Biotech Hangout: Episode 194 - August 28, 2026

Sourced by podcast-ingest on 2026-08-31. Auto-transcribed via AssemblyAI (universal-2, en). Speakers identified by AssemblyAI Speaker Identification using the per-podcast host/regulars hints; the resulting label→name mapping is in the frontmatter. Duration: 1h01m. Episode page: https://podcasters.spotify.com/pod/show/biotechhangout/episodes/Episode-194---August-28--2026-e3o1e5j. Audio: https://anchor.fm/s/55bdff38/podcast/play/124876403/https%3A%2F%2Fd3ctxlq1ktw2nl.cloudfront.net%2Fstaging%2F2026-7-28%2F430737408-44100-2-fecf85b2fff15.m4a.

Show notes (from RSS)

On this week's episode, Daphne Zohar, Eric Schmidt, Sam Fazeli, and Graig Suvannavejh open with a strong week for biotech, partially driven by M&A, noting it's already past 2025's full-year total. The group turns to Moderna, whose melanoma cancer vaccine data sent shares up nearly 200% and stirred some mixed feelings from investors. Contrastly, BioNTech's decision to halt its colorectal cancer vaccine trial was also noted. In data news, Revolution Medicines' FDA approval of daraxonrasib (RASONQUE) for pancreatic cancer drew attention for its potential first-line use and implications for trials behind it, while Akeso/Summit's ivonescimab was approved in China for NSCLC and also reported positive Phase 3 data in biliary tract cancer, reinforcing the case for VEGF/PD-1 bispecifics. Also in data news, AstraZeneca's full dataset of eplontersen for ATTR-CM raised doubts about the class of RNA-targeted silencers over currently marketed drugs that “silence” TTR proteins, while EyePoint's Phase 3 miss in wet AMD sent shares down about 70%. The conversation shifts to policy, where the group discusses pros and cons of FDA commissioner nominee Heidi Overton, the HHS plans for two new deputy roles, alongside concerns over declining U.S. IND filings versus China's rising trial volume. The episode concludes with Amylyx raising over $500 million on strong avexitide data in post-bariatric hypoglycemia, and J&J's Imaavy earning a second indication, expanding the anti-FcRn class. *This episode aired on August 28, 2026.

Transcript

Daphne Zohar: You're listening to Biotech Hangout, a live and unedited weekly discussion of all the latest news in our industry with a group of biotech experts. I'm Daphne Zohar and my co hosts today are Eric Schmidt, Sam Fazeli, and Greg Suvanovich. For more information about our hosts and guest speakers, or to listen to the most recent episode, please go to biotech hangout.com Sam I can't. I think, Sam, you need to go on to mute. I can hear you in the background. So it's been a great run for biotech. I haven't looked today. I think it's down. But overall the XBI was up around 80% over the past 12 months, massively outperforming the S and P, which was up only around 20% over the same period. Despite all the noise around China, MFN tariffs, FDA leadership and general policy uncertainty, biotech capital markets have been pretty strong. We've already seen 20 IPOs this year versus just nine in 2025, including some of the largest biotech IPOs on record with Parabolas and Kylera. Part of this is driven by the M and A momentum, which doesn't look like it's anywhere near slowing down. We're already past 2025's full year deal total with more than $30 billion plus deals and roughly 138 billion announced year to date. A lot of that is being driven by Big Pharma's patent cliff. We've talked a lot about that. An estimated 180 billion of impact there through 2032. So they need the growth and they're increasingly willing to compete for it. There's more bidders per deal. There's less patience to wait around for data. Interestingly, premiums have actually been compressing a bit even as the bidding gets more competitive. I assume some of that is that M and A expectation is already priced into public stocks. One interesting side note is if you look at XBI's membership since a lot last peak in February 2021, of the 169 components back then, only 74 are still in the index today. So that's roughly a quarter. I'm sorry, roughly half. Roughly a quarter of those exits were the good kind acquisitions, but a third fell out by dropping below the market cap threshold. And one of the things that I think is really important to note is that the mix underneath this rally looks pretty different. So if you look back to the last peaks, mid cap Bio M and a was about 67 billion and 66 billion was the equity issuance. So issuance and M and A were balanced this year. This past year, SMID Biotech M&A has run around 143 billion, which is more than double the 2020 and 2021 pace. And there's only been about 59 billion of equity issuance. So M and A is running well ahead of issuance now. And IPOs while coming back, are much more selective. I don't know if you guys know of one, but I don't think there's been a preclinical IPO this cycle versus 19 in the year before the last peak. So this week was also a bit of a throwback with Moderna driving generalist interest in the sector. Eric and Sam, can you comment on the Moderna news and its broader impact on the sector? We'll start with Eric.

Josh Schimmer: Well, I think Sam's going to talk about the news itself, but let's talk about the influx of generalist interest that you just noted, Daphne, that has come with this news. I mean, first, you know, not only has it been a great year for biotech, but it's been a great month for biotech. We're taking it on the chin today, as you've noted, down a few percent, but I think we're up about 7% in the month of August. And I think a great majority of that performance was probably driven by the big headline news that Sam will discuss how an MRNA vaccine was able to prevent recurrence of cancer and melanoma. So everything Moderna always gets exaggerated and everything with MRNA vaccines adds another level of interest. And we saw the indices up meaningfully about 7% on the day of the news. We saw Moderna go up almost 200% on the day of the news. And it wasn't just this stock. It was anything and everything around cancer vaccines that also went higher and really anything to do with biotech that went higher that day. So conversely, and Sam and I were emailing about that, you might think that with all the success we've had in biotech over the past year that you very keenly noted, and then topping it off in August with another great few weeks of performance, that biotech investors would be on Cloud nine. Yet conversely, a lot of people have been bitching over the last couple weeks and they've been bitching about the, the somewhat, I guess, unsophisticated influx of investment that they perceived becoming into the space with generalists, overflowing specialist interests and generalist funds going into, quote, all the wrong stocks. A lot of people of course, were short Moderna. A lot of people, of course, who are using the XBI benchmark to judge their performance did not own Moderna long only funds. And as a result, the Moderna influx made a lot of people very, very unhappy. I think we were both picking up on that. Sam, is that, is that correct?

Sam Fazeli: Yeah, absolutely. I mean, you know, the stock was trading around the 50, $60 range for about six months. And then on the day August 19, we, we're looking at 170. It closed at just over 170, which was a. I mean, you know, if you were short, that was a very tough one. So. And now I've settled around 140 range. Yeah. Shall I keep going on the, on the news itself, Eric? So August 19th, definitely news. The Moderna melanoma trial with their cancer vaccine. I apologize that I'm going to call it cancer vaccine. It just rolls off the tongue a lot easier than intismidin autogene or individualized neoantigen therapy. Cancer vaccine. The world's decided that's what it is. Interpath 001 trial, phase three. Very well designed. Looking at the vaccine which is generated per patient. Each patient goes in after their surgery. The tumor is used using their algorithm, which is an important point. Identify the neoantigens, I don't know, 2030, I can't remember the exact number, goes into an MRNA machine, MRNA is produced and you inject that into the patients over several weeks along with Merckx Keytruda. And it was being tested against the standard of care in this setting, which is Keytruda. And these are patients with completely resected tumors, stage 2B to 4. And apparently it worked, which is what the headline news is. Recurrence free survival hit key secondary endpoint of distant metastasis. Free survival. Quite a key one there because that means you're potentially also impacting micro tumors or whatever you want to call them that are elsewhere and not just the primary tumor area. So that's good and clinically meaningful. Merck said, although we did a quick AI check, does use that phrase regularly in his trial readouts. And of course the market has now decided that this is at least the share price reaction to us suggests. Having done a deep analysis of every indication they've got ongoing that this is worth a lot more than what we come up with. Obviously our pricing assumptions may be wrong or whatever, but we get to about 12 billion if everything worked. Not risk adjusted. Now, Eric, I'm pretty sure someone at Cantor has done something similar or other houses have done. I don't know what the range will be, but it's a good number. And remembering that half of that is shared by Moderna in some fashion. So that was the news. And then of course, now we have another trial coming out in kidney cancer. Also adjuvant. I think Moderna has been very clever about the way they've done these trials with Merck. So measured, calculated, no cold tumors, which of course is the problem that maybe Biontech has phase. So that's where we are. And of course they've just led today with a $2.6 billion convertible offering. Relatively smart deal. It has a conversion that is meaningfully above the current share price and, you know, 2.6 billion. I think it would have been tough to get specialists going for a 2.6 billion equity raise. So well done to them, pushes the cash out, will be on into 2030, 2031, assuming everything works out in terms of COVID vaccines over.

Daphne Zohar: This one hasn't been owned by some of the usual specialists. Do you think that they participated in this offering or any. Are you guys hearing anything about that?

Sam Fazeli: Eric, do you want to have a go at that?

Josh Schimmer: Well, I think they participated only if they were looking to cover their shorts somehow through some other currency. But no, I think a lot of people, even though, as Sam mentioned, the stock has pulled back meaningfully, a lot of people are still struggling to see how so much value was created in this stock based on this one melanoma result and then, you know, whether it'll translate at all into other tumor types. Sam, I assume you're going to talk about Biontech as well. Maybe. I'll just add one thing that I thought was very interesting about this announcement, which was the algorithm. Sam, you did mention this, but we don't know exactly how these neoantigens are chosen by Moderna. I assume they're going to keep that trade secret. And, and if that's the case, there will never be a generic form of this vaccine. Right. So this is going to be a forever franchise that lasts and lasts and lasts as long as nothing better comes along. And from that standpoint, durability, it could be an extremely valuable franchise.

Sam Fazeli: Absolutely right. And that is where I think the models can be a bit more confusing. Although our model does go out to 2040. So, you know, I don't, I don't particularly. I don't know what the time value of money would do to whatever we calculate past that. But so, and then Biontech, we know that Biontech had a failure once in Metastatic melanoma. You know, most people put that down to very large tumors, very hard to deal with for immune system, which. But of course that's not quite true because immunotherapy does work there. So they've had that failed. And then today, actually I was telling Eric in the middle of a webinar we were running, talking through our Moderna numbers, they announced that the colorectal cancer trial, which is perhaps not the best trial to have done, failed or has been at least we knew it failed, but it has been stopped now. It failed futility back in October 2025, company decided to continue in case separation came later. Apparently there was another interim look, no safety issues in April. And then suddenly today announcement comes out that actually there's an imbalance in survival. It's a phase two. Why there's an imbalance, I don't know. Remember, this trial is vaccine only in CTDNA positive patients who've had surgery versus watchful waiting. So it's maybe not the most potentially positive trial or high probability of success trial you could have done in this setting. But credit to them, they're going after very tough trial tumors where they're cold and colorectal is at the very cold end in terms of immunotherapy. So I'm not going to read too much through to Biontech on this just to say that it kind of begins to create a bracket for you with melanoma having worked, hottest tumor, colorectal had a problem, coldest tumor. What happens in the middle Time will tell over the next few years, starting with RCC by the end of this year over.

Daphne Zohar: Right. So big news. Another big story in cancer has been Revolution medicines and it just got FDA approval for pancreatic cancer. Eric, I actually think. Were you on the board there in the past,

Josh Schimmer: I was very proud to have been able to serve with such a wonderful company that is now bringing remarkable therapy to patients.

Daphne Zohar: That's amazing. Congrats. Maybe you can walk us through why this has been such a big deal clinically. And then Sam, I know you wanted to get into the speed of review and the pricing.

Josh Schimmer: Well, I mean it's a big deal clinically because this is a very substantial tumor type pancreatic cancer, as everyone knows, about 40 or 50,000 deaths in the US per year. One of the top killers. And we've had nothing. We've really had no good therapy. And the average survival in the second line setting where RAS on cue is now approved is only six or seven months. I think everyone's quite familiar with the RAS through two data that showed essentially a doubling of survival and justified this very rapid approval. The drug was approved with just over a month review at the FDA. So congrats to not only the RevMed team for some terrific execution, but also the FDA for getting this to patients as quickly as possible. I mean, in terms of what's a little bit interesting or remarkable going forward, I think we've all now seen the data that was presented at ASCO and that's certainly remarkable. But one thing about the label and the approval is that it was approved in part for patients who were ineligible for multi agent systemic therapy that is ineligible for chemotherapy, which has been the frontline standard of care. So if you're too old or too frail or don't tolerate chemotherapy, you don't need to go through chemotherapy. You could just get RAS on cue as a frontline agent. And that is going to be very, very interesting to watch. Certainly if I or a loved one were unfortunate enough to have pancreatic cancer, I'd be asking for RAS on Q as a frontline agent, not a second line agent. So we'll have to see what physicians do. And this has implications for the development of agents that are coming behind ResnQ because if this drug is increasingly used in a first line type of setting, it's going to be very, very difficult to do clinical trials in either the first or second line setting. So huge implications for the development space. Fortunately, there are a lot of great new therapies that are coming to the market potentially behind RUS on cue for pancreatic cancer, not just the RAS isoform inhibitors, but the PRMT 5 inhibitors. So a lot of great stuff going on. But Sam, I'll turn it over to you for any thoughts on pricing and whatnot.

Sam Fazeli: So the speed was great because of course they had the, the special voucher that the FDA has had started or has started. I don't know what the status of it will be or is or going to be. And you know, I think most people expected approval. This, not necessarily this quick. So it's been available free of charge for folks for the past, since April I would say. So that's going to be interesting as they roll over into the, into the paid group. And as Eric said, this is clearly two things happened here. Why Revolution medicine, although it's down today, and I can't quite fathom that except that it's with the XBI maybe. But two things happened. It changed our numbers because we had assumed a pricing that was kind of in the middle of the range of recently approved small molecule drugs with special for small populations of patients, not particularly that small, but mostly focused on cancer. And we ended up with something like $275,000. It was our estimate and of course it came out much higher than that. So that makes a difference to our model. So we've gone up to 12 billion potentially in PDAC. That of course depends on whether there's a gross to net, which of course we know some drugs are new valence drug is dealing with that. They have a gross to net. But their drug pricing came out at $478,000 which is not the highest today in terms of an annual cost. VitraCV, which is the NTRAC fusion, very small numbers of patients is at about a $518,000 cost based on our maths. So 478 puts it massively above the one next to it, which is 300 2000, which is Retevmo for RET mutant tumors. It's a big number. Our assumption is that we're going to end up with a gross to net, we assume 20%. And I don't know how Europe's going to be able to manage this. It doesn't fall under MFN as far as I know. And then of course you've got this additional patient population that might benefit from it, which is the frail, I would say ecog3plus. On the other hand, this drug isn't the walking dead park either. So let's see. Over.

Daphne Zohar: Yeah, it's interesting. I heard a lot of negative pushback regarding this and the financial toxicity that cancer patients face. So I guess we'll see. I'm not really sure how much of it gets covered by insurance. So let's move on to the regulatory side. Heidi Overton was officially nominated by Trump to be the next FDA commissioner. And Greg, I think you've been tracking this closely, so love to hear what you think. And how do you think she'll run the agency?

Josh Schimmer: Yeah.

Greg Suvanovich: Thanks Daphne. Thanks to everyone for the invite back as a contributor. So yeah. Last Wednesday, President Trump nominated Dr. Heidi Overton as new permanent FDA commissioner. Recall everyone that following the departure of Marty Makary in May. Kyle Diamantes, if I'm pronouncing that correctly, the current Deputy Commissioner for food at FDA has been serving as an acting FDA commissioner on an interim basis. So you know, we've been waiting to see who President Trump was going to nominate. Maybe just in terms of Dr. Overton's background. She is a medical doctor. She earned her degree from the University of New Mexico School of Medicine. She's also earned a PhD from Johns Hopkins. She did complete her training in residency at Johns Hopkins. She's also a board certified. She's also board certified in public health and preventive medicine. So someone who clearly is in the medical field. She did first serve in the first Trump administration in 2019-2020 working in what is called the Office of American Innovation and also the Domestic Policy Council. And after leaving when the first Trump administration moved on, she joined the America First Policy Institute, that is a Trump aligned think tank and she served there as chief policy officer and she led its center for Healthy America. We returned back to the Trump second administration and has served as a deputy assistant to the President focusing on health policy. So she's got a total of about three to four years of experience working in the government, but again only during the Trump year. So confirmation hearings are set for. Well, they're not set, but they're expected when the summer recess for the US Senate is finished. Interestingly, dates have not been set just yet and the date will be set by the chair of the Senate Health, Education, labor and Pensions Committee. That's Senator Bill Cassidy, who is relatively outspoken and he has already expressed some concerns publicly about both Dr. Overton's management experience and her role in recent vaccine policy initiatives under RFK Jr. So it'll be, I guess, another interesting confirmation hearing for a Trump nominee. Now, for the purposes of our biotech hangout though, and with our audience in mind, I think the most significant and meaningful thing we want to know is if Dr. Overton is indeed confirmed, what could this mean for the biotech sector in terms of next FDA views or biases or policies? And based on some work I did in prep for today's podcast and yes, with the help of AI, I'm going to highlight, I think some potential pluses and minuses when it comes to how we think about Dr. Overton in terms of kind of what she stands for. And then maybe I'll also talk about maybe some therapeutic areas that could benefit or areas that could face some challenges based on what we know. Again, we won't know her official views once she is confirmed if she is confirmed. But I think from a bull case perspective, she appears to be pro innovation in terms of, you know, what the FDA should be doing so that that is good for all of us. She does seem to be supportive of faster cures. She is likely to be supportive of clinical trial modernization efforts. Again, she is a physician with public health cred and Given her prior experience at the White House or in the Trump administration, perhaps her influence could help push reforms relatively quickly. Now, in terms of things that have been highlighted that perhaps present a little bit of a bear case, she does have limited management experience. The FDA is a huge organization and she doesn't seem to have a lot of experience managing large organizations. She has less direct FDA experience than past commissioners will obviously question the potential independence that she might have from White House politics. Again, this is speculative. There are some vaccine controversies that might come about if she does indeed get confirmed as FDA commissioner. And so we'll just have to see what the Senate confirmation hearings, how they progress and whether she does get confirmed. Confirmed. Now, I think in terms of potential areas, if she is confirmed that could benefit, it does seem that rare diseases potentially could be the biggest winner. Again, this is the emphasis around faster cures and innovation and clinical trial reform. So gene therapies and maybe even gene therapies could be the areas that could particularly benefit. We also think that, or at least I think that maybe the neurospace could be another area. It's a place that's near and dear for me given my background and my areas of focus. You know, neurology has got long clinical trials, difficult endpoints, large placebo effects, some high failure rates. And so clinical trial reform could be helpful, you know, especially around maybe things like biomarkers, streamlined study designs. And so I think neuro could potentially benefit. Interestingly, AI has also highlighted cell therapy as an area that could benefit. And we know that the cell therapy space is very challenging, manufacturing CMC requirements, post approval commitments and so cell therapy might benefit. And I think the last two areas that I'll briefly mention are psychedelics. We know RFK Jr. Has been very instrumental in highlighting and promoting faster development of psychedelics. And I would say also precision oncology and just very briefly on could face some challenges. I did mention vaccines. I mean this is an area of uncertainty, but she has played a role in vaccine related White House initiatives. And again, as I mentioned, Senator Bill Cassidy, who will chair the confirmation hearings, has already made some public comments. And one last area is reproductive health or women's health companies. Again, this is around maybe abortion pills or reproductive health regulation. So those are just some of the areas I think as we think about Dr. Heidi Overton, kind of the pluses and minuses and areas that could benefit in areas that might face some challenges.

Daphne Zohar: Thanks Greg, this is very helpful. And there's a few other regulatory related policy related news items. I'm going to hit them really quickly and then I want to open it up for discussion. So you talked a little bit about reform in terms of I think one area that we've all been focused on is how the US can be more competitive and less slow to get new medicines into the clinic. And Alex Harding wrote a nice piece in response to Operation Trailblazer, which the HHS announced in June to try to keep early trials in the US and one stat that Alex mentioned that stuck with me is that US INDS are down more than 10% since 2020, while China's phase one trial count nearly doubled over the same period from about 600 to over 1,100. My own take is that we, like most of our peers, still run phase one and two A trials ex US in our case, we've chosen Australia before bringing the program to the US for phase IIb and beyond. And the policy conversation is the right one to have. But it seems to me like there's a lot of these well intentioned initiatives like Trailblazer which they talk about. They become almost like these sound bites but then are very slow on implementation. And my perspective is until the FDA divisions actually embrace some of these talking points, sponsors have to keep planning conservatively. You know, for example, one area they've talked a lot about is only one pivotal study needed for approval. But we're not necessarily seeing that being embraced yet by the divisions more broadly. So I think a lot of great efforts. And then I'll maybe I'll pause for a second, then we can talk a little bit about China because there's a new push to reject clinical data from China. So we'll talk about that in a moment. Does anybody want to comment on either Heidi Overton or this push to improve the efficiency of getting new drugs, to market new drugs to the clinic in the U.S.

Josh Schimmer: maybe just on Dr. Overton. I mean, Greg gave a terrific summary and an overview of her qualifications and background. You know, it does appear that she is essentially a mentee of Dr. Makari's and in many ways maybe a bit of a Dr. Makari clone in some ways, you know, a physician scientist, but someone who doesn't have a lot of expertise at the FDA and maybe in other ways not a lot of qualifications to run a big organization. I think that's going to be problematic, to be honest. The other big, big, big strike around her is RFK Jr and she is very much associated with the Maha contingent, as Craig discussed. And you know, just this week we saw a couple of deaths due to measles in Pennsylvania, something that should never, ever be happening in the modern day and age. So I thought more tone deaf comments from RFK Jr about vaccinations, about the need or lack thereof to get vaccinated, about why some people are vaccine hesitant, something that he's not been accountable for or is unwilling to rally against. And it's just sad. So I would hate to see yet another healthcare leader appointed who shares any of those views.

Daphne Zohar: Yeah, and Bill Cassidy, he, you know, he talked a lot before the RFK appointment but, you know, ended up supporting it, you know, after talking a lot. So I, I don't really put a lot of weight into what he says. So let's talk a little bit about China. Republican lawmakers John Molinar and Ben Klein are asking the FDA to reject clinical data from China unless a trial site has been recently audited by the agency. And the backdrop here that I don't think is getting enough attention is that this letter follows reporting on three deaths. Endpoints had a good article about this. Three deaths across three separate investigator initiated trials in China. So Moulin are and Klein are saying that offshoring early trials to China risks rewarding a system that has shown it's willing to treat children's death as an acceptable cost. So they want the FDA to reject China generated data for INDS, NDAs, or BLAS alike unless the site's been audited within the prior year. This is a high bar given that FDA staffing and access constraints are already quite challenging. So what's interesting here is Moulinar has been on this for a while. He chairs the Select Committee on China and already got similar language into the FDA appropriations bill. But Klein is more interesting to me because he's part of the Biotech Caucus, which has generally been more industry friendly on China. So having him co sign suggests this isn't just the usual China hawks anymore. I mean, I know there's been a ton of debate. You know, I talk a lot with Peter Kolchinsky and all the folks that are pro China. And I've also heard from others that are, you know, not supportive at all of the push towards China. I know we've talked about it here, but anyone want to comment on this?

Sam Fazeli: Yeah, definitely. I'll jump in. You know, I've been,

Josh Schimmer: a lot of

Sam Fazeli: people have been to China recently. I'm actually going back again in a couple of weeks just before the World Lung Conference. There is, there is a, I am hearing that trials, or at least products that are manufactured in China and not outside of China are not making it through. Clearly clinical data out of China is not going to be enough to getting approval. I mean that's been something that's been said for a while. So asking companies to bring drugs out of China to manufacture them in the US or the west for the use in the region and doing the clinical trials in the west and the U.S. i don't think is anti competitive. I think that should, that should be the case given the current geopolitics. But any going beyond that to try and crimp the ability to do deals with Chinese biotech companies is just, it just does not make any sense to me. So I'm still very strongly of the view that that would be absolutely the wrong thing to do. Just let the market make its decisions. When you look at these IPOs that definitely you just suggested, look at the, we've just done it just published today, look at the year to date, China, Korea, IPOs, their performance, how much money they've raised versus the U.S. it's chalk and cheese the U.S. still leads to by far if the science is allowed to flourish and if the science is allowed to be converted to companies and the scientists are left to do their job. And that's the problem that I think we're dealing with here. So I think that momentum is still there and that's what we need to make sure that we continue to keep not trying to destroy another country and stopping people from getting access to other assets elsewhere. Yeah.

Daphne Zohar: Since we're on the topic of China, Sam, do you want to talk about Aquizo and Summit?

Sam Fazeli: Oh, that's a good, that's a good segue.

Daphne Zohar: Yes.

Sam Fazeli: So a bit of news. So I think a little bit like Moderna and I think Eric talked about this. There's so much emotion involved in when you've decided that you know, a company has something that you don't like about them and that just keeps playing on you and therefore that colors your judgment different. Now a lot of very good professional investors can overcome that. But as an analyst I also feel that I get sometimes drawn by that and to a degree I'm always kept sitting on the fence or the, or the negative side of the fence as regards Ivanissimab. And I think this last event that happened, which is a kiso hitting, although again his headline story, efficacy in terms of progression free survival and OS in biliary tract cancer, carcinoma in China with evenissimab, which is their PD1VEGF, which is obviously partnered with Summit in the US and kind of pushed me over the line to the positive side of the fence, I think something's going on here that is different, has to be than PD1 +VEGF. Remembering that invigor. Oh, God, I forget the code. Now, the Roche trial to Centric plus Elastic failed to show any OS path benefit. The Kaplan Meier curve was like two lines on top of each other. Now, that was a PD L1. It was Avastin. It was a little while ago, but it just didn't work. And it was phase two, but it was a randomized phase two of meaningful size, so it just failed. So currently the standard of care is single agent or other versions of combinations that are used, not vegf. So here you show a benefit in a tumor that had failed before. So sorry, standard CAR is durvalimab plus chemo. So there we have a situation here where you've got another tumor showing an OS signal. Now, nobody's running a trial with these bispecifics in the west in btc, but it just gave me that little extra help to start thinking maybe we really do have something different going on here. Over.

Josh Schimmer: Sam, welcome to the club. That's wonderful.

Greg Suvanovich: Took a while.

Josh Schimmer: Yeah. Well, good for you for having the. The flexibility of thought to. To change your mind here. Look, I agree this is yet another brick in the wall, right? I mean, we've now had multiple studies of ivanescamab working where you would not expect a PD1 to work and where you would not expect a PD 1 plus a VEGF to independently combine or a combination to work. So it's getting really hard, I think, to make the case that this new class, the VEGF bispecific. VEGF P1 bispecifics, is not doing something that's a little bit special. And yet you're right. The majority of our clients are still remaining kind of glass half empty in their views toward this drug. I don't think anyone should be surprised if the Harmony 3 study reads out positively. Of course, we need to wait another six or so, maybe nine months for that data. But if that trial does work, it will be the clear and deciding variable. And this stock summit is going to go through the roof because people are still so skeptical. Much like Moderna shares have gone through the roof on similar entrenched skepticism.

Daphne Zohar: Yeah, so there was a lot of regulatory news this week. We won't get to all of it. A rough one was, I point, their phase three data missed the primary endpoint on maintaining vision and wet AMD, and the stock fell 70%. Greg, you cover the name do you think that the reaction was justified and do you want to take the other side of this one?

Greg Suvanovich: Yeah. So yeah, thanks for giving me the opportunity to talk about iPoints, the name we do cover and one that we've historically liked a lot and we still the phase three data were negative. There are in which the primary endpoint was trying to prove non inferiority versus the current standard of care treatment. That's IAH2 milligram remember wet AMD is this blinding condition mainly affects elderly. There's probably over a million patients in the U.S. we have a very large and established anti VEGF market that is about $15 billion in totality in terms of branded sales, very well known brands in the space. But these treatments are given once every two or three months. And so the uniqueness of what I point is trying to do as well as a competitor company called Ocular Therapeutics which I don't cover but those companies are like biotech's attempts to try to introduce a very first maintenance treatment. So trying to get patients off of once every two to three months. These are direct injections in the eye. Who wants that? And so what Eye Point and Ocular are trying to do is develop treatments that are given once every six months. So it's basically trying to, you know, relieve patients of that treatment burden. Trying to relieve the system of frequent visits to a retinal specialist's office. The data were negative. Daphne, as you mentioned, the stock is down about 70 plus percent in the time since there is some controversy with the data though the company did acknowledge missing. But they also identified nine patients that they consider kind of like representing a cohort of patients that skewed the data. Now no one, including myself, we don't like seeing companies cherry pick data, especially whether it's on a post hoc analysis or let alone an ad hoc analysis. But there were definite signals of efficacy, very strong data on secondary efficacy endpoints. The drug generally seems to be well tolerated and safe. There is a second bite of the apple though. And while the market has spoken, the second phase three set of data are expected in October. You know, if investors had completely written off this drug, instead of the stock being down 70, 75% it'd probably be down 90% or so. I think that is a reflection that some investors are still potentially optimistic that the second trial will work. It is a large study. Each of the studies were over 200 patients. And we'll just have to see there is precedent case in the ophthalmology space where FDA has approved drugs where Even though the standard is two positive phase three studies for wet AMD or other retinal diseases, there have been two case studies or precedent cases where the FDA actually accepted and approved two products. One was the Apellis Pharmaceuticals product for geographic atrophy, safe ovary. And the other, more recently was for a small biotech called Outlook Therapeutics, which got branded Avastin approved. So we'll just have to see. It's still an interesting one. It's a name that we still like, but we completely understand if the market and investors have spoken and have, you know, for the most part kind of voiced their, you know, skepticism that the second trial can work. But we'll see.

Daphne Zohar: Yeah, thank you. So another story that's generating a ton of discussion is data from AstraZeneca and Ionis Cardio transform study presented at ESC this morning showed that their ATTR cardiomyopathy drug added no cardiovascular benefit on top of a stabilizer. And while it's not Alnylam's data, it seems to be impacting them as it raises the question of whether gene silencing drugs meaningfully benefit provide benefit over oral stabilizers at all. So a lot of discussion about this, Eric, I don't know if you had a chance to look at this one and if you have any commentary.

Josh Schimmer: Yeah, nice little introduction there, Daphne. Yes, the cardio transform data were presented at and then also published in the New England Journal. So the full data set is now available. We knew this trial had failed because the top line results were announced, I think, back in June. And this study did test Eplan Turson, which is an antisense molecule for AstraZeneca ionis on top of a population that for the most part was on a stabilizer, for the most part on Defamatis from Pfizer. I think about 80 or so percent of the patients in the study were on a stabilizer. And what you saw is that when you add a silencer on top of the stabilizer, there was no benefit. In fact, patients on the combination did a little bit worse. So maybe, you know, number one, that was surprising. Perhaps we didn't expect to see massive benefit because stabilizers certainly are very good drugs. Don't let the stabilization moniker convince you that somehow, like a gene silencer is necessarily better than a stabilizer. Stabilizers have been shown to be very, very successful on their own at preventing death and cardiovascular morbidity. So not shocking necessarily that we didn't see massive benefit, but surprising that we saw potential harm. I think that was the number one conclusion Then of course, today, as you referenced it, Daphne, everyone's trying to figure out what does this mean for the silencer class, despite the wonderful name of gene silencing, does it really do much, if anything, on top of a stabilizer, which most patients are on today? Our friend John Maragonori would certainly argue that this data set today from cardio transform is very specific to an antisense molecule, which is a plantarsin. And, and it does not necessarily have read through to vertisiran. Vitiseran, of course, is Alnilam's RNAi based therapy for ATTR. And I think there's some validity to that. We just don't have as much data on vitisiran in this setting on top of a stabilizer. But there had been a fair bit of use in the commercial setting where patients on stabilizers were adding on top these silencers in particular Vuxxeran, which is commercially available. And I think for better, for worse, doctors no longer have any evidence to do that. So I would expect that we're going to see less combination therapy in the market until proven otherwise. But anyone else, please feel free to comment here.

Daphne Zohar: What's one that's got very active discussion? We shared some posts and maybe we'll share some more. And I think it's. You did a really good summary here. So another story that's generating or that generated a lot of excitement, I think actually last week was Amylix and so we were out last week and we can come back to that one positive data. And then that was followed by an upsized $500 million raise. So that one is really interesting. I think also in terms of the, the company and its journey and the management team gained, in my opinion, tremendous credibility when they shut down their previous program and reported on it, honestly. So I'm really happy for them and love to have Greg walk us through what happened there.

Greg Suvanovich: Yeah, thanks, Daphne. So, yeah, Amelix Pharmaceuticals. Many people might remember this company as an ALS focused company. I mean, it's been a neuro or neurodegenerative disease focused company. They brought a drug to market it several years ago called Relivrio. We know how awful ALS is. We don't have very many treatments at all. And the treatments we have are modest at best and just a huge unmet medical need. And with a lot of fanfare several years ago, Amelix was able to get on positive phase 2 data a drug approved called Relivrio. And it was a conditional approval. The company launched the product. It was actually a Very sharp uptake, and I think it was annualizing at close to 400 million. But there was another phase, confirmatory phase 3 study called the Phoenix Study that was ongoing. And in March 2024, that study read out negatively. And Daphne, to what you mentioned before, I think the co CEOs and it's a remarkable story. These are two classmates in college that in essence thought up of Relivrio while in college and remarkably got this drug approved. But when the confirmatory study did not work, they took the high road. They pulled the drug off the market and earned high praise, I think universally from market observers on kind of that courageous decision when typically you might see biotech companies resist at all costs to go down that route. But the company did reinvent itself and brought in an asset called Avexitide. This is a GLP1 antagonist. It's not an agonist. We all know from obesity headlines. This is an antagonist and it's for this rare orphan condition called post bariatric surgery related hypo glycemia, for which there are no FDA approved drugs. And a phase three lucidity study read out last Tuesday. The stock had been running up into the data and many times the market interprets that as confidence that the trial will work. And in this case, it actually did work and it worked remarkably well. Like the P value on the primary endpoint had like four zeros before it. It might have even been. And so the drug was able to reduce the rates of level 2 and level 3 hypoglycemic events. These are very serious hypoglycemia events which could make a patient lose consciousness. And again, there are no approved therapies. So the stock reacted quite nicely. And leading into the data, the stock was in the 20s, it's now closer to the 40s. And with that in mind, they were successful in raising over half a billion dollars. So kudos to the Amylix team there and we'll just wait for approval.

Daphne Zohar: Yeah, it's a great story. I'm really happy for them. So, Eric, you flagged this story, which I think points to a general thing that we've been seeing, which is generate biomedicines. And they had some draft posters for three studies leak out early. Vienne Edgar filing ahead of the embargo for a conference. This is something we're seeing. We're seeing these leaks a lot in different areas. Do you want to talk about this one and then maybe zoom out as to how often these are happening and any implications?

Josh Schimmer: Yeah, sure. I'll give it A shot, it does seem like. Daphne, you're right. Every three or six months now, some medical conference is breaking its own embargo by maybe mistakenly posting or allowing investors to access information ahead of the embargo. In this case, that's exactly what happened. I think we woke up on Tuesday and Generate Bio stock was going a little bit wild. It was up about 15 or 20% at one point in time. And news came out that an abstract that was to be presented at the European Respiratory Society meeting ers was available. Few of our investor clients had access to it. The data in the abstract were honestly not that remarkable. They were about what I would have expected. But perhaps even because they were selectively disclosed, it took on a bit of a life of its own and the stock reacted quite meaningfully. The next day the company did put out an 8k through Edgar saying that here are the. The abstracts. We know they were leaked and now everyone had access to them. And the stock almost immediately came right back down to earth, giving up its gains. So for the most part, no harm, no foul. Except it was a bit of a fire drill and. Except there could have been some selective disclosure that cost some folks some money and allowed others to make some gains. I don't know why these medical conferences are having so much, much trouble protecting their own data and information and their own URLs and websites. Oh, maybe the others have a view on this. It's annoying for all of us in this space to have to go through this. We want a fair playing field. I think all investors prefer full and fair widespread disclosure and the fact that certain organizations, maybe they're not as sophisticated or attuned to the needs of investors. Certain organizations that run these conferences can't get their act together. You know, it's. It's just unfortunate, but happy to have other guys. Chuck, chime in on this.

Daphne Zohar: Yeah, I remember this happened also with Pfizer, I think, at Asco, in like a year ago. Yeah. Anybody else want to comment? No. All right, so we've got a bunch of other news stories. I don't know if anybody wants to jump in, but we have, let me

Josh Schimmer: see,

Daphne Zohar: a number of different things that we still have to get to. So we have AstraZeneca discontinuing phase three trial. We have REGENEXX bio, we have Ultragenics. Takeda.

Greg Suvanovich: Yeah, maybe I'll jump in because I wanted to comment on a couple of approvals that we saw in the space. One in particular that just recently happened is one for an anti FCRN antibody based Treatment that J and J called Imavi, I believe I'm pronouncing that correctly. But Amavi was approved for actually for a second indication. So this is a drug that was Approved first in 2025 for myastena gravis. And for those who are following the MG space, we are all very aware of the remarkable success that Argenex, a very successful European biotech I used to cover some time ago has had with the launch of Vivgart, which is now approved in multiple indications in Vivgart. Remarks remarkably is I think 2025 reported sales were over 4 billion and so that was the first anti FCRN antibody that was approved and there have been two others that have been approved in the time since. With JJ's Imavi again initially approved in 2025 for myastenograms, but they just got an approval for an indication called Warm autoimmune Hemolytic Anemia or WEIHA as I will call it for short. And that is the second indication for Imavi. JJ hasn't disclosed sales of Imavi since the drug was approved. Again it was approved last April for Myasthenogravis but this adds a second indication that builds on another product getting approved as well. So we have three anti FCRNs. It has been a very interesting and well followed space amongst investors Roivant has had had through its Immunovant company and Anti fcrn. They've had some mixed success with their Anti FCRN efforts but it is an important and I think exciting new mechanism of action. I wouldn't be surprised if there are others behind it. And with that said, it's always great to see a treatment for a condition where we haven't really had treatments approved for previously. So kudos to J and J on getting Imavi approved.

Daphne Zohar: Yeah. On the topic of Royvant, their Provant subsidiary just got FDA approval and that's a nice win for Roivant and our colleague Mack Line. So what are your thoughts on that one Greg?

Greg Suvanovich: Yeah, so that's a jak tic 2 inhibitor for dermomyositis. I don't know the condition but I think it's also representing our very first FDA approved therapy for the that condition. It's an oral small molecule. I think the JAK and tick 2 inhibitor class is one where there's been very good commercial success. But the JAK inhibitors do have a black box warning for cardiovascular complications, blood clotting complications. And with that in mind, it's always great to see a brand new product again. I don't know this particular, I'm assuming it's a rare orphan disease, but certainly from a roivant perspective, it's great to see them get a drug approved and I'm sure it will, you know, be very welcomed by the medical and patient community. But kudos to the Roy Van team there.

Josh Schimmer: Maybe just the other thing to add on top of Greg's comments there, you know, Bravo did get approved with a black box. So it is similar to other members in the class, the Jack class, that is. But what's different about it is the pricing. I know we just talked about diraxon, Rasa, Bressonique and Ras on Q and the very premium pricing at which it came out at repo is priced at a little over $400,000 per year. That's probably two times or more the higher pricing of the nearest JAK inhibitor. So yet again, another example of a new drug coming to market being priced at a premium and. And potentially at some point, this is something that the system is going to need to figure out whether or not it can handle or not.

Daphne Zohar: Yeah, I wonder what goes into. I mean, I think that there's obviously the commercial and the ability to generate revenues and all of that, but the blow to our industry from something like this I think is really significant. It just, you know, during a time where it feels like the industry's finally climbing out of a lot of negative sentiment, it's not helpful at all. So I don't know if you want to. Anybody wants to talk more about pricing. We only have a couple minutes left, so I would suggest we keep it open for the next few minutes and just talk about general topics as we wrap up.

Greg Suvanovich: Yeah, I'm going to comment just on pricing. So I didn't know what the pricing was, and again, I don't know. Dermo know myositis very well and kind of what patients experience and the severity of the disease. But, you know, for those of us that are observing approvals and companies that are launching new products and the pricing approaches that they're taking, I would agree on some level that it is serving as a little bit of a black eye to the industry. You know, I don't know what the median household income is here in the United States, but it's certainly Nowhere close to $400,000 a year. And sure, insurance picks up a lot of it. If you do have insurance and not everyone has insurance, but even whether it's, you know, out of pocket that someone has to come up with, it's tough. Obviously, companies do offer patient assistance programs and that's very helpful and I think that is a credit to our industry that we do do that. But I think bigger picture, I mean, there's the pressure of biotech companies many times who are publicly traded, who have investors who are looking for a return on their investment. And as Eric and I do, we build out our models, we project revenue, we take assumptions on peak market share, you know, pricing considerations, and we try to be thoughtful about, you know, the unmet medical need. And I'm sure companies are as well. But it seems more and more that these new drug approvals are coming at more premium pricing versus what we might have assumed. And you know, companies usually don't say what they're going to price a drug at until the drug is actually approved because you need to see what the label is and need to know what you can claim. But we talked about Amylix before with their post bariatric hypoglycemia drug. And we initially had a $200,000 a year base case pricing assumption. But if we looked at a more recent analysis that we did, if you looked at the last eight or so rare endocrine disease drugs that got approved, like the average is closer to like 280, $285,000. So, you know, we just said, look, we don't know what they're going to price this at, but if we just took the average, we're now closer to $300,000. So, you know, like, I want to make sure that there's good market access for patients, but pricing is very challenging.

Sam Fazeli: I mean, I'll just jump in that conversation a bit. Remember ISIS in Europe, where we are very price conscious and quite to a degree, rightly so, because we don't have endless gdp. The, and this is a. Most of the countries in Europe are public health care systems. So there's no, I mean, there is some insurance, if you, if you're lucky, to be able to pay for it, but not across the board. So the issue ends up being, I do wonder, I know this sounds a bit Machiavellian to a degree, whether some pharma companies or biotech companies think, well, this is what I need in terms of revenue. I'm going to divide it by the number of patients and assume a relatively okay penetration. That's what I need to sell it at to get to my number. I can't imagine any other way. I mean, I don't want to have a go, you know, in Lexo from Johnson and Johnson is a, is a great drug, a great product because It's a formulation for non muscle invasive bladder cancer. But I, I can't imagine how they came up with it. I don't know, $650,000 a year, 700,000 doll price for this. Aside from say, thinking they've got a $5 billion market that they want to get to or sales they want to get to, how many patients are there? So I know that sounds probably not real, but, but I can't imagine how you get to that number for that sort of price. And, and you know, nobody takes, cares about what ISA says or anybody like that. But those are just crazy numbers. Right?

Greg Suvanovich: We'll say example, as someone who did spend time on the corporate side at Biogen and Abbvie and having the benefit of seeing how the sausage is made of sorts, I mean companies I think are very, they do try to be thoughtful about, you know, the, the market access and the pricing strategies that they take. I know they hire, you know, third party consultants to try to understand like the cost of the medical system. And look at many times, times companies are bringing out innovation, they are improving on the standard of care. And if you can, and this is every company's responsibility, if you can prove to the payers that what you're bringing in terms of your new product does represent an advancement to whatever's out there now. And if you can find a way, and it's up for companies again to demonstrate this, if you can save the health care care system money in the longer term, then I think companies can craft a very objectively thoughtful and rational pricing strategy that can be justifiable. Again, the rubber will hit the road because you know, the healthcare and drug cost to this, you know, this US system is in my opinion something that is a ticking time bomb. But we'll just have to see how all industry participants are able to kind of figure this all out.

Daphne Zohar: Yep, it's our industry balancing the best interests of patients with the fact that you need to raise money to be able to bring these drugs to patients and that whole business element. But I think this is a great discussion and we'll continue it next time. We're out of time, so thank you all.