Latest / BioSpace / Data leak kickstarts ESMO, BMS reports autoimmune CAR T death, pharma M&A outpaces 2025
Transcript
- Jef: Hello, and welcome to Biospaces the Weekly. I'm your host, Jeff Axt. With ESMO 2026 now in the rear view, we will recap some of the biggest news coming out of Madrid. This includes results on Merck and Moderna's personalized mRNA based cancer vaccine that actually leaked ahead of the conference, as well as phase three data for Merck's trope two directed antibody SAC TMT. We'll also discuss continued safety concerns with the use of CAR Ts for the treatment of autoimmune disease. So late last week, BMS revealed that a patient with multiple sclerosis had died after taking its cell therapy, and this follows trial pauses from both BMS as well as Novartis in the autoimmune space. We'll also have some updates for you on the overall state of the biopharma sector, with recent analyst reports showing continued momentum for IPOs as well as MA. Let's get started. Hi guys. Hey Emily, I see you're ready for Halloween just like I am. I'm wearing my costume a little bit early. Annalee Armstrong: I'm so ready. Jef: I guess for our listeners who aren't watching on video these days, we should say Annalia is wearing a beautiful skeleton sweatshirt and I've got a Heather: Hmm? Hmm. Jef: great camp crystal sweatshirt. I'm gonna be a camp counselor and my husband will be Jason. Annalee Armstrong: Yeah, I I wouldn't say Heather: Ooh, love it. Annalee Armstrong: I have a costume plan, but this sweater is a pretty easy one. Jef: Nice. Heather: My costume plan is this set of pumpkin earrings and a black shirt, so Annalee Armstrong: I love them. Jef: Very nice, classy. Heather: yes. gabby: I have I Annalee Armstrong: If you add a cape, you're good. Jef: Ha ha ha. Heather: That's true. Yeah, okay, I'll add a cake. gabby: Halloween is normally my favorite. I normally go all out, but I haven't had a chance to plan this year, so I might just have to use my my devil horns that I keep in reserve. Annalee Armstrong: You you just never know when you're gonna need that. Jef: Parrot with that's right. Heather: Mm. Pair with like a s a yeah. Jef: Parrot with a little black dress, you're good to go. Heather: Yeah, or a sexy red dress if they're red. Yeah. It's a gabby: Exactly. Mm-hmm. Annalee Armstrong: Ha ha Jef: All right, well, the other thing we do need to update on is the World Series. Heather, can you fill us in on what's going on? Heather: Yes, this is very important. so to me. so the the Milwaukee Brewers are on the cusp of winning their first championship, World Series championship. They I think you basically have to say destroyed the Tampa Bay Rays last night, 10 to 1. Jef: What? Heather: the Rays were this close to getting out of the inning too. I think it was the fourth or fifth inning, but a call was overturned at second base and the Brewers went on to score eight runs. Annalee Armstrong: Yikes. My my Jef: my gosh, that's heartbreaking for the Rays. Heather: Yeah. Annalee Armstrong: husband's family is all from the Tampa Bay area, so this is this is Heather: no. Annalee Armstrong: heartbreaking for the Armstrongs. Heather: I I'm cheering for the Brewers, but I don't hate the Rays. And it I I just looked at their faces and the dugout and it was just like they they knew. I mean, no team has ever come back apparently from a three nothing deficit, three games to none in the World Series Jef: Yeah. Heather: to win it. So that's kinda over. Yeah. Jef: Yeah, see I don't have a stake in the game at all, but I do like to see closer series. a game seven is always fun, so it's looking like it's not going that way. Heather: I know. Well, maybe they can get one, Annalie. gabby: Being in Wisconsin Being in Wisconsin, it's been so fun. I don't know if you guys have been to a Wisconsin bar before, but if you if you have, people are losing their minds. So it's been super Heather: No. gabby: high spirits here. It doesn't take a whole lot. Jef: That's pretty fun. gabby: yeah. Heather: Yeah, it was like that last year here with the Jays in the World Series. It's it is fun. Jef: I love that. All right. Well I'll root for Milwaukee just so you can enjoy the last little bit of the world series in your neck of the woods, Gabby. gabby: Thanks, Jeff. Jef: All right, so diving into our show then, I guess we should get around to some introductions. Annalie, why don't you start us this week? Annalee Armstrong: Yeah, I am Annalie Armstrong, senior editor here at Biospace, and I do the weekly Biofarm executive newsletter. Jef: And Heather? Heather: I am Heather Mackenzie, senior editor at Biospace, and I put together Clinica Space, which will have a lot of Esmo content this week. Jef: Absolutely. And last but not least, Gabby. gabby: And I'm Gabrielle Mason and I'm a senior editor with Biospace and I curate our daily gene pool newsletter and then our manufacturing newsletter, which goes out every Tuesday. Jef: Awesome. And once again, I'm Jeff Axt, managing editor. And first up our agenda today is, of course, ESMO. So this year's European Society for Medical Oncology Congress, better known as ESMO, officially kicked off last Friday in Madrid. But even before the conference was fully underway, news was flying. And it wasn't just from the released abstracts. One of the most highly anticipated sessions, the updated results from Merck and Moderna's personalized mRNA-based cancer vaccine. leaked online Thursday morning, days ahead of the reveal, as scheduled. So Analie, you jumped on that one right away last week. I remember you reporting that the sentiment was actually disappointment. but then the full presentation came over the weekend and the sentiment was buoyed. So what's going on here? Annalee Armstrong: Yeah, this was an interesting one. I had other things to do on Thursday, but Jef: Ha ha. Annalee Armstrong: you always gotta follow the news. so yeah, this was like kind of one those crazy indicators of just how like fickle investors can be, particularly in this industry. So Merck and Moderna were supposed to be the headliner of what's called the presidential symposium at ESMO. that's like the centerpiece of the conference. It's reserved for some of the biggest, like potentially practice-changing news and results. So they were expected to present that data on Saturday, and it was coming from the phase three Interpath 001 trial that is testing the company's joint personalized mRNA cancer vaccine project in melanoma. so the news leaked on Thursday. Everybody scrambled to to put out news on this result, us included. so We already knew that this trial had been successful. It really surprised investors and analysts who really hadn't put a lot of stock into this program, almost literally. so then once the the program was announced to be successful, everybody got very excited. So when the more detailed results leaked, it led to some initial disappointment, which was a bit surprising. So the vaccine reduced the risk of recurrence or death by 42% when combined with Keytruda. So that had a hazard ratio of 0.58. So a lower hazard ratio translates to a lower relative risk. So analysts had been expecting or had been hoping for a hazard ratio of 0.60. So the data did clear that bar, but apparently this kind of initial reaction was that it wasn't enough. And that spurred a sell-off for both companies at the markets that day. Jef: Yeah, so they they hit the expectation but still had this off. That seems like an overreaction. Annalee Armstrong: Yeah, pretty much. And I think that's what William Blair said like a couple days later. After the dust settled and the investigators actually got to get on the stage, describe the data and provide more details, which is why we do this whole conference thing, analysts came around and said that the results were actually pretty good. the vaccine likely has a future on the market with the based on these results. However, BMO Capital Markets is still they still have some reservations about like exactly what position they're gonna have on the market, whether this is enough. And investors are really interested to see more data from additional tumors. Jef: Do we know when we might see those data? Annalee Armstrong: Yep, there's gonna be lots coming in 2027. I think the nearest term one is looking like a renal cell carcinoma readout that could come the end of this year, but probably into 2027. I asked Mark directly and they were a little, you know, they didn't want to tell me exactly when, but that's when analysts are expecting it. Jef: All right. Well, we'll definitely keep an eye out for those future readouts. This is, of course, one we've been following closely. We've talked about it, I think maybe as recently as last week, but I commented. I think this is a really interesting and exciting space. One personalized cancer vaccines have been in in theory for decades now, and they're finally coming closer to clinical validation, but also very much so for the mRNA space, which kind of got rocked through COVID and there's a lot of controversial sentiment around that. So if we can show the mRNA. Can prove its worth outside of infectious disease. That might just be the saving grace for the whole modality. So definitely one we'll continue to watch. back to other ESMO results. That actually wasn't the only big news that Merc had to share this year. So the company also provided an update on another closely watched asset, the Kellen biotech partnered SAC TMT. Heather, you covered this one. Fill us in on the details. Heather: Yes, and I really appreciated that nobody leaked anything on my Merck stories with SAC TMT. Jef: Really helpful. Heather: it was great. well Merck's yeah, so the it's a trop drop two directed anybody, drug conjugate. SAC TMT really made a splash this weekend. so it had been making kind of like tiny little ripples over the past few months, but Merck presented data from a phase three trial of the drug and Endometrial cancer, where it cut the risk of death for patients with an advanced form of the cancer by more than a third. and survival without disease progression was nearly seven months higher for patients taking the ADC than those on chemo. so Merc told me that SACTMT is the first TROP2 directed ADC to do that in this setting. And a trial investigator I spoke with was excited because she said that this is really the first new therapy that oncologists can offer patients after immuno oncology. So, based on these data, the FDA has accepted Merck's application for approval of SAC TMT in in this indication and granted priority review. the agency has set a target action date of June 15th. However, Merck also has a commissioner's national priority voucher for SAC TMT. they were one of the first to to receive a CMPV. so that could happen even earlier. Jef: Yeah, that will be interesting to see if if that review does accelerate due to that voucher. So this is Merck's first global phase three win with SAC DM TMT. Heather: Yeah, so they they've succeeded with the ADC in China based trials in lung cancer. SAC TMT is actually approved for three indications in China, triple negative breast cancer and two types of non small cell lung cancer. Jef: Okay, another one that we'll keep an eye on. Thanks for that update. Heather: Yeah. Jef: And then one more we'll throw at you, although do check out biospace.com for all of our Esmo coverage. There's way too much to cover here. but one more that we wanted to highlight on the show was a readout from Tango Therapeutics. Gabby, you have a little bit more on this one for us. gabby: Yeah, so the pancreatic cancer space has also been, you know, a key focus of ESMO, with Tango Therapeutics presenting new data for its investigational asset in combination with Revolution Medicine's recently approved Razon Q. So this new update demonstrated an 82% response rate for patients with specific types of advanced pancreatic cancer in a phase one, two trial, which was down from the 92%. Response rate that the biotech had reported earlier among fewer patients. So analysts were pretty unfazed by the kind of response decline here. And Tango said it's planning on talking with the FDA about a potential path forward for accelerated approval for the experimental combo in a second-line setting. At the same time, Tango launched a strategic reprioritization. Of its RD activities. And that included letting go of about 14% of its workforce. So our jobs trend writer Angela, she figured that based on past employment counts, likely about 20 people will be impacted by these cuts. and so as another part of the effort they're deprioritizing their novel target discovery activities and just certain preclinical activities. So really early science. But they're discontinuing and then that fourteen percent layoff. Jef: Yeah, maybe putting their focus more on their assets that are a little further along, bringing this one to market. That'd be really exciting gabby: Exactly. Jef: to see another option hit the market for pancreatic cancer. You you mentioned RevMed's recent approval of Razon Q. That was huge. That drug showed really impressive survival benefit in its pivotal trial and is you know, recently approved really important movement in this space, which is just a devastating cancer. and there were actually the you know. As you mentioned, that was not the only readout in pancreatic cancer at ESMO. It did seem to be a bit of a focus. again, check out all the information on biospace.com, but one other one I'll just throw out there is that Insight did report some early results for a KRAS inhibitor and specifically to the G twelve D mutation inhibitor. This is relevant because I don't know if you guys remember that subgroup analysis that the FDA put out after RevMed's approval. Showed that Rason Q was actually weakest in this particular subgroup. So there's definitely room for improvement there. There are RevMed and others are targeting that G12D mutated pancreatic cancer, but just throwing out that insight positive result as well. Hopefully continued positive movement in this space to help these patients who, again, the five-year survival rate for this is just abysmal. So definitely need some movement. All well, that's Esmo in a nutshell for you. Moving on now, we're gonna talk a little bit more about autoimmune and specifically CAR T cell therapies and autoimmune. So we've talked about this before. There was, and to some extent, still is a lot of excitement about the larger market potential that autoimmune represents over oncology for these CAR T cell therapies. But there have been some safety scares that have really shaken the space, with some questioning whether the risks are worth it, especially for these patients with autoimmune disease. That is well managed by existing therapies. they're not on their deathbed like a lot of cancer patients are, unfortunately. So is it worth the risk that CAR Ts potentially bring? the safety issues took center stage late the summer when news broke that Novartis had seen three patient deaths in its studies of its CAR T candidate, Rap Cell. And then they decided to pause the trials. And at the same time, we learned that BMS had also paused some trials in autoimmune studies of its CAR T Zola cell. Also due to apparent safety issues, although they didn't give us details at the time. So the new news is that BMS late last week reported a death associated with Zola cell in a CART trial of multiple sclerosis. The company did tell Biospace that this death came after the trial pause earlier this year. So this is yet another safety signal adding to the narrative here. Heather: Yeah, so last week BMS revealed that a patient in a phase one trial of Zola cell died from septic pneumonia. Now this news came ahead of a presentation of data from the phase one break free two study at an MS meeting in Toronto. so the death occurred after the infusion of the cell therapy, BMS said. the patient experienced late onset. non-immune effector cell-associated neurotoxicity syndrome, better known as ICANNS, motor symptoms, which is a safety signal that researchers are always watching for in CART trials. The patient died unfortunately a day after developing the pneumonia and 44 days after the infusion of ZOLA cell. BMS did say that there haven't been any other deaths in ZOLA cell programs and autoimmune disease. Jef: Yeah, it really is those immune reactions. And, it makes sense. We're messing with the immune system with these CAR T cell therapies. And it can be a real positive. They can help your immune system fight cancer, for example. But even in the cancer space, the these risks are there of triggering the immune system to do things that aren't so good and cause health issues. So concerning, but again, potential for real benefit here. So we'll watch for any updates on when these trials might be restarted. We did get a little update from Novartis. I mentioned Novartis was the other company that had paused some CART T trials in autoimmune. Novartis had its third quarter earnings call on Tuesday, and the update they gave us here was a bit of a nothing burger, but the CEO did say that there were no further safety events to report and that the studies do remain on hold in the US and Europe. the company has gotten feedback from physicians and patients about the clinical benefits of these CAR T therapies, which you know we do have some hints of already. And Novartis hopes to be able to identify the root cause of the deaths and provide updates in the coming months. So again, not a whole lot there, but something that everybody is closely watching. We would like to see these trials be able to continue on and and hopefully yield some positive results. But all that's a little bit in question right now. All right, bigger picture. I love these segments. I love to talk about the health of the whole industry. So we are going to move on to some of the bigger trends in IPOs and MA. Hopefully, we'll get some more ideas from companies on on what they're thinking. certainly in the big pharma world on the MA space. I know there was a new analysis from Lyric Partners that you covered, Annalie. so we'll get into that on how much firepower Big Pharma has for continued MA activity. as I said, Novartis reported on Tuesday. It really kicks off the next leg of Q3 earnings. We had J and J a few weeks ago, but we are officially in Hell Week. for the rest Annalee Armstrong: Yeah. Jef: of this week, we have no fewer than 10 big farmers reporting, including BMS on Thursday. So we may hear more about what's going on with that latest death in the multiple sclerosis trial. we'll also here from AstraZeneca, Merck, GSK, and Eli Lilly. So Elay Lilly is a great segue to that and A analysis. We know they're one of our biggest spenders this year. So what are you what did Lyric tell you this week, Annalie? Annalee Armstrong: Yeah, Lee Rink had this really great report that has a ton of analysis on MA in it. But one of the trends that really stuck out to me is this list of companies that are likely buyers. this is always something that investors, you know, want more tea on. so Lee Rink is not the only one out there saying right now that the industry is on track to surpass last year's deal count. so big farmers have about one hundred and eighty-eight billion dollars in cash on hand to spend right now. That's down from one hundred and ninety-nine billion a year ago, which if you think about it, they've been very busy, so they've spent some of that cash. Jef: So who's gonna be the next to strike a deal? Crystal ball. Annalee Armstrong: Right. That's what everybody wants to know. So Lee Rink, of course, took out the crystal ball. Very appropriate for the Halloween season. and they believe that Johnson Johnson, of course, they have technically the most firepower to be able to execute on MA right now. They have about $21 billion in cash on hand. CEO Yaquin Duado has also said that they are looking for some earlier stage bets. they don't need to do MA, but they are looking for those and keeping an eye out. They want to bulk up their portfolio later in the decade rather than execute on big transformational deals. So they are definitely a likely buyer. of course we have Amgen, Lily. Lily has just been on, you know, we I think maybe we use the term deal spree a little too, you know, liberally around here, but That's what you the only way to describe what Lily's been up to this past year. They've already done eleven MA transactions and have spent a total of thirty one point seven billion dollars. So they are I mean, it's sorry, I'm gonna stop. Yeah, yeah. Jef: They're on a spree. They're on a spree. Annalee Armstrong: And it's they're very likely to keep keep it going. Jef: Yeah, those numbers for a single company are are pretty astounding. That's a lot Annalee Armstrong: Yeah. Jef: of money to be thrown. But they have it. And we've talked about how they're reinvesting all that GLP one money that they're getting. So it's it's fun to watch. All right. Well, now looking toward the earlier side of the biopharma lifecycle, we are all also keeping tabs, of course, on the health of the public market. So, Gabby, you've really kept up with all the IPOs that have been announced this year. And last time you updated us, we are had already blown past last year's low. but also have exceeded total number of IPOs for the last few years, ever since that crazy pandemic high of twenty twenty one. So what's the latest here? gabby: Yeah, so last week I reported that there had been 31 IPOs this year, and now there's actually been 32, with Lycia Therapeutics raising 365 million in a upsize offering on Monday. So that's 32 so far for 2026. And when you compare that to 2025, like you mentioned the low of when only eight biotechs IPO'd for the entire year. So massively And also actually much higher than the IBO numbers that we saw in 2022, in 23, and even in 24. Still nowhere close to the a hundred debuts that occurred in 2021, which of course was when all the kind of pandemic investments poured in. Jef: That number still surprises me every time. I know it. I know that many companies debuted in 2021, but it's still so shocking. And we'll probably never get back to that level, and as experts will tell you, we don't want to. But it is good to see that IPO activity is still plugging along at a healthy pace now. gabby: Yeah, and exactly what you said. and that's okay that we don't get back to that level. But yeah, there's at least three other biotechs that have already kind of mapped out plans to go public as well still. So that number will keep on, rising. and then while exit activity, you know, has stayed really strong in the third quarter, the overall kind of public market performance for biotechs has actually fallen a little flat in the most recent quarter. So Performance for the industry's XBI was basically unchanged from the start to the finish of the third quarter. But for the year as a whole, the XBI has still outperformed the broader market. So those gains are largely from the first and second quarters. So then just looking now at the fourth quarter, so that would be just the last few weeks of October, the XBI has declined slightly, like one or two percent over the last month. So We'll see if that continues and how the year will finish out as a whole. Jef: Awesome. Well, thank you for tracking that. We have our IPO tracker up on the site now that Gabby started earlier this year. It is really helpful for understanding not just who's gone public and for how much, but how they're doing now that they're on the market. So keep check that out. As well as her most recent IPO report and Annalee's report on Big Pharma's M<unk>A firepower. Both of those will go out in Biofarm Executive this morning, Wednesday, as you're listening to this. If you're not subscribed, be sure to sign up. Well, that's our show for today. Thank you as always for listening. Subscribe to this podcast and enjoy your Halloween. We'll see you back here next week.