Episode 144 - June 6, 2025

You're listening to Biotech Hangout, a live and unedited weekly discussion of all the latest news in our industry with a group of biotech insiders. I'm Brad Lancer and my co-hosts today are Eric Schmidt and Sam Bazelli. For more information about our host and guest speakers or to listen to the most recent episode, please go to biotech hangouts.com. And I don't know if uh the biotech hangout crew uh tweeted this or or teased this, but John Crowley was actually supposed to join us today. We had a lot of policy issues to talk about, but sadly, he had a scheduling change and won't be with us today.

1. Sanofi Acquires Blueprint

There is a lot to talk about. It's always nice when we get M&A. It's been lacking, at least in a big way, ever since January, when we had the big J&J neuro deal. But Sanofi announced that they're going to acquire Blueprint Medicines for over $9 billion. That's a pretty good deal. I'll kick it over to you guys to comment. Eric, you go first.

Sure. Big picture, you're right. It's always great to have M&A in the space. This is, I think, the 2nd-largest deal we've seen after ITCI this year, so it's sizable. The premium wasn't all that big, coming in at about 27%.

But I guess from my standpoint, I've been involved with Blueprint Medicines for a while. I had the good fortune of taking them public. I think what's great about this acquisition is that this is the way biotech success stories really should play out. This company went public about 10 years ago. I think the IPO price was $18 per share. At the time, not very many of us had even heard of the diseases they were going after. Systemic mastocytosis sounded like Greek to me.

We came to learn that there were certainly a lot of patients suffering from this disease, both the advanced and indolent forms. Kudos to the team at Blueprint at the time. It was led by Jeff Albers, and Kate Haviland has followed Jeff in his CEO shoes. Of course, Alexis Borisy has been a longtime chairperson there. They identified that there were these patients in need, and they created a solution.

I think they really executed to a T, and they built a ton of shareholder value—almost a 10-bagger over 10 years. What a great ride. This is the way that biotech should play out: You should invest wisely, treat patients, and bring better solutions to the world.

We're going to lose Blueprint, but the world is probably a better place because of this company's existence. That's what I would say here.

Yeah. I was listening to our friend Adam Feuerstein on the podcast that they do on Thursdays, and he was lamenting a little bit—or I don't know if you could call it lamenting—that we're going to lose, again, another company that could have been more of a success story, therefore not getting to the future Amgens.

Frankly, we seem in the biotech world to want our cake and eat it. We ask for M&A deals, and when the little ones get done, we go, “Oh, well, that's too little. It doesn't really count.” When big ones get done, we go, “Oh, see, there could have been an Amgen in the future.” I'm not having a go at Adam, but God forbid.

It is something that I think is exactly the right thing to happen. Hopefully, fingers crossed, some of that cash gets redeployed back into the sector. I don't know, but I'm assuming that would be the case. I'm hoping that a lot—at least some—of the specialists will have to do that still.

I think you're right. I've counted 11 M&A deals on our database since the beginning of the year. The next-largest one was Eli Lilly's acquisition of Scorpion Therapeutics. That was also a cancer indication, although these guys have a cancer indication, too. This is not the main driver for this asset.

What about from the perspective of Sanofi? It fits rare diseases, and it fits in the immunology space that they want to be the world leader in, and that is a stated hope. It gives them a possible—if consensus is right—$2 billion drug by 2030. You're paying $9.1 billion; that's not ridiculously stretched. I can't imagine this is a low-margin product, in terms of the need, the way you sell it, and how you find the patients.

I don't know. You could probably speak better to that, but it fits well in the general story. It's not a game changer for Sanofi, but I suppose M&A deals generally of this size will not be a game changer for large pharma, right?

That's actually the thing that stood out to me. I hate to say this, but Sanofi has a reputation for paying a lot for risky things, many of which have blown up in the past, and I feel like this is a really mature deal for them. I think it's probably a really good thing, and the timing is right as well.

All companies, even good ones like this that have a lot of meat on the bones, have had their valuations affected. If you can strike for a pretty big deal like this at a time like this, I think it's probably pretty smart.

Yeah. It would be interesting to see if there were lots of other bidders out there, because the multiple—or the premium—wasn't eye-watering, right? On the other hand, $10 billion or $9.1 billion isn't bad.

I quite like the idea that this is one time where the CVRs kind of don't matter. It's $129 per share and the $2 CVR for development milestones and $4 CVR for regulatory milestones. I'm assuming most of them are achievable, given how low they are. But you almost wonder why they're even there.

2. Summit Faces The Survival Test

All right, let's move on to the other deal. We could probably talk for an entire hour about all the VEGF/PD-1 deals, and, of course, Bristol Myers Squibb struck a deal and has partnered with BioNTech on theirs. We recently had the Pfizer–3SBio deal. They paid $1.25 billion up front and up to $5 billion more. We saw some of 3SBio's data at ASCO this past week.

We also had the huge Summit-Akeso news, which was pretty controversial. I think there was something for both bulls and bears in there. Maybe I'll start with Eric. I know I read a report that you put out really questioning the sell-off in Summit after the ASCO news. Let's maybe start with that: What was your reaction when you saw that? Of course, the headline was that the PFS hazard ratio looked fantastic. I think it was 0.52, but we still don't have a win on overall survival yet.

Maybe just a step back for the bigger picture here. I guess Summit and Akeso, their partner, are kind of the granddaddy of them all in the PD-1/VEGF bispecific space. They're in the lead, they're running multiple Phase 3 studies, and this is the drug ivonescimab that really started it all. It got people excited about the field.

As many of you know, Summit and Akeso have now worked on 2 head-to-head Phase 3 studies against pembrolizumab, the world's largest pharmaceutical today, and beaten Pembro head-to-head in lung cancer. That's why the excitement is here.

One remaining piece of the puzzle that we just had not seen at all before was whether the Akeso head-to-head data were going to translate into the United States. All of the big key studies have been done in China, and I thought this was by far the biggest bear case on the stock—and a reasonable one to boot.

We've definitely had KOLs note that Chinese patients have different genetics, different cancer genetics in particular, and the translation from a China population to a U.S. population cannot be assured. The news from late Friday last week, as you know, was the HARMONi-A study. It was the first data set that included not just a China population but a U.S. population.

In my opinion, Summit really went out of its way to tell us that the 2 geographical subsets in the study had consistent data. We got to see them at the ASCO conference and spent some time with the management team. They're pretty adamant that they've checked this box—that translation, at least in this case, is consistent across the geographic subsets.

This is not the largest of markets. In the case of the HARMONi-A study, we're talking about a second-line subset of lung cancer—those that are EGFR-positive. At least in this HARMONi-A trial, management was quite adamant that there's consistency across the geographic subsets, which is what investors really wanted to see.

As you noted, the stock sold off—not up, but down. I think that was because, in this second-line EGFR-positive population, which to me is a fairly small market, the company acknowledged that it may not be able to submit for FDA approval because it barely missed its overall survival endpoint. The P value was 0.057, which is not statistically significant.

They've spent all of their alpha at this time point, so the P value will never be statistically significant. Even if the data mature and the P value crosses 0.05, it will still be a nominal P value going forward.

The Street is really keen to see a survival result. I'm curious about your views here. I understand that survival is important, but when we talk to people, if you have a hazard ratio for survival that's anywhere in the 0.8 range, it seems like a strong trend. It seems like a drug that's going to be used based on very strong PFS and borderline OS. Please tell me what I'm missing.

Well, what we're missing is that there's still no real conclusive hypothesis for why this combo and a bispecific should work. Roche studied VEGF and PD-1 separately and in combination and never really succeeded. There's always that hypothesis out there that VEGF can accelerate mets initially, or shrink tumors initially but accelerate mets over the long term. Without a clear hypothesis for why the bispecific would be better than one drug—why one is better than two things together—and with nobody actually hitting on OS yet, I think it's still a legitimate risk.

I'm in the camp that this is all going to succeed in the end, but I do think we're not there yet. So, I do think there's legitimate risk still on the table.

I was going into this thinking the value of this trial is not the potential to get approval and get some sales, because there's an incumbent out there called Johnson & Johnson with a different regimen for post-EGFR patients. It was just approved, and in fact, it was approved without an overall survival signal. Even on the second interim read, they haven't hit it yet, but it's out and approved. There are other drugs coming—AstraZeneca is working on Dato-DXd—and there are other ways that people are trying to treat this particular patient group.

So, commercially, why would I care? Even if it doesn't get approved, all I was looking for was this read-across from China to, as Eric said, to the West, if you like. The issue I also heard a few people say—and I don't know if you want to call it misinformation, or if you just want to be a bear—was that even that patient group was so immature that it couldn't possibly have made a difference to the hazard ratio.

You look at it and think, “Hang on, how's that possible?” The last patient was treated before recruitment closed in August, and the trial had been open for 2 years, or roughly 2 years, or at least a year and a half or so. So, it's very possible that, at least on the progression-free survival hazard ratio, a lot of the US patients were already counted in there. Maybe on OS, you haven't had enough events in that latter group, and perhaps it doesn't work out in the end for OS.

I was just listening to someone tell me this, and I think people are looking for excuses, which is natural. It was the same thing people did in the early days of CARVYKTI, if you remember. They were just trying to find reasons why it wouldn't work. I'm not just trying to parallel it to yet another Chinese asset. The issue then also ends up being that you just have to wait until you see the actual detail.

It was 0.52, Eric, versus 0.47 or 0.46, depending on which data point you want to look at, back in China. So, you can start doing some magic math—which I hate doing because it's pretty much always wrong—to see what the hazard ratio was in the US population. Let's say it's 0.62. Why is that bad? I'm also a bit agog at the share price reaction.

Do you guys have any thoughts on Bristol partnering with the BioNTech asset specifically?

No, sure. I'll kick that in, and then Eric—I’m pretty sure he has some meaningful thoughts on it too. One of the things that I always worried about with the BioNTech asset—and there's another company that has a PD-L1/VEGF bispecific, and that's Instil Bio—is that, on the one hand, if you took a vote around the conference, anyone you bumped into would say, “Is PD-1 better than PD-L1?” They'd go, “Yes,” because of the history of what we know, right, versus durvalumab and atezolizumab.

Then you ask them, “Do you think a PD-L1/VEGF bispecific would be better than a PD-1/VEGF bispecific?” They start getting hypothetical. Hypothetically, PD-L1 should really be the thing that you use to target things to a tumor, because it's expressed on the tumor, but it always made me worried that, in the background, people are eventually going to find that this ends up going down the road of other PD-L1s.

The deal kind of takes some of that risk away. I don't think it clarifies the situation, but it takes some of that risk away. Now you have the opportunity, partnered with Bristol, with Bristol taking some of that cash—$3.5 billion, pretty much guaranteed—to possibly do a combo with a PD-1.

Initially, you think, “What?” But if you think about it, if you're using the PD-L1 as a targeting molecule and you've got the PD-1 to do its job on the T cell, there is some kind of logic. I'm not going to be designing those trials, but that's what I thought about, and I think it was really good for biotech.

I think you're touching on something that's really important in this debate. There's just so much that we don't yet know about these drugs, these bispecifics. We know that they're interesting and active. I think we know that they're differentiated, and I'll take you up on your prior point that this could be a VEGF plus PD-1 monovalent antibody combination. It's possible, but I think we're seeing some differentiated properties here too.

We're not seeing the side effects that you'd expect from systemic VEGF inhibition. We're seeing activity in squamous tumors that you wouldn't expect from VEGF, on a safety-profile basis. We're seeing head-to-head versus pembrolizumab activity that we wouldn't expect. We're seeing activity in second-line EGFR-positive patients, where you wouldn't expect PD-1s to have an impact.

There's a lot going on here, right? That's why there is all this interest, whether it's from Bristol, Pfizer, or others. I just think that we're going to need to be a little bit patient. We'll probably need to buckle up because the world has shown us that Summit is going to be extraordinarily volatile as a security as we turn over some of these cards. But over time, data will win.

And then, did you guys have a chance to see the 3SBio poster? I didn't, but it looked like from Twitter that everything was pretty positive and genuinely impressive.

I did, and we wrote on it. One of the first things that you look at as an analyst when you see data updates is to compare them to the last data update. We've got a little table that follows it from the J.P. Morgan Healthcare Conference 2025 to the ASCO abstract. They went from 24 patients to 25 patients in the ASCO abstract, and then in the data at ASCO itself, they went up to 34 patients.

The overall response rate did soften a bit, from about the 70% range to the 67.5% range. Is that even fair to call it softening a little bit as you add more patients? The cutoff is March, so there's room for some of those responses. Maybe some of the stable patients might progress or become a responder. The disease control rate remained at the top end, so nearly 100%.

When you look at the spider plot, one of the things that people always say about VEGF is that it's a first-scan effect—that you're getting that vascular impact potentially on that first scan. When you look at the Summit ASCO PFS curve, it does give you that little hint that possibly you get a big drop on the first scan, and then it's a parallel line on the Kaplan-Meier curve of the PFS.

But when you look at this data and other data from other presentations in this area in general, you see that the patients in the spider plot keep getting deeper responses. So, this is not just about the first scan in the same patient, right? It's not just the first-scan effect. I'm pretty sure somebody much more knowledgeable than me can explain that in a different way and say, “Actually, no, it's still a first-scan effect. You're wrong.” I don't think so, but it just looks pretty good. It looks like it could be one of the best out there.

When you look at the AEs, one thing I do worry about is that I always look at proteinuria and hypertension in these trials, because that is the VEGF signal, right? The signal isn't low: 17% grade 3 hypertension, with no proteinuria. I mean, this compares with a much larger data set for Avastin, at 5% grade 3.

So, these molecules are different. They're not all doing the same thing. Of course, when you start looking at the BioNTech one, you see even higher numbers, but it's often combined with chemotherapy. We haven't seen many single-agent BNT327 data sets, so that gets a bit complicated to try to understand. But frankly, it looked pretty decent.

3. Vera Challenges IgA Nephropathy

All right. We'll get back to ASCO in a second, but let's talk about some other really interesting data that came out that's non-oncology this week. The first one, Eric, is Vera. So, that's the IgA nephropathy space. We just had some news from a competitor company about that today at EULAR as well, right?

Yeah. What a round trip so far this week for the Vera guys. I can imagine their heads spinning. So, you're right: they came out on Monday of this week with what we thought were some really fantastic data in the IgA nephropathy space.

For those less familiar with what's going on here, again, it's been sort of an untreatable disease for decades. Standard of care is essentially symptomatic management or nondisease-modifying therapies that allow the kidney to function a little bit better, but don't reverse or slow the downward progression.

All of the therapies we're about to talk about, and others, are operating on B cells, which it appears are fundamentally causative agents in this disease. The folks at Vera have a drug called atacicept, and it's a BAFF/APRIL inhibitor. The phase 3 data that they put forth earlier in the week showed wonderfully strong reductions in proteinuria, placebo-adjusted, kind of in the low 40s.

We already know from previous data sets that atacicept also slows, if not completely prevents, the degradation of kidney function in patients. So they've got a very comprehensive data set, and with this phase 3 result that came out on Monday, they intend to file for approval toward the end of the year.

Meanwhile, a competitor was just on the tape today: Otsuka, with its drug sibeprenlimab. This is an APRIL-only inhibitor, so it's very related in its mechanism. We're not quite sure whether there's a benefit to inhibiting both BAFF and APRIL versus APRIL alone, but at least in preclinical models, the dual inhibitor does look a little bit better.

Nonetheless, Otsuka has some, again, very solid data of its own. If anything, they're showing proteinuria data that's a little bit better in terms of absolute magnitude of reduction than Vera's. I don't think you can make a comparative efficacy claim on that. I will take issue with our friend at STAT News who published that the Otsuka data were better. I don't see that in the database.

I think there are some baseline variables that confound any such analysis. Honestly, what kidney patients care about, and what doctors care about, isn't whether you have lower protein in the urine; it's whether, over time, your disease is more stable in terms of downward progression of kidney function. And again, that's data that Vera has, and so far at least, Otsuka doesn't.

Bottom line, these are both going to be very quickly and widely embraced therapies for IgAN patients. We think this is a huge market. We think it's probably a $15 billion-plus opportunity. I feel for the folks at Vera, who had some wonderful data and now are maybe playing defense in an area where, again, we've talked about this before on this show, there is no usual one-winner-take-all phenomenon in biotech.

We're probably going to talk about this when we talk about Bicara and Merck in a few minutes. This IgAN space is certainly big enough for 2 players, and I think both companies are going to make a lot of money here. But I don't know if you guys have additional thoughts.

I would just say I always want to be careful about talking about M&A, but that's kind of the Vera story. As you pointed out, this is a huge market, and when I see data like this that's trying to compare 2 different companies, I think about what this drug might look like commercially one day in the hands of a much bigger pharmaceutical company, especially given what a huge market that is.

So I think Vera is having a pretty good week. I don't know what will happen with them, of course, but to be as competitive as they are in this space puts them in a really good position. And, as you know, there's been a lot of deals in the nephrology space over the last couple of years. It's definitely an area of increased focus for the larger companies.

Yeah, I just wanted to add something. Not specifically on this, but I know how I feel. I can almost sense you two—I’m not going to say that is the case—but we're all exhausted from ASCO. But actually, we've had a pretty exciting week.

I don't know if others are hearing us as enthusiastic and enthused, but I just want to make sure that folks listening are not thinking that, because we've had a week that started with 2 deals—one much bigger than the other—we're down in the mouth. We've had a ton of good data, some share-price moves in the wrong direction, but some in the up direction, too. And the XBI, for however much we love it or hate it, is meaningfully up in the week and also since its low.

I just want to make sure that I suspect we're going to go and talk about all the amazing stuff that we've seen at ASCO, but I want to make sure people don't walk away thinking, “Oh, God, this is not a very good week. They thought these guys were all down in the mouth.”

4. Protein Degradation Takes Flight

Well, yeah. And in fact, I'll take that handoff real quick and transition to our next piece of data that I thought was super exciting.

One thing that biotech always needs is a new technology to get really excited about. I think the PD-1/VEGF and just the whole bispecific space is turning into that. One new technology that I'm really excited about, if you think about it, really in the first inning, is protein degradation.

Arvinas, weeks ago, had the first-ever phase 3 trial readout of a PROTAC, and the market viewed it as disappointing because it was a breast cancer trial and they degraded the estrogen receptor, and it only worked in a subset of patients. But it was a successful phase 3 trial for 40% of this particular breast cancer group.

Then, I think, really excitingly, Kymera had an announcement on Monday. This is just healthy-volunteer data, but they're big believers in the STAT6 target. The whole idea of this class is to have a new modality that can potentially be made into a simple oral therapy. The idea here is a once-daily oral competitor to Dupixent.

They had data, again, in healthy volunteers, so we have to see how it translates into people with actual inflammatory diseases. But from doses at 1.5 mg and up—they went to 200 mg, some huge number—from 1.5 mg and up, they had 90% degradation and a really clean safety profile.

Even in biomarkers that you look for when potentially treating diseases, which is pretty tricky in healthy volunteers because, by definition, they don't have the disease, the type 2/Th2 biomarkers showed really nice reductions in TARC and eotaxin-3, as well as other biomarkers that would suggest that this might work in actual patients.

They've already moved to the phase 1b portion of this, so we'll see actual atopic dermatitis patient data sometime in the fourth quarter, toward the end of the year. Now they're moving it into other things like asthma.

I think protein degradation is going to be a technology that could add some real excitement to the biotech sector over the coming years. It's very early, and like any technology, there are going to be ups and downs. I guess you could argue that we saw that with the Arvinas data, but in terms of something new around the corner, I think it's something to be excited about.

Yeah, I think you're absolutely right, because it gives you a whole new set of targets to work with that may not be amenable to standard enzyme inhibition, if you like. It just opens such a big window of opportunity, assuming you can get the molecule design right and the pharmacology right.

It is absolutely, I think, going to be a cornerstone of future drug development.

For sure. Ironically, on the exact same day, Nurix struck a STAT6 deal with Sanofi. Nurix will have BTK data at EHA next week, and we already saw BeiGene have BTK data at the last ASH. I think it's something to watch closely.

5. ASCO Shows Biotech Innovation

Let's go back to ASCO. Eric, why don't I start with you? What were your overall impressions? Was this an up year, a down year, or kind of middle of the road?

Yeah. I'll come back to your comments. I hope that our tiredness—I’m just exhausted. It seems like this week won't ever end—but I hope that our listeners are not interpreting that as anything but a wonderful week for biotech and a wonderful week for oncology.

I think in terms of ASCO, maybe you could say it was a down year in terms of there not being any major headlines or big, game-changing clinical trial results that we were previously unaware of. Certainly, there were some game-changing results. I'm sure some of you might want to talk about tarlatamab and so forth.

But what I thought was the real theme here was just how much innovation was ongoing. Maybe a lot of that was in small-cap biotech, maybe a lot of that was in earlier-stage data sets, but this innovation kind of creeps up on you.

I think both of you are old enough to know that when we used to talk about pancreatic cancer or melanoma, or some of these really difficult-to-treat tumors, we used to say, “Wow, this company's got a 7% response rate, a 12% response rate. That's the best we've ever seen. That's an active drug.”

Now, in some of these tumor types, like pancreatic cancer or melanoma, we're kind of sticking our nose up at response rates in the 20s, 30s, even 40% on occasion. So things have changed, and even at this ASCO in particular, I'll point out some newer targets in pancreatic cancer and melanoma that I think are going to continue to be game changers.

Everyone knows in pancreatic cancer that the KRAS inhibitors revolutionized medicine, kind of leading the charge there. But a new target that we're increasingly excited about is PRMT5. That's being pioneered by Bristol Myers Squibb and Amgen, to a certain extent. Maybe Tango could be one of the emerging leaders in this space as well.

The data from Bristol at ASCO are showing about a 25% response rate in pancreatic cancer, which, again, is a tumor type that's never really seen any meaningful success other than the KRAS inhibitors.

So that's highly encouraging, and I think we'd love to see that combined with a KRAS inhibitor, or PRMT5 plus KRAS, and just see how far this presumably fairly well-tolerated targeted combination can go.

Then, on the melanoma side, one thing that struck me was the Immatics data. This is a European company that's pioneering a PRAME-directed TCR cell therapy. I know you love the cell therapy space, and I'm sure you were very happy to see that they've got response rates in refractory melanoma. Again, an indication where we're used to saying something in the 20% range might be interesting, they've got a 55% response rate in those patients. It looks quite durable now, with follow-up out to over a year, and there's a lot of excitement and enthusiasm for their phase 3. All of the KOLs were really raving about this candidate, at least those that we spoke to. So, great to see that innovation. It does sneak up on you, and sometimes, being away from ASCO, you kind of come back after a few years and say, “Wow, this is why we do this job.”

And I think if you had to declare a winner of ASCO, probably most people's bets would have been on AstraZeneca. Of course, Enhertu, with their partner Daiichi Sankyo, had another important year in breast cancer. Tell us about AstraZeneca's ASCO.

Yeah, I hear people go, “Oh, this is not a very exciting ASCO to go to.” And then we all come back with all these new molecules—PRMT5, the evolving data for KRAS, which I'm sure we'll talk about a little bit—and then here you get trials that are going into tumors that have not necessarily had the best of luck so far, pancreatic being one of them.

So I'll start off by saying this felt like another AstraZeneca ASCO, or at least one of the key players was AstraZeneca. Seven years in a row they've gotten a plenary, and they're very happy to keep highlighting that. No standing ovation, though. I was sitting next to a friend of ours who's on the buy side, and they were looking for a standing ovation, and they didn't get it this time, but there was lots of clapping.

So, what did we get? We got Imfinzi in the MATTERHORN study in gastric cancer: a really unprecedented event-free survival benefit. That was, I think, pretty much ready to give you a practice-changing setup. And then Enhertu in the first-line HER2-positive setting in the DESTINY-Breast09 trial also seemed to suggest that it's opening up another significant patient population or opportunity. And, of course, as Eric highlighted, Trodelvy in the ASCENT-04 trial—first-line PD-L1-positive triple-negative breast cancer combined with Keytruda—had a really impressive PFS hazard ratio of 0.65.

So, you add that to the ASCENT-3 data that we had in PD-L1-negative patients, and the results really do suggest a meaningful opportunity here for Gilead's Trodelvy in that space. Breast cancer—when I talk to folks outside the field saying, “Look, cancer is cured,” everyone asks, “Is there a cure?” I'm just saying there are now people with myeloma or breast cancer who live long enough to die of something else. If you can't call that a cure, I don't know what you're looking for, right? I'm just hoping melanoma is the same, right? I'm just hoping that the same will start happening with some of these other tumors, and the early data that we see at ASCO is what gives us hope that we're going to get there.

Yeah. And I would echo—I think Gilead had a really good ASCO. This is their biggest ASCO in years and years, and Trodelvy is really starting to bloom. These breast cancer indications that they're succeeding in now are a really big deal. And let's not forget that cell therapy is cooking, too. Kite is now about $2 billion a year in revenue for them, which is really amazing. A lot of critics would never have predicted that.

I'd also say that I don't feel like we talked a lot about cell therapy at this year's ASCO, but they had some interesting brain cancer data that I thought was fascinating. Getting back to Trodelvy, one thing that really stood out to me as I was thinking about that is: look at all of the investments. They bought that asset for over $20 billion, and look at the roller coaster that has been. One thing that I thought of, just thinking of the long road of how they've taken it from where it was to where it is now—really accelerating—I don't think a smaller company could have done that. With some of the clinical-trial setbacks and the changes that they had to make, and the amount of money that they've invested in the development program, I think it really makes an argument for the value of scale and big companies for certain assets. I think they deserve a lot of credit for always being full speed ahead on Trodelvy when a lot of critics—maybe us included—at times were really critical of that deal and their development program.

Speaking of AstraZeneca, one of the companies that I interviewed for Biotech TV was Arcus, and they had their HIF-2α data at ASCO. But I know one thing that we were talking about on the sidelines is the whole TIGIT field and all of the disappointments that we've seen there lately. Roche, of course, had the big SKYSCRAPER miss. A lot of companies have divested of their TIGIT programs. BeiGene did recently. We just had iTeos literally close shop about a week ago.

Interestingly, there are 2 companies that are full speed ahead on TIGIT. One of them is AstraZeneca, and they're specifically doing bispecifics, and the other one is Arcus. I think it's setting up to be potentially a fascinating story because there's something those 2 things have in common: both of those programs are Fc-silent. I know both companies strongly believe that's a huge factor that makes them day-and-night different. What's your take? I think AstraZeneca now has 10 TIGIT studies going full steam ahead, right?

Yeah. Yeah.

I mean, look, I'm a simple person. So, when I think about having an Fc-active antibody on a molecule that binds to a T cell, it just worries me a little bit, right? You think, well, why would I want antibody-directed cytotoxicity against the T cell? So that's the only argument I find for having the Fc, and maybe you can also manage the side effects a bit better if you didn't have the Fc active.

But in terms of AstraZeneca, they're really putting their money where their mouth is, right? They've got 10 trials. What have I got here? 1, 2, 3, 4, 5 in non-small-cell lung cancer, 2 in biliary tract, 1 in HCC—hepatocellular carcinoma—1 in endometrial, and 1 gastric. What's interesting here is this adds up to about 8,000 patients, all phase 3, right? Ten trials. So they have seen a signal, and Susan Galbraith talks about this signal. They had a poster on it at SITC, which unfortunately is the one conference I didn't go to this year and probably had that one little interesting nugget at it.

They're seeing an interferon-gamma signature response in some of the patients. I don't know the full story; I need to see the poster. The reality is that they presented 2 sets of data, and, just by the way, out of these 10, only 1 of them is monotherapy. This is not monotherapy, right? This is a bispecific, this is PD-1/TIGIT. The rest are datopotamab deruxtecan, or Dato-DXd, which is TROP2, so it brings you back to thinking about how that could play out for Gilead, given that they've got access to the Arcus drug, as far as I remember. But they must have given up, right? I don't know if they've given up. You remind me; I'm getting a blank here. They have not given up. There you go.

So you can imagine a combination of Trodelvy plus TIGIT if one of these trials reads out. And they have T-DXd, so in HER2 combinations they've got chemo. They've got a scheme involving tremelimumab. In fact, that's their answer. Every time somebody asks them, “Why don't you get a PD-1?” they go, “Well, we're actually doing TACE, you know, bevacizumab plus Imfinzi in the hepatocellular carcinoma setting.”

So the data they presented was on this drug called rilvegostomig, right? I have to say it looked pretty decent when I'm looking at the lung cancer data that they showed. I think TROPION-Lung04: we had a 71% ORR in the PD-L1-high patients, 40% in the negative patients, right? All the cuts surpassed the monotherapy results that we saw—surpassed the rilvegostomig monotherapy results that we saw. Of course, you have to watch out for adverse events. As soon as you put 2 in there, a whole bunch of new adverse events come along, stomatitis being the one that really upsets people. 53% was the rate in the trial. So how this panned out into the phase 3, I don't know.

And then they had the biliary tract cancer trial, the GEMINI data, which was a combination with rilvegostomig versus Imfinzi, and they showed a higher objective response rate here—31%, only slightly higher than, I think, the TOPAZ trial, if I remember correctly. And so, again, another positive signal on pretty much every line. And then, of course, now it's in BTC in 2 phase 3 trials. So the signals are there. AstraZeneca is going for it, and we're going to see the real outcome of all this from 2026 or 2027, I think, as the trials read out.

Maybe this is how AstraZeneca is going to win in 2026, 2027, 2028, and beyond.

Who knows? But I think 2026 will probably be AVANZAR.

Which is TROP2. Yeah.

Brad, I love your thoughts on the Arcus HIF-2α that you mentioned. It looked pretty good to me. Do you think it's differentiated?

Yeah. Well, I think it's almost like the IgAN discussion we just had. I think it's potentially such a huge market that if they're second and even just comparable, I think it's a huge market and a huge opportunity for them. I do think that their data looks slightly better than Merck's right now, and people really like this asset because, of course, you have a validated target that's on the market right now.

I would say if we were talking 2 years ago, everyone would have said that TIGIT was Arcus's main program. Given all the volatility that it's had and how Merck succeeded with HIF-2α, I think HIF-2α is now Arcus's main program, and I think it's super interesting.

Graig, can I just correct myself very quickly here, just for perfection's sake? The GEMINI trial is rilvegostomig plus chemotherapy in HER2-negative BTC.

All right. I'm going to move on. Eric alluded to it earlier, but something that was a really interesting bull-bear debate at ASCO. I always preface this by saying we're rooting for everyone's success. Obviously, in our industry, everyone—the companies themselves—wants patients to succeed. But the reality of our business is that we do have competition.

I think the big competition at this year's ASCO was Merus versus Bicara. These are head-and-neck cancers, which traditionally are very difficult cancers to treat, and the checkpoint inhibitors by themselves have very low response rates. We definitely need something new, and these 2 programs are slightly different. Bicara is a fusion protein that's EGFR × TGF-β, and Merus is more of a traditional bispecific antibody that's EGFR × LGR5.

Eric, I'll pass it over to you. I don't know if you cover both of these companies or just one, but I'm interested to know your thoughts on this potential competition.

Yeah, and thanks, Brad. We covered just Bicara, and I think the theme of our discussion today is this fight-to-the-death competitive match between drugs in the same class. On Wall Street, we always like to pick a winner. We always like to think we're capable of picking a winner, and we always like to think that it's a winner-take-all battle. That's rarely how these markets play out.

We can go back to our discussion of IgAN or the discussion we just had on HIF-2α, and now we're heading into a similar discussion on the frontline head-and-neck cancer marketplace, which is a big market—probably a $3 billion or $4 billion market. There's a real disconnect here between what the doctors are saying and what investors are saying.

Physicians are much more even-handed in their views toward these 2 molecules. They're saying that both are pretty much off the charts, better than anything we've seen before. We've got response rates in the 50–60% range for both of these molecules on top of Keytruda in the frontline head-and-neck cancer setting. That's about 3 times the response rate you would expect from Keytruda alone. This is coming back to our other theme of the day: major, major innovation in the cancer space.

Both companies are now in phase 3. Merus is a little bit ahead, and Merus certainly has some potential competitive differentiation that might become an advantage for it. On the other hand, the Street has accorded Merus essentially winner-take-all status in this battle. Merus has a market valuation of around $4 billion-plus, and Bicara, much like Arcus, is trading a little bit above its cash balance. Generally, these 2 companies are getting very little credit for having competitive entrants in the space.

We think the Bicara molecule, ficerafusp alfa, which, as you called out, hits not just EGFR but TGF-β, is looking differentiated in ways that might be positive from a competitive standpoint. The depth of response and duration of response here look very good to me. So, sure, Bicara and the class are probably undervalued in some of these competitive battles, but markets have a way of evening out over time, and we're hopeful that Bicara will get its due. What are your thoughts?

Well, I think, Eric, one of the things that people are questioning about Bicara is that the Merus one seems to be working in both HPV-negative and HPV-positive disease. I know HPV-positive is a much smaller indication, but people are using that as a benchmark for comparing the 2.

If one is working in both patient populations and one company seems to have pretty much abandoned that HPV-positive group, maybe that says something about the strength of their assets. What do you think about that argument?

That's a great point to make. Thank you for bringing it up. Interestingly, we talk about head-and-neck cancer as head-and-neck cancer, but physician experts increasingly think about it as, as you just parsed out, HPV-positive and HPV-negative disease, and almost view these 2 disease states as very different—as if they're different histologies, different tumor types altogether.

You're right. It is true that Bicara has selected the HPV-negative subset. It actually has very good biologic rationale for pursuing HPV-negative patients. That's based on preclinical data and now increasingly translational data in the clinic to support the use of not only the EGFR aspect of the molecule but also the TGF-β aspect, and as to why, molecularly and mechanistically, this makes sense to go after HPV-negative tumors.

I'm a big believer that they've actually turned what could be a negative into a positive by selecting out the patients that are most appropriate for their therapy. This may be where we do see some differences. The Merus molecule doesn't work through TGF-β. It may be active in HPV-positive patients, but it also may not be as active in HPV-positive patients. So, again, we've got something to learn here, and it's probably not going to be a one-size-fits-all market.

I did 15 interviews throughout the 4 days of ASCO for BiotechTV, and the one I did with the CEO of Bicara, Claire Mazumdar, was actually my favorite. I've always been a big believer that the best CEOs, just like the best leaders in our industry, period, want to do media when things are terrific and going great.

Not to say that she had a bad ASCO, or even that the competitive argument was necessarily negative—as you're hearing now, there's a strong argument to be made for this—but it was controversial. Especially doing video, it's a whole different thing. People get nervous about saying the wrong thing on video or whatever.

She came and really stood up for herself, her company, and her data. We had a good, balanced discussion about it. I brought up a lot of the bear arguments, and I'll let viewers decide on the substance of the answers, but I thought she did a terrific job of being out there and being visible at a time when her stock price wasn't so great after they put out the abstracts and some analysts were being hard on this comparison.

I just want to give her credit and point out that that's what true leaders do. Credit to her for doing that. I thought it was a great discussion.

6. The FDA Backs Innovation

We only have a couple of minutes left. It sadly would have been great to have him on, but as I mentioned at the start, we almost had John Crowley on today. Given everything we've talked about, I don't know how we would have fit in all the policy stuff that's been going on, but I think maybe we'll just briefly touch on one thing.

There was a big cell and gene therapy meeting, and of course everyone is wondering, with Vinay Prasad and some of the previous things that he said about gene therapies like Sarepta and things like that, what the FDA's stance is going to be on some of those types of emerging technologies. Did either of you guys see any of that meeting or any of the comments out of it, and do you have any thoughts?

Well, I guess I'll start. I actually had the benefit of speaking with John this week. We hosted Mr. Crowley on a Cantor webinar. I know he was at the meeting, and for those of us who are listening in, I think we all came to the same conclusion: right now, we're hearing great things from the FDA.

I want to emphasize “hearing,” because talk is cheap, and we still need to see the follow-through. There are still, in my opinion, some concerns about staffing and resourcing that need to be addressed. But wow, I don't think the FDA could have had a better week either.

They came out not just at that meeting, Brad, but the day before, Dr. Makary made some comments that were well received. I know he was also at a conference on Wall Street, saying pretty much exactly what investors wanted to hear, which is that he's pro-innovation.

He's pro an efficient registrational and regulatory body, and we're not going to be going back into the dark ages as far as winding back some of the progress that we made under the prior administrations.

I saw a comment in the news, too. I think it might have actually been his own tweet. I saw that RFK commented on the base editing of the UPenn baby who happily went home this week as well. So I thought that was, like you said, words, but a good vote of confidence in the whole gene-editing field. So maybe that's a positive.

And then, of course, I'm sure everyone's seen this. The FDA also had their first meeting. They're trying to meet with the CEOs of companies in the industry. They had their first one in the DC area, and I know they're headed to the Bay Area and San Diego. Around BIO time, they're going to have one here in Boston as well.

I'm sure that some details of those meetings will start trickling out as they start happening. So maybe we'll get a little more clarity on their relationship with the industry and our industry's ability to give them feedback on what's really affecting us and what's important to us.

I don't want to end today's session on a down note, because it has been so wildly positive in so many different ways this week. Sam, you're right to call that out earlier in the call. But John did mention that we're still not in a good place with MFN. We may be in a better place with the FDA, and I think we're all feeling pretty good about that.

But where BIO really does need our support, and where I hope all of our listeners will stand up, join hands, and fight for the industry that we all love and believe in, is on the drug-pricing side, where, unfortunately, things have not progressed as favorably as they have with the regulatory bodies or the other topics that we're talking about this week.

I guess, Eric and Brad, I think we're also all holding our breaths—hopefully not for much longer—on the tariff front, right? I don't know how much time the Section 232 investigation might take. It might take several months, from what I understand. So you've got that still hanging over our heads. But MFN is the bigger one, and how it gets implemented.

Let's just remember that we've just had a week of great cancer data, and some pancreatic cancer patients, hopefully in a few years, will be sitting in a world where you're looking at second-line and third-line therapies which are active. That would be great.