AstraZeneca buys into Summit, UniQure drops on 4-year data, FDA on a roll bölümünün tam dökümü

not me. If if you wanna guess my age. Jef: Yeah. I think you just aged us. All right. Well let's get to something that our audience does know about, which is biopharma. So I guess before we dive in, we do have to get to introductions. Heather, why don't you start us off this week? Heather: Sure. I am Heather McKenzie, self-declared Backstreet Boys fan and Jef: Ha ha. Heather: Clinica Space editor. senior editor here at Biospace and Clinica Space comes into your inboxes every Monday at three AM Eastern. Jef: Gabby, go ahead. gabby: And I'm Gabrielle Mason, senior editor at Biospace, self-declared MUNA fan, and Hillary Duff. and I curate our manufacturing brief, which goes out every Tuesday, and then our Gene Pool daily newsletter. Jef: Very good. And Annalie, go ahead. Annalee Armstrong: All right, well, Annalie Armstrong, senior editor, punk rocker through and through as a teenager, but secret and sync fan. And yeah, I curate the biofarm executive newsletter every Wednesday. Jef: Minor details there. And finally, I'm Jeff Axt, managing editor. And yes, I did listen to Marky Mark. And actually I'm a little bit late to this, but I finally just watched Boogie Nights, which is an excellent movie starring Mark Wahlberg. So recommend that as well. Okay, so diving into gabby: Wait, Jef: our show. Yeah? gabby: is Mark Wahlberg Marky Mark? Jef: YOU Heather: Okay, I didn't know that either. gabby: Serious? Annalee Armstrong: This podcast is off to a great start. Heather: Mm Jef: Yeah, I know. Heather: I've gabby: Are Heather: got his face right now. gabby: you seeing Wow, okay. Jef: So, with that little lesson, very important lesson there on who Marky Mark and Mark Wah Wahlberg are, one in the same. This little Clark Kent Superman action going on there. Okay, so yes, first up on today's agenda in the biopharma world outside of pop culture, we are gonna talk about a sizable update from Summit Therapeutics. This is to the tune of $2 billion in an all stock stock deal with AstraZeneca. So Summit, as we know, has partnered with China as a key so to develop the PD1 VEGF bi-specific Ivaneskimab. This is perhaps the hottest asset in the hottest new class of immunoncology drugs. So we watch it very closely. It's already snagged a couple of approvals in China, but Summit is now running a slew of global phase three trials to generate the data needed for an FDA approval. Summit does already have one accepted regulatory filing with the agency. We are expecting a decision on that on or before November 14th. But as I said, Summit's got these several ongoing trials and phase three trials are, as we know, very expensive. So Summit was running a bit short on cash, And this vote of confidence from AstraZeneca was certainly very welcome for the biotech. Annalee Armstrong: Yeah, Summit really needed this. We've been reporting this for some time. they had about six hundred and ninety million dollars in cash left as of the as of July, when they last reported, which was about enough for about a year of runway. you know, these phase three trials are very expensive, and Summit is running a lot of them. So now AstraZeneca has contributed $2 billion more in an equity deal. This is a little bit different from what we typically see in biotech at this stage, which is a licensing deal where the biotech would basically give up rights to a drug that they're working on in exchange for some cash. They might work together and they might share commercialization down the line. That's a little bit more typical. So here, Summit actually gets to keep Ibaneskimab, but AstraZeneca is going to get a share of the company without buying all the way in. I think that Summit has been a Bit of a, you know, rumor in terms of MA. So we see a company taking a big stake, but not quite going all the way here. gabby: And the investment really creates a a meaningful strategic position, according to BMO analysts, with analysts at Stiefel expecting the money to carry the biotech between two to four years. So that's pretty significant considering their previously predicted runway was projected to last less than a year. Jef: Yeah, they were definitely starting to to see the end of that runway. And, you know, again, with all of these ongoing trials for a hot, hot asset, you know, they needed that money. So we weren't sure where it was going to come from, but pretty sure it was going to come from somewhere. AstraZeneca stepped up to give them that money. And as I said, they do have some it does have a filing in with the FDA that has been accepted. This one is specifically an EGR FR mutated non-small cell lung cancer. That's due in November. But we're gonna see more applications down the line. All right, so moving on, next up we have another biotech that tends to steal a lot of headlines, and that's Unicure. So a lot of the headlines in the past year have revolved around a lack of consistent and transparent messaging from the FDA. In Unicure's case, the company had planned to file for approval of its Huntington's disease gene therapy earlier this year, after three-year data showed an impressive 75% slowing of the disease. The FDA had originally agreed. That the ongoing phase one, two trial could support that filing, but then the agency changed its mind. And then the agency reversed course again after former Commissioner Marty McCarry and CBR director Vinay Prasad exited the agency of spring. So at this point, fast forward to September 2026, the company has indeed filed and expects that application to be accepted this year. But unfortunately, this week we got an update that could put a little wrinkle in those plans. It the company released four-year data for the Huntington's disease gene therapy that was kind of disappointing. Heather: Yeah, well, Unicure has definitely been through the regulatory ringer, and these results may not help. So the four-year data, they were long awaited and just under the wire, because Unicure had guided for Q3 and Q4, as we all

know, begins on Thursday. but they didn't impress investors very much. so the analysis showed that 12 patients taking the highest dose of AMT 130, the gene therapy. Saw a 44% slowing of disease progression, which was the study's primary endpoint. That's quite a bit lower, obviously, than the 75% seen at three years, as you mentioned, Jeff. But executives on an investor call on Tuesday morning essentially emphasized that the results are still, quote, unprecedented, as there is really nothing else, there is nothing else disease modifying for Huntington's on the market. A noisy natural history database was also a big point of contention for Unicure, as the new results were based on an updated enroll HD natural history database, which includes more patients but also a higher rate of missing data. So the executives on the call emphasized that this database therefore underestimated disease progression, which could have contributed to the lower four-year results. but you could tell on the call that they were they were trying to exude confidence, but it basically came across as trying to defend a thesis. Jef: Yeah, I mean, external controls was the source of a lot of the drama here with the FDA. It is hard. External controls are just that. They're not controlled within the confines of the study. And so it's a lot harder. And if you know this updated database doesn't accurately represent the disease progression, it's going to be really hard to compare your treatment data against that. So tough situation for Unicare, obviously, all these rare diseases and external controls. make it really hard to evaluate, which is why the FDA has scrutinized it so much. But like you said, there's nothing else out there for Huntington's, which is an absolutely devastating disease. So really hopeful that these patients could have some sort of option. We'll see, hopefully soon. Hopefully we'll find out, I guess, later this year if the filing was accepted. And then I would imagine that would put a deadline for the FDA decision into early or mid twenty twenty seven. Heather: Yeah, they're going for a priority review and they're expecting to hear whether the application has been accepted in the fourth quarter. Jef: Okay, got it. Well, speaking of the FDA, we got a tiny little update here on the FDA Commissioner, the role that still is yet to be fulfilled on a permanent basis. So Donald Trump's pick to be the next FDA Commissioner faced a Senate committee last week, Heidi Overton. She's currently the deputy assistant to the president for domestic policy. She was grilled by senators about her ability to stand up to Trump. And actually, many of the senators noted that Overton had stood behind Trump in August when he signed that executive order to split. the combined MMR measles, mumps, and rubella vaccine. And that's something that got a lot of pushback from the scientific and medical community. So I think senators were pointing to that as like, are you just gonna fall in line, even if it doesn't align with scientific standards, or will you be able to stand up to Trump if necessary? She has yet to be confirmed. So we're really waiting for that top role to be locked down. In the meantime, though, as I said at the top of the show, the agency has been on a bit of a roll with approvals. so we had a number come through in the past week. Eli Lilly, for example, got a green light for its weekly insulin shot. That will set up another front in the Novo rivalry, because Novo has one as well. separately, Miriam got an approval for the third option for an ultra-rare bone disease that for decades had no treatment at all. So that was definitely noteworthy. But one that we wanted to talk a little bit more on to about on today's show is the FDA's nod for Abby's new Parkinson's drug. This is an asset that Abvi picked up in its eight point seven billion dollar buyout of Cerevel back in 2023. So this had to have been good news for for Abvi. after the lead asset from that Cerebelle acquisition in Mackladine for schizophrenia, that failed a couple of years ago. And that was huge news. Was this a failed buyout? So it's good to see that at least one of those cerevel assets has now made it to market. gabby: Yeah, that was such a big buyout. So this new Parkinson's approval is really great to see. And it it stems from a phase three program called Tempo. and that study showed AB's asset significantly improved motor symptoms and symptom control. So now the candidate is sold as Juvemo, and it's actually the first selective D1 D5 receptor agonist to become available in the US. so the drug received a pretty broad label, so it can be used across early and later stage disease and it goes for about fifty-nine thousand dollars annually, according to William Blair. Jef: Yeah, that broad label was very interesting, not only early and late stages disease, but with or without L DOPA or Levadopa, which gabby: Yeah, yeah. Jef: is really good for the Parkinson's community to have just another option and not a mutually exclusive option to help manage their symptoms and treat their disease. Alrighty, so now moving on to a space that's taken a bit of a hit recently. So this is CAR T and autoimmune disease. You'll recall that a few weeks ago we learned that Novartis and BMS had both paused a number of trials for their CAR T assets and autoimmune indications after three deaths among patients who had taken a Novartis treatment and other safety signals. So that news had some in the industry calling into question the whole idea of using CAR T's to treat autoimmune disease. These are generally chronic and not fatal. So perhaps not worth the same level of risk that CAR T carries that may be acceptable in oncology for a deadly cancer when patients have no other options. But the front runner in CART and autoimmunity, Kiverna, is still very much focused on bringing one of these cell therapies to the market for autoimmune. And this week the biotech had some promising

results. Heather: Yeah, so everything seems to be coming up kyberta. they're definitely knocking on the FDA's door after more positive data from their CAR T therapy MIB cell in Stiff Person syndrome, which is a debilitating autoimmune disease. So MIP cell improved mobility and leg function and showed a favorable safety profile in 26 patients with the disease. And maybe most importantly, the therapy continues to have a clean safety profile. And as Jeff mentioned, this comes just weeks after Navortis reported three deaths in autoimmune trials of its own investigational CAR T therapy RAP cell and paused several other trials subsequently, along with BMS, who saw some safety signals and paused their trials out of an abundance of caution. But in Chyberta's one-year readout, there were no high-grade cytokan release syndrome. immune affector cell associated neurotoxicity syndrome, which is better known as ICANNS, and no immune effector cell associated hemophot okay. I E C H S. we'll just we'll just call that and you can you guys can Jef: I applaud you for even trying that one, but yeah. Yes. Heather: look it up. I apologize, I just can't get that word. it's it's basically a life threatening hyperinflammatory syndrome that Novartis attributed its death to. Jef: Yeah, exactly. And you know, these inflammatory reactions make sense when you're when you're messing with the immune system. And it makes sense that Heather: Mm-hmm. Jef: in oncology, you know, we need to reignite the immune system to fight the cancer, because often it's immunosuppressed and the tumor is otherwise avoiding the immune system. But the reverse in autoimmune disease, right? Autoimmune disease is where your immune system is attacking your body. So you want to quell it. So all of this makes sense. These side effects, they're in line with the way that these therapies are functioning. But obviously, so Heather, you dug you dug into this a little bit more for a feature I know. So the events with Novartis and BMS kind of reignited this debate about this risk benefit proposition for CAR T therapies and specifically, like I said, for non fatal diseases like autoimmune disease. So what have you been learning in your reporting? Heather: Yeah, so a lot of people have different perspectives on this. but basically what it comes down to is should patients and and drug developers take the risk, which can be increased with CART therapies, when there are are already decent options out there. So the other side of it it is with a lot of these conditions, the quality of life is not great. And these therapies have been shown to put some diseases, including lupus, into remission. So you can you know, it's a it's a it's a gamble, but but one that I think a lot of patients with autoimmune diseases, from what I've read, would be willing to take. you can read more about that on Monday in my deep dive feature. Jef: Yeah, it really seems like it's not gonna be a one size fits all. Nothing rare, you know, rarely is anything a one size fits all. But I can imagine that this would be a really important option for certain patients. And so I do think it's a worthwhile endeavor for these companies pursuing these, but it may not be the full scale of the market. I know that was one draw initially when this was a very young field. The idea that autoimmune could be treated with CAR T, that's a much bigger market. than individual oncology indications. So maybe we're not looking at the full swath of a particular autoimmune disease, but maybe for a subset of patients, these CART Ts would really be valuable. All right, well now moving on to our last segment of the podcast where we talk about Biofarm Executive. What we got coming up this week, Annalie. Annalee Armstrong: Yeah, so this week we continue our series on women in leadership in biotech. Remember, we're taking a close look at first-time CEOs, which has been a really fun angle to take. Gabby has a feature on that, but before she previews that, I'll also tell you about our lead story, which is taking a look at kind of the broader leadership environment. last year we had a really cool trend that was a lot of the major MA deals featured Biotechs that were helmed by women. There were 11 deals, including three of the top four largest deals of the years, of the year had CEOs that were women. I loved that trend last year. It was super fun to track. We did a lot of coverage of it. So this year I took a shot at redoing that analysis. and unfortunately, there is no such trend. so there were 11 out of 72 deals last year were biotechs that were led by women. This year there are just two biotechs that were led by women that have been bought so far. Out of a total of seventy three, and we are only three quarters through the year, MA has picked up considerably. So unfortunately, I don't know if that trend is going to recover. Jef: Yeah, no, it was gabby: Maybe not. Jef: definitely a little almost surprising to see the number of deals that were led by women. But unfortunately, like you said, not that trend is not holding. Annalee Armstrong: Yeah. So on the positive side though, Gabby has a really cool story on by Kara. Why don't you tell us about it, Gabby? gabby: I've I've loved doing this series with you. I got to speak with Bicara co-founder and CEO Claire Masendor, and I got to hear about her kind of realization that it was time to hand over the CEO reigns to Bicara's chief operating officers, which she's worked with for more than 10 years. and she also kind of told me how she built a team environment that was free of Sunday scaries. and just how she's approaching the leadership transition that's coming up, all while going on parental leave. So I love speaking with her. I hope that everyone loves, reading it as well. Jef: Yeah, it was a really great story. Quick poll for you all. Any of you guys experience the Sunday scaries before coming back to our group? Annalee Armstrong: Only when I see big news Heather: Mm-hmm. Annalee Armstrong: break on the on the weekend. Jef: I will admit I I did not know that term before I read it in your story, but it made complete sense. I can definitely, you know, envision a job that you dread and like Monday's coming up and you're just dreading it on Sunday kind of kills the weekend for you. gabby: It was used in college too, but it was more used as a like what did I do this last weekend? I have the scary. Heather: Ha ha. Jef: Ha ha ha All right, we'll definitely check out all those stories coming out on Wednesday, the morning that you're listening to this, hopefully, in your inbox and biofarm executive. If you're not subscribed, do so at the top right corner of our website. And if you like our podcast, please subscribe and like. Thanks so much for listening. We'll see you next week.