
[19:51] Yeah, Richard Pastor's recent comments, if you saw that he's
[19:56] saying he didn't leave the FDA, the FDA left him points to
[20:02] ongoing disarray at. At the agency, Very, very
[20:06] frustrating. Eric, maybe kind of before we
[20:10] get to the topic of the carry and the outlook for him, talk a
[20:15] little bit about what's been going on with Reply Immune.
[20:18] That's been one of the most amazing, whipsawing names of
[20:22] regulatory prospects I think I've ever seen.
[20:27] Well, yeah, I mean, first great reporting on the part of Stat
[20:30] News and the Santa Fe Commissioners voucher story.
[20:33] I I find that store to be highly ironic.
[20:38] The same week that Doctor Makari, who is we're going to
[20:41] talk to be talking about in a moment, is essentially fighting
[20:44] for his job and and going on CNBC to defend himself and his
[20:49] agency around the criticism that the agency has been too
[20:54] conservative in terms of the approval of Rep lens RP one for
[20:58] for Melanoma. I think many of you know this
[21:00] drug was rejected now twice by the agency despite having clear
[21:04] activity in Melanoma and and despite having a support many in
[21:07] the community. Dr. Mccrory's defense was all
[21:10] based around the fact that senior FD officials should not
[21:14] intervene in review staff decisions.
[21:16] They obviously didn't intervene with regard to the reprimion or
[21:21] that it appears they did not intervene with regard to the Rep
[21:23] and application. But but certainly, as was just
[21:27] pointed out, senior administration officials have
[21:30] intervened and many decisions under this administration.
[21:34] So the irony that he's defending himself and saying it's quote,
[21:38] disastrous when senior administration officials do
[21:41] intervene and review staff decisions.
[21:44] And yet the very same week we have one of one more example of
[21:48] this and that also, I guess maybe Josh brings us to the
[21:51] Atara news this week too. For those of you who don't know,
[21:55] Atara now seemingly with their partner Pierre Fabre has an
[21:59] opportunity to bring their EBV cell therapy to the market.
[22:02] This after it having been also rejected.
[22:06] That rejection seemingly was all about Vinay Prasad.
[22:09] Vinay actually wrote a piece in the in the JAMA about how he
[22:13] thought that cell therapy drugs should not be approved on single
[22:17] arm studies and then subsequently went in and
[22:20] rejected the Atari product. Now looks like Atari and Peer
[22:24] February are going to have an opening opportunity to to refile
[22:28] despite not having any new data. So great to see that reversal,
[22:32] but then again highlights another example of senior
[22:35] administration officials interfering with the agency.
[22:38] Yeah. I feel like once, once we get to
[22:40] a point of stability, reliability and transparency
[22:43] from the FDA, we're going to be so appreciative having gone
[22:48] through this. Era of almost the the opposite.
[22:50] Very, very frustrating. Very, very challenging, but.
[22:54] I think the other thing that. Richard Pastor has noted is that
[22:57] he's he's optimistic that there's still enough.
[23:02] Appropriately oriented decision makers left at the FDA that the
[23:07] wheels have not fully fallen off the agency's bus and that things
[23:12] actually can can continue and and hopefully.
[23:15] Feel far less choppy and and volatile, but I guess Speaking
[23:19] of that, Allison catches up on. I guess the point that Eric's
[23:23] alluded to what what's going on with with Doctor Mccarry?
[23:27] And and his his tenure at the FDA.
[23:30] Yeah. I mean first to one of I think
[23:33] the comments that that Eric made, I have heard from folks,
[23:38] investors on the private side who are, you know, dealing with
[23:42] the agency these days that and there are there are certain
[23:45] segments of the agency that are kind of functioning as normal.
[23:49] You know, things are moving through the system and there are
[23:53] other areas where they are experiencing contradictory
[23:58] guidance and, and we are seeing some of these seemingly play out
[24:03] in, you know, in public examples as with Atara.
[24:07] And I think that kind of brings us to this week.
[24:12] It seems like there's really been kind of a fever pitch of
[24:15] conversation around Commissioner Makari's tenure at the FDA and,
[24:20] and what the agency looks like now after a little over a year
[24:25] of his leadership. I think, you know, this is
[24:29] something that Scott has been covering since since the get go.
[24:33] But we also saw a lot of reporting this week from
[24:36] Bloomberg, from the Wall Street Journal talking about the
[24:39] personnel issues beside of the agency, the pressure that
[24:44] apparently the White House and President Trump have put on
[24:48] Commissioner Makari to approve fruit flavored baits, which he,
[24:53] according to a Wall Street Journal story, Commissioner
[24:56] Makari had initially approved, opposed the approval because of
[24:59] the public health concerns that if you're introducing, you know,
[25:04] lollipop flavored or not lollipop grape flavored vapes
[25:07] that that appeals to children and what's the public health
[25:10] concern about that? But this week we did see those
[25:14] actually get approved. And, and there's been a lot of
[25:18] other conversation about what's been going on with the agency.
[25:21] Even, you know, Lizzie this week noting in the in this great
[25:24] piece that Josh, I think that you, you quoted, quoted Rick
[25:28] Pastor saying that, you know, he didn't believe the agency, the
[25:31] agency left him in Lizzie's piece this week, looking at what
[25:34] we've lost over the last year, the agency, after having laid
[25:39] off 3500 people last year, is now aiming to hire 3200 people.
[25:45] So there there's, it seems like, you know, still big questions
[25:48] kind of swirling about the agency.
[25:50] And the tenor of conversation is that patients with Commissioner
[25:57] Makari might be wearing a little thin.
[26:00] I mean, the Wall Street Journal in an op-ed said as much as it's
[26:03] time for President Trump to pull the plug on Makari.
[26:09] And we did see, you know, Commissioner Makari on CNBC this
[26:11] week. He was at Milken defending his
[26:15] leadership. Hey Allison, can I, can I ask a
[26:17] question? Who do?
[26:20] You guys are so well connected. Who do you guys think is picking
[26:23] the head of Sieber and what do you think the criteria is that
[26:26] they're weighing between rare disease flexibility versus
[26:30] someone that maybe is still a little bit unorthodox on
[26:35] vaccines or COVID? This is, you know, I haven't
[26:39] gotten into this myself, but I know from my colleagues
[26:43] reporting and the conversations that we've been having kind of
[26:47] internally that there's a question about whether
[26:53] Commissioner Macari is the one who will ultimately make that
[26:56] pick or whether the White House is going to be asserting more
[27:00] control over that decision. And I, I, I do, I do find myself
[27:07] wondering if we're going to land in the latter stage given, I
[27:10] mean, just everything that we saw, you know, with between
[27:15] Prasad and Ted Marsh and, you know, some other and then, you
[27:19] know, Rick Pastor leaving the agency in a very high profile
[27:22] way. There's been reporting out there
[27:26] that also the White House's confidence in Commissioner
[27:29] Makari, I think to kind of set up a leadership team is also on
[27:34] thin ice. But that's, that's my, not my
[27:38] direct knowledge. That's just kind of what I'm
[27:40] hearing. So I'm.
[27:43] I'm kind of. I think I just can say that call
[27:46] she is, is saying that the odds of Doctor McCrory making it
[27:49] through the end of the month are about 5050.
[27:52] So we'll see, but that's very interesting.
[27:56] Oh no, we're getting, we're putting call.
[27:58] She bets on this. I got to stop that.
[28:01] So I I feel like I need to start a call sheet account.
[28:05] Like I feel like I'm way I'm a late adopter.
[28:10] I will note that it's stat policy that we do not bet on any
[28:16] of. These topics.
[28:18] By the way, that that was a joke for the very poorly the joke.
[28:26] The FDA has always made controversial decisions
[28:30] approving drugs, not approving drugs, issuing CRLS, and then
[28:36] eventually turning them into approvals without necessarily
[28:40] requiring new clinical data. So, so here's some questions for
[28:45] for the group. Why is it different now?
[28:49] Is it, is it the way that these decisions are being made or
[28:53] communicated? Is it because CRLS are now being
[28:57] published and we get to see some of the FDA concerns that we
[29:01] never got to see in the past? Is it because we no longer agree
[29:05] with the agency's decisions on some of these more subjective
[29:10] judgement calls? Why is there so much scrutiny to
[29:15] this FDA's decision making process compared to prior FDA
[29:20] leadership? I think the way they've drawn
[29:24] attention to themselves or gone on TV and you know, the whole
[29:29] thing with like whatever you think about uni cure, the whole
[29:31] thing of like going on TV and talking about morbidity with the
[29:35] procedure and the way they've defended themselves has
[29:38] definitely been like more defiant and specific than I
[29:41] think like I've ever seen. Right.
[29:43] And and and we can see it in the market.
[29:46] We. We can hear you both.
[29:50] Yeah, I can hear you. Both.
[29:51] OK. I, I was just saying like the
[29:52] way that they, so I think the way they like communicated
[29:55] publicly has been really different.
[29:56] I think the second thing, at least from like the rare disease
[30:00] side, is there's been such a crazy contrast between what some
[30:05] of the companies were saying, what the FDA's own guidelines
[30:08] were saying, and then what's actually happened, right?
[30:10] Because you know, I can remember with this whole municure
[30:13] situation that has been really close to me, right, that they
[30:15] had their data and you know, there was their three-year data
[30:19] and then a week later there were published guidelines from the
[30:23] FDA around open label studies, Natural History controls, right?
[30:28] That was Vinay Prasad Sieber, right?
[30:31] Maybe that was drafted months ago and was almost like
[30:34] published, but not actually indicative of what the current
[30:37] agency was thinking. But I've never seen like, and
[30:40] you guys have done this like longer than me, but I've never
[30:43] seen this many real time contradictions in a matter of
[30:46] weeks or months. And and then maybe the last
[30:49] thing I'll say is like, at least I've generally thought of, you
[30:53] know, a Republican administration.
[30:55] Obviously there's many sort of complexities to kind of how
[30:58] different parties view healthcare in general, but at
[31:01] least as it relates to the regulatory environment is like
[31:03] somewhat more libertarian. And this has been the opposite.
[31:05] So I mean, those would be my factors.
[31:08] I I'm shocked how much the Wall Street Journal like publishes on
[31:12] it, right? Like, not because I don't think
[31:13] they do good work, but because I didn't even realize how, like,
[31:17] broadly the world outside of our bubble, you know, really would
[31:20] care about this. Well, well, thanks for referring
[31:23] to us as the old timers call as as the folks with the with the
[31:27] Gray or or or no hair. But I remember a time that.
[31:32] You know, I look up to, I look up to all of you still.
[31:34] Oh. No, that's right.
[31:39] Yeah, I remember when Rick Pastor came in and really
[31:41] disrupt disrupted the oncology division, really raising the bar
[31:45] for innovation. And you know, he rattled some
[31:48] some cages and ruffled some feathers.
[31:50] But at the end of the day, you know, it was a very defensive
[31:53] position expecting oncology innovators to to generate
[31:57] stronger data sets and better drugs.
[31:59] But he never came under fire like this.
[32:02] So Paul, like I like, I really like your the point you're
[32:04] making, which is well, they came in and and shifted the goal
[32:08] posts like in in the blink of an eye.
[32:11] And maybe if they just hadn't shifted them so rapidly and
[32:14] nudged them, we wouldn't have so much drama.
[32:18] But on the other hand, I mean, didn't didn't work.
[32:20] Pastor kind of get away with it without without this kind of
[32:23] attention innovation. Maybe it was before social
[32:26] media, maybe that's part of the difference.
[32:27] I'd love to hear others others thoughts.
[32:29] You know, one, I love the question.
[32:31] I think you're right, Josh, I love the question.
[32:33] We could probably spend a whole episode on this and Paul had
[32:35] some some great initial thoughts.
[32:37] The one thing I would add is, is science.
[32:40] At the end of the day, this is a scientific organization.
[32:42] And when the public has trust that decisions are being made in
[32:47] a rigorous way, analytically based on the best science, you
[32:51] get the benefit of the doubt. Unfortunately, under this
[32:53] administration, whether it started with the anti vax stuff
[32:57] or or even the CNPV's which have their own political angle to
[33:01] them, we're not always talking about science.
[33:03] And when you when you lose that credibility, it's a very
[33:08] slippery slope. Well, well, for the most, I'm
[33:10] going to push back on that. I hear what you're saying.
[33:13] We we've definitely lost some of the scientific rigor in certain
[33:17] realms, but many of these CRLS were, I mean, Vinay presides to,
[33:22] I mean, to his credit, brilliant, really very.
[33:25] Thoughtful, maybe, the the way that he.
[33:27] You know, led the agency was far from brilliant, but he had
[33:31] robust rationale for for each of these decisions.
[33:36] Many are many are actually judgement calls, not clear
[33:38] science calls. So I'm going to push back that
[33:40] these were anti scientific decisions, but would love to
[33:45] hear if you if you you disagree on on these CRLS in particular.
[33:51] Well, I don't know if it's suit well, look on vaccines, I think
[33:53] we can all agree that it is anti scientific.
[33:55] We're still I think there was an article just this week saying
[33:58] that they have suppressed the FDA has suppressed an internal
[34:02] report on the safety of vaccines.
[34:05] They won't see the light of the day because because you know,
[34:07] the safety has been supported in the publicly in in the vaccines
[34:12] have been approved for public use.
[34:13] So that's very, very concerning. I mean, on other hard CRL type
[34:18] decisions, sure, it's a judgement call.
[34:22] I I do think that when you have a leader at the FDA, maybe this
[34:26] is vape side, but potentially more Makari who has said and
[34:30] done things that are abjectly political, it undercuts the
[34:35] entire tone from the top. And I think that's what's
[34:38] happened. Well, do you do you blame them
[34:40] or do you do you do right? I mean, they're they, they
[34:42] report to. HHS leadership and they either
[34:45] have a job or they don't have a job.
[34:47] And if you if you're not going to play that ball, you have no
[34:50] job. Is is there anyone who's going
[34:51] to? Fill that role and be able to
[34:54] withstand pressure from the from senior administration.
[34:58] So again, it's like, it's like what's the root cause and and I
[35:02] think these are all great points that that we're bringing up to
[35:06] create like a bigger picture maybe to.
[35:08] Explain the the nuances. Well, I, I, I think Josh, I
[35:13] think that there's a couple of things going on and that the way
[35:16] I guess we, we see it and I think you just nailed one on the
[35:19] head. I think that there was a sea
[35:21] change in a way that is from outsiders, which is not
[35:26] necessarily a negative, but the way was redacted to practice was
[35:30] fairly aphazard in a way that really was a little bit of a
[35:34] scorched earth. We're going to go in a very
[35:36] different direction and and tear down an organization that that
[35:40] that was very successful mostly in its history and then brought
[35:44] in outside that are not experienced managers, certainly
[35:48] on organizations of that size. And then put together policies
[35:52] which seemed to to have been crafted aspirationally very
[35:56] quickly and then very poorly redacted to practice and
[35:59] inconsistently immediately on top of a lot of political
[36:03] overtones that were concerning. And that's why I think it's it's
[36:06] drawn so much scrutiny. I mean, pastor, look, pastor was
[36:10] a maverick pastor. The first thing it did was was
[36:14] Dr. accelerated approvals, right.
[36:15] We all remembered Velcade and the magical 20%, which actually
[36:20] by expedited very quickly therapists to the market, but
[36:23] they also made very good scientific judgement and the
[36:26] things that got approved very much deserved to get approved,
[36:28] at least the vast, vast majority of them.
[36:30] So I think it was maybe their track record and the way they
[36:34] went about it was also very different.
[36:36] Allison, where are you going to? Yeah, I was going to say, I mean
[36:41] from from my perspective, I like Bjorn's comments about, you
[36:45] know, the manner in which things are being approved.
[36:46] I mean, one, the introduction of this commissioner's voucher
[36:50] program as a new Ave. for, you know, drug approval was
[36:56] naturally always going to get everybody asking a lot of
[36:59] questions like how are people, how are companies being selected
[37:02] for this program? What is the criteria on which
[37:05] they're being judged? Why were they not, you know, a
[37:08] candidate for more traditional drug approval?
[37:10] That's just like one example. But I think I mean, just I'm
[37:13] going to go back to like the fundamental concept of when,
[37:17] when this administration new started very quickly they laid
[37:23] out there were big, big changes coming to this agency.
[37:28] And just from a journalist's perspective, anytime that, you
[37:32] know, any sort of organization says we are going to lay off,
[37:37] you know, thousands of people and we are going to change the
[37:40] way that this agency does some things, that's going to make us
[37:44] look and say, OK, well, how, how is that process of change going?
[37:48] How what does that look like? And there have been areas, I
[37:53] think rightly so, where this, you know, there are
[37:57] contradictions that you are raising questions.
[38:00] I mean, even, you know, we're getting the CRL letters, but now
[38:04] where are all of the ad Toms? The flow of information out of
[38:09] the agency has also changed. And I don't think that is
[38:14] helping the situation. I guess in hindsight, probably
[38:19] not a good idea to let anyone run wild on healthcare.
[38:22] It's it's not it's not a framework that you can run wild
[38:26] on without dismantling it in in very negative ways.
[38:32] All right, well, why don't we move on to some of the data
[38:34] updates this week. There's there's a whole bunch
[38:36] cooking Paul's side of kinetics. Really interesting update for
[38:40] their non obstructive. Cardiomyopathy program.
[38:44] Yeah. And I'm assuming others have
[38:47] coverage in this area, so I can like kick it off and then maybe
[38:50] others can can chime in a bit. But but yeah, Cytokinetics had
[38:54] data this week from the Acacia trial which was for Affacampton
[39:00] and non obstructive HCM. The set up here was that I, you
[39:05] know, I think this was a study in a catalyst that a lot of
[39:09] investors were positioned positively for, you know, Mavic
[39:13] Hampton, the Bristol compound did not work and not
[39:16] obstructive, but when the full data came out, it showed that it
[39:19] was pretty close, which I think made people at least cautiously
[39:22] optimistic. The cytokinetics could, could
[39:24] thread the needle, you know, some of the kind of discussion
[39:27] coming out of the data. And then there's some laterals
[39:29] and then I'd love to hear others chime in or just, you know, one
[39:32] like how strong is how strong is the efficacy?
[39:34] The, the end points here are KCCQ and peak VO2 and you know,
[39:39] KCCQ, the effect size wasn't huge in the grand scheme of
[39:43] things, but you know, maybe good enough, you know, some debate
[39:47] around safety and EF and things like that.
[39:50] And you know, there's other companies in this area too, Like
[39:52] there's, there's edgewise right where there's that, which I, as
[39:56] I sort of understand it, I don't cover it, but my colleague does,
[39:59] is a pretty polarizing company as to whether or not they have
[40:01] something that, you know, is better than at the Hampton and
[40:04] could be safer or something that actually, you know, might have
[40:06] its own sort of issues that they fib.
[40:08] You know, there's Braveheart, there's a private company in
[40:10] this space. So huge market though, right?
[40:14] And, and huge catalyst and I think an important catalyst for
[40:16] sentiment because you know, Cytokinetics had, you know, some
[40:20] coverage in the media, you know, we can't really verify if it's
[40:23] right or wrong, right? But it was in sort of M&A
[40:25] discussions a number of years ago that was reported on that
[40:27] fell through, stock went down a lot.
[40:29] It's it's back up, you know, well over 100% off the bottom.
[40:33] They were able to raise a lot of money.
[40:34] So yeah, interesting data and a lot of offshoots and
[40:37] implications for others. Would would love to hear your
[40:39] guys perspective as well. Yeah.
[40:42] Anyone else following this space?
[40:48] No, if not, that's OK. We got we got a bunch of other
[40:51] updates to to go through. Maybe I'll I'll cover Artiva
[40:55] data this morning for their LONK platform combined with fluid air
[41:01] beam cyclophosphamide and Rituxan showing some very good
[41:05] data in rheumatoid arthritis with ACR 50 scores in the 70%
[41:11] range. A couple of one really
[41:13] interesting observation is that the responses seem to deepen
[41:18] over time. A lot of the CAR T programs and
[41:20] bispecific programs kind of have the opposite dynamic where they
[41:24] start strong and then and then give up some of the some of the
[41:27] efficacy, but but still finish with with robust product
[41:30] profiles. The Ottiva product profile
[41:34] actually got better as they followed patients longer.
[41:36] So we'll see how that evolves. They they also came out with a
[41:40] pivotal path forward and agreement with the FDA for her
[41:45] trial in rheumatoid arthritis comparing against Rituxan with
[41:50] what looks like a fairly sizable difference in ACR 50 rates
[41:55] relative to what Rituxan has reported.
[41:58] So kudos to, to Fred Aslan for, you know, for the work he's done
[42:03] at Ortiva for advancing this platform for, for kind of
[42:06] finding within a very crowded space of B cell depleters, some
[42:11] pretty significant room to, to navigate leveraging the
[42:16] strengths of their platform, much of which is, is really
[42:20] around tolerability and not having cytokine release syndrome
[42:24] or icons to worry about that, that can make the protocol much
[42:27] more amenable to, to use in the rheumatology community settings.
[42:33] Those those specialists can't really handle even low rates of
[42:37] CRS or icons just not really equipped to deal with it.
[42:40] And there there are the fairly sizable number of treatment
[42:44] refractory rheumatoid arthritis patients.
[42:47] So and Fred had been fairly modest and humble along the way
[42:51] quietly just executing and and and enrolling and and delivering
[42:56] not only just really meaningful set of data, but also all the
[43:00] way to A, to a right agreement with the FDA on the path, path
[43:06] forward for them. So not sure if if folks are
[43:09] following this general B cell depleting space or have thoughts
[43:12] on our TIVA or or or Fred. I'll just say that this is a
[43:21] space that I'm following. I think there's a lot of really
[43:23] exciting potentially game changing treatments that are in
[43:27] development here for patients. So I think it's it's an area
[43:31] where there's a lot of conversation and as we we get
[43:33] more and more data, we will see that become very competitive
[43:37] very quickly. Yeah.
[43:38] But but like just so many patients as we've seen in the I
[43:42] and I space, there's, there's so much room for so many successful
[43:46] products even if they're only modestly differentiated and if
[43:50] they're meaningfully differentiated.
[43:52] So nice to see that. For, for Fred, Josh, I was going
[43:55] to ask. You, you're the rheumatologist
[43:57] here, right? Fred's one of the few that seems
[43:59] to be going after RA as a first indication, probably not the
[44:02] area of greatest unmet need. I don't know what you thought
[44:05] your thoughts are there, but but it does it make sense to do
[44:09] rheumatoid arthritis? Are there other areas where you
[44:12] see this going in the future? Obviously others are doing
[44:15] myositis and MG and and everything other than RA.
[44:19] Maybe also common on on Sjogrens because the Sjogrens state I
[44:23] thought was what caught my attention.
[44:25] And, and Scleroderma systemic sclerosis.
[44:28] So I, I, I think the challenge right now is that there are a
[44:32] lot of really promising programs and it's the subtleties and the
[44:36] evolution of each program that'll determine the niche that
[44:40] it, it, it fits and. It's nearly impossible at this
[44:44] stage to have precision. Right, to to say, well, this
[44:49] product, this class, this modality is going to get this
[44:51] percent of share in this setting.
[44:54] And from from the big picture perspective, you just kind of
[44:57] have to have to step back and and again acknowledge like
[45:00] Otezla's still a multi billion dollar drug in, in psoriasis,
[45:04] right? Like, like, like the big picture
[45:07] here is just such a huge amount of unmet medical need that you
[45:13] know, there, there should be a seat at the table for
[45:15] differentiated products and that and that they're not all the
[45:18] same, right. And, and that means different
[45:21] specialists will gravitate towards different options,
[45:23] different patients will gravitate towards different
[45:25] options. The error bars are, are huge and
[45:29] there is still a lot to sort out first mover advantage going to
[45:31] be super important. Yeah.
[45:34] And, and in, in terms of RA and and the unmet need there, I
[45:38] think the answer is, yeah, there there's still important unmet
[45:41] medical need, but you got to have the right product, right?
[45:43] If you're coming with an ACR 50 score of 20%, probably not a not
[45:48] a lot of room for you in the treatment armamentarium.
[45:51] But if you can come with a much more meaningful ACR 50 score and
[45:57] by the way, a CRACR. Scoring itself is kind of a
[46:00] quagmire of, of of challenging data sets to it to interpret for
[46:04] nuances that are probably 222 expensive to get into at at this
[46:10] stage, but. Yeah, like, like I'm, I'm
[46:12] tracking a lot of it. It's hard to know who's going to
[46:15] be left out. It's hard to know who's going to
[46:17] be in. But having a first mover
[46:20] advantage and a strong data set and a differentiated profile is
[46:24] it's a pretty good start. Paula, I want to, I'm going to
[46:27] jump towards to a different topic because I know you're
[46:29] going to care about this one. And and this was the the clean
[46:33] update, regulatory update for their ALS program.
[46:37] Allison, your colleague Adam Foerstein wrote a pretty
[46:39] scathing note about his perspective of clean but
[46:43] irrespective of. What Adam I I know.
[46:47] Old Adam. Old Adam back.
[46:52] Biotech is. Back an old sassy Adam Paul, but
[46:56] path forward now, based on neurofilament data, this seems
[46:59] like a major shift in in the agency's willingness to consider
[47:04] this biomarker. Well, yeah, I mean, it's
[47:08] interesting the clean data is, you know, the the sub one drug
[47:15] tofersen from Biogen and Ionis, you know, failed in a
[47:18] placebo-controlled study. But that study for ALSI think
[47:22] it's widely viewed whether or not you believe in that drug or
[47:24] not that that study was too short, right.
[47:26] I think it was like 6 months placebo-controlled, which is
[47:28] insane for disease modification and neurodegeneration.
[47:32] And then over time as they followed patients for a longer
[47:34] patients on drug look like they were, you know, theoretically
[47:37] doing better than Natural History, but also they reduce
[47:39] neurofilament pretty substantially.
[47:42] Now the NFL reductions that they were seeing were closer to like
[47:44] 40%. And I think, you know, I'm glad
[47:49] you called on me, right, because I could just nerd out a
[47:51] neurofilamin. I really, really hugely believe
[47:53] that if you reduce neurofilament beyond the single to noise
[47:56] ratio, it needs something. I, I, I think neurofilament is
[48:00] like a metabolite of dead or damaged neurons.
[48:02] I think the evidence is so strong across 10 different
[48:05] conditions, you know, as it relates to clean, I'm not super
[48:09] in the weeds on their data, right?
[48:10] But, you know, it's not clear if the reductions they're sort of
[48:16] pointing to are, you know, maybe as unequivocal.
[48:21] Are you as close to that data, Josh?
[48:22] I mean, yeah, I understand Adam's perspective too.
[48:24] I mean, the kind of the the mechanism, you know, whatever,
[48:28] right, we can, we can kind of get into it.
[48:29] But as a release of neurofilament, I mean, I thought
[48:31] the Topherson example was sod one showed that the FDA kind of
[48:36] agrees with our view. I think the challenge is that no
[48:39] one else across neurodegeneration really is
[48:43] being able to show much on neurofilament like, but you
[48:45] know, Denali had an NFL data that was supported for their
[48:48] Hunter program. And to be honest, when the
[48:49] Denali NFL data became really meaningful at 18 months, I mean,
[48:53] that really made me a true believer.
[48:55] That drug is having a big impact.
[48:57] Yeah. But Denali I think was pretty
[48:58] clear that the FDA would not consider the neurofilament data.
[49:02] They focused exclusively on the on the heparin sulfate data that
[49:06] that was the puzzling part to me, right.
[49:08] Like all of a sudden, like for for Denali, which just got
[49:12] approved, not because of the neurofilament data to toggle
[49:15] over now and say clean. Oh yeah.
[49:16] Well, we'll look. At it is different divisions,
[49:18] though. Like to be like, it is like like
[49:20] Denali's dealing with the group that's approved, like all the
[49:23] bomber in drugs who just really haven't done nearly as much in
[49:26] neuroscience. It's a fairpoint.
[49:29] I mean, I guess that I guess this FDA has set some precedent
[49:33] for accelerative approval with Tofersen, right?
[49:36] The SOD one drug that again did not beat placebo, but lowered
[49:39] neurofilaments. So maybe because of that, like
[49:42] this has to be at least reviewable.
[49:44] I don't know. I do.
[49:46] Are you aware of like other data Clean has Josh that suggests the
[49:49] drug is working? I'm, I'm not close to the story.
[49:52] I've just like you covered Denali and have have also like
[49:56] you nerded out on, on neurofilaments as a biomarker
[49:59] and always wondered why the FDA was not amenable to considering
[50:04] them. And so I don't think it's
[50:05] inappropriate that they're considering them now.
[50:07] I just wonder what changed between like a year ago and
[50:11] today. They're like, Oh yeah, yeah,
[50:12] file on neurofilament and we'll we'll consider.
[50:16] Is this is this C Burr or they're both neuro and C dur?
[50:21] Der. Der, which approved Topher as
[50:25] well, that was. Totally.
[50:28] Yeah, same division. Yeah, I don't know.
[50:33] I think neurofilament is I, I think the biggest issue with it
[50:35] is like we just don't know how much you need to lower it to be
[50:38] clinically significant. But you know, if you remember
[50:42] the Huntington's program from Roche, right, that did worse
[50:45] than placebo in a phase three neurofilm, it was way elevated
[50:50] on drug versus placebo too. So there's even like in very
[50:53] different neurodegenerate diseases, there's like bi
[50:55] directional support of it. I I think it's, I think it's
[50:58] pretty good, but I don't know if I, I don't know how unequivocal
[51:01] this, this clean data is. I'm just not as in the weed all.
[51:05] Right, cool. Couple of other topics to to get
[51:08] through Allison coming back to you and into the I and I space.
[51:13] J&J had some interesting IBD data for its combo.
[51:19] Yeah. And Josh, I'll be interested to
[51:22] hear what you thought of this data, which was kind of a
[51:26] closely watched follow up to a 2022 trial that Johnson and
[51:32] Johnson read out for what is like the first combination
[51:36] therapy in development for ulcerative colitis and Crohn's
[51:39] disease. Their initial study a few years
[51:43] ago had shown that this could potentially double the effect in
[51:49] patients, which is great because so many patients with those two
[51:53] forms of inflammatory bowel disease just cannot find relief
[51:57] from the treatments currently on the market.
[51:59] This study, which tested their drugs Tremfya and Simponi
[52:04] together, didn't meet statistical significance.
[52:08] It didn't meet that primary endpoint, but the company was
[52:11] pleased enough with the data that they are going to move it
[52:14] into Phase 3 testing. They're going to move it forward
[52:18] specifically for highly refractory patients, patients
[52:22] who have tried two or more treatments for IBD and have
[52:28] failed to find relief with them. That's where you're looking
[52:31] through the data. Johnson and Johnson said that
[52:33] there's really nice signals in the data for that group and that
[52:37] could still be, you know, a nice market opportunity for them.
[52:41] Josh, what did you think of the data?
[52:44] I'm sorry. I've been a little perturbed at
[52:47] the way J&J has been reporting some of their clinical trial
[52:52] data and maybe painting it in a brighter light than it should
[52:57] be. I think we saw this routinely
[52:59] within Lexo and in a head scratching way that to be honest
[53:02] has made me wonder if they continue to really follow the
[53:05] credo of of really putting patients 1st and and nonprofits
[53:09] first. Good.
[53:09] Just just given some of those the the dialogue and and
[53:13] watching them go, you know, try to bash CG oncology in the NMIBC
[53:17] space. We're going to come back to that
[53:19] and then in a second if we have time is it was quite off
[53:21] putting. Especially because at the end of
[53:22] the day, J&J was just way off base with what they what they
[53:25] were saying their their drug was going to do so.
[53:27] Again, I'm with you on the, the what looks like a a clear
[53:31] benefit in the refractory patients.
[53:34] Not sure there's there's much to do beyond that.
[53:37] And to me, I I would have preferred a press release that
[53:40] perhaps was a little truer to the data I.
[53:43] Don't know if you agree or disagree with the back comment
[53:45] you. Know, Josh, it's funny that you
[53:48] mention that speaking to the team, they really were very much
[53:56] viewing this as a positive and pitching this as a very positive
[53:59] outcome for this data. And I'll tell you some anecdotes
[54:03] offline, but no, they, they were really pitching this as like
[54:07] very good outcome for this duet study.
[54:10] That's the name of the clinical trial and that this was
[54:13] overwhelmingly positive. But at the end of the day, it
[54:16] didn't meet statistical significance.
[54:19] It didn't meet their primary endpoint.
[54:21] And while they are advancing it, it is in a subgroup of patients.
[54:24] So, you know, it's not a total loss, but I do think that this
[54:30] may be, you know, it would make me look at, you know, other some
[54:34] of the other companies that are working on combination therapies
[54:37] to see if they fare better than particularly some of the
[54:40] companies that are working with not just existing drugs, but
[54:44] drug can, you know, new candidates that they are are
[54:48] folding into combination therapies, which we're seeing at
[54:50] the Inspired Therapeutics both do.
[54:53] Yeah, I guess I find J&J communicates often like a small
[54:57] cap biotech company. Rather than very mature from the
[55:02] company and, and I don't know it just it just seems a little
[55:05] misaligned relative to what I might expect from from J&J, but
[55:08] that might just be my own perception and and bias and so
[55:13] or not. But it is, yeah, good.
[55:16] Yeah. And I was just going to time, I
[55:17] mean, I think that the, the we've been doing a fair amount
[55:19] of work in IBD and talking to a lot of care was into this for
[55:22] for other reasons. And I think this data stuff at
[55:25] what was expected. People expected a much better
[55:29] data set. PNF is sort of the weaker of the
[55:33] new mechanism. So I would say the weaker of the
[55:35] mechanisms and there's obviously more interest in sort of newer
[55:39] mechanisms. So interesting.
[55:43] I don't think it puts to rest the concept of combo, but I
[55:46] think the newer sort of regiments are potentially going
[55:49] to be a lot more interesting. I had asked one of the Vice
[55:54] presidents over at J&J about something, you know, like words.
[55:58] Are you guys thinking of, you know, some of these newer
[56:01] mechanisms and folding that in, you know, licensing one of those
[56:06] or requiring one of those and, and trying to create a new
[56:09] combination therapy around that? Because it seems I mean
[56:12] particularly coming out of this, this clinical study and you know
[56:16] the discussion that their, their Aisle 23 is not the best
[56:20] Illinois 23 out there, that the components might be not the
[56:24] strongest out there. And they were very entertained
[56:28] that I tried to ask that question.
[56:29] And basically like we're not even going to go there.
[56:31] Don't even, we're not going to tell you anything about our
[56:34] plans for potentially, you know, a next Gen. approach with some
[56:38] newer mechanisms of action. And this is, by the way, a space
[56:41] that China is very active in. And so you always have to keep,
[56:45] you know, eyes open 24 hours a day from back your eyes to see
[56:49] what what China has. They move fast.
[56:51] They they move with speed, obviously low cost and now with
[56:55] real excellence and so. In the race to figure out what's
[56:58] going to be the best China, especially areas and fields that
[57:02] China's focused on, I and Ibn One got to be.
[57:06] Cognizant that that there might be things happening there that
[57:09] that we're. We're a little bit.
[57:12] Blind to and and can come out of the blue and and surprise.
[57:15] Maybe last topic, kind of the Segway from discussion of J&J
[57:19] and the NMIBC Space Engine providing an update for for
[57:24] their data in NMIBC for their immune stimulant.
[57:28] That previous kind of data look like it might have been a little
[57:31] bit more competitive with the leaders that include J&J with
[57:35] the and Lexo and CG Oncology and kudos to to Arthur and Amba and
[57:40] the team there for just doing an exemplary.
[57:43] Job with recruitist imaging and and navigating in this, you know
[57:47] ever shifting and MIBC landscape.
[57:50] But it looks like the the update for Ng now is has fallen a
[57:54] little bit short of. Expectations and and the stock
[57:57] is down. A little today we'll we'll see
[58:00] what, what path forward there there may be.
[58:03] And, and also, you know, keep in mind that in, in theory, there
[58:07] may be multiple lines of, of therapies that NMIBC patients
[58:11] are able to receive. I think the question that many
[58:13] of us are struggling with is how many before ultimately
[58:16] physicians say we've tried enough medical options and it's
[58:19] time to move. To a a cystectomy, which is not
[58:22] a not a fun procedure, but by far high rate of morbidity and
[58:26] and mortality but. I think also highlights this
[58:29] world of innovation that we're in.
[58:31] The bar keeps getting set higher and higher because of the
[58:33] quality of products that are that are coming along from this
[58:37] really incredible industry. And as a result, you know when
[58:40] that bar gets set higher, you have to stay competitive and and
[58:43] if you can't stay competitive, figure out exactly.
[58:45] Where you're going to fit in I. Think we're at the top of the
[58:48] hour? Unless anyone have any closing
[58:51] remarks or topics that you wanted to quickly touch upon
[58:54] before we close up? I had a question for Eric from
[58:58] Adam. This was a special request.
[59:03] We will make time for this. Could we just time as needed for
[59:08] this? We just say Happy Mother's Day
[59:10] to all and end the call. Right now, please.
[59:15] Eric, what do you think about these Ivanessimab Flyers?
[59:19] Boy, Adam and I have been talking spending.
[59:21] Both of us have been spending way too much time on on this
[59:26] this discussion. So fortunately, ASCO is what,
[59:29] about 2 1/2 three weeks away? We're going to see the data
[59:32] there and I can't wait. My guess is it'll be quite good
[59:36] on the overall survival endpoint.
[59:38] But yes, the Flyers have been causing much discussion and and
[59:42] scuttleblow on the street, and Adam's article was terrific.
[59:47] I was hoping it was going to be so much juicier than that.
[59:49] Sorry. Don't worry.
[59:52] Next. Time get something really juicy.
[59:55] All right, folks, I'm. Curious who made these Flyers
[59:58] that make it look like this is like the drug to end all drugs?
[1:00:02] Well, that's the $64,000 question.
[1:00:04] And so far, no. But well, again, my sources
[1:00:08] suggested that that Kesso is in fact the originator of of the
[1:00:12] artwork that you referenced and it is quite juicy once you get
[1:00:15] into it.

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