[Music] Welcome to this week's episode of The Readout Loud, a weekly biotech podcast from STAT. I'm Allison DeAngelis. I'm Adam Forstein. And I'm Elaine Chun. It's Thursday, May 7th, and on this week's episode, biotech IPOs are back. After a prolonged downturn, investors now seem to be much more open to public offerings. Seaport Therapeutics is one of the companies that just went public and their CEO, Daphne Zohar, joins us to discuss the experience. But first, a recap of this week's news and a word from our sponsor. [Music] Drug development and kidney disease needs more than broad, real-world data. It needs precision. Green aside IQ, Natarah's kidney-focused clinical genomic database, links genetic, clinical, lab, and claims data across the large longitudinal population of patients living with chronic kidney disease. That means bio-pharmate teams can better identify meaningful patient subgroups, understand disease trajectories, and make smarter decisions across discovery, trial design, biomarker strategy, and commercialization. Green aside IQ helps turn kidney genetics into actionable development insight. To learn how real-world evidence can sharpen your nephrology strategy, visit natarahsrena site
[email protected]/renasite IQ. So, I heard that this is the 400th episode of The Readout Loud. What's your source? Elaine, you heard correctly. That is still stunning to me that has not sunk in. Adam, how does it feel to have done 400 episodes at this podcast? It's kind of crazy, honestly. I've done something 400 times. I don't know, that's a lot. It means that if you calculated, that's almost eight years of the podcast. I know. Think about that. I wonder if there's anyone who's listened to 400 episodes of The Readout Loud. If you're out there and you've listened to 400 episodes, you need to get in touch with us because we will bring you on the show and interview you. I assume this one person called Rick Burr. Yeah, you can't be employed by stats. It does not count. Someone out there who is not employed by stats has listened to all 400 episodes. I mean, God bless you if you have. But yeah, we want to talk to you. We'll bring you on as a special guest in one of the future episodes of The Podcast. Reach out. All right, folks. Should we get into the news on this lovely 400th episode? Yes, speaking of 400, I wonder if how many days has Marty McCarty been FDA commissioner? Has he been FDA commissioner for 400 days yet? It's been over a year. Yeah. Actually, we probably missed his 400th day because he got confirmed in what February 2025. Somebody can do the math. I just wonder. See the fact check us. I don't know if he's going to be the FDA commissioner for his on day 600 or maybe, I don't know, it seems like he's a little bit on thin ice. Yeah. What are you guys hearing? Yes, there have been reports this week that FDA commissioner Marty McCarty, his future is a bit in question after the agency has faced controversy after controversy, including most recently, apparently pressure from President Trump to approve flavored vapes. The Wall Street Journal reported this week that McCarty was hesitant to give in and approve flavored vapes because of some concerns about public health risk and that it would appeal to young people and those particularly under 18. Yeah. I mean, also this week our colleague Lizzie Lawrence reported that Santa Fe, which had a commissioner voucher for its type one diabetes drug, Santa Fe has actually asked the FDA to pull the drug out of the commissioner voucher program because well, this comes after Lizzie reports after top drug regulator Tracy Beth Hogue disagreed with a staff decision to approve the drug. So this is another instance which in the past we rarely saw of a center director getting so closely involved with a drug review decision. Yeah, we were joking folks right before we started recording the podcast like we wanted to check the wires to see whether or not McCarty saw the job because it does feel like it feels like it's building up to this moment where you know, he may he may no longer have a job. We obviously don't know that right now. You know, with our luck, it'll happen this afternoon after we record this podcast. But it's interesting, you know, it's you know, the agency on number, Cari has been highly politicized as as our colleague Lizzie Lawrence has reported and others have reported. And you know, the general tone seems to be that he McCarty has become a bit of a distraction from the White House's perspective and that's not what somebody wants or not what the White House wants in a you know, in a political appointee atop of a very, very important agency. So anyway, it's a long way of saying we'll see what happens. Yeah, and to be fair to McCarty, well, it's fair as you can't be. It's kind of a mix of like, it seems the White House is upset about the decisions that appear to be politicized, you know, like maybe some of the ways the voucher program has has been executed. The reversals and rejections of gene therapies under the Nipersaw that we've talked about before, you know, but at the same time, the White House also seems to be wanting the FDA and McCarty to follow its political agendas. Like Allison just talked about how Trump pressured McCarty to approve the flavored vapes, even though McCarty, according to the Wall Street Journal reporting, was hesitant to do that given the public health risk. So it's kind of like, you can't really have it both ways in that position. Yeah, and also to be fair, it's interesting I was just talking to Adventure Capitalist yesterday and asked them how they were feeling about, you know, working with regulators over this last year, how it compares to previous years. And, you know, this, these folks said that for the most part, there are still, you know, good people at the FDA, they have, you know, in some branches of the FDA, things are really moving like normal. You're getting very consistent feedback. There's just kind of a few areas of the agency where things are just difficult to work with. And even in some cases, they were saying they're getting, you know, one group at the FDA says one thing and then another group says something that completely contradicts them. But I mean, for the most part, on the whole, the agency is doing the work. Drugs are being approved. They are getting feedback. You know, most of their companies are not seeing, you know, huge upheavals. There were just these pockets at the agency where the, the ability to kind of interact with people get consistent feedback has been tricky over this last year. So it's not as if the agency, it seems as a total like dumpster fire right now, but there are things that need to, you know, that are still very much influx at the FDA. Yeah. And the last thing on the FDA here during this podcast is, yeah, a rubber story today about you may have remembered the case of a tar off by our therapeutics and Pierre February pharmaceuticals developing a drug called Evvalo for Rare Cancer, a rare type of cancer that was rejected back in January. And, you know, that it caused some controversy because at the time, the reasons for the FDA is rejecting the drug around, you know, around the use of a single arm clinical trial kind of came as a surprise to both of those companies. None of these sort of concerns that the FDA had raised in the complete response letter had been actually had been raised with the company during the review process. Well, there are some news today. Both companies, again, Pierre Frabre and Etara have reached an agreement with the FDA that kind of walk back that that concern that the agency had about the use of a single arm clinical trial and the agreement now calls for the company is going to basically provide new data updated data a few more patients longer term follow up from this same clinical trial and they will be submitting those data to the FDA for another review of a valo. So the important point here being that the companies do not have to conduct a new and entirely new clinical trial. See, this is like a perfect example of it feels like what's happening at the agency these days, which is that there are cases where for the most part, it seems like things are operating. There are weird cases where you're having things be walked back, contradictory opinions, and so on. So I guess we'll, you know, we'll see what what the agency looks like this time next week. So we couldn't have a 400 that episode of this podcast without speaking about obesity. Elaine. Yeah, but I wonder what how far into the podcast did that actually start happening? Did obesity start actually? I don't know, you know, it used to be, it used to be that this podcast always talked about Alzheimer's. That was the running joke now. It's obesity. Yeah. I almost forget the pre obesity times. That was before. Are you sure that's not a mirage? That was before my time. I've only, I've only, I've only,
ever experienced obesity times. You only lived in the readout loud obesity era. Yeah, obesity, AD. OK, so we got more numbers this week about the oral GLP1 market. So far, it looks like Nova Nordisk is winning when reporting earnings this week. Nova said that there are now more than 2 million prescriptions of its Wagobe pill since it launched in January, which Nova says makes it the strongest ever GLP1 volume launch in the US. On a call with reporters, Nova CEO Mike Duster said that nearly 80% of those on the Wagobe pill hadn't been on other GLP1 treatments previously. And there are also signs that patients are moving from competitor products to the Wagobe pill. Duster also said that Nova hasn't seen any hit disales since Eli Lilly last launched its GLP1 pill found AO. So so far, it looks like Nova's Wagobe pill launch was going really strong. On the flip side, there was some controversy this week around Lilly's pill. Investors noticed that in the FDA's adverse event reporting system, there was a case of hepatic failure reported in a patient taking found AO. This is important because observers, investors have long questioned the risk of liver toxicity, even though Lilly said that it hasn't seen any liver concerns in its found AO trials. The drug is a small molecule. And there had been some investigational small molecule, GLP1 candidates that had shown liver concerns. And also, if you recall, Lilly got found AO approved through one of these commissioner vouchers. And as we just talked about, this is a very controversial process. A lot of people are concerned about it being politicized. And so there are a lot of questions around whether found AO received a thorough enough review before it got approved. Elaine, how has the reaction been to this case of hepatic failure? There's so much attention on Lilly right now, Lilly and Novo and the launches of their pills. Having a case like this pop up seems like it could be something like a big topic of conversation. Yeah, I think that there was definitely a lot of talk about this liver failure case, at least on the part of analysts. And then investors also, they seem to mostly brush it off to be fair. We know that the FDA adverse reporting system is all self-reported, so we don't know for sure if these events are actually caused by the drug itself. It was one case. And when you have a drug given out to many, many people inevitably, there will be rare cases popping up. So it's hard to read much into that one case. But this goes back to something we've talked about in this podcast is the question of whether investors, analysts, are a little too easy on Lilly. Yes, this was one case. I think a lot of people brush it off. But I do think it's reasonable for people to have questions and to continue to watch out for these cases. I mean, analysts have been treating Lilly as if anything they do is great and they can do no wrong. At least from what we're seeing now, they kind of got it wrong on how competitive Lilly's pill would be because so far, novos will go be pill is dominating. I know it's still early days, but earlier analysts were all predicting that Lilly's pill would be the blockbuster and would dominate the world market. All right, well, we will always keep an eye on everything happening in obesity. I'm curious if if by episode, let's say 600, obesity is still the dominant topic. Or if we've moved on to something else. But in the meantime, Adam, tell us what's happening with cytokinetics. Yeah, I guess a nice round of applause for cytokinetics and its CEO, Robert Blum, this week. They reported that their drug, mycorzo, and I think I'm pronouncing that correctly, significantly improved heart failure symptoms and cardiovascular fitness in patients with an inherited heart disorder called non-obstructive hypertrophic cardiomyopathy. That is a mouthful. Save it three times fast. I will not do that. You may recall mycorzo was recently launched as a treatment for a more severe condition, a related condition called obstructive hypertrophic cardiomyopathy. But with these new results in the non-obstructive form of the disease, cytokinetics is getting closer to potentially marketing the drug to people to a much larger set of patients and could potentially double sales of the drug. (upbeat music) Biotech IPOs are back. You will recall that Wall Street debuts were few and far between during biotech's dark times, but the market has rebounded and investors have become more receptive to biotech IPOs. So far in 2026, 10 companies have gone public, raising almost $3.2 billion in total. Seaport therapeutics was one of these biotechs that are going public. Last week, Seaport, which is developing neuropsychiatric medicines, raised $255 million, selling just over 14 million shares at $18 a piece. Joining us now to chat about the IPO and what Seaport intends to do with the money they've just raised is Daphne Zohar, Seaport's co-founder and CEO. Daphne, welcome back to the podcast. Thanks, it's great to be here. - So Daphne, you're a week removed from the road show and the closing of the Seaport IPO. Was it exhausting? Have you recovered? What was it like? - Yeah, it's actually been a crazy few weeks. I was in a very serious car crash with my daughter, mid-April, and she's fine. A drunk driver hit us at a stoplight while he was going for 80 miles per hour. Yeah, his carlet on fire, both cars were totaled. I knocked the headrest off the seat. It was surreal, and for a minute, I was like, is this it? But thankfully, everyone was fine. I fractured my leg and I was in CP, and I just kind of had to suck it up and start a road show and have 120 meetings. So luckily, it was almost entirely virtual. So it was almost like a movie ending to be ringing the bell on NASDAQ with my family and the team just a couple weeks later. So nobody could see me hobbling up to the stage. But it was also fitting that Friday was a first day of mental health awareness month, and for reinforcing the mission. And I'm happy to say more about that. Yeah, can you tell us more about that? And what's he port is developing? And the motivation behind the drugs that you're developing? Yeah, so first of all, there's about a billion people struggling with mental illness in the world. There's over 300 million people struggling with depression, living with depression, living with anxiety. And many of us are inspired by somebody that we know that's been having a hard time. In my case, I have several family members, including my daughter has previously supported me sharing her part of this because she wants to raise awareness and reduce the stigma. So for us, it was really, I think it's really important to remember the mission. And one of the things that I would note is that depression is not only disabling. These conditions can also be deadly. And one alarming stat for me, as a parent, is that suicide is among the top three causes of death and adolescence right now. So we really need better medicines. And if you look across the medicines that have been developed for depression and anxiety, they have helped millions of patients. They have been really commercially successful. And-- but they still have limitations. And these are limitations like they take weeks to work. They don't work for many patients. They have unfavorable side effects, like sexual dysfunction, weak gain, and sleep disturbances. And so we really are aiming to do better across all three of those parameters with the medicines we're developing at seaport. So definitely, I mean, you've been working on new medicines for mental health and psychiatric disorders for a few years. Seaport is kind of your follow-up to coronetheraputics. How is seaport different from caruna? Are there any similarities or kind of through lines in your experience developing psychiatric medications? For sure. So there are some similarities to caruna. And then there's also some important differences in the case of caruna and seaport. And we're starting with medicines that we know work. The parent molecule works. So in the case of caruna, we knew that it's a normal and worked. We came up with this idea of CARXT, which now is called Co-BENFI, App CareTech, my former company. And then we-- I think one other important piece of this is designing and executing clinical studies. Because in this arena in our psychiatry, it's really important to do that with a team that has experience and has, I would say, scar tissue. But in the case of caruna, there was three successful registration in major-length studies. And so we're applying some of those learnings. And I'm happy to talk about those. In other ways, we're really-- we have some differences that we-- I think actually advantages that we didn't have when we were forming caruna, including-- when we started caruna and the CARXT program didn't have composition of matter IP. So we have a pipeline. We have composition of matter IP. And we also have this glyph platform, which is, I think, really--
exciting platform that we're working on. Can you tell us a little bit more about the glyph platform? Yeah, so the glyph platform cloaks the drugs that the body recognizes it as if it were a dietary fat, and then it traffics it through the lymphatic system. So it's almost like a side root bypassing the liver, bypassing first-pass metabolism. What that does is because less drugs metabolized by the liver, more drug can get the brain. It also helps to overcome issues. For example, like poor drug-like properties, like low oral bi availability, high PK variability, liver-related AEs, and you can get the same exposure of a drug at a lower dose, which can help with side effects. And we can also take drugs that previously could not be administered orally and administered them orally. So those are some of the things the glyph platform can do. And importantly, every time you glyph a molecule, you create new composition of matter, IP. So, Devon, your lead drug in the pipeline is called SPT 300 or glyph aloe. You're developing it for a major depressive disorder. Tell us how you're applying this glyph technology to this molecule and what would be the potential benefits or advantages of it. Yeah, so unmodified aloe-prignan alone. When you administer it orally, over 90% is lost to first-pass metabolism. And you can't actually administer it orally. So one of the things that we're doing is we're enabling oral administration of endogenous aloe-prignan alone. And aloe-prignan alone has been shown to work in a form of depression called postpartum depression, which is characterized by a high anxiety. It's also been, actually, people remember it as not being approved in MDD, but five out of six studies with serranolone, which is a chemical analog of aloe-prignan alone, actually met their primary endpoint. There's a number of clinical design and execution features that were addressing as well. So that was the old sage drug, right? Sage was developing that in depression if I recall correctly, right? Right. So that's a chemical analog of what we're developing. We're developing an oral aloe-prignan alone. They did have an IV version of aloe-prignan alone, but that was administered via 60-hour IV infusion. So a number of things that we're doing differently from clinical sign perspective include dosing for the full six-week primary endpoint. They only dose for two weeks. They had this, I think, theory that it could be a one-and-done treatment for depression, and we view this as more of a chronic condition. So, definitely going back to the comparisons between Karuna. And now, when Kabanfi was approved in 2024, it was seen as the first new treatment for schizophrenia in decades. However, we've seen lately that the commercial launch under Bristol has been challenging. Sales have not met initial expectations. Is there anything you take from the Kabanfi experience into now? And is there anything you see from Kabanfi that changes the way or impacts the way that seaport is developing its own medicines? Yeah, so I'll start with the launch, and then I'll go to the clinical learnings because the clinical learnings are quite relevant. So, in terms of the launch, I understand it's going a bit slower than expected, but analysts are still projecting multi-billion dollars in annual peak sales. So it could be very big, particularly if dementia-related psychosis data look good. As you mentioned, it's a new mechanism, and physicians need to learn about it. Kabanfi has a few important advantages, including the ability to address the negative and cognitive symptoms, and the fact that you don't have the weight gain or Parkinsonian, like movement disorder, AES, that other schizophrenia medicines have. But some of the challenges I, from what I understand, come from the BID or twice daily dosing in this population, coupled with a food effect, protrospeum, which could affect xenomal and AES if it's not taken as prescribed. So in this population, that can be challenging, but less so for dementia-related psychosis patients who are given their meds. They've also had some reimbursement challenges, which I understand they're working through. In terms of learnings for seaport, all the medicines we're developing have one daily dosing, so we don't expect that to be an issue, we don't expect a food effect. And I'd also say depression and anxiety are much larger indications with over 300 million people affected for both of those indications. But there are a number of other learnings from Karruna that I think are very relevant to seaport, particularly in applying the approaches to clinical design and execution that led Karruna to have three successful registration enabling studies. And as you probably know running clinical studies in nurse psychiatry has been challenging, it's important to have a teen that has experience in designing and executing studies to manage, for example, placebo response, ensure that there's qualified patient participants and select the right sites. So a couple of things that we're doing that build on what Karruna did. For example, one of the things that we are doing is to reduce the placebo response, we're optimizing the frequency of clinician and administered assessments, and including a single treatment part. And that's really important, that was something that Karruna did, because both the frequency of assessments and the number of active farms are known to increase the placebo response. And that sort of makes sense, right? Because if you're a clinician and you're administering the ham D to a patient, you're interacting with that patient, and that has therapeutic benefits. If you're doing that very often, that can increase the placebo response. Or the number of active arms, if a patient believes that they have a higher likelihood of being on drug, there's an expectation bias. We're also doing some things like scrutinizing site selection, patient enrollment. And I think, for example, there's patients in role multiple studies, there's databases where you can find out who those patients are, and exclude them from your study. There's some patients that improve a tremendous amount from screening and baseline, so those are excluded from our study. Definitely, I want to jump back to the IPO process, because it's something that we are seeing more biotech's weight into, and more biotech's even simply consider than a few years ago. Why take C-Port Public now? Did you in the board consider alternatives? What made you guys think that this might be the best way to raise money for the company? So we've been functioning pretty much like a public company in terms of the way that we approach the milestones, the budget, all of those things. And as we grow, and if we have success in our clinical studies, being a public company enables you to access capital to quickly be able to run the next studies or your medicine. So it's the right place for a company that's rapidly growing, moving towards potential commercialization. And there was no question. The question was more a question of when to do it. And of course, there's always, I think, in this area where these are really large indications, there of course, large pharma companies who are interested and everything. But we have a lot of conviction in these medicines, and we believe that we like to develop them ourselves. So that's part of it. So definitely, I want to follow up on that because these are large indications that require oftentimes quite large clinical trials, which can end up being very costly. And it feels as, from my perspective, as the biotech market has begun to bounce back, we've seen a little bit more openness to the neurofield. And I'm not sure to what extent that's related. What do you think? Yes, so maybe I'll start with the second part of that. There's almost like a neuroscience renaissance taking place. And there's an explosion of new science. I pointed to the recent approval from Denali. And there's a lot of really exciting science. But there's also a renewed interest on the part of pharmaceutical companies as they look for the next obesity-like opportunity to have an impact on society. In terms of the studies and the design of the studies, I do think that it's important to be capital-efficient, to think about the best way to execute the studies. I'd say that neuropsychiatry studies are sort of in the middle. I mean, obviously, if you're doing schizophrenia and it's inpatient, that's going to be more expensive than an outpatient study in major depression. So definitely, you are a biotech veteran. As we mentioned before, co-founding seaport, you know, you go founded and led pure tech health, which was also publicly traded. I believe, correct me if I'm wrong, I believe pure tech's IPO was something like in 2015 on the London Exchange. How were these two IPO experiences the same or different for you? Yeah, they were quite different. So I'll go back to pure tech and founding of pure tech. And it was much harder to raise that first $100,000 from angel investors at pure tech than it was to raise hundreds of millions of dollars right now. And that's part of, I think, just career development and having developed a track record. So I'll talk, I'll say a couple of words about that. We had a lot of interest, both in our series A, series B, and of course, as we talk to investors, it's part of this process. And that gives you a sense of tremendous responsibility and you have to remember to be humble and maintain sort of that capital discipline that you had before. But I would say from an early career perspective, it might be really important.
reassuring for people to know that there's a tipping point. Like it's really hard in the early days and it gets easier as you execute and prove yourself. So that's one piece of it. In terms of the differences and similarities between what we were doing at PureTech and what we're doing here at Seaport, there's a few things that we've ported over that I think were really good that we did at PureTech. So one of the things relates to having a platform in multiple programs and what that does is it aligns, it aligns you with your shareholders and that if you have something that's not working, you're going to move your resources to another program. So you have multiple opportunities to have success and you're completely aligned in that. Whereas if you only have one product, there's a tendency to want to continue and kind of see the best in data, post-rock analysis and all that kind of stuff. Another thing that I think is positive that we've ported over is some of the biggest successes with PureTech, including Karuna and also I would point to that their recent phase to be read out with an IPF. Our drugs that had proven efficacy before and then you're enabling them to reach patients by doing something different. So there's innovation on the part of patients, but the science is based on older clinical studies. And here we have the parent molecules that we're pursuing have shown efficacy and what we're doing is we're enabling them to really have an impact on patients. Well, definitely. We are very happy that you and your daughter are okay after that car wreck and I hope we hope that the leg heals well and that yeah, it's pretty amazing that you did all that right before an IPO. That is sort of crazy, but again, thanks for joining us and sharing the story with us. Yeah, thanks so much. It was great to speak with you guys. It's always a pleasure and yeah, really fun to talk to you. Thank you. And that does it for another episode of the Readout Loud, the 400th episode. Thank you to Hyacinth and Bonato for producing this week's episode. Hyacinth also has been around since the very beginning. Woo! Hyacinth! Yeah, yeah. Our senior producer, Isalisa Ambrose, our executive producer is Rick Burke, our favorite listener and the one who probably listens to us most often. I'm kidding. And our theme music is by Brian Joel. We'd love to hear from you. Tell us what you like about this week's episode, what you didn't like, and I really want to hear from that person out there who's listened to all 400 episodes. So please get in touch. You can do all that by sending us an email at Readout Loud at statinist.com. And if you like what we do, leave a review or rating on Apple podcasts or whichever platform you use to get your podcasts. We'll see you next week. Onward to 401. Onward to 401.
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