Jef Akst: are y'all's easters?

Annalee: was good.

Heather: Great! It was spring then, it is not. ⁓

Annalee: ⁓ Heather and I are suffering through what is this like fourth or fifth winter in Canada. It like warmed up nicely over the Easter weekend and then it just now we're, I know, we have like probably two inches of snow and it's still coming down. It's insane.

Heather: Mm-hmm. Yeah. You ever seen...

Jef Akst: ⁓ that's unreal. I didn't realize it was still snowing.

Heather: You have two inches? Ours just looks kind of like a powdered doughnut and it's supposed to melt tomorrow. It's going to be 46 degrees, so it better be. Because this is...

Annalee: Yeah. Yeah. No, I'll have to go out and take a picture. It's like not stopping and I have to drive somewhere a little while and we got our snow tires off our vehicles because we thought it was spring.

Jef Akst: Meanwhile, over

Heather: course. ⁓

Jef Akst: Virginia is threatening summer over here. It was almost 90, not quite. With Heat N X, it was almost 90 on Saturday, and the kids and I were out for a walk, and we were all just burnt out from the heat. We're like, where did spring go? ⁓

Heather: Wow.

Annalee: mean, I know I left Virginia, like I chose this, but like, I do miss that.

Heather: You know why I think this is happening? It's because tonight the Rogers Center, they are celebrating the Jays 50th anniversary of their opening day when it snowed. So I think this is why. Yeah, I think this is they ordered it up. Yeah. Yeah, I suppose. ⁓ in other news, biopharma. let's introduce ourselves.

Annalee: ⁓ really? All right, well, that's very fitting.

Jef Akst: A white celebration.

Heather: Jeff, you want to go first for a change?

Jef Akst: Sure, of course. Yes, I'm Jeff Axe, Managing Editor, and I'll let you two introduce your own newsletters, but other ones that you all should sign up for are our daily newsletter, Gene Pool, as well as Manufacturing Brief, which hits your inboxes on Tuesday, and Career Insider on Thursday.

Annalee: And I am Annaleigh Armstrong, I am senior editor and I am in charge of the Biofarm executive newsletter which goes out every Wednesday.

Heather: And I am Heather McKenzie, senior editor, and I am in charge of curating your Clinica Space newsletter that goes out every Monday. last week on the show we mentioned how we were eagerly awaiting the approval of Eli Lilly's Orpher Glyphron, and didn't have to wait long.

Jef Akst: No, it was like few hours later after the show published.

Annalee: And we had already started planning it, like as soon as we got off the podcast last week, so we were ready.

Heather: Yeah, we were like, oh, maybe, you know, it had been on my to do list forever to, to pre-write some of that article. And, and I was like, yeah, maybe we should get on this. It's, it's April now and very next day. There it came. Yeah.

Jef Akst: and time.

Annalee: Isn't it nice to have regulatory certainty? That's what this is.

Heather: Yes, one area of regulatory realm, it is. What did guys think of the name, Fondeo?

Jef Akst: It reminds me of Fandango, honestly. That was my first thought.

Heather: I thought fondue.

Annalee: Yeah, I don't mind it. I don't hate it. It's not, know, actually, I would say that lately, some the new drugs that have been approved, the names have been all right. No, no weird cues and because it always bugs me, especially when they do a cue without a U, like I know you're being fancy, but like,

Heather: Yeah. ⁓ yeah, yeah, I don't have to shorten that to found or something. That's ⁓ yeah, it's good. Well anyway, about found day out. So, you know, we obviously that Nova Nordisk got a head start in the oral obesity game, with, with their December approval for oral Wigoby. so now the battle is on.

Jef Akst: found a it was easier to say that or for clip right. ⁓

Annalee: ⁓ absolutely.

Jef Akst: Ha ha.

Annalee: Yeah. Yeah.

Heather: Within an hour of publishing the news, we actually got an email from Novo claiming Oral Wigoby's benefits. And so they were right on it.

Annalee: Yeah, this is the next step in a really major rivalry between these two companies. been battling it out in obesity for several now with their injectable medications and both of their pipelines. They've been going back and forth kind of trading barbs in the clinic. And Lilly shares up 4 % on the approval of what is now Fondeo and Novo dipped a little on the approval, which kind of like highlights this balance that these two companies are experiencing. ⁓ Analysts think that Lilly's offering quote blunt the uptake of oral wagovi. That according to William Blair. But obviously, you know, with Novo kind of going on the defense immediately, we saw pretty unprecedented ⁓ response from Typically when a drug gets approval, it's just like, okay, whatever, or a rival drug, I should say. ⁓ When they approval, companies just kind of move on. But Novo really went on the defensive. They released some new trial results and previewed some upcoming presentations. They really wanted to get out ahead of this.

Jef Akst: I think it makes sense that that's the expectation for a Wigovia uptake to kind of be blunted by this new approval because we've learned previously that most of the oral Wigovia users were new GLP-1 users. So it wasn't like they were scooping up from the injectable crowd. was a whole new user. So people who didn't want these drugs unless they had an oral option, now they have two oral options. So what are the key differences between these two pills?

Annalee: Right, know, Novo again, they came out and talked about the efficacy and, you know, it does seem that oral Wigobi has the edge on efficacy. As far as the existing studies have told us, there has not been a head-to-head trial between the two, but we kind of can read through, you know, what's out there. Oral Wigobi achieved a little over 16 % weight loss in the clinical trials that supported its approval, whereas Fondeo achieved about 11%. So there's definitely a difference there. cross trial comparisons, blah, blah, the essential caveats here, oral has achieved more in the clinical trials to date. One of the major differences where analysts say the battle is really gonna play out is on how these drugs can be taken. Oral Wigovie has to be taken on ⁓ an empty with a big glass of water and you have to wait 30 minutes before you eat anything else. Whereas Lily has no food restrictions. You can take it without food, it matter.

Heather: Mm-hmm.

Annalee: that could make a big difference to a patient who has to take this drug every single day.

Jef Akst: Yeah, I agree that is a pretty noticeable difference and it was interesting to me that that was one of the things that was Nova was almost defending, just sip and go, you no big deal. But that seems like a potentially big deal.

Heather: was going to say, have a refreshing glass of water, which is a good idea. I love water.

Annalee: Yeah.

Jef Akst: Right.

Annalee: But you know what, that strategy, the way that they put that marketing little tidbit out there really highlights the strategies that these companies are doing. They're trying to appeal to everyday people. This isn't just any old drug that they're launching. They are going straight to consumers to try to show them that their drug is better than the competitor. this is going to take a few months to play out. drug needs to get coverage. And so we're not gonna probably see this until maybe next quarter, quarter after that. But this is going to be another big area of rivalry for Novo Nordisk and Eli Lilly.

Jef Akst: Hey, Anneli, can you start that revenue tracker that you made with like years of history or the injectables? I want to see this for the Orals and how they go.

Annalee: Yes! I will add them in as soon as we start to see revenue.

Jef Akst: Thank you.

Heather: Speaking of the oral obesity space, we're going to have a special edition in Clinica space coming out in a couple of weeks on, I believe that is April 20th? No, what's the Monday? I think it's the 20th. Yeah, okay, the 20th. So stay tuned for that. We'll take a deep dive into this.

Jef Akst: I mean, 28th is a Monday. Yeah.

Heather: in other news, &A, Bolton deals keep chugging along. This it was Gilead Sciences and Neurocrine making the buys. So Gilead put out 3.5 billion upfront to acquire its partner, Tupilis, which an ADC specialist. ⁓ so called this deal a strategically sound bolt on. And, you I there. So Gilead is a big cancer player. has ADCs like Trodelvy, which is marketed for two of breast cancer. But they have struggled a little bit in this space as well in the past couple of years. In 2024, Gilead pulled Trinelby in bladder cancer after a disappointing confirmatory trial.

Jef Akst: Yeah, interesting to see Gilead continue to deal. Like you said, they had those other couple already they were saying like, know, we're in no rush to buy more companies. And here we are three months into the year and they have three new companies under their belt.

Heather: Thank You

Annalee: also like the structure of this deal. Pretty ⁓ Tubulus actually gonna basically tuck in under Gilead and continue existing as this ADC factory. So it doesn't seem one of those deals where they're just gonna kind of take what they want out of it and get rid of the company. Hopefully some of expertise will stay, ⁓ which we always to see in such a tough hiring and employment market in biotech.

Jef Akst: Definitely. I don't know if the same can be said for the Neurocrin deal. It's maybe. I didn't look that far into it to see about the workforce, but it is not going to stay as far as I know continuing to operate as an independent company, the one that they bought. So that is Solino Therapeutics. Neurocrin bought it for 2.9 billion. So another one of those bolt-on deals seems to be the theme of 2026 so far. was the premium is about 51%. So is paying $53 a pop and that's about a 51 % premium over the average trading price for Soleno's shares over the past month. But despite that seemingly sizable premium, Stifle analysts were actually surprised how low that purchase price was. And they said it's a good exit for Soleno, but it's a really good buy for Neurocrine. So ⁓ harkens back to something you've reported on Annaline where there's pretty high premiums going for ⁓ &A this year in a pretty hot competitive environment trying to get some of the last biotechs out there that have late stage or commercial products. here, the centerpiece of the deal is a commercial product. March, Salino got approval for a drug that will treat extreme hunger in patients with a rare disease called Prader-Willi syndrome. The drug is called Vicat, and like I said, it was approved last March. So that further entrenches Neurochron into the endocrinology and rare disease spaces for which Neurochron already has two approved products. You've got Increza, excuse me, these are... A mouthful of names here, ingresa, that's for tardive dyskinesia, and cronesity, and that's for congenital adrenal hyperplasia. So add to that, ViCat, and we'll see how neurocren's numbers grow this year.

Heather: I like by cat. That's a good name of by cat. That's easily rememberable. Well, Emily, tell us who's next. Is this pace going to keep up? I we were just talking this morning, we keep using all these fish eating other fish or swallowing other fish as photos, which I love the fish. But are we going to be doing more fish?

Annalee: Yes. Yes, the fish eating fish stock art market really needs to pick up because ⁓ it does seem that in biopharma, at least there is going to be no slowing to the deal activity. Many analysts are just kind of saying that all of these recent deals are really galvanizing excitement in the space. And they think there's going to be more, which is news, really exciting stuff to cover. ⁓ It kind of shows that there's been a rebound. are finally starting to buy companies after, you know, kind of a lot of this talk of all the patent clips that are coming up, ⁓ they're executing. So BMO Markets kind of gathered up all these deals and took a look at what companies are likely to strike the next ones. They predict that Amgen, Abbey and Bristol Myers Squibb still have some space to make deals. know, Vartis, which has actually been one of the busier companies, ⁓ they could also buy some Of course, Lilly, they've got lots of cash on hand from their obesity portfolio. could make a few more, but they might be a little more selective. So BMO says that if the pace of deals over $500 million continues, we're actually on track for a record year in terms of the volume of deals and altogether, this could reach to deals totaling about 172 billion in total, which would be a pretty big escalation on the year before.

Heather: Wow. Well, I'm looking forward to seeing who's next. Maybe tomorrow. Well, yeah, who knows? Or maybe right now. They're famous for doing things right while we're recording. So check. Well, another thing that finally happened this week, President Trump his long-promised tariffs on the pharma industry.

Annalee: later today, there's, you know, sometimes they do them after market clothes. right. So yeah, it's been, I kind of forgot the tariffs were still a thing, but in the background, the Trump administration was continuing to analyze the situation as promised. They never stopped doing that, but they announced 100 % tariffs that are going to apply to imports from 17 large pharma companies, starting in about 120 days. Smaller companies will have a little bit longer at 180 days. You know, the headline of this was kind of jarring, but there's so many exemptions that it's really kind of unclear how much of a big deal this is gonna be. exemptions for orphan drugs, cell and gene therapies, ADCs, ⁓ several companies are also gonna have a different rate just, you know, based on deals they've negotiated. ⁓ So it's little unclear exactly how big of a this is going to be at this point.

Jef Akst: The other thing that's unclear to me here is who the tariffs will apply to. There are lists that were given to us, but they're not totally congruent with what we understood based on the deals that pharma had been making with the White House. as a reminder, there were several companies that have struck deals with the White House agreeing to Trump's most favored nation pricing to equalize, to bring down U.S. prices and equalize them with countries around the world, and also to invest in U.S. manufacturing. many of these companies explicitly stated that in making these deals, they would get a reprieve from tariffs. And so the clearest example for me is Pfizer, the first big pharma to show up at the White House, have a big press conference touting this deal, you know, in addition to agreeing to MFN pricing, agreed to a certain amount of investment in US manufacturing, and specifically said that they would be receiving a three-year reprieve from tariffs. But Pfizer is not on the list of firms of companies with tariffs agreements. and is on the list of businesses subject to the 120 day deadline. So I'm really unclear what's gonna happen. Johnson and Johnson and GSK have also disclosed deals with the Trump administration, but are also on the list of companies facing near term tariffs and are not on the list of drug makers with White House agreements. So I'm a little unclear as to how the White House is deciding which drug makers deals are sufficient to exempt them from tariffs and which will still be subject to them.

Heather: Yeah, that's a good thing that we'll follow up on. Well, speaking of MSN pricing, this is really impacting Europe in terms of new drug launches.

Annalee: Yeah, so something that kind of has emerged in the past few weeks is that pharma companies are actually starting to rethink their launch strategies in Europe. So they're considering ⁓ either launches or not launching at all in Europe, just to avoid setting a reference price for their drugs that could used to set pricing in the US. This idea really shook me, ⁓ the idea that patients would be actually denied new medicines just so that Americans can be charged more. It really seems to go against the spirit of innovation and helping patients, which is a reputation that pharma has been working really hard to build in the past year. I tackled this in an editorial this week. just this that patients might not get medicines just because of this policy in the US is really just hard to take. So you can check out at a biospace.

Heather: I'm glad you called that out, Annali, because it just really, that does not go down well. It doesn't go over well. yeah, I mean, ⁓ in charge of ⁓ over there might want to consider that, because yeah.

Annalee: Yeah, like, you know, alert on my editorial, I don't offer a solution here. Like I know that innovation needs to be paid for. But this just seems like a really dark moment and a pivot away from what I think should be important to this business, this industry.

Heather: I'm Yeah. Well, on the regulatory roundup this week, the Trump administration came out with its 2027 budget proposal on Friday, and they have several proposals in the HHS and FDA space. So overall, president is seeking a slight increase for the FDA up to million, which is about 232 million over this year. The general gist of the proposals is that they to go from having a reactionary system at the FDA to a more proactive system. That's according to Commissioner Marty McCary. So one of these proposals is sure to be really popular and that is that the FDA is seeking to permanently authorize the Rare Pediatric Disease Priority Review Venture Program or PRBs for short. currently these need to be reauthorized by Congress every few years. The authorization expires in 2029. And a clinical trial notification pathway would apparently expedite the current investigational new drug authorization. process procedure, or sorry, the current, yeah, investigational new drug authorization procedure for stage trials. And this program aims to make the US more competitive at this stage as many companies are conducting their early stage trials abroad.

Jef Akst: Yeah, both of those are noteworthy for sure. We've heard so much about how companies are going to China and elsewhere because it's so quick to get into inhuman studies. So to be able to accelerate that part of the process would be awesome. We've heard a lot in the past year about accelerating drugs to market, but accelerating drugs to clinical trials is another big part of this. And then that voucher one, you guys both have reported so much on this rare disease voucher program when it lapsed in late 2024 and it was basically absent for a full year. We weren't sure what was going to happen. There was a lot of

Heather: Thank Mm-hmm.

Jef Akst: billions of dollars left on the table potentially. So if that became permanent, that would be excellent.

Heather: Yeah, that's thrown so many companies for a loop. And I saw that, was like, yes, go for that. So terrific.

Jef Akst: Yeah. We also noted a number of manufacturing proposals in this document. So the FDA is seeking more power to regulate post-approval manufacturing changes, such as moving production a different site or working a new API supplier. The agency is proposing legislative changes to give it that power. They also want lawmakers to confirm and expand its ability to disclose and use certain kinds of information related to drug impurities and even withdraw products from the market if companies fail to report things on such as how much API they source from different suppliers. basically the agency, the FDA is saying that these changes should lawmakers enact them into law would allow them to have greater visibility into the supply chain. And then the budget proposal also

Annalee: So basically.

Jef Akst: $9 million and full-time employees to accelerate advanced manufacturing, something that we've talked a lot about here. And that includes initiatives, funding initiatives like PreCheck, which is a program launched just earlier this year that's meant to help companies build manufacturing facilities in the US. So again, fits with that theme of US manufacturing, manufacturing of US drugs onto US oil.

Heather: Yeah, I think there's some really great ideas in here, honestly. But it ⁓ at a time of controversy for the FDA. And I think a lot of this controversy is honestly from the pieces I've been writing lately and the people I've been speaking to, I think a lot of it just has to do with nuance and the constant tug of war the FDA seems to be in between unmet needs for these rare diseases especially, and then obviously cancer and just so much unmet need ⁓ and So last week, the Rare Disease Advocacy Biotechnology and Investor Coalition, and that's made up of advocates and biotech execs, wrote a letter to HHS and FDA officials calling on them to really restore ⁓ clarity as they consider Vinay Prasad's replacement at CBER. So just a quick reminder, Prasad is going to leave the FDA at the end of this month. That was announced last month. And we haven't heard anything on who might take his place. So I think they and a lot of other people are wondering about that. At our webinar last month, the panelists also talked about a need for clarity. But a key for me was really just this tightrope that agency is walking between scientific rigor and meeting unmet needs. And I think always the case. You know, last month, Holly Fernandez-Lynch, she's an ethics professor at the Penn School of Medicine, told me that the FDA reversals that we keep seeing and that I've reported on ⁓ aren't necessarily inappropriate. And that just because the FDA under a former administration has given certain guidance, ⁓ the administration isn't necessarily beholden to follow it if it disagrees. Now, Holly also said that obviously it's a big problem from a business standpoint if companies are this previous guidance from a previous administration to make decisions that ⁓ really key to shareholders.

Jef Akst: Yeah, I was about to chime in and say the same thing. I think if things are going to be shifting, and I've made this point before, change is fine, change is good. Communication is key, though. And I feel like the concern with these reversals is not just the reversal of course itself, but the fact that the companies felt blindsided and they were unexpected and they thought they were, you know, full speed ahead to the market. And then suddenly they weren't. So I think that's where things seem to be falling short at times is communication. But absolutely, it's a it's a hard line that the FDA is trying to walk.

Heather: Another area, and I wrote a piece about this one was out Monday, is external control. So externally controlled trials. leaders, biotech leaders want more clarity in this area because it really like some external controls and some innovative trial designs like single arm studies are ⁓ accepted by FDA and then others, it becomes a problem when you get to the review stage. So on this note, Harpreet Singh, who often comments for us, she's a former oncology regulator and currently CMO at Precision for Medicine, said something that was really of poignant. It's incredibly complex to determine whether an external control is appropriate.

Jef Akst: Yeah, the FDA seems to support the idea of external controls, but again, there seems to be a breakdown in the communication for which external controls will be acceptable in which cases.

Heather: Thank you. Yeah, exactly. Well, moving back to business, Annalee, what do we have in biopharma exec this week?

Annalee: I had the incredible joy of getting to interview Sabrina Martucci Johnson, who is the CEO of Dare Biosenses, of the only, if not the only biotechs that's actually working on therapeutics for women's health. So Johnson is working on a crowdfunding initiative to support Dare, which is, and her goal is to try to bring in investors that wouldn't normally participate in kind of these bigger, more traditional biotech funding rounds. ⁓ So they're actually encouraging everybody to participate. People can get involved for as little as 250. It ⁓ feels I'm selling something, but I just thought this idea was so cool. The website very geared towards people who have never invested before. know, Johnson really people to get involved. ⁓ She would love see more companies just like Dare out there who are working on therapeutics for diseases and disorders that affect women. So. You can learn more about that in Biofarm Executive this week. We also, of course, got a nice update on what Daraea has been up to and what their year ahead looks like.

Jef Akst: I think it's an interesting idea to crowdsource funding for an area that is chronically underfunded. I mean, I bet she would have been happy to go through the traditional channels if the funds existed there for women's health, but it seems like there's this gap. And so, yeah, maybe just everyday women can help fill it.

Annalee: Yeah, she said something like 1 % of institutional investor dollars go towards women's health, is like just crazy. in her time that hasn't improved at all. she's like, maybe if we see more women quote, voting with their wallets by that maybe some of those big investors might come back to this space finally.

Heather: Wow. Godspeed to you Sabrina. If it wasn't ethically frowned upon, I would vote with my wallet. My accountant just told me I'm not allowed to do that. ⁓ we'll leave you on that note ⁓ ⁓ be back with you next week when hopefully it will be spring again.

Annalee: Right, right.

Heather: Hi, welcome to the weekly Biospaces weekly news show. I'm your host, Heather McKenzie. Either Lilly's or for Glypron, now Foundeo, won approval last week, officially launching what promises to be a heated battle between Lilly and chief rival Novo Nordisk. Plus, the ⁓ &A train keeps chugging through biopharma, with Gilead and Neurocrime making buys this week. President Trump finally levied tariffs on the pharma industry, up to 100 % within 120 days. But car votes will keep some companies safe for now. Finally, the FDA's 2027 budget proposes making rare pediatric disease priority review vouchers permanent and a new pathway to first in human trials, as well as legislative changes to give the agency more power in regulating manufacturing. Let's dive in.