Jef: Hello and welcome to Biospaces the Weekly. I'm Jeff Axt, Managing Editor, and we just returned from covering bio in San Diego. I was out there with Annalie Armstrong, so we'll have a lot to talk about in terms of the regulatory and business environments facing biopharma at the moment. The good news is that sentiment is overwhelmingly positive, but it is nuanced, so we'll get into that in a little bit. In today's show, we'll also address the biggest headline of the week so far, the retraction of a pivotal study for Amgen's rare disease drug, Tavnios. It's been on the FDA's radar since January when the agency requested that Amgen pull the drug from the market. But now the pivotal study, published in the New England Journal of Medicine, has been retracted. Finally, it's officially the start to the second half of the year, so we'll take a look back at the deals struck so far and what it means for the overall health of the industry. Let's dig in. Hi everyone. How are y'all doing? Annalie, do you feel recovered from our week in San Diego?

Annalee Armstrong: Do yeah. I you know, I had a smooth travel experience that as everybody who I've talked to at any of these conferences knows, that is never the case. So yeah, feeling good.

Heather: That's that's a literal miracle, Annalie. ⁓ and by the way, welcome back and thank you for coming back. ⁓ yeah, it was it was long week. it was but you guys were helpful, even you know, with with news from from San Diego. I couldn't believe how, you know, how smooth it actually went.

Annalee Armstrong: I know. You two were hustling. We we could tell.

Jef: Yeah. It was a true team effort, but glad to hear we were missed and glad to be back.

gabby: So, see you guys.

Heather: Hustle culture. Yes.

Annalee Armstrong: Yeah. You guys, I get to introduce a new member of our team. This is Bingo. our listeners, at the bio conference, I won a ⁓ Bluey prize pack, which included a little stuffy of her sister bingo. So now bingo is going to be on my desk forever, and I am so excited. Everyone was like, Annaline, you should give that to your kids and then you don't have to get them anything and I'm like, No, no, no, she's for me

gabby: How is Bingo going to help the Biospace team, Annali? You're already putting her to work?

Annalee Armstrong: Yeah, I mean she's got a little hat that kinda looks like an old school reporter's hat, so I'm sure she can do some investigative journalism, I think. Yeah.

Jef: Yeah, send her out in the field. All right, well, like I said, we're gonna get into some of our takeaways from bio in just a little bit, but let's start off the show with Amgen and the crazy discussions around Tavnias. So this drug was originally approved in 2021 when it was still under ownership by its developer, Chemocentrix. This is it was approved for a group of life threatening immune-mediated diseases that affect small blood vessels. Then a gen Amgen swooped in and acquired chemocentrics in 2022 for 3.7 billion. And things still went fine for a few years. in 2025, Tabnios generated nearly half a mil half a billion, excuse me, 459 million in global net sales. Again, just kind of sailing along, not a blockbuster, but no issues until January this year, when the FDA announced it had identified issues with chemocentrics. an analysis of the pivotal efficacy data that had been used to support the drug's approval. At that time the FDA asked Amgen to voluntarily pull the drug from the market. Amjun then refused, and nothing seems to have gone right since.

gabby: Yeah, so a wild saga there and it hasn't really calmed down. So here a couple months later, you know, on the last day of March, the FDA attributed more than 70 cases of drug induced liver injury to tapneose. that included eight deaths. So some of those deaths were tied to a very specific adverse event called Vanishing Bile Duct Syndrome. Amgen had apparently already requested this issue to be added to the drugs label, but that doesn't appear to have happened. So the FDA is still calling into question, you know, the integrity of the data used to support Tavneos's approval and seemingly aiming for its market saying that CDER can no longer conclude that there is or ever has been valid demonstration that Tabneos is effective. Amgen still stands by Tabneos and not only ⁓ a hearing with the FDA, but also enlisted the Duke Clinical Research Institute to conduct an independent review of the data that they use to underpin their application. So the retraction of its pivotal study from a leading medical journal really does not help support the Pharma's case.

Jef: Yeah, I'm very curious to hear more from this independent review. I don't know if we have a timeline and when that'll be coming out, but in the meantime, as you said, the FDA is still looking to get this drug off the market. It has now been linked to eight deaths. So that's not a good thing.

gabby: Yeah, it will be really interesting to see what happens next.

Jef: All right. Well, like I said, we'll get back to some of our takeaways from bio later in the show, but let's get started with introductions. Annaly, why don't you start us off?

Annalee Armstrong: Yeah, so I am Annalie Armstrong, senior editor. I do the Biofarm Executive newsletter each week, which hits your inboxes on Wednesday.

Heather: ⁓ I am Heather Mackenzie, senior editor, and I curate Clinica Space, which ⁓ arrives in your inboxes bright and early at three AM Eastern Monday mornings.

gabby: And I'm Gabrielle Mason, senior editor, and I put together our manufacturing which goes out weekly ⁓ Tuesdays, and Daily Jean Pool newsletter.

Jef: And once again, I'm Jeff Axt, managing editor. All right. Well now as promised, we are gonna pivot back to bio. We kind of divided and conquered with Annalie going to as many of the business related sessions as you could. and you talk to a bunch of business folks on the sidelines of the conference. And we're gonna start there. In the meantime, I was hustling with the FDA folks, trying to get as much intel inside the agency as I could. So I'll give you those updates in a minute. But first, Annalie, what were your big takeaways?

Annalee Armstrong: Yeah, I think the headline of the entire conference was China. like literally every panel, China was brought up. Even if the panel wasn't about that, ⁓ it somehow came around to China. Although I am actually proud to say that I did not mention it one time during my panel that I did on building kinder and gentler ADCs, but that's actually more because I ran out of time, which happens.

Jef: is never enough time in those panels. They do kind of fly by.

Annalee Armstrong: Yeah, yeah. And it was really it like it was well, why don't I pivot to my panel? It was really fun. I got to talk to a bunch of experts in the ADC space and talk about how we can make ease the the treatment journey for patients. So that was a really cool one. yeah, like besides China, there was, you know, a lot of discussion on the really vibrant deal making environment. Lots of told me that the number of deals and IPOs this year ⁓ have really booing the sector and helped keep the sentiment very positive.

Jef: We definitely got that impression even going into bio, but it was really I would say validating. It was really strong the sentiment when we were there. Everybody seemed to be in good spirits.

Annalee Armstrong: Yeah, for sure. And like, you know, the the biotech ⁓ biopharma kind of conference schedule really starts in January with JP Morgan. And I was in San Francisco for that conference, people were positive, but they were still a little cautious. So it's really nice to see that thread kind of stay through this half. and I feel like people were a lot more confident. another thing that I think was new for me is that I was starting to hear that early stage companies are getting a lot more visibility with investors. So to me is a bit of a change from what we heard just six months ago at JP Morgan. So yeah, overall very positive vibe coming out of bio.

Jef: the same on the regulatory front. So again, you were following all the business trends, and I was really trying to get a sense of what's going on at the FDA. As we know, we recently, you know, said goodbye to very controversial FDA Commissioner Marty McCary, along with a handful of other senior leaders that all seem to have this tight circle and we're at the center of a number of controversial decisions and actions. So now we're a good six plus weeks out from that latest leadership shakeup. And again, just an overwhelmingly positive vibe. I already got this impression from some of the initial sessions I went to folks talking, including bio president CEO John Crowley, talking about, you know, he had noticed this change in sentiment around the FDA, and things were getting seemingly better in ways, vague ways. ⁓ but then I s went to a town hall with acting leadership. So this inc included acting CEDAR director, acting CIBER director, and then the acting deputy commissioner all sat down with Crowley. And they really spoke about the efforts they have undertaken to do just that, to turn morale around, to to and support the existing staff, to reduce the amount of attrition, because you know, we had all those major layoffs last year, and then there were all those incentivized early retirements and other programs. And the amount of the number of folks leaving the FDA over the past year has been it has continued, even you know, beyond the news cycle about it. And so ⁓ Current leadership has really tried to reduce that attrition, and they say that they have back down to historical levels. And then the biggest headline for me coming out of that town hall, and of course I wrote a story about it right away, was that they're actively hiring and not just a few people, 2,200 people, which is more than two-thirds of the total number that got axed last year. So it really seems, in terms of staffing and morale and culture and leadership, like things really seem to be turning that corner. And then, you know. That's great. And we want to hear that. But then we also want to see it in the policy making. And that was the other thing that came up. We are seeing it in the policy making. So just last Monday, while we were at bio, FDA announced this new IND pilot program. I know ⁓ Gabby and and Heather talked about this on the show last week. And the discussion around it was the fact that this came through a normal FDA, you know, press release. It didn't come out through a journal, through social media. It was open for public comment. Mike Davis, the acting director of CEDER, said they had a town hall meeting, internal town hall meeting with FDA staffers. More than 2,000 attended virtually or in person. And they really tried to explain the program, explain the meaning behind and the impetus behind the program, which, getting back to your point, Annalie, has everything to do with China, right? The data are there showing that more and more trials are going to China instead of in the US. And the FDA is really trying to make the clinical trial process and in particular entering early stage trials easier in the US. So again, the the that the policy has come down for me was the most heartwarming to hear. And everybody seems to kind of agree that we are moving in the right direction at this point.

Annalee Armstrong: Yeah, your piece on the hirings at FDA seemed like such a notable change. Like that panel just seemed to have really open, transparent vibes, which is, you know, the previous FDA leadership was really they they were suggesting that they were doing radical transparency, but it was nice to just hear these leaders sit down and say, listen, we made some mistakes. Here's what we're doing. Here's, you know, that that seemed like a really market change for me.

Heather: I was gonna say and they they seem to be doing the same thing, admitting that maybe they've made a mistake with all the rare disease reversals lately.

Jef: Yes, Crowley brought that up, you know, talking about how the FDA is now looking back at some of these decisions that were con contested or were a bit of a surprise and and pretty controversial when they came out under old leadership. And yeah, to your point, Annalie, I would say that the the kind of non the more qualitative I got from that FDA Town Hall was openness. They really seemed genuine. And, you know, It's hard to tell anything when you're not face to face and having an intimate conversation. You know, I'm just in the front row of the audience listening to this happening on stage. But more than ever before, I got this real genuine feeling from all of the leaders as they really tried to feel their way through kind of the mess they were handed, right? Like none of these leaders have been in their positions very long at all. And single one of them said that their number one priority was the staff. And I think that's a Great way to start because that staff was completely demoralized after a year of turnover and layoffs and a lot of other changes. but they are all just acting positions right now. We ⁓ lack permanent FDA leadership, and that is a concern. but there was an interesting report from RBC analysts last week that kind of hinted at who might be the next FDA commissioner.

Heather: Yeah, no, I I and I I wanted to write about this as soon as I saw the note. But so Kyle Diamantis he he's he's rave reviews so far as acting commissioner. but his time is limited. You know, it'll run out in I think it's early December. And the White House is apparently homing in on a few potential candidates, including military physician Heidi Overton. another name that made the list was actually John Crowley. and I which I found also interesting since I was reading about him on edits. but he was formerly the chief executive at Amicus Therapeutics and a well known patient advocate. And RBC ⁓ said his impact on biopharma would be quote, likely positive, especially for those rare disease companies.

Jef: Yeah, I thought that was a very interesting bit of RBC's note, especially because Crowley and a couple of times when I saw him throughout the meeting, you know, given his keynote speech or hosting this FDA Town Hall, he did talk very openly about how he had seen and the sentiment he had gotten even before this meeting was that things had really shifted in the last four to six weeks since that last leadership shakeup with the departure of McCarey. And I thought it was very interesting in that RBC note, they speculated that this positive commentary from Crowley could quote Perhaps be working to pave the way for a possible nomination. So I hadn't even put that together, but if Crowley wants this job, he's, you know, getting himself in position to possibly get that ⁓ nomination. So he is an interesting pick, in part because he, like you said, Heather, he's got those strong industry ties. You know, he spent the first part of his career launching amicus therapeutics to save his kids with Pompeii disease. There's a movie about it, Extraordinary Measures. And I actually learned just at bio last week that. Crowley himself has a cameo as a venture capitalist. So now I really want to go see and find if I can pick him out. but I think that's interesting because the FDA under Trump has talked about wanting to distance itself from industry ties.

Heather: Hmm.

Annalee Armstrong: and actually over the Axias reported a few extra candidates that have emerged to the top of the list. ⁓ in addition to Overton, there's oncologist ⁓ Jeffrey Vaserka and senior Pentagon Health official Steven Ferreira. Ferreira is apparently the front runner of the pack. ⁓ he was previously the chief medical officer for the Navy and CIA. ⁓ so hopefully we will get some official announcements very soon. The FDA could really use that little extra boost of stability.

Jef: Yeah, the sooner the better. Although I did ⁓ read in the RBC note they don't actually anticipate anybody coming on before the midterms, which does make sense. So we might have a little bit of a wait yet. Yeah. was the total length of time that ⁓ Diamantes could serve Heather? Something like two hundred and ten days or something? Yeah, something like that. So

Annalee Armstrong: That is a long time.

Heather: Yeah. It's like two hundred and ten, I think. Something something that would would have put him around December ninth or something. I think this is the in my head I remember. ⁓

Jef: Okay. Yeah, and analysts are predicting that the the agency is really gonna push that to to the limit. And honestly, you know, is that such a bad thing since things seem to be going so well? Maybe let them settle in and recover a little bit and then put a new leader in place that can adopt something that's a little bit more manageable than maybe what someone would have adopted if they stepped in directly after McCarry.

Heather: That's a good point. He he's known to be a very good leader and a very good manager. So maybe that kind of is what he's doing, sort of cleaning up the mess.

Jef: Yeah, it does seem like they're they're, like I said, broken record at this point, but hopefully turning that corner. ⁓ we talked specifically, of course, about the culture and the morale and the staffing. but I did want to dive in a little bit deeper to some of those controversial decisions that now seem to be given a second look. So we talked a couple of weeks ago about the agency's reversal of course on Unicures Gene Therapy for Huntington's disease. That's one that McCary himself, along with former CIBE Director of Anai Prasad.

Heather: Mm-hmm.

Jef: Had in the spring said would require a sam a sham surgery controlled trial. That was something that surprised the company and raised serious ethical concerns. But now ⁓ Unicare is proceeding with a filing based on the existing data after all. So that was the first bit of good news. That was a couple of weeks ago. And then last week, Replimoon announced that the FDA had accepted a resubmission for its twice-rejected melanoma asset. RejetX Bio had two bits of good news for us. First, the company will resubmit its Hunter gene therapy thanks to an FDA change of heart. And second, it will seek approval for its Duchesne muscular dystrophy gene therapy. So all of these companies and products that seem to get kind of the shaft from the FDA in the last ⁓ year or more, some of the original decisions came down ⁓ last year, are back at it, refiling ⁓ and seemingly with FDA alignment. And then just yesterday, we got an announcement from Skyhawk. on some new data for their own Huntington's candidate, and they actually pointed to Unicare's situation as a positive sign for their regulatory filing.

Heather: Yeah, ⁓ as I wrote in my article yesterday, the momentum is mounting again for Huntington's disease and patients, which is really excellent. so Skyhawk reported twelve month ⁓ functional data. this is from a a mid stage trial of its oral ⁓ Huntington's candidate, which has shown early signs of motor and functional improvements. now the data's early but but hopeful. ⁓ but I spoke with CEO Bill Haney late last week, who said that he hopes the FDA's new position on Unicure will translate to to their drug Sky ⁓ 0515, which which is actually a pill, so it may be easier for patients to this is word, stomach, ⁓ than a gene therapy. but Skyhawk already has so they've got a a phase three trial that they're currently enrolling, and they've already got 140 patients enrolled in that trial. ⁓ but Haney said the company ha has had discussions with the FDA about a potentially accelerated timeline.

Jef: Yeah, that's definitely in line with what we're seeing now with some of these other being invited to be resubmitted or to be submitted for the first time in the case of Unicure. So hopefully that bodes well for the patients, which is who matters in the end if we can get some of these rare disease drugs to market sooner. Another company that was blindsided by FDA decisions under McCarry was Capricor. they have a Duchenne muscular dystrophy cardiomyopathy cell therapy that was rejected last July. But this one's got an interesting couple of twists to update you So, first the company was seemingly already headed in the right direction back in March when the FDA did accept a resubmission, even under McCary. It was given an action date of August. But then last week, Capricor yet another surprise when the FDA decided that this decision would require an advisory committee meeting, and that's something that's been largely absent in the past year.

Heather: Yeah, Capricorl just really seems like they're on a roller coaster lately, like a just goes round and round, or maybe a carousel. but but there were actually two outcomes announced on Friday. So Replimune got one too, for its advanced melanoma therapy RP1. But that one made to me because there's been a lot of recent debate around ⁓ around that therapy between the FDA and physicians. So yeah, it sort of made a bit more sense. But since it's July twenty. twenty-five rejection, Capricor's Demia Cell actually aced a phase three trial, ⁓ meeting all the, you know, the primary endpoint and the secondary endpoints. so Capricor CEO, Linda Marbain, was surprised. she spoke with me on Friday and said the FDA communicated any issues that they want to discuss ⁓ with Capricor. Marbain offered a couple of possible theories why they might have scheduled this. this advisory committee meeting that is ⁓ ⁓ the Diamantis has said that he wants more adcoms so this could be in response to that and two the recent regulatory friction in the DMD space ⁓ or the Duge space rather last year with Serepta's Alevitus and the the two deaths that were linked to that drug. so ⁓ Marbane said quote maybe they're extra careful.

Jef: A lot sense to me. you the Sereptis saga last year was was pretty crazy. The the deaths themselves and then the lack of disclosure of that third death that was associated with an experimental gene therapy that used the same vector technology. So I think that was kind of egg on the face at the FDA. Maybe they're trying to recover a little bit from that. and, you know, it's a good point too about agcoms coming back. I made the point that they've been largely absent in the past year, but again, that was under old leadership. And now adcoms do seem to be coming back. Moderna was another one that had a recent adcom that was for its mRNA-based flu vaccine. As a reminder, that's the one that Prasad himself r like controversially refused to even review. But that decision was quickly overturned. And in the end, it, you know, they accepted the filing. Moderna got an adcom, and the adcom recently voted unanimously in support of the new flu vaccine. So yeah, both good theories. I think that it's good to be extra careful around. the Duche and muscular dystrophy space where we do have a history of safety issues that were publicized and not well handled. but yeah, adcoms are coming back. Yet another sign that FDA might be returning to some normal procedures, which is great. So we'll be on the lookout for that. We'll definitely keep you updated with the results of that adcom and all of these refilings on these rare disease areas. but moving on finally from the FDA, we do want to talk a little bit about the first half in particular deals. Annalie, what can you tell us?

Annalee Armstrong: Right. So I have my quarterly deal outlook coming out in Biofarm Executive this week. You can check that out online now. and no there a lot more deals than the year prior or the half pri wait, the first half last year. Woo, too many quarters. so there were about 50 deals signed over this first half, which compares to about 32 last year. So like a pretty significant uptick. Leading the charge, ⁓ no surprise was Eli Lilly with nine deals and about somewhere between twenty-five and thirty billion dollars spent, which is just if you think about it, nine deals, that's not a ton of money spent, but Lilly is really making a statement with this recent acquisitive streak.

Jef: Thank you for bringing up Lily. We can't go a whole podcast without mentioning Eli Lily. Bio took too much of our attention this week, I guess.

Annalee Armstrong: We almost did. Look at us. I know. So the other two busy companies ⁓ that you can read about were Gilead and GSK. They had three apiece. ⁓ and there were also a lot of fun, smaller companies that did some deals. UCB two companies, which is something they haven't done since, you know, in in like six years. So ⁓ you can that out ⁓ at Biospace.

Jef: Definitely another one of those signs that the industry as a whole is heading in the right direction. So on that note, we'll say goodbye and we'll see you back here next week.