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Biotech Hangout · · 61 min

Episode 186 - June 12, 2026

Graig SuvannavejhEric SchmidtPaul MatteisOliver Barnes

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TL;DR
  • Biotech is quietly winning within healthcare: the XBI is up ~10.5% year-to-date, only ~70bps behind the NASDAQ and ~350bps ahead of the S&P 500, while healthcare overall is down 0.4%. Parabilis Medicines set a fresh IPO record at $771M—topping the $719M obesity raise from two months ago—just five months after a $305M Series F, and ~12 IPOs raising $4B+ by midyear leaves what Eric Schmidt calls a “Goldilocks scenario”: “selective, quality-driven, and data-oriented, but not closed.”
  • Paul Matteis flags a subtle regime change: binary catalysts that eight or nine weeks ago would have compensated investors “unequivocally” are now trading sideways or down, and the buy side is asking whether to “play a little bit more defense” into H2. Eric’s bull-market arc—launch stories in 2025, “shiny pipeline” assets in 2026, platform stocks and “science projects again” in 2027—drew Paul’s uneasy question: “Is that the end of a bull market there?” Eric: “I think we all fear that.”
  • Summit pulled a ~$500M offering after its ASCO plenary data drew a destructive U.S. KOL discussion, leaving the company “half-pregnant with the need to raise capital” into the binary global HARMONi-3 readout at year-end. Eric thought the data themselves were “very good” and mused that the discussant may have cost the company “billions of dollars” of market value; Paul’s BD lesson from experience at large companies is that cash is negotiating leverage—without it, strategics can “dictate terms.”
  • Tango’s PRMT5 inhibitor plus Revolution Medicines’ multi-RAS inhibitor posted a 90%+ response rate in MTAP-deleted pancreatic cancer (~40% of PDAC patients)—“off the charts” versus historical teens-to-20s—alongside a $500M-plus Tango offering and several hundred million dollars raised by IDEAYA on the same data. Eric argues “1 plus 1 equals 3” pushes Tango and Revolution Medicines toward cooperation rather than rivalry, and calls RAS the pathway “most ripe for deals”—with J&J’s acquisition of Firefly, whose lead asset is a RAS inhibitor from a degrader platform, as an example.
  • Incyte’s up-to-$2B purchase of Star’s subsidiary Vega ($1.25B upfront) is new CEO Bill Meury’s opening move—Graig Suvannavejh says Meury told him, “you should consider us as the first of several.” VGA039’s monthly infusion for von Willebrand disease could be a blockbuster as Jakafi comes off patent “as early as 2028.”
  • GSK’s roughly $10B-plus Nuvalent takeout ($124/share, ~$9.4B enterprise value) is Luke Miels’ “biggest swing yet” back into oncology—and, per Oliver Barnes, effectively an arbitrage on peak-sales variance: bears at ~$2B, bulls at $5–6B. Eric’s verdict on a decade of dabbling after the 2014 Novartis asset-swap exit—Tesaro, Sierra Oncology and IDRx—is that “with Nuvalent, they’re fully in”; GSK probably needs more oncology assets to become a real player.
  • Oliver’s view on M&A leaks: most have no strategic logic—“the closer you get to a deal being announced, the more people know about it,” and human nature makes people loose-lipped. His health warning for retail is to trust outlets with rigorous verification, including the FT, the Journal and Bloomberg; publications with one-in-ten or two-in-ten hit rates are “generally not worth your time.”
  • The regulatory-flexibility trade may be turning back on for genetic medicine—Paul says “it feels like the scale is tilting back” in light of Marks leaving, while Novartis’ FSHD biomarker data led Eric to say, “this drug should be approved in my opinion.” Neurogene completed pivotal Rett dosing, with no early recurrence so far of the severe inflammatory event seen at a higher dose, though follow-up continues. The brutal flip side: Sensorion discontinued its otoferlin hearing-loss program because Regeneron got to market first and is giving its therapy away for free.
Digest · the substance, structured for research

1. Biotech beats the rest of healthcare while the IPO record book gets rewritten

  • Graig’s scoreboard: XBI +10.5% YTD versus NASDAQ +11.2%—only ~70bps behind despite the AI data-center trade and the host’s comments about today’s SpaceX IPO ($75B raise, $2T+ market cap)—and +350bps over the S&P 500, while healthcare broadly is down 0.4%. “Within healthcare, biotech, I think, has been a clear winner.”
  • The Parabilis Medicines IPO raised a record $771M, surpassing the $719M raised by obesity player Kailera Therapeutics less than two months earlier—remarkable for a company that raised a $305M Series F in January and signed a $2B-plus Regeneron collaboration last month. It is an oncology company built on a proprietary Helicon peptide-based platform; Eric’s read on why it excited people: “a drug that maybe, for the first time, can hit the Wnt pathway... it could be, in theory, the next med.”
  • Cardiovascular-focused Cardurion Therapeutics is set to debut on NASDAQ early next week; by midyear, ~12 IPOs will likely have raised $4B-plus collectively. On the private side: Sonothera’s $125M Series B for ultrasound-based gene therapies addressing the challenge of delivering larger genes, with Duchenne muscular dystrophy as a first target; a $100M Series B for John Maraganore’s City Therapeutics, an RNAi company focused on cardiovascular disease and ophthalmology; and an $11M Series A for Aethereal Bio, focused on antibodies for immune diseases.

2. “Year of the shiny pipeline asset”—but the buy side is edging toward defense

  • Paul’s forecast with Josh Schimmer—Paul guessed 12 IPOs this year, while Schimmer guessed 50—may end near the midpoint. The window is open, but “the bar is higher than it’s been historically,” sustained by a backlog of private companies with “real data in Phase 1/2-type studies” or valuable technologies accumulated while the window was shut.
  • Paul’s change of read was explicit: if his coverage’s binary events had read out “eight or nine weeks ago,” the Street would have unequivocally paid investors for taking on the risk. After recent readouts led stocks to trade sideways or down, and expected financings failed to appear, there is “a little bit more consternation among the buy side” about playing defense into the summer or second half of the year. His self-aware caveat: “Like a true seller, I’m a little bit of a lagging indicator.”
  • Eric’s cycle arc: launch stories in 2025, shiny pipeline candidates in 2026, platform stocks in 2027—“science projects again.” Paul asked, “Is that the end of a bull market there?” Eric replied, “I think we all fear that.” Both characterized today’s IPO market as a Goldilocks scenario: selective, quality-driven and data-oriented, but not closed.

3. Dual-tracking: pharma keeps picking off the IPO class—but desperation has become competitive tension

  • Paul’s observation: proof-of-concept private companies increasingly dual-track an IPO versus a sale, and “over the past year there’s been a lot more private M&A at a meaningful dollar level than I really ever remember.” Eric wondered whether public-market investors get “the worst of the IPO class.” Oliver cited Tubulis, which had been gearing up for a large IPO before being acquired, and Vega, whose parent Star was working on an IPO simultaneously with the Incyte deal.
  • That is why Parabilis—and perhaps Kailera and Maze—matter to Oliver: these companies were able to “break through any valuation ceiling that pharma was willing to pay” and create value for public-market shareholders.
  • Oliver’s counterpoint was Metsera: looking at the filing before its listing, he thinks Novo put in a bid, but Metsera went public anyway. In the last couple of years, with biotech capital markets broadly shut, private sales were sometimes driven by “a degree of desperation.” Now, he sees “actual real competitive tension”; Star was pursuing an IPO while working on the Incyte transaction, giving its VCs optionality. Eric responded that public-market participants want “all the good stuff for ourselves.”

4. Summit’s pulled offering: how one ASCO discussant may have cost billions

  • The contrast of the week: Tango had an offering in the $500M-plus to $600M range, and IDEAYA raised several hundred million dollars on the heels of the same PRMT5 data, while Summit—despite ASCO data Eric “actually thought were very good,” a substantial market capitalization, multiple Phase 3 studies to fund and a relatively weak cash balance—pulled its ~$500M deal. Eric inferred that a clearing price existed but was “distasteful” to management, whose members remained large shareholders. The company is now “half-pregnant with the need to raise capital” ahead of a binary event.
  • Graig attended the plenary. After the formal presentation, a U.S.-based KOL delivered a cautious, “quite destructive” rebuttal: longer follow-up was needed, the data came from a Chinese study with limited applicability to the U.S. population, and the overall-survival benefit needed to be confirmed in the global Phase 3 study. Eric said it was “interesting to think about how many billions of dollars that discussion may have cost the company” in market value, and called the criticism somewhat disingenuous against a seemingly strong dataset. He speculated that Akeso, which ran the study, may have been responsible for communicating with ASCO and helping the discussant reach a better view.
  • Paul’s mechanism: a pulled deal creates a self-fulfilling overhang—buyers wait for “a better entry point or a better liquidity event,” and trading concerns “can transcend the actual fundamentals.” Possible responses include a royalty deal, “rip the Band-Aid off” with the financing anyway, try a PIPE, or wait and roll into the year-end HARMONi-3 catalyst. A miss would leave Summit needing to fund Phase 3 studies in nonsquamous lung cancer and colorectal cancer, which read out in 2027 and beyond, probably at a lower valuation.
  • Paul’s broader BD lesson is that raises are not only about runway. Ample cash is a strategic asset: it lets a small company tell an interested strategic, “Thanks for your interest. We’re good on cash. We don’t need you,” and use its balance sheet to seek better terms.

5. PRMT5 × RAS: 90%+ responses in pancreatic cancer, and a pathway “on fire”

  • Eric’s numbers: MTAP deletions occur in about 40% of pancreatic cancer patients, and Tango’s PRMT5 inhibitor TNG462 combined with Revolution Medicines’ multi-RAS inhibitor daraxonrasib produced a 90%-plus response rate—“off the charts” in a cancer where response rates have historically been in the teens or 20s at best.
  • Paul asked whether Tango could threaten Revolution Medicines’ potential end market. Eric said Revolution Medicines is clearly in the lead with its RAS inhibitors, and daraxonrasib “should be approved, I’d hope, almost any day now” once filed. Other potentially combinable multi-RAS inhibitors are being developed by AstraZeneca, Astellas, Novartis and, Eric believes, Roche. But switching partners would force Tango to pause and restart some development, so “1 plus 1 equals 3”: a frontline combination study, longer duration on therapy and joint, combined sales all support cooperation as the fastest route to patients.
  • The same logic helps explain J&J’s acquisition of Firefly, whose lead asset is a RAS inhibitor from a degrader-based platform. “There’s probably no pathway that’s more ripe for deals, acquisitions and collaborations than RAS inhibition right now. The thing’s on fire.” Graig’s wider frame after 20 years covering the industry: “The advances we’re seeing in pancreatic cancer... it’s breathtaking.”

6. Incyte–Vega: Bill Meury’s “first of several”

  • Oliver’s mechanics: Incyte is paying $1.25B upfront in cash plus $750M later for Star’s subsidiary Vega and VGA039, a Phase 3 von Willebrand disease drug that could benefit from accelerated approval. The current standard of care is an infusion several times a week, so only the most severe patients—“a few tens of thousands”—tend to receive it. VGA039 offers a monthly infusion, potentially expanding use among existing patients and into prophylaxis and creating a blockbuster opportunity.
  • That matters because Jakafi, Incyte’s JAK drug for blood cancer, could come off patent as early as 2028. For a midsize drugmaker, high hundreds of millions of dollars in revenue approaching $1B is strategically meaningful, unlike the multiblockbuster assets sought by $100B-market-cap pharma companies facing patent cliffs.
  • Graig said the process was competitive and that Vega was also considering an IPO. He spoke with new CEO Bill Meury after the deal and said Meury told him to consider Incyte “the first of several.” Hematology is a natural area, with ophthalmology and oncology as adjacencies; deal sizes will generally cap out at a few billion dollars. Graig said Incyte’s stock is up roughly 50% over the past year.
  • Meury previously sold Karuna to BMS and later led Anthos, which was sold to Novartis. Paul gave a shout-out to Dave Gardner and said it was encouraging to see Incyte transact on a private company generating investment-community buzz. Paul also said that people who know Dave and Bill know “they’re not wallflowers,” and expressed confidence in the team’s diligence and ability to find attractive assets.

7. GSK–Nuvalent: a roughly $10B-plus bet on peak-sales variance

  • Oliver’s arc: GSK’s “slightly wacky” 2014 asset swap under Andrew Witty traded oncology away for Novartis’ vaccines division. Emma Walmsley then spent considerable time rebuilding GSK’s oncology presence. Luke Miels, who became CEO at the beginning of this year, has now taken “their biggest swing yet”: $124 per share, putting Nuvalent’s equity value at $10-something billion and its enterprise value at about $9.4B. It is effectively GSK’s largest deal since the company was created at the beginning of the millennium, signaling that more may follow.
  • Nuvalent has several drugs targeting different mutations in non-small-cell lung cancer, with two potentially able to receive approval this year. The spaces are competitive, and one drug’s recent frontline data at ASCO were perceived by investors as a setback. That helped produce a wide range of peak-sales estimates: the bearish view is roughly $2B—“they’ve probably overpaid, but it’s not a total disaster”—while the bullish view is $5–6B across the pipeline. Oliver characterized the deal as an arbitrage on that variance: if sales are toward the bullish end, it could be a very good deal for Miels.
  • GSK’s oncology re-entry has included Tesaro, bought in 2018 or 2019; Sierra Oncology, a smaller transaction; a big collaboration with Hengrui; and IDRx last year, which was development-stage. Paul said the Tesaro deal did not work out for GSK, while the Sierra deal was smaller and IDRx was still development-stage. “You can’t do a $10 billion transaction and not be in oncology,” Eric said; GSK probably needs more oncology assets to become a real player.
  • Oliver also recalled, with a caveat, that GSK ranks fourth on a list of pharma companies by deal count, behind Eli Lilly and possibly Merck among the companies he remembered. Graig said he needed to verify the list.

8. How deals leak—plus the week’s licensing tape

  • Oliver’s demystification, prompted by the question of night-before leaks: retail attention and high premiums make biotech M&A gossip unusually visible, but “on the whole, there’s not really” strategic logic to most leaks. Occasionally a story can put a company in play, help get a deal over the line or make a process more competitive. Mostly, leaks reflect reporters’ relationships, persistence and “clue work”—trying to work out what is happening in the industry.
  • His simple answer on timing: “The closer you get to a deal being announced, the more people know about it.” Two months out, when a deal may still be delicate, the chance that someone with only a sliver of information will discuss it is “absolutely zero”; hours or days before signing, more people know and human nature makes them loose-lipped. Oliver cited breaking the Novartis–Avidity talks in August before the deal printed in October as the kind of early information that can matter to an arbitrage fund.
  • Oliver’s health warning for retail investors was to distinguish outlets with rigorous checks—including the FT, the Journal and Bloomberg—from publications with one-in-ten or two-in-ten hit rates, which he called “generally not worth your time.”
  • Graig’s licensing roundup: Novartis renewed and expanded its Orionis Biosciences molecular-glue collaboration for up to $1.4B in biobucks; Lilly in-licensed a gamma-secretase modulator for Alzheimer’s from Sweden’s AlzeCure Pharma for $1B-plus in biobucks but only $10M upfront; and Corvus invested further in its Chinese partner Angel Pharmaceuticals to fund soquelitinib, an ITK inhibitor for oncology and immune disorders.

9. Regulatory flexibility “tilting back”—and gene therapy’s brutal edges

  • Eric discussed Novartis’ Phase 1/2 FSHD data, which the company has called pivotal or potentially pivotal. The study showed target engagement against DUX4, including reduction in the blood biomarker KHDC1L, as well as reductions in creatine kinase, a marker of muscle destruction. “The data look good,” Eric said, adding, “this drug should be approved in my opinion.” He thought Avidity, had it still held the program, would have aggressively pursued accelerated approval, while Novartis appears to be pulling back somewhat from that approach.
  • Paul’s regulatory-flexibility thesis: companies have reported that, in light of Marks leaving, the FDA has been meeting with genetic-medicine companies and seems receptive to getting back on track with flexibility. What flexibility means remains “super-duper subjective,” and companies with prior regulatory setbacks may still get another opportunity. Paul said it may take permanent FDA leadership, but “it feels like the scale is tilting back.”
  • Neurogene completed dosing in its pivotal study of NGN-401, a gene-replacement therapy for Rett syndrome, and overenrolled the study. At a higher dose in Phase 1/2, a severe inflammatory event resulted in a patient death; the question was whether the risk would recur at the lower dose. The study is not over, but the perception is that such events would happen early and that they have not so far. Neurogene is one of two companies developing AAV9-based therapies for Rett syndrome, and both are expected to have pivotal data next year. Both have sign-off on single-arm studies evaluating developmental milestones, creating another test of regulatory flexibility.
  • The counterpoint is Sensorion’s discontinuation of its otoferlin program after Regeneron got to market first and gave its therapy away for free. Paul retained an insight from a CEO in the space: otoferlin is the “first, most obvious target” because it is one of the few genetic hearing-loss conditions in which the inner-ear biology is preserved at birth. Other conditions involve changes in the ear and cell communication in utero, so “the window for intervention might not be as wide.”
Full transcript
Graig Suvannavejh

It is great to be back as host on Biotech Hangout. Summer is in full swing here in New York City, a city swept up in New York Knicks basketball fever. Knicks in 6 is the call here.

In any case, we certainly had another busy week in the biotech industry. We're going to try to get through as much as we can with our jam-packed agenda, and I'm looking forward to having Eric, Paul, and Oliver chime in. To start off, as I often like to do as host, let's begin with a bird's-eye view of where things are in the biotech market. I'll speak on sector performance and then provide some initial commentary on capital-markets activity as well.

1. Biotech Holds Its Lead

At a high level, it's been a bit choppy of late, but I think things overall are still pretty healthy in biotech. Looking at performance year to date, biotech, with the XBI as a proxy, is still nicely in positive territory. As of yesterday's close, the XBI is up about 10.5% year to date. While the AI data-center chip trade, so to speak, has dominated as of late—and, of course, we have the huge SpaceX IPO taking place today, with, I believe, a modest $75 billion raise and now trading at over $2 trillion from a market-cap perspective—the NASDAQ is up 11.2% for the year, so it's only doing about 70 basis points better than biotech, or the XBI.

The XBI is outperforming the broader S&P 500 by about 350 basis points. Meanwhile, healthcare, more broadly speaking, is actually in the red so far year to date; it's down 0.4%. Within healthcare, biotech has been a clear winner, and, of course, we'd love to see this trend in biotech continue.

Let's take a look at some capital-markets activity. This week in biotech, we had the Parabilis Medicines IPO, raising a new record of $771 million in total. That surpasses the $719 million that obesity player Kailera Therapeutics raised less than 2 months ago.

Parabilis is an oncology-focused biotech with a proprietary Helicon peptide-based platform technology. I only first heard of Parabilis after it signed a collaboration deal with Regeneron to the tune of over $2 billion just last month. After looking into it just a little bit more this morning, I think it's incredible that this IPO for Parabilis comes just 5 months after the company raised $305 million in January of this year in a Series F financing. Congratulations to the Parabilis team on its great success there.

Then we have the IPO of Cardurion Therapeutics, which is a cardiovascular-disease-focused company. I believe that IPO is set to debut on the NASDAQ early next week. By midyear, we'll likely have had 12 or so companies IPO, raising collectively over $4 billion. Given this positivity, I'd like to think that the window for private companies to consider an IPO remains very open and that investor appetite is there. Obviously, though, it will depend on the type of story.

Just quickly on the private side, we saw a number of financings as well. I'll mention a few. We had a $125 million Series B for a company called Sonothera, which is focused on novel ultrasound-based gene therapies that address the issue of trying to get larger genes into a gene-therapy construct. Duchenne muscular dystrophy is a first target for that company.

Then we had a $100 million Series B for John Maraganore's City Therapeutics, an RNAi company for cardiovascular disease and ophthalmology. Lastly, we had an $11 million Series A for a company called Aethereal Bio, which is focused on antibodies for immune diseases.

We've had a number of public-market deals as well, and I think I'm going to have Eric take that one. But before we talk about public biotech financings that we've seen, I think Paul is on now, and Eric, maybe I'll ask this question to you both: Based on your conversations with companies and investors, do you want to offer your take on what we're seeing as it relates to private companies and the landscape for them?

Paul Matteis

I'm gonna go. No.

Eric Schmidt

You go. All good, man. You got more interesting things to say, Paul.

Paul Matteis

There's 0% chance of that, Eric. I think you're totally right, Graig. There's still a window. All of us probably have a window into some sort of slice of a pipeline that could continue to test the markets later this year.

2. The IPO Window Stays Open

I still feel like the bar is higher than it's been historically. But at the end of the day, given how long the window was closed, I think there's still a backlog of private companies with real data in Phase 1/2-type studies or real technologies that have value. I think Josh Schimmer and I last year each guessed how many IPOs were going to be this year. A number of people who've listened to this podcast have reminded me that I think I guessed 12, so I was totally wrong. Josh Schimmer guessed 50, so we'll see. That would be pretty amazing, but it seems like the true answer might end up being at the midpoint.

I will say that, and I'd be curious, Eric, if you agree with this or not, we've talked on past podcasts about how last year was sort of the year of the launch story, and this year is the year of the shiny pipeline asset to some degree. I mean that less about, say, a RevMed comment and more just as a generality. It feels like large-cap companies that don't have an interesting pipeline asset are out of favor.

We've seen a number of development-stage biotech companies trade up 100% into data. I'm wondering if that's changing just a tiny bit. I have a couple of big binary events coming up in my coverage, and I feel like if those catalysts were reading out even 8 or 9 weeks ago, the perception from people would have been unequivocally that you could get compensated significantly for taking on that risk.

After a few readouts recently, some stocks traded sideways or traded down. Maybe there wasn't a financing when one was expected. I think there's a little bit more consternation among the buy side about whether investors need to play a little bit more defense going into the summer or the second half of this year. I don't think it's been a massive sea change, but I've definitely noticed that.

Like a true seller, I'm a little bit of a lagging indicator, reacting to the choppy markets. But on a forward-looking basis, it feels like the Street feels a little bit differently about catalysts and risk-rewards than people did a couple of months ago. Eric, do you hear the same thing at all?

Eric Schmidt

I love your comment, Paul, about how this is the year of the shiny pipeline drug or candidate. I think you're dead right there. I think that's honestly what made Parabilis such an exciting IPO for a lot of people. They've got a drug that maybe, for the first time, can hit the Wnt pathway, which is implicated in so many different cancers. They've got some data. It's still Phase 1/2 data, but it could be, in theory, the next med, right? That's what people are looking for.

We also had, I'm sure we're going to discuss, the Tango data. The PRMT5 inhibitor class—Tango and others, for that matter—are in vogue these days for kind of the same reasons. I don't know. I haven't seen that end yet. I guess the natural progression is to go from launch in 2025 to shiny pipeline candidates in 2026 to platform stocks in 2027: science projects again.

Paul Matteis

Is that the end of a bull market there?

Eric Schmidt

I think we all fear that, right? We don't want that. I think you're right also, Paul, that today's IPO window is a little bit of a Goldilocks scenario. It's selective, quality-driven, and data-oriented, but not closed. That's exactly the kind of market that we've always asked for.

Paul Matteis

Right. Makes sense.

Eric Schmidt

Graig, do you have any thoughts?

Paul Matteis

You might be on mute, man.

Graig Suvannavejh

Thanks so much. My visibility into private companies and their aspirations for IPOs comes from conversations with private companies. Some certainly are hopeful that they can get out this year. I think some of them have more real prospects than others.

Given how closed the IPO window has been for so many companies, I do think the cream rises to the top. By that, I mean companies with de-risked data and a good investor base. Based on where I sit relative to both your platforms, you probably have much better insight into things than I do.

At 12 by the midpoint of the year, I think we're in a good spot. Paul, I was on that same webcast when we were talking to Josh, and he had 50 while you had about 12. I chose the easy path and went last and said somewhere in between.

Again, I think the comments we made back then were that we just want to see a very functional biotech IPO market in 2026 that hopefully will lead to an open window for companies in 2027.

So, fingers crossed. For those of you listening, I hope you're doing the things that you can to get ready. For those of you who are perhaps not there just yet, let's keep an eye to 2027.

Paul Matteis

I think one other comment here, and it might segue into—if Oliver and Eric want to talk about the Insight deal—is that definitely the narrative for many private companies, and obviously this depends on the stage, right? It's more for companies that have some proof of concept. This is the whole dynamic of dual-tracking: doing an IPO or looking at whether or not there's a buyer of the company.

I think some people would say that's always been the case, but I don't have a good stat on this. It feels like over the past year there's been a lot more private M&A at a meaningful dollar level than I really ever remember.

Eric Schmidt

Well, Paul, that's a great question. I wonder if you feel sometimes like I do that we in the public markets get the worst of the IPO class.

Oliver Barnes

Yeah. We have seen Tubulis, which we know was gearing up to do a massive IPO. They got picked off. I think Orum was another one that was at least considering going public and got picked off. I don't know what Vega was doing, and that was the company that was just acquired this week by Insight.

It's a little bit concerning that you know pharma is looking at everything and that these private companies are looking at the dual-track process. Now, that's why to me something like Parabilis is so wonderful. Maybe Kailera and Maze fall in this boat here too. These are earlier IPOs from earlier in the year, but these are companies that were able to break through any valuation ceiling that pharma was willing to pay and create a lot of value for public market shareholders, despite maybe there having been a dual track. Who knows? I don't know, but I love your thoughts on that.

There, I was going to say a counterpoint to those, though, which was Metsera, I suppose, because if you look at the filing for Metsera before the listing, I think Novo put a bid in and then it ended up going. I think one of the things I've observed with the dynamic between IPOs, M&A, whether to sell before the IPO, the whole dual-track thing, is in the last couple years, because broadly speaking biotech capital markets have been shut down a lot, there's been a degree of desperation driving some of the private sales.

Whereas I think now we're seeing a different dynamic, where there's actual real competitive tension. The Incyte deal with Star to buy Vega, a subsidiary of Star, is a perfect example. Star was working on an IPO simultaneously with working on this deal. I think generally that's good for the sector, right? Because it creates real competitive tension in terms of giving the VCs optionality in what they want to do.

Paul Matteis

Well, Oliver, you're speaking from a VC mindset, which is, I agree, great for them. But those of us who operate in the public markets, we want all the good stuff for ourselves.

Oliver Barnes

You're getting greedy. You're getting greedy. [laughter]

Graig Suvannavejh

Well, let's—I mean, we'll eventually talk about the M&A that we've seen in the space. We did just comment on some financings we're seeing on the private side, but we've had some good datasets, which have come with some concomitant public biotech financings. Eric, I think I'll turn it over to you just to go through a few higher-profile ones that happened this past week.

3. Data Drives Public Financings

Eric Schmidt

Yeah, there's maybe 1 interesting area here to discuss and debate, which was the Summit deal that didn't get done. But first, let's start with the 2 that did: a couple of very large offerings, 1 from Tango and 1 from IDEAYA. Just continuing the trajectory we've seen from earlier in the year, where companies that have data, especially good data—and I don't know, we'll probably talk about the Tango data either now or later in the podcast—but the data were exceptional.

Unprecedented results in PDAC, where pancreatic cancer is still a huge unmet need, and better data than we've ever seen before from any other drug combination. Hats off to the guys at Tango. They deserve to have been out there raising $500-plus million—$600 million—and they could put it to good use.

IDEAYA was able to raise on the heels of that same data set because they, too, were in the PRMT5 field and are beginning to generate probably similarly very interesting combination data. Again, a company that was able to raise several hundred million dollars on the heels of what looks like a terrific clinical result that's going to help a lot of patients.

The anomaly here was Summit, right? Summit, of course, had their data set last week at ASCO. I'm sure we talked about that on Biotech Hangout. I wasn't part of last week's episode, but the data were criticized from a few different angles. I actually thought they were very good.

Summit went public with a raise of about $500 million. Certainly, this company has a very substantial market cap. Certainly, as we've talked about, the environment for fundraising is very good. Certainly, this company can use the money. They don't have a particularly strong cash balance, and they've got a lot of things they can do with the money. They're running multiple Phase 3 studies.

All signs pointed to that offering being successful, and yet it was pulled. I assume there was a price at which the deal would have cleared. I assume that price was distasteful to the Summit management team, which, to their credit, remained huge owners of the security—huge shareholders. So they must have chosen to pull away when the price wasn't right.

I don't know what kind of advice they got or why they expected the price to be a lesser discount than, I guess, it was. But now they're seemingly a little bit stuck, right? Because the world knows that they're half-pregnant with the need to raise capital, and there is a pretty binary event coming from them toward year-end.

We sometimes see this happen. I'm sure you've seen it before, but I'd love your views on where this leaves Summit, or when companies go out and don't quite get the price point they want, what they ought to be doing.

Graig Suvannavejh

Go ahead.

Paul Matteis

Go ahead.

Graig Suvannavejh

No, you can go again.

Paul Matteis

I feel like it puts you in a really tough spot, right, Eric? It almost creates this self-fulfilling prophecy. If you're an investor looking to buy the stock, you're almost wondering if there's going to be a better entry point or a better liquidity event.

We've seen how concerns about how a stock might trade can transcend the actual fundamentals of the stock sometimes. Again, I don't cover Summit. I don't know anything about the transaction, but people can create a financing overhang into being a much bigger deal than it actually is. This feels like it would add fuel to that fire.

I don't know what you do. I'm not a banker. Do a royalty deal or rip the Band-Aid off and just do the financing anyway. Try to do a PIPE. I don't really know what else you can do, or just wait it out and roll into the catalyst, right?

Graig Suvannavejh

Yeah, I'll just add that I don't cover Summit. I don't know the story well enough, but I was at ASCO. I was at the plenary session where they announced the data. Eric, I would agree that on the face of the data themselves, the data are good.

It would have been very interesting to see what would have happened to the stock if the follow-up presentation by a KOL who could opine on the data went very differently. For those who were maybe not familiar with what happened at ASCO, after the formal presentation, there was a U.S.-based KOL who was incredibly cautious around the data.

Again, for context, these data were from a Chinese study. They were very good data, as Eric referenced, but the criticisms were things like: “Hey, longer-term follow-up is needed to verify this. There's limited applicability to a U.S. patient population. We're going to need results of a global Phase 3. Because of this, I'm not really quite sure if the OS benefit will be maintained, because we just need a longer follow-up period.”

It was quite a destructive type of rebuttal of the data. I'm just curious whether the receptivity to that data would have been different at ASCO. It'd be curious to know if this company could have maybe much more easily raised $500 million, if not more.

I don't know what the next catalyst for this company is, so I don't know. Eric, you might be in a better position to know what the news flow is and whether there's another financeable event, but I do think it puts the company in a pretty tough spot.

Eric Schmidt

No, I agree with your views. It's interesting to think about how many billions of dollars that discussion may have cost the company in terms of market value. Unfortunately, there's a third party here, Akeso, which ran the study and probably was responsible for communicating to ASCO and the discussant, and maybe helping her get to a better point.

I don't know where that communication fell apart, but I agree, it was a little bit disingenuous of her to prompt all those criticisms against a seemingly very good data set.

But yeah, we're left with what we have. The next data point is going to be the HARMONi-3 study. This is the global study that everyone's been waiting for. You referenced just that, Graig. The data are coming at year-end, and it's going to be binary.

I think the company wanted to put another $500 million or so in its coffers because it's now running multiple Phase 3 studies in other indications, including nonsquamous lung cancer and colorectal cancer. These studies are going to read out in 2027 and beyond. If this HARMONi-3 study at year-end doesn't go their way, they're going to have to raise a lot of capital to fund these ongoing Phase 3s, probably at a lower valuation. So, it's not ideal from a strategic standpoint.

Paul Matteis

Yeah. I think I'll just comment, too, having had the benefit of doing business development at 2 rather large companies: It's really important for smaller companies to be able to raise money not only to fund their trials, keep the lights on, and keep the staff employed, but also because having cash is a very important strategic asset, especially as you're negotiating with potentially interested partners.

I'm not saying that, in the Summit case, that was a main consideration, but generally speaking, when you see companies raise money, it is obviously to capture some meaningful value inflection and hopefully to extend the cash runway. But many times, too, which is often unsaid, it's really just to be able to have a substantive cash position so that when you're talking to strategics, they aren't there saying, “Well, we know you're not in a good position from a cash perspective, and so we'll dictate terms.”

Usually, if you're the smaller company with ample cash, you can use that as leverage to say something to the degree of, “You know what? Thanks for your interest. We're good on cash. We don't need you. We'll just continue on, and if you want to reengage under better terms, we'll have that conversation.”

I've got my fingers crossed for all biotech companies. Without knowing specifically the Summit story, I hope the data for them from HARMONi-3 are positive. Can I ask a question, guys? I'd be interested—I don't know if any of you cover Tango. They've got this trial that's a combination with Revolution Medicines' pancreatic drug, right? I'd be interested to know how much Tango is seen as somewhat of a threat to the possible end market for the Revolution Medicines drug. It's super interesting.

Graig Suvannavejh

Eric, do you want to comment? I think you cover Tango.

Eric Schmidt

Yeah. For those who are maybe a little bit less aware, the data this week showed that Tango's drug, called TNG462, is a PRMT5 inhibitor. The mutations called MTAP deletions that enable a PRMT5 inhibitor to work are found in about 40% or so of pancreatic cancer patients. So, it's a minority of the market, though a large minority, that the TNG462 drug is directed toward.

All the data that we've seen—well, I shouldn't say all the data; the exciting data that we've seen—is in combination with the Revolution Medicines RAS inhibitor. The most exciting is the combination of daraxonrasib, the multi-RAS inhibitor from Revolution Medicines, with TNG462. That's the data that showed a 90-plus percent response rate, a response that is off the charts and that I don't think anyone would have fathomed days ago, let alone months or years ago. That is just a tremendous result in a cancer where we're used to seeing response rates in the teens or 20s at best.

In terms of the competitive dynamic with Revolution Medicines, it's interesting, right? Revolution Medicines clearly is in the lead with regard to its RAS inhibitors. Daraxonrasib should be approved, I'd hope, almost any day now. As soon as they file it, it should be turned around and ratified, and they're clearly going to have a leadership position in this market.

But there are some other multi-RAS inhibitors in development that, in theory, could be combinable with the PRMT5 class—namely, compounds from AstraZeneca, Astellas, Novartis, and Roche, I believe—so we'll see how this plays out. Obviously, in this case, 1 plus 1 equals 3, and that, in theory, could make for some kind of collaborative or cooperative relationship between Tango and Revolution Medicines.

I'm told the companies have a very good working relationship, and hopefully that will continue. Hopefully, there will be financial incentives for them to continue to work together, because that would be the fastest route to get this combination to patients. There's no doubt that if Tango were to go with any of the other RAS inhibitors, they'd have to take a bit of a pause and restart some development.

Their path forward right now is with daraxonrasib. They're talking about a frontline combination study, and that probably means both companies are going to benefit from longer duration on therapy and joint, combined sales. But I don't know if anyone else has views on this.

Paul Matteis

I don't know much about the Tango story. I do follow the PRMT5 inhibitor space along with you, Eric, but that is incredible data. I also have exposure to the pancreatic cancer space.

From a high-level perspective, without talking too much about the specifics of Tango plus Revolution Medicines, for all of us who've been covering the biopharmaceutical industry for the past 20 years, the advances we're seeing in pancreatic cancer are breathtaking. So, congratulations to all the companies that are working on this. It's just great to see this kind of data for patients.

4. Big Pharma Makes Bigger Bets

Graig Suvannavejh

All right. With that said, we did reference a couple of deals that we would discuss today. There are 3 in particular that we're going to talk about, but there are also a number of partnership deals. Let's start by talking about 2 smaller deals first, and then we'll shift to a pretty sizable deal that we saw this week, and that's GlaxoSmithKline buying Nuvalent.

On the first deal, which we referenced earlier, with Incyte making a splash and buying Star Therapeutics' subsidiary Vega Therapeutics for $2 billion or so in total consideration, Oliver, did you want to lead that, or Eric, did you want to talk about that?

Oliver Barnes

Sure. I can run everyone through the facts of it. In a way, there's a bit of a line you can draw between the Incyte deal and the GSK deal from my very macro, not-in-the-weeds perspective, which is basically new CEOs.

With Incyte, about a year ago, Bill Meury, who's probably pretty well known to the whole VC biotech community, took over as chief executive. He was the chief executive who sold Karuna to BMS, then went to the Blackstone Life Sciences company Anthos, which ended up selling to Novartis. So, he's one of those classic veteran executives, often involved in a lot of deals.

The market perceived his new seat at Incyte as a clear indication that Incyte was going to start doing bigger bolt-on M&A. To date, they focused on business-development deals, like sub-$1 billion. So, this deal for Star, or Star's subsidiary Vega Therapeutics, is basically the same thing. It's up to $2 billion: $1.25 billion upfront in cash and then a further $750 million down the line.

Incyte's main drug is Jakafi, right? It's a JAK drug for blood cancer. What they've basically bought with Star—or with Vega Therapeutics, the subsidiary of Star—is this drug, VGA039, which is a treatment for von Willebrand disease, a common inherited blood disorder. A kind of version of hemophilia is the best way of thinking about it, and it's in Phase 3 trials. It could benefit from an accelerated approval process.

Effectively, right now, the standard of care for von Willebrand disease is a several-times-a-week infusion. This means that the only patients who are ever treated with it tend to be those with the most severe cases—right, a few tens of thousands. What this new Vega drug offers is basically a monthly infusion.

There's a possibility of converting those patients who are doing the multiple-times-a-week infusion and also using it for prophylactic reasons, for prevention. What Incyte effectively sees is potentially a kind of blockbuster drug. I've discussed this a bit on Biotech Hangout before, which is that when you think about a blockbuster drug, the $100 billion-market-cap companies in big pharma are tending to go after multiblockbuster drugs, right? Because that's what they need to fill the hole in their revenues that comes from patent cliffs.

For Incyte, with Jakafi coming off patent as early as 2028, getting high hundreds of millions of dollars in revenue, toward $1 billion in revenue, is a big deal. That's why we often see these midsize drugmakers hunting for these smaller biotech targets increasingly nowadays.

Paul Matteis

Fascinating.

Graig Suvannavejh

I don't know if anyone else wants to chip in.

Paul Matteis

I just want to say shout-out to Dave Gardner, who I'm sure multiple people on this know, who went to industry. We've seen a lot of times people from Wall Street go to industry in certain strategy roles and hope to maybe be more active, or maybe get sort of—I don't know, I'm generalizing—but maybe get a little bit hamstrung by the politics and impediments to actually doing deals and things like that.

And it's cool to see Incyte transacting on a private company that was generating a good deal of buzz in the investment community and seems pretty interesting.

Graig Suvannavejh

Yeah. To add to that, it wasn't just creating buzz. The process was competitive; I think there may have been other bidders around it. Second, they were thinking about an IPO process, right?

I suppose with Dave and Bill, the new CEO, this shows the appetite that Incyte has to go and do deals. I spoke to Bill after the deal was announced, and what he was basically saying was, “You should consider us as the first of several,” right? I imagine they're going to look—hematology is a natural area for them, but they could also look in ophthalmology and oncology. There are obvious adjacencies.

They're not going to do everything, and it generally is probably going to cap out at a few billion dollars, but there are clear adjacencies that they could push into. I think the market has actually responded pretty well to them. The stock's up over the past year, like 50%.

Paul Matteis

Yeah. Anyone who knows Dave and certainly Bill knows they're not wallflowers. These guys are going to be active. Congrats. This is the first somewhat larger deal, at least, that we've seen from the new team.

I have a lot of confidence in this team and its ability to do diligence and hopefully find some good assets.

Graig Suvannavejh

Eric, did you want to mention the J&J–Firefly deal?

Eric Schmidt

You know, I think we've talked a lot about private transactions already. This is another one of similar size and ilk. Maybe the thing that's most interesting to me here, Graig, is that the lead asset J&J is acquiring from Firefly is again a RAS inhibitor.

This is a pathway that's drawing a lot of attention, including from new oncology players like J&J. If you look forward to future M&A and business-development transactions, especially focusing on oncology, there's probably no pathway that's more ripe for deals, acquisitions, and collaborations than RAS inhibition right now.

The thing's on fire, and as we just talked about a few minutes ago, we're seeing better and better clinical results from combinations and all sorts of other players in the field. So, welcome, J&J. I'm sure they won't be the last.

Graig Suvannavejh

Yeah. And I think it's interesting, too, that I wasn't familiar with Firefly before, but that being said, it's got a degrader-based platform technology, and we just saw a whole host of deals in the degrader space, which we'll mention in a little bit. But you marry degraders and RAS inhibition and pancreatic cancer, and I'm sure Firefly was like, “I think we're at the right place at the right time.” So, congratulations to the Firefly team.

Oliver Barnes

Sure. I was all over it, but not just because of the English accent and GSK being a U.K. pharmaceutical company, although it's cool to see them do stuff.

Graig Suvannavejh

Funnily, I was talking with someone after the deal was announced, and they were saying that, when you run the numbers—

Oliver Barnes

On the number of deals they've done, I think GSK comes out as number 4. Number 1 would be Eli Lilly, and then I can't remember who goes after that. It's maybe Merck, then there's one more, and then GSK comes out as 4th.

Most of the deals they've done in the past few years have been small. They've done, you know, like 35Pharma[?], which was a billion-odd-dollar deal. I think one of those is private and one is public. They did Boston Pharmaceuticals[?], too.

But on the whole, the thing that's striking about this for GSK is its size and, in a sense, its ambition in oncology. Let's trace the story back to 2014. GSK did this slightly wacky deal under Andrew Witty where they got out of oncology. They did an asset swap with Novartis, took Novartis's vaccines division—which has helped them build a pretty successful vaccines enterprise—and got rid of their oncology division.

Then Andrew Witty left and Emma Walmsley came in. She spent quite a lot of time getting GSK back into oncology, right? Luke Miels, who was the CCO—the chief commercial officer—for much of that period and is now CEO of GSK as of the beginning of this year, has effectively taken their biggest swing yet in getting them back into oncology.

Nuvalent has several drugs targeting different mutations of non-small cell lung cancer, as I understand it, both of which could get approvals this year. Both are in quite competitive spaces, so there are other drugs that have been commercialized or are going to be commercialized in those areas.

Recently, at ASCO, one of those 2 drugs got some new frontline data, which was perceived by investors as a bit of a setback for Nuvalent. Broadly speaking, I think Nuvalent hasn't really had that many inflection points of late, and it's one of those classic biotechs that has just been sitting there as it approaches its PDUFA dates, waiting for someone to come and buy it.

It's an interesting deal for GSK. Setting aside the asset swap, it's basically their largest deal ever since the company was created at the beginning of the millennium. That's a big thing for a new CEO who's just 6 months into the job, and I'm sure he's telegraphing to the market that this is something we can probably imagine is going to continue.

The reason I think it's an interesting deal—and after it was announced, I spoke to people and got the perspective of some of the bankers and investors—is that I think it's quite smart in a way. They paid $124 a share, which put Nuvalent's equity value at $10-something billion. Its enterprise value, because of the cash on the balance sheet, was around $9.4 billion.

The reason it's a reasonably smart deal is that there's a huge variance in where people—and where analysts—think peak sales lands, because of how competitive the landscape is for these drugs. The most bearish take on Nuvalent is that peak sales land at around $2 billion. The most bullish take puts it at maybe $5–6 billion across its pipeline.

If it lands at $2 billion, that's not great, and they've probably overpaid, but it's not a total disaster. Whereas, if it lands on the more bullish side, it actually ends up being a very good deal for Luke Miels. I think that's the bet.

It's an arbitrage on a company that a lot of other large-cap pharma companies may have passed on, and GSK saw a pretty unique opportunity to take a big swing in oncology. That's where they've done a bunch of their deals recently, including Sierra Oncology. They also did a big collaboration with Hengrui, which included a partnership on several early-stage cancer drugs.

It makes sense. I think it surprised the market, but it makes sense. I'd be interested in your opinions. Maybe I'll just add that it is surprising that GSK is number 4 on that list of companies.

Graig Suvannavejh

I need to verify this list, by the way. But, yeah—

Oliver Barnes

I don't think that's the impression people get. But if the stats are the stats and the numbers are the numbers, I'm not in a position to opine on where GSK's needs are.

That being said, it is interesting to see how that company has evolved over the past 2 decades or so. Are you in? Are you out? If you remember, they brought in Hal Barron some time ago, and then he left. Obviously, there was a big movement to upgrade the R&D organization, and then I think there was some transition. But here we are again. Certainly a big, bold move by GSK.

I don't know, Paul or Eric—any comments you might have?

Paul Matteis

The only thing I would comment on is their role in oncology, or their place in oncology. As Oliver said, they got out of the business very vocally in 2014, but just a few years later—I think it was 2018 or 2019—they bought Tesaro.

Eric Schmidt

And then, a few years after that, in the early 2020s, they bought Sierra Oncology. Then there was another deal just last year, IDRx. So they've kind of been dabbling with smaller oncology deals for the last 10 years after expressly stating they're not in oncology.

I guess with Nuvalent, they're fully in, right? You can't do a $10 billion transaction and not be in oncology. We'll see how this plays out, but the Tesaro deal didn't work out for them. The Sierra deal was a much smaller transaction. IDRx was development-stage. They probably need more in oncology if they're going to be a real player.

Graig Suvannavejh

We have a lot to get through, and we're probably not going to get through all of it.

Paul Matteis

But Graig, can I ask Oliver about this leakage?

5. M&A Leaks Follow Human Nature

Graig Suvannavejh

Yeah, definitely go there as well. I think there's some controversy out there about M&A getting leaked and what the motivations are, but Oliver, you're in the thick of things. Do you want to opine for a couple of minutes there?

Oliver Barnes

Sure. I think it's kind of like how the sausage is made, or whatever. I've been following biotech for a few years now, and I cover deals across sectors. I see the dynamics and how they work—media leaks in industrials, oil and gas, not just in biotech. In biotech, I think you tend to see more of them, and sometimes more interest in them.

I've often chalked that up to a couple of things: a lot of retail investors follow the space, right? M&A tends to happen at quite a high premium, so there are lots of incentives to work out how to read the tea leaves on what's going on with M&A and the chatter and gossip in the market. I'm on X, or Twitter, all the time, right? I see the excitement—sometimes misfounded—that a lot of the retail investor community in biotech has over certain M&A leaks.

There are a lot of publications where you read what they publish, and it's nonsense. They have no verification process; they just publish what they hear. But because they may have a 1-in-10 or 2-in-10 hit rate, people still pay a bit of attention to them. Obviously, I'm not talking about the FT, the Journal, or Bloomberg. I'm talking about other, random ones. They're generally not worth your time.

It's interesting, right? Most people, particularly VCs and executives at companies, tend to assume that there's a strategic logic to a lot of the leaks. On the whole, there isn't really. Sometimes deal reporting and putting something out can put companies in play, help get a deal over the line, or make it a more competitive process. That does occasionally happen, and sometimes, in my role, I can end up being a conduit for that—whatever strategic leak—but on the whole, it's much more to do with the reporters. It's to do with me, the relationships I have, who I spend time with, and the fact that I spend a lot of time in biotech.

Generally, I kind of like biotech as a type of M&A because it's one of those areas where I'm not an expert, but I can see the chess moves now. Without any inside information, I can see the chess moves of what certain companies would and wouldn't do, in a way that's slightly murkier with other industries.

We were just talking about the GSK–Nuvalent deal, for instance. The idea that a new CEO, freshly empowered to do deals at a company that's been spending quite a lot of its business-development dollars on oncology, would take a big swing at an oncology company isn't that surprising. On the flip side, you look at Nuvalent and you're like, oh, a company that's had most of its inflection points with regard to data, is awaiting 2 PDUFA dates, and is about to launch—which is the sweet spot for all biopharma acquisitions, right? Large-cap pharma groups are often better at the launch process than biotechs. It makes a lot of sense that they would want to sell, right?

A lot of the work that I do is clue work, in a way, and that's not totally dissimilar, I think, to a lot of the advisers. People who are inside a deal and working on a deal, and people who are outside a deal, want to work out what's going on in the industry. Deal reporters play a role in that, right? We're trying to ambulance-chase a bit and work out what's going on here. People are hearing chatter about this company.

My health warning for whoever's listening from the retail investment community is this: there are publications to pay attention to when they report on M&A, whether it's described as early stage or it's happening tomorrow or in a few days. And then there are other publications not to pay attention to, because I know a lot of my peers, and I know the ones who have very rigorous checks and balances about when they publish something. We would never publish something unless we absolutely know it to be the case, and that tends to differ at other places.

I'm not talking about Bloomberg and the Journal. They're also A1. They would publish stuff only when they know it's the case. But I just know that in biotech there's a lot of attention paid to these slightly random publications, and maybe I would encourage people to pay slightly less attention to them. I don't know if I'm putting shade on people. [laughter]

Graig Suvannavejh

It's always fascinating to hear the rumors, whether they're true or not, and then see the deals get announced when they do, and see the sources. As always, we appreciate high-quality work like the work that you do, Oliver. Thanks for that fascinating perspective.

Oliver, I know we're running tight, but this trend that we're seeing, where companies, or maybe board members, or even investment banks, are leaking information the night before a transaction: frequently, we'll wake up and see something on Sunday night that says DLX[?] is going to get done, and we wake up Monday morning and it's on the tape. Obviously, this has been signed, sealed, and negotiated for days on end. What's the point of leaking something less than 24 hours before an announcement? How do you guys feel about that?

Oliver Barnes

I mean, for the average investor, it has way less value, doesn't it? It's simple. For example, last year we broke the Novartis–Avidity deal when they were in talks. I think the deal printed in October, and I think we broke that they were in talks in August or something like that. For your arbitrage hedge fund, that kind of information has more value, right? It's something that gives them a long lead time, and they can ask, “Do I trust this reporter? Does this make sense?”

With regard to the stuff that comes the night before, sometimes companies have a complex deal that they want to make sure the market really understands. Working with someone and explaining that can be a good way of setting out their stall. But on the whole, as I said, most of these things don't have a strategic logic to them. It's more to do with me or my peers, the energy we put toward things, and trying to work them out.

Generally, if you want a simple answer, it's this: the closer you get to a deal being announced, the more people know about it, so the more likely it's going to get out there, right? If we think about GSK–Nuvalent, I don't know when the talks kicked off, but whenever they did, the likelihood that anyone who had a sliver of that information was going to talk about it two months ago, when it was probably still in a delicate position, is absolutely zero.

Once things are hours or days away from getting signed, and there's more confidence about it and more people know about it, just like basic human nature, people tend to be a little bit more loose-lipped about it. But most of the time, there's no strategy to it. It's really just the energy and persistence of my peers or myself in trying to dig this information out.

6. Biotech Shifts From Deals To Data

Graig Suvannavejh

Thanks, Oliver, for that. Again, we've probably got a few more minutes left. I just want to comment on 3 deals that we saw this past week that were more BD transactions—partnerships or licensing deals.

Novartis renewed and expanded its collaboration with private company Orionis Biosciences, which has a molecular glue-based platform, for up to $1.4 billion in biobucks, as I like to call them. We also saw Eli Lilly in-license a gamma-secretase modulator candidate for Alzheimer's for $1 billion-plus in biobucks, but, interestingly, only a $10 million upfront payment. That was from a Swedish biotech company called AlzeCure Pharma.

Lastly, in a much smaller deal in terms of the financials involved, San Francisco-based Corvus Pharmaceuticals participated in an investment in its Chinese biotech or pharmaceutical partner, Angel Pharmaceuticals, which is actually a company that Corvus specifically helped to create to help develop its drugs in China.

But this was for further funding for Soquelitinib, which is a novel ITK inhibitor for both oncology and immune disorders. Let’s talk about some data sets. In particular, I know Paul wanted to talk about some Novartis news with one of their candidates in FSHD. Paul, can you summarize?

Paul Matteis

Actually, maybe Eric, you want to kick it off? You covered Avidity, and I just think there’s an interesting conversation with FSHD and DM1—a number of these indications and how we should be thinking about the bottom line. But you were the Avidity expert. Really, just quick, because I know you want to get to the fun stuff.

Eric Schmidt

Yeah, interesting data coming out of Novartis are from a phase 1/2 study, but they have been calling it a pivotal study, or at least a potentially pivotal study. What they showed in FSHD, a rare muscle disease, is that you can essentially hit the target. The target is DUX4, and their biomarkers are turned on by DUX4 activation. DUX4 is a transcription factor, and one of the biomarkers, KHDC1L—I butchered that name, I’m sorry—is a blood-borne biomarker that was reduced, as you would have expected it to be. They also showed some reductions in creatine kinase, a biomarker of muscle destruction.

The data look good, and I think what you’re going to get, Paul, is that if these data were still in the hands of Avidity, they would have taken them to the FDA and probably aggressively tried to go for accelerated approval. There was a quote in the Novartis press release saying that they’re going to have a conversation with regulatory authorities, but obviously Novartis is pulling back a little bit from that gas pedal and maybe being a little less aggressive than a smaller company with a lot more riding on this might be.

Paul Matteis

Yeah. I cover a small handful of these genetic-medicine companies where there’s a trade or an investment thesis around regulatory flexibility. There’s been a lot of reporting, or anecdotes from companies, that in light of Marks leaving, the FDA has been meeting with people in the space and has been receptive to trying to get back on track with flexibility. Obviously, the dynamic of flexibility is super-duper subjective—what that actually means—but I guess I don’t know how you feel.

I’m hopeful that, obviously, Avidity didn’t have a setback in the past year, but some of the rare-disease companies that have had setbacks on the regulatory side might still get their day in court and may get kind of a replay-like situation. Maybe it’ll take until we have a permanent FDA head or permanent leadership in place, but it feels like the scale is tilting back. I don’t know—I thought the Avidity data seemed pretty convincing. The drug is doing something, wouldn’t you think?

Eric Schmidt

I agree. There’s a huge unmet need here. This drug should be approved, in my opinion. I hope they can bring it over the goal line. But other than being someone optimistic like you, Paul, we still lack some data points at the FDA to see how things are going.

Paul Matteis

Totally.

Graig Suvannavejh

We’ve got a few minutes left, but Paul, I know you had some interesting things you wanted to talk about in terms of the gene-therapy landscape. Maybe as we look to wrap this up, I’ll have you talk about 2 news items of the week.

7. Gene Therapy Faces Its Next Test

Paul Matteis

Yeah, sure. Neurogene earlier this week announced that they completed dosing in their pivotal study for NGN-401. It’s a gene-replacement therapy for Rett syndrome, which is this terrible neurodevelopmental disease. It’s important news for 2 reasons. One is that, in their phase 1/2 study at a higher dose, they had a severe inflammatory event that ended up in a patient death. I think there had been this lingering question as to whether or not this was a risk at the lower dose in their pivotal study.

As it turns out, the study is not over—they’ll still be following these patients—but the perception is that if these events happen, they would happen early, and they didn’t. That’s very encouraging. They overenrolled the study. Neurogene is one of 2 companies in this space developing AAV9-based therapies for this, and both will have pivotal data next year. This will be another test, assuming these studies work—or, I guess, if these studies work—of regulatory flexibility. Both companies have sign-off on these single-arm studies looking at developmental milestones.

And then, Graig, you pointed out that Sensorion is discontinuing the otoferlin program in light of Regeneron getting to market first and giving it away for free. There’s a very interesting conversation in the gene-therapy space in hearing. We had a lot more buzz here about 5 years ago. There was Akouos, Decibel, and I’m sure there’s still tremendous potential, and people much smarter than me will figure it out.

We’ve had this success in otoferlin deficiency, where these drugs are amazing, right? Patients potentially don’t need cochlear implants. One thing that one of the CEOs of these companies said to me, that I’d forgotten, is that otoferlin is the first, most obvious target because it’s one of the only genetic conditions of hearing loss where all of the inner-ear biology is preserved at birth. There’s the potential to rescue the pathology by simply delivering the gene, whereas in others there are in utero changes in the ear and in how these cells might communicate with each other. As a result, the window for intervention might not be as wide. It’s a space to monitor. It’s unfortunate for Sensorion, and they have another program that looks interesting but might be higher risk.

Graig Suvannavejh

Yeah, I think this space is fascinating. There are lots of different gene-therapy approaches. It’s great insight you have on this particular mechanism and why it makes the most sense.

I just think it’s interesting that Sensorion, which probably spent a fair amount of time and resources developing something where clearly there’s an unmet medical need, just decided to give up, given that someone beat them to the punch and was going to give it away for free. That’s a great service by Regeneron, but I guess that’s how quickly the business environment can move.

Let’s just hope there are still going to be plenty of good options for patients who unfortunately go deaf, whether it’s congenital or just from some trauma. I thought it was a very interesting development.