Ep. 316 - Trends in Pharma Deals

BioCentury’s third annual analysis of pharma company deals finds that bispecifics and degraders are in, cell and gene therapies are out, and China is bringing much more than me-too assets to cross-border deals. On the latest BioCentury This Week podcast, BioCentury’s analysts assess a year’s worth of deals between pharmas and biotechs to tease out emerging trends.
The analysts also discuss last week’s FDA approval of a vector-based immunotherapy from Precigen to treat a rare respiratory disease and whether the decision will set a precedent of more flexibility for rare disease therapies. They then take stock of recent translational coverage in BioCentury, including a report by Denali of a way to avoid a key safety issue of anti-amyloid-targeting mAbs.
BioCentury’s Grand Rounds — Europe will take place in Cambridge, U.K., Sept. 17-19. The conference seeks to bridge academia, industry and investors for breakthrough innovation.

View full Story: https://www.biocentury.com/article/656802

#PharmaDeals #CrossBorderDeals #Bispecifics #TargetedProteinDegradation #RareDisease #Neurodegeneration

00:00 - Introduction
01:38 - Pharma Deals
10:41 - Precigen
14:40 - Denali's BBB Tech
25:20 - Grand Rounds Europe

To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.

Chapters

• 0:00 Introduction
• 1:38 Pharma Deals
• 10:41 Precigen
• 14:40 Denali's BBB Tech
• 25:20 Grand Rounds Europe

Transcript

0:00

[ AI-generated transcript ]

Jeff Cranmer: 0:01

BioCentury's third annual pharma deals analysis finds that bispecifics and degraders are in and cell and gene therapies are out. And of course, when we talk deals, you gotta talk China. China is bringing more than me-toos. We'll discuss m y colleague Lauren Mart's analysis of Pharma deals on the latest BioCentury this week, plus FDA's Vinay Prasad signaled flexibility with last week's decision on a rare disease therapy from Precigen. But will it read through to other decisions? And we'll take a look at our latest translational coverage, translational analysis, a big strength among my colleagues here at BioCentury. And one topic will be. Data from A CNS penetrant, amyloid monoclonal antibody from Denali plus some other gems. I'm Jeff Cranmer, executive editor here at BioCentury, and joining me today on the BioCentury Podcast are my colleagues.

Selina Koch: 1:12

Selina Koch, Executive Editor.

Lauren Martz: 1:14

Lauren Martz, Executive Director of Biopharma Intelligence.

Karen Tkach Tuzman: 1:17

And Karen Tkach Tuzman, Director of Biopharma Intelligence.

Jeff Cranmer: 1:21

Karen, great to have you back on. I know you've been immersed in all things Grand Round Europe. We'll talk about that in a little bit. Simone and Steve Usdin are off, as I'm sure you heard about, uh, last week. And let's see here. Lauren, you're putting the final touches on your third annual pharma deals analysis. What are you finding?

Lauren Martz: 1:48

Thanks Jeff. The analysis looks at deals that were announced from mid-year last year to mid-year this year, you know, through the end of June. Overall, there were far fewer deals than there were in the prior 12 month period. And something that stood out among the set of deals that we did have this year is that. There appears to be less appetite from the set of 21 pharma companies that we analyzed for, sort of the well validated, you know, late stage assets that we've seen a lot of companies, looking for in the past few years. Anecdotally, we haven't heard that this is less of a priority among pharmas. We don't know exactly why. This is the trend that we've seen. But, among m and a deals, there were very few Phase III and later deals, similarly among the partnerships. So that, that was just one of the trends that we found. terms of the content of the deals, the types of assets that companies, were interested in. I think one of the biggest, most shocking well, maybe not shocking, but one of the most dramatic changes from the last period was the decline in the cell and gene therapy deals. There was a dramatic drop this year. And a lot of these deals happened before. The shifting administration and before a lot of the things that happened with the gene therapy concerns around Sarepta's program. So this is something that's been in motion for a few years.

Selina Koch: 3:11

And something that could possibly be worsened by recent developments that really happened, you know, towards the tail end of this period.

Lauren Martz: 3:20

Exactly. it's an area that we follow closely. It's something that, that I'm really interested in. I hope that this is not something that continues to worsen, but I, I think we'll see what happens. Sort of within the modality space, what we did see is that there was an increase in the number of deals around bispecific antibodies and targeted protein degraders, as I think you mentioned earlier, um, that went along with a decrease in antibody-drug conjugates. And so sort of digging deeper into those antibody based modalities, we look specifically at deals with biotechs in China, and there was a steep drop in the number of a ADC deals. And what I think is really interesting about sort of the breakdown of modalities in technologies coming out of China is that it's much more broad than it was in past years. You know, there are all different kinds of modalities. So the sense is that, you know, the multinational pharmas are looking globally for, technologies and there's, you know, maybe less of a, this region's good for this technology, that, that region's good for that technology.

Jeff Cranmer: 4:21

Yeah, and if you're looking to tap into what's going on in China, BioCentury and BayHelix and McKinsey are putting on our 12th Annual China Healthcare Summit in October in Shanghai, and we will have the CEOs of many of the top biotechs from China, Innovent, 3sbio. You name it. So it's a great way to get a firsthand look at that scene.

Selina Koch: 4:48

You got this provocative line in there that underscores what you were just saying about i n the eyes of pharmas, how did you put it? Regional specialties may be dissolving, like historically, we think of certain places as being really strong and certain things like gene therapies in Europe and antibody engineering in China, and those things are still true. But it seems to me that one thing you found in these deals is that a lot of places are now getting better at a wide range of things.

Lauren Martz: 5:15

Exactly, that's exactly what we found. You know, a few years ago, if we looked to the deals and the technologies coming from China, it would've been, heavily dominated by MABs and by ADCs. there's a chart in the story that is just very telling of, the expansion of biotechs globally following, the science, you know, not necessarily the specialty in that region.

Selina Koch: 5:36

Yeah. And then for China in particular. This latest wave of, of assets is much more weighted towards first in class, things than we have seen in the past. So that, that also seems to be changing.

Lauren Martz: 5:48

Absolute.

Jeff Cranmer: 5:49

China speed. I mean, when we talk about it, you know, we're usually talking about clinical development, but as I know, Simone has pointed out, you've pointed out Selina and, and Lauren, I think. From what I'm hearing, China speed, like obesity's hot, China's in obesity. Now it's moving quickly to, add newer modalities. and, uh, the deals are changing. terms of the deals are getting a little richer, no longer a discount. and so this is a space that we'll continue to follow.

Karen Tkach Tuzman: 6:18

And Lauren, I recall you kind of picked up on a vibe shift around ADCs a while back, um, saying that bispecifics were kind of surging ahead more broadly, and this data really seems to back it up. What do you think is going on there?

Lauren Martz: 6:32

Yeah, this is a, it's something that we've kind of found hints of in, in various data sources over the past year or two years. that huge interest in ADCs. I don't think that it's necessarily declining. I think, you know, one possibility is that there are just so many deals around ADC assets over the past few years that, big pharmas are bringing these through their pipelines and generating data and, they've, acquired the assets that they were looking for in that space. I think, on the flip side is that bispecifics, I've just really been having a moment, you know, we have the VEGF PD-1 bispecifics that everyone wants to be in that space, and, you know, we've had some amazing data come out of, biotechs in China around this specific modality. So, that's been a big trend that has been driving the bispecifics, uh, surge that we've seen in deals. And it's, it's not just that, it's just that, you know, this is a modality that has been optimized. That companies are figuring out how to make it safer and more effective and more in line with, how a CAR T cell works, or finding new applications like autoimmune diseases for the bispecific modalities. I think it's just one of those kind of gradual shifting trends that we see. and, you know, the antibody focus, I think it, the both of those modalities are, are, still very important. Um, I think it's just there's a growing interest in bispecifics right now.

Selina Koch: 7:51

One more thing we should mention before we move on from this, even though g ene therapies of all sorts, including gene modified cells, kind of dropped off substantially in this. Um, in this analysis, there's one category of gene therapy that made an entrance. Do you wanna mention?

Lauren Martz: 8:12

Yeah, so in vivo CAR Ts are sort of that bright spot in the cell and gene therapy space. I think it was three deals that we saw around in vivo CAR Ts, three different pharma companies getting into, um, this technology. And so I think the reason that this is different is because. It's something that could solve a huge problem. You know, the issue with cell and gene therapies or one of the biggest issues is access. It's, the cost and the complexity. And we know that CAR Ts work really well. We just know that it's hard to get them to all of the patients who need them, and there are some toxicities. So in vivo CAR Ts would represent a huge, solution to that problem because this is, you know, you're delivering an off the shelf gene therapy vector, basically, that targets the T cells inside a patient's body instead of having to take the T cells out and edit them and put them back in. And so there may, you know, we've seen early clinical data. That suggests that this may be working as people hope it will be. it was just all of the, right ingredients were coming together for companies to take a chance on this, despite the overall environment and, sentiment around cell and gene therapies right now.

Jeff Cranmer: 9:22

Well, we haven't published this yet, so I don't want to give too much more away, but, um, there are some other interesting trends that, uh, Lauren has found, including on the size of deals. including what looks like a drop off in, large M&A by pharmas. So, keep an eye out this week for Lauren's analysis. Uh, should be out any day now. We're gonna take a quick break. I teased Grand Rounds a t the top, we're gonna hear a little bit about Grand Rounds, and then you'll hear directly from Karen and then we'll be back to talk Precigen.

Alanna Farro: 9:57

BioCentury This Week is brought to you by BioCentury Grand Rounds Europe. Grand Rounds, BioCentury's R&D conference, will make its European debut in 2025. Join us to debate key translational bottlenecks and unlock scientific breakthroughs with commercial potential. Connect with VCs, academic innovators, and biopharma R&D and BD leaders to explore cutting edge advancements in early stage R&D as we dive into disease biology, therapeutic modalities, and enabling technologies. Join us for the inaugural BioCentury Grand Grounds Europe in Cambridge. U.K. the September 17th to 19th. Register and learn more at BioCenturyGrandRoundsEurope.com.

Jeff Cranmer: 10:41

Okay. Last Thursday, FDA approved a vector-based immunotherapy from Precigen to treat a rare respiratory disease, the biotech had sought accelerated approval, but it received full approval for its Papzimeos to treat recurrent respiratory papillomatosis or RRP caused by HPV six or HPV 11. the disease results in recurrent benign tumors. In the respiratory tract, and it affects an estimated 27,000 adults in the U.S. The decision surprised investors who bid up the company's stock 60%. maybe in part because it comes at a time when, uh, some other biotechs have been disappointed or surprised by FDA decisions that went against expectations. Lauren, Prasad and Commissioner Makary have talked a lot about prioritizing rare disease therapies. How are you seeing this approval?

Lauren Martz: 11:47

Well, I think it's of course, it's great for cell and gene therapies. It's, you know, it's showing that there a pathway still exists to, get these modalities on the market. And I think that that is the message that the leadership of CBER and FDA is trying to get across with, this decision to grant full approval for an application that was intended for accelerated approval. and then I also think that this is an example, possibly a rare example of a case where, this was possible and maybe not that provocative to, do it. for this particular program. So the endpoint in this Phase I/II study was something that they call complete response. this is different than, the complete response that, you would measure for a cancer trial. They were looking for the percentage of patients who can go a year without having to have surgery for the condition. Which for these patients is, is an important endpoint because the patients were having three or more surgeries in, in the year prior, to dosing in the trial. They found that more than half of the patients, more than 50% of the patients in the study were able to go a full year. Most of them went two years, without requiring surgery. So, the efficacy looked very solid. A lot of times when companies are seeking an accelerated approval that will be based on a surrogate endpoint that won't necessarily measure a clinical benefit or clinical efficacy. In this case, you know, a reduction in surgery, this, may affect how a patient feels, functions, all, all of the requirements for an FDA clinical endpoint. So, There is clinical efficacy based on this Phase I/II trial, and then when you look at the confirmatory trial that this company has already started, it's structured very similarly. The endpoint is the same. It's basically a trial to follow patient, a larger number of patients. Basically this company had proven that it has clinical efficacy, benefited patients in the way that you would want patients with this condition to benefit. it's great that they've done this. I think it's also, you know, I don't know how much we can read through to other cell and gene therapy programs that are seeking accelerated approval, whether they'll get approved, whether they'll be able to bypass the accelerated approval. I don't know that this suggests that.

Selina Koch: 13:56

Right this seems like a step in the right direction. Like if your clinical endpoint indeed measures a real clinical benefit, a hard benefit, right? Something that you would want to see as confirmatory evidence. It's not that uncontroversial to then go ahead and grant full approval. there's just these cases, like this one meeting, this profile I feel like are few and far between. So it was a little bit of an, an easy c ase to make, if they were looking for something to base this signal on to the broader community.

Jeff Cranmer: 14:27

And I'll drop a link in the show notes to the story, which, Lauren co-wrote with our news editor, Paul Bonanos. Paul keeps us on top of everything around here, which is awesome. Alright, let's turn upstream to BioCentury's translational coverage, which is. Led by Karen, with an assist, from our colleague Danielle Golovin. last week Danielle took a look at a recent science paper from Denali, and here to talk about that is Selina, who I believe spoke with, someone at Denali, uh, late last week.

Selina Koch: 15:02

Yeah. First I wanna say we do this every week. It's called our Science Spotlight. For those of you who don't know it, and I think Karen will talk more about this later. I really enjoy this column, because. As a former scientist, I love to get into the nitty gritty of the papers that are coming out, and the team does a great job of looking through all the literature and picking the ones that have the most relevance, translational relevance, you know, for all. You out there listening? yeah. So the one that Danielle picked a kind of be on top of last week's Science Spotlight was a paper from Denali. It's on its, blood brain barrier delivery technology for biologics. Denali is one of the, um, well, it's one of the originals, one of the first companies to say publicly it was trying to solve this problem of getting, therapies into the brain, such as enzyme replacements, antibodies, and genetic medicines. All of these things are hard to get in the brain. You have to, for instance, with ASOs, you're talking intrathecal delivery, which is not awesome, you know, for the patient. the only approved antibody therapies, right, the beta amyloid, um, mAbs, just the tiniest fraction of those actually makes it inside the brain and they have real safety concerns. so. Not only has Denali been kind of one of the, the originals in this space, but it's one of, been one of the most prolific at, at publishing its papers and showing its progress to the community. But, there's been so many companies entering since Denali started doing this. Large to small, including the major pharmas. Right. That I was like a little surprised at first when I saw this come out in Science.'cause Science is what it is. They have a super high bar for novelty. So that was like one of the things I wanted to ask Ryan about when I chatted with him and he said he thought it was really because what they've shown with the construction of their transport vehicle, which. basically what it does is it binds to a receptor in the endothelial cells in the brain, vasculature receptor's called transferrin and triggers transcytosis. So that receptor gets internalized, it moves across that cell and releases its cargo on the other side of that barrier into the brain. the way that different companies construct their vehicles, these delivery vehicles differently. And what Denali showed in its paper and why, you know, Ryan thinks it, it got into Science is that they can engineer the FC region in such a way that there's no effector function in the periphery. So transferrin it transports iron, right. It does this not just in the brain and other places. So if you have too much effector function, you can cause peripheral tox. You can bind reticulocytes and deplete blood cells and. also just lose a lot of your therapy in the periphery, and so you can get rid of that activity, but they could do it. They showed, they can do it with a clever engineering trick in a way that still enables effector function in the brain, in the sense that it still stimulates the microglia, which are like a resonant immune cell type in the brain to phagocytose. You know, eat up the amyloid plaques. Um, so that was cool. but yeah, it, this is, this is a huge area. There's many companies working on this and it feels like it's reaching a sort of critical mass where it might be solved.

Karen Tkach Tuzman: 18:11

Selina, you had a really interesting panel all about brain shuttles like this, at our Chicago Grand Rounds. what were some of the takeaways from there that you think kind of contextualize what we're seeing from Denali and others?

Selina Koch: 18:24

Okay. Um, well if you look at like recent developments in terms of deal activity, there's been. Deals around these shuttle technologies where the proof of concept therapy is linked to an amyloid antibody, right? There's like quite a lot of these, and so one of the questions that was asked on the panel is why? Why is everybody using amyloid? And the reason is I think that there's precious few validated targets for neurological, for neurodegenerative diseases. Amyloid happens to be one of them, but not just that. It's a good case study. Because of the, the specific ways in which there's room for improvement. So amyloid plaques are in the brain, right? But they also surround vessels, the major arteries in the brain and cause cerebral amyloid angiopathy. And when a naked antibody without any carrier leaks into the brain, it kinda comes into the choroid plexus and travels along these. Lymphatic pathways, which really follow these major arteries. and so you get a lot of activity an of the antibody on these vascular plaques, which erodes the integrity actually of the vessel wall. And you get something called ARIA. it's uh. A nice name for a very, not, not very nice side effect that can cause swelling and bleeding in the brain and can sometimes be very serious. So that's a class-wide issue with anti amyloid antibodies. and so what you do when you have a brain shuttle is transferrin is much more highly expressed in the capillary beds than in these major arteries. So you shift the distribution to something that's. Away from the cerebral vessel plaques and just a lot more diffuse and distributed throughout the whole brain. So you can get much wider, much more consistent, application of your drug. And you can do it away from the place that causes a safety issue. And you can do it at a fifth, the dose. Right? So The Ben, the problem with these antiamyloid maps has been the risk benefit ratio is, you know, questionable from both sides of that equation. But if you can really dial down that risk and deliver less dose and get more effective plaque clearance and inside the brain at the same time, maybe you can get a little bit more out of these in any way. companies try not to load up on their biology and technology risk at the same time, so. was one of the things that was discussed in that panel.

Jeff Cranmer: 20:52

Karen, can you tell us a little bit more about, uh, the Science Spotlight series? Maybe a shout out to the Distillery as well, uh, which, which you edit and, uh, what else you're seeing in the translational space.

Karen Tkach Tuzman: 21:05

So, I have the privilege of sitting down with a wonderful team every week and we, consume abstracts from about 27 journals. And, among them we sort of sort out different things. We make these, uh, piles. Sometimes we kind of come out with analyses that group things together, because that's, often something we're looking for is clusters of innovation around a similar thread. in our science spotlight series, which, Danielle Govin is the queen of. we're often there pointing to, uh, well first of all, it's a place where we can get into some of the company. Technologies that we're seeing, published in papers. So that includes things like the Denali paper that Selina just, talked about where it's known that this company is working on this space, but this paper provides kind of a detailed scientific dive, that, we believe folks in our audience would want to look at and be aware of. but another thing we do with our Science Spotlight series. Is we love the competing interest section of papers. down at the bottom. That's where, authors often academics will disclose any links to companies. And that is where we often find what we call our NewCo that we publish in little tables, where basically we're seeing signs of life from companies that are still young, maybe stealthy. you know, the world hasn't heard their story 8 million times or even perhaps even once yet. And then we get to point out and say, Hey, you know, here's some papers from NewCos. And so if you're in the type of role where you like to scout NewCos and the science that they're after, Or in, you know, various different contexts. That's something to keep an eye out. It's usually, the last segment of our Science Spotlight articles. And, some recent ones, for example, were, in the same analysis that, Selena mentioned, the, one last week we spotlighted some, uh, NewCos, including, a company called Aethox, spelled interestingly, uh, founded in 2025, a spin out, I believe, of King's College London. And, looking at small molecule inhibitors that target macrophages, with a recent Science Translational Medicine paper. and that along with a couple others were the focus of our NewCo table t here. So that's something to keep an eye out for. in addition to kind of spotlighting companies and what they're doing, we will also in the Science Spotlights look at work from academics that you know, it's often a platform technology, something that could affect. Multiple disease areas, multiple products, and we'll particularly highlight clusters of innovations. Um, sometimes you see clusters and published in the back to back way within a, a given journal, but oftentimes we will, be able to see, oh, across a couple different journals. Hey, there was a cluster of things. examples of this were, recently, Danielle spotlighted clusters of. Papers about TCR mimics, the de novo protein design of TCR, mimic biologics that bind, peptide MHC. And so could be used for, say, bispecifics, going beyond just those cell surface antigens that are, you know, can be bound directly and maybe getting at those intracellular antigens that are presented on peptide MHC. she also had a really nice roundup recently of molecular glue innovations that we were seeing across different papers. Some with company affiliations, some just out of universities. And one thing we've, spotlighted. Across this series over time is that TRIM21 is, an E3 ligase that is coming to the fore in terms of, being a, a new cornerstone for degraders, uh, you know, cereblon and VHL or kind of the classic first generation ones. That people have focused on. But, TRIM21 has getting, a lot of, play in, preclinical innovations we're seeing in the literature. yeah. And then, you know, within the Distillery, that's where we really focus on purely academic innovations that propose new target. or a new compound, for a specific disease, or set of diseases.

Jeff Cranmer: 25:14

Karen, you're blinding me with science as, uh, Thomas Dolby might say. Um, Grand Rounds coming up. it's our third grand rounds. It's our first one outside the U.S. it will be in Cambridge, U.K. the old school, Cambridge. What are you most excited about?

Karen Tkach Tuzman: 25:32

Well, I. Always get excited about our scientific poster spotlight. At our Grand Rounds, we really highlight innovations at the academia industry interface, things that are emerging, not quite yet, super advanced. And so, part of that will be this kind of Science Spotlight and Distillery come to life through the poster, displays. Which include, a lot of our presenting companies, many of which are academic spinouts from the area. We really try to spotlight the local innovation, but we're also bringing in innovators from, Belgium and, elsewhere, in the U.K. and Europe. and so, the presenting companies display posters, but we also invite, academic innovators, to share their sort of pre company innovations. And so we're excited for folks to find, some new gems there. And then, the panel program is, really exciting. Again, we're doing this sort of. Three part focus on, on one hand emerging biology and biomarkers of disease. So Targets and Selina's got a really interesting session there in precision neuropsychiatry. We've got another, uh, segment that's focused on the modality innovation, so the actual compounds, themselves. And in addition to spotlighting next generation approaches to biologics and small molecule designs, we're gonna have a, a panel that I, I, I was very proud of this name. It's a always the platform, never the product, lessons from modalities that have yet to break through. So, people tend to have strong opinions about that. And if you're one of those, maybe you can come and join the conversation. And then, the third segment, is the sort of geekiest part, which I love is the, enabling technologies, and tools portion of it that kind of makes the other things run. And, there we'll have a spotlight on Biobanks.'cause, you know, the U.K. Biobank and now our future health. They're kind. Next generation, biobanking initiative. a lot of the research community already draws on, U.K. biobanking resources. And so, uh, it'll be really interesting to hear about what's next, for those, super important. Data troves. And then, there'll be a panel on quantum computing. We're taking that conversation to the next level. so if you got a chance to read, what I would call my primer, my one oh one on quantum computing and life sciences, this is the kind of next level, discussion on that. and we'll also be diving into foundation models. All sorts of things. So, basically, you know, it's the Geekstbury, the, Geek Festival of the U.K. hope to see you there.

Jeff Cranmer: 28:10

Excellent, and you can go to BioCentury Grand Rounds to learn more. September 17th to 19th, presenting company slots and poster slots are sold out. But there's still a chance to become a delegate. so go to the website, check that out. And if you're interested in coming to Shanghai, we are still recruiting, presenting companies. Feel free to reach out to me, or go to our website and check it out there. Thanks for tuning in. If you liked what you heard, subscribe. Leave us a note, ask us a question. We'd love to hear from you. Special thanks to our production engineer Cole Travis and to Kendall Square Orchestra, which provides the music for all of BioCentury's podcasts. We'll catch you next week.