Heather: welcome to the weekly. I'm Heather McKenzie, filling in for Jeff Axed. This week is all about adcoms and earnings. released briefing documents for two advisory committee meetings taking place today and tomorrow, and it's looking like both Replimune and Capricor are in for a tough slog. Meanwhile, GSK, AstraZeneca, and Roche announce Q2 results. Serepta has a new CEO, and Angen has launched a full court press to defend its embattled rare disease drug Tavnios. Let's get started. Hi Annalie, welcome back.

Annalee Armstrong: Hi, thank you. Yeah, I feel like have I been off the podcast for two two weeks? Three weeks?

Heather: Two weeks. Yeah, I don't think yeah, we we we missed you, but how was how was your vacation? How how's your garden looking now?

Annalee Armstrong: My vacation was good. It was a little long, but it was nice. and yeah, I c I came back. I had somebody taking care of my garden the whole time, but it turns out I've been like lovingly nursing a weed, which is now like five feet tall in my garden. I thought it was a dahlia. It's not.

Heather: Maybe you could get it classified as something else, like a new flower. Hmm. Hmm. Okay. That's great name.

Annalee Armstrong: Well, I wish, but it does already have a name. It's apparently called pigweed. Yeah, yeah. It's like it's a type of amaranth, which is a plant that some people grow for beauty, but not this particular variety. It's just a weed. So I'm not I now I have to decide what to do with it because it's like really tall and like as tall as my other dahlias. No?

Heather: Is it pretty? No, yeah. Maybe maybe just maybe maybe it's it's run its course. yeah.

Annalee Armstrong: Yeah. And and I don't know, maybe I can put in some petunias or something in that spot just because

Heather: Yeah.

Annalee Armstrong: I feel like something should be there.

Heather: Well, I've had a a garden win, although it's not really my own win because I don't have a green thumb, but my mom does and I bought a sunflower plant earlier this year and it was dying, like May or June, it had no chance. but my mom saved it and it now has fifteen nice sunflowers.

Annalee Armstrong: Amazing. I love my sunflowers. I have a few of them and next year I don't know. I need to plant a million of them. They just bring me so much joy.

Heather: I know, they're my favorite my favorite flower. Well, Gabrielle is not with us this week, just because she has some technical difficulties. so it will just be Annalie and myself. But let's get to intros. why don't you go first?

Annalee Armstrong: Sure, Annalie Armstrong. I am senior editor at Biospace and I do the Biofarm Executive newsletter each week, which hits your inboxes Wednesday morning.

Heather: Alright, and I am Heather McKenzie, Senior Editor at Biospace, and I curate Clinica Space, which hits your inboxes very early on Monday morning. Well, let's get right to it. Let's start the show off with maybe maybe what's the most dramatic news of the week. the FDA's big advisory committee comeback. so the Capricorn therapeutic Sega continues. the FDA is now disputing the success of Capricor's phase three trial. The disagreement over whether or not Capricor's Duchenne muscular dystrophy therapy met the trial's primary endpoints was revealed in briefing documents on Monday ahead of an FDA advisory committee meeting, which is happening Wednesday, which is today, if you're listening to us.

Annalee Armstrong: Yeah, so this has been a pretty busy week for the FDA on the regulatory front. so starting with Capricor, the FDA released their briefing documents ahead of that meeting on Monday, and they revealed that they disagreed with Capricor's claims that a phase three trial met its primary endpoint. This was pretty stunning. I don't can't think of the time that I've ever seen this. the FDA basically said that Capricor, after Capricor completed the randomized double blind Part of the trial. Changes were made to the pre-specified statistical analysis plan during the open label portion of the trial where all patients received the cell therapy. And that generated at least two additional versions of that analysis.

Heather: Yeah, and you're not the only one who was stunned. I I spoke with Capricor CEO Linda Marban yesterday afternoon and she I mean, yeah, she she she had already said that she was surprised that the meeting was called. she she didn't know why or what issues they wanted to discuss. well Capricorps is in the know now. so apparently this the SAP or statistical analysis plan the FDA reviewers analyzed in in the documents was a draft that Capricorps only submitted After the FDA asked for all SAP drafts. So there seems to be some communication issues here. But she expressed confidence that the ADCOM members would, quote, be able to see through the statistical analysis plans and not turn this into something mathematical, but instead look at the effectiveness of the therapy across all of Capricorse trials.

Annalee Armstrong: This has been a really tough journey for Capricor, right? Like, this has been going on for more than a year now.

Heather: Yeah, I've been following this story for it feels like two years, but I guess it maybe is only a year. It's just been really long year, especially for Capricor. but yeah, it's been very long and windy. this was in fact one of the biotechs that was featured on an awesome graphic that Anna Annalie made of a roller coaster. a little bit of background here if you if you haven't been following the story. Capricor's first application for a drug called a cell therapy called Deremia Cell was rejected in July last year. and this was after a planned adcom was canceled without the company's prior knowledge. So Capricor Deremiacell have also been at the center of an internal FDA clash last summer. so the first adcom, the one that never happened, was scheduled by Nicole Verdun, former top regulator of cell and gene therapies at Cedar. Seber, sorry. and then then former Seber head Vene Prasad unilaterally cancelled the meeting, and Verdun and her deputy Raquel Anatol were soon to follow out the door.

Annalee Armstrong: So this all ties back into the crazy right leadership upheaval that's been having happening at the FDA. now we're seeing a return of these adcom meetings. but it seems like the FDA is really kind of holding the line on some of these decisions that came down over that tumultuous period last year.

Heather: Yeah, which is surprising because it seemed like it was going the other way. We've we've written a number of articles the past couple of months about how the FDA has seemed to be a little bit more flexible. and and now it's kind of seeming like like last year again. But Linda Marbane is not the only one who is surprised at at the course that some of these adcoms are taking. One of our writers, Michael Gibney, spoke with ex-regulators and other experts. And some of them were surprised that the FDA has actually resumed adcoms at all while they're still trying to staff back up. And others have questioned the rationale behind the meetings and and others that are are scheduled. so you can check out that piece in Clinica Space this week.

Annalee Armstrong: Yeah, and now jumping over to RepliMune, which is also having an adcom this week, we just wrote that up on Tuesday morning in the FDA briefing docs. Again, the FDA came out really strongly and saying that the data package that Replimune has submitted is is potentially not sufficient to support approval. the FDA is still very critical of Replamune's use of a single arm study to support the application for the drug in melanoma. They said that the phase two study, which is called Ignite, is not interpretable, interpretable. This is a tough word. I really struggled. but anyway, so so they also questioned

Heather: Yeah.

Annalee Armstrong: the benefit that was shown in the trial. So it was again a really strong statement from the agency coming out in these documents. Replomune, of course, had the chance to defend themselves in their own response to the documents. They said that a randomized trial would have been unethical in this population, and they cited experts who have said that. They also argued that other companies like Iovance, Merck, and Prystalmeyer Squibb have actually received approvals in melanoma based on single-arm trials. So there's some precedent here for the FDA executing regulatory flexibility. So after all, or With with these documents out now, the meeting will occur on Thursday. The adcom has been asked to vote on whether the efficacy results are valuable and clinically meaningful. And just a reminder, the FDA does not have to follow what an adcom does. They typically do. In very rare occasions, they'll go against what an adcom says. but I think we can definitely expect some pretty robust discussions at these meetings.

Heather: Yeah, and and th this whole thing regarding the the single arm trial that Replimune used, th this has been the FDA's issue from the very beginning. It was mentioned in the first complete response letter that was last July, and then the second one in April of this year. so it might sound kind of dire for Repl Imune and and RPA one right now. How however this drug has a lot of advocates out there. there were about I think there were twenty-two clinical leaders. scientists who submitted a petition last year in support of RP1. So y you know, you just have to wonder are are any of those guys on on the committee and what chance do they really have? But but we will have coverage, continuing coverage of both Capricor Replamune this week. Well turning to second quarter earnings, at Biospace we like to playfully call this earnings Hell Week, but Annalise secretly loves it.

Annalee Armstrong: Hell week, but anyone. I do.

Heather: So let's start off with G S K.

Annalee Armstrong: Yeah, so Gabby Mason covered this one this morning. so and some big news on this call. GSK announced a three-year savings plan that is ultimately supposed to save $2.5 billion. This is money that CEO Luke Meals says will largely go back into accelerating RD efforts. he took the reins of GSK at the start of this year. So this is like his first really big Implementation of kind of like a s a change at this company. He's executed a couple of deals so far, but definitely a change in tone from Emma Walmsley, who stepped down at the end of the year. She's still actually with the company until September in an advisory capacity, as often happens with these big CEO changes. So definitely the ship is changing, moving in a different direction at GSK. So we'll see how this goes.

Heather: It was a good second quarter publication or presentation because they got a six six percent bump in those in the stock this morning. Yeah.

Annalee Armstrong: Yeah, absolutely. Investors really reacted favorably to this news. and elsewhere in their earnings, they announced a bunch of other changes. They're going to be investing $530 million to relocate an RD center to Cambridge. at the same time, they also incurred a $2.4 billion impairment charge for RD efforts, which last year that was only $633 million. So that's a pretty big jump. a lot of that came from the discontinuation of Camlipixant, which was in chronic cough. That drug had come from the $2 billion buyout of Bellis Health a few years ago. So unfortunately, that drug did not stand up in the clinic as GSK had hoped, so they've had to write that one off. they're still kind of pushing that drug in irritable bowel syndrome, so we'll see if it has maybe some market hopes. But that was certainly a a a disappointment for GSK.

Heather: Well, GSK's British neighbor, AstraZeneca, also announced earnings this week. And despite their stumble a couple of weeks ago with their ATTR drug, Wynua, which failed in late-stage ATTR CM, executives don't seem concerned. So CEO Pascal Soria said Monday that the company is, quote, very much on track, end quote. to hit its twenty thirty goal of reaching eighty billion in revenue. so we'll we'll see how that goes. still to come this week we have Sanafi, BMS, Moderna, and more. but I personally always find the smaller biotechs more interesting.

Annalee Armstrong: Yeah, for sure. And we have taken a look at five biotechs that have some exciting quarters to report on. I think what a really cool trend is about a lot of these companies is that they are kind of pushing their own therapies onto the market themselves, which is really cool. These are some scrappy biotechs. We always love to see that. So you can check out that report in Biofarm Executive this week. We go into detail on Agios, Arrowhead, and a couple other companies. and give you an expectation of what will happen on the earnings calls to come.

Heather: Alright, looking forward to reading that. well in other business related news, Sarepta has named a new CEO who started on Tuesday.

Annalee Armstrong: Yeah, so this is big news, kind of wrapping up a story that we've been talking about for a while. I mean, the Sarepta saga is not over. There's still a lot to come from this company,

Heather: Yeah.

Annalee Armstrong: but this closes one chapter as Doug Ingram steps away. so Sarepta has hired Michael Severino. He was most recently the CEO of flagship pioneering biotech Tesera, which does gene writing. so Severino stepped down from that role earlier this month to le and apparently now to lead Sarepta. Doug Ingram is retiring, according to Sarepta. This was kind of a a stunning story earlier this year. He announced his departure and said that two of his family members had been diagnosed with one of the conditions his company is actually researching, which is called myotonic dystrophy. So that was a pretty unique situation at Sarepta.

Heather: well Severino is going to have a pretty tough job. so Serepta is awaiting two FDA decisions for full approval for its Exxon skippers, Amondis forty-five and beyond as fifty-three. and those are both for Deschenne. and they both failed their confirmatory trials. So those decisions are expected early next year. Well speaking of drama and sagas, another biopharma Sega got another chapter on Friday when Angen launched a full court press to defend its rare disease drug, Tavnius.

Annalee Armstrong: Yeah, so this is something we've been waiting for for a while. Amgen has been really fiercely defending this rare disease drug, but now they have officially responded to the FDA's request to withdraw the therapy. they did that in a rather large statement. They they provided some data and some real-world analysis to the agency, and they are now requesting a hearing with the FDA to discuss the matter. Earlier this year. Amgen's Japanese partner revealed that 20 patients there had died after taking Tavnios from a complication, potentially. And now both the FDA and European medicines agencies have recommended the have recommended that the drug be withdrawn. So and then there was also news that a key study that was used to support the approval was withdrawn from the New England Journal of Medicine. That is kind of one of the premier medical journals out there. so Amgen is is continuing its defense. So in this data package, they are including real-world evidence and some patient testimonials. The company argues that patients are seeing real benefit from Tavnios, including relief from taking steroids that can have really difficult side effects.

Heather: Yeah, I think isn't Tafniel's the the only drug that that's shown efficacy in this population, I I believe. I I I'm not entirely sure on that, but I I know there's a really high unmet need. well finally, Annalie, what else have we got in Biopharma Exec this week?

Annalee Armstrong: I took a deep dive into the intellectual property challenges that come with all of these deals that are happening in China. So we have farmers going over to China, they are finding assets that they really want to license and bring back to the United States. however, that can raise a lot of challenges when it comes to IP. So I talked to a bunch of patent attorneys to figure out where the risks may be. One thing they appointed to very they really wanted to highlight was that the Biosecure Act could raise some risk downstream. So these are early assets. However, if you have a patent for manufacturing that was signed earlier, patent attorneys who were doing these deals really need to understand that and make sure that if that company is flagged as a company that could be a danger to national security, they could have some problems later on with manufacturing. So You can check out that feature in BioFarm Executive this week, in addition to the earnings recap for biotechs.

Heather: Well sounds good. that's it for us this week. enjoy the rest of your July, and we will be back with you next week when it will be August.