Episode 200 - October 23, 2026
Daphne ZoharBrad LoncarChris GarabedianSam FazeliEric SchmidtJosh SchimmerMatt GlineAli Mortazavi
- Moderna’s cancer-vaccine selloff followed a valuation that “needed absolute perfection.” Sam Fazeli contrasts a market cap approaching $100 billion with roughly $2.2–2.3 billion in annual revenue and established melanoma competition. Brad Loncar disputes the disappointment narrative: the stock had traded at $150 for a month after the success announcement and, after the selloff, remained about $50 above that level; the data made the medical and commercial case “a stronger yes.”
- Unverified position-unwind theories may help explain biotech’s weak tape, but the panel cannot establish them as fact. Matt Gline describes shorts covering Moderna while selling longs, followed by benchmark-driven buying that compounded the divergence. Loncar adds that XBI’s rise from 108 to 150 conflicts with the gloom: expiring acquisition bets can leave options holders losing money during a strong equity year and “poison” the discussion.
- The panel sees a difficult quarter within a stronger financing and acquisition year. Chris Garabedian argues that the optimistic Endpoints survey largely captured conditions before the latest deterioration. Daphne Zohar says dealmaking is “not pencils down,” citing Stifel’s assessment that 2026 could rank second only to 2019 for biotech M&A; falling share prices can nevertheless separate boards’ expectations from buyers’ acceptable premiums.
- Silence’s announced 1.3 billion cash sale follows a long scientific and corporate reset. Ali Mortazavi recounts joining a £5 million AIM-listed company, abandoning an oncology program he distrusted, rebuilding around GalNAc delivery, and watching later management redirect TMPRSS6 development into PV. He calls that indication switch “one of the best biotech corporate decisions ever made”; Merck KGaA’s offer carried an approximately 130% premium.
- Tango’s pancreatic-cancer results provide the episode’s clearest example of strong clinical news meeting a falling share price. Eric Schmidt highlights an 82% response rate and 88% non-progression rate at nine months in heavily pretreated patients receiving its PRMT5 inhibitor. The opportunity concerns an MTAP-deleted subset, perhaps 30–40% of patients; he calls the results “game-changing” and attributes the stock decline entirely to selling the news.
- China licensing remains active while proposed Treasury restrictions could disadvantage venture-backed company creation. Garabedian cites Roche’s 400 million upfront deal with 15 billion in headline “biobucks” and Gilead’s 1.3 billion upfront oral-peptide IL-23 transaction. His concern is conditional: rules that burden venture investment more than direct licensing could give multinational pharma another reason to “bypass biotech.”
- The 2031 debate centers on delivery, commercial execution, and an unresolved AI timetable. Schmidt hopes genetic medicines become commercially successful, first with AATD and Beam’s program; Loncar favors brain shuttles and degraders. Garabedian expects a recognizable industry with AI falling short of its current hype, while Mortazavi argues hypothesis generation and outsourced synthesis could shift value toward clinical operations: “do the trial on time, right patient population, get the result.”
1. Moderna’s valuation reset obscures a stronger clinical story
Fazeli’s starting point is the valuation: Moderna approached $100 billion, roughly $10 billion above Sanofi, against expected annual revenue of $2.2–2.3 billion. The cancer-vaccine expectations embedded in that price were enormous. “You needed absolute perfection,” he says, while questioning whether investors were searching for fundamental explanations for what might simply be “traveling and arriving.”
The competitive objection was already known, Fazeli argues. NADINA’s two preoperative cycles of ipilimumab and nivolumab produced better recurrence-risk reduction than the vaccine trial, in his comparison. The regimen is included in US guidelines and is becoming reimbursed in Europe, even though Bristol Myers Squibb has never filed it. That existing competition suddenly became a profit-taking rationale after Moderna’s roughly 200–400% rise, depending on the starting point.
Loncar’s pushback is worth keeping: “I almost dispute the context of the question.” Moderna traded around $150 for a month after the August success announcement; the subsequent $250 price was an overheated reference point. After the selloff, it remained about $50 and tens of billions of dollars above the earlier baseline. Knowing the actual data made medical success and substantial sales “a stronger yes.”
Fazeli leaves the broader vaccine opportunity open. Kidney-cancer results are coming, while a pancreatic-cancer poster showed T-cell induction in 19 of 20 patients despite that being a “cold tumor.” He explicitly stops short of calling this “a big, big win.” The observation supplies another angle on the platform, rather than establishing a clinical outcome.
2. Positioning and options can overwhelm the fundamental discussion
Schimmer describes a “bearish biotech tape,” partly masked by Moderna. Schmidt adds that diagnostic companies in the XBI are also meaningfully outperforming, masking the underlying weakness. He lists interest rates, upcoming midterms, AI concerns, lack of M&A, and negative catalysts as possible explanations. He sees generalists rotating out of biotech and, to some extent, tech, and into Moderna and a couple of AI names. The XBI is in an unusually challenging setup, but fundamentals still seem strong; he says the sector is well positioned—more profitable, revenue-generating, and appealing to generalists—provided the midterms don’t revive drug-pricing concerns.
Gline carefully labels the widely discussed squeeze explanation an “elaborate conspiracy theory,” whose truth he does not know. Moderna shorts were allegedly forced to reduce both short and long exposure, selling good stocks and buying more Moderna and other names they were short; that drove prices further apart. Moderna’s growing benchmark weight then prompted long-only asset managers to buy it, driving the price up further. His complaint is that headlines instead imply prices continuously reflect considered assessments of clinical data. Such technical noise adds another difficulty for operators.
Schmidt says sector-wide “degrossing” is being discussed this way for the first time in his experience. Expanding, neutral-weighted platform funds may add little net capital while generating large swings. An unidentified co-host extends the account: heavily shorted Iovance and Twist rose as pod funds’ longs fell, and structural issues may now rival fundamentals. That speaker says they don’t know whether the explanation is true, but it “feels like” the best explanation for the valuation swings.
Loncar adds a different distortion: “too many people own options and not stocks.” XBI began the year at 108 and reached 150, yet normal pauses become crises for holders of decaying options. Abivax illustrates the problem: investors betting on a particular acquisition month can lose everything while owning exposure to an exceptionally successful stock. Those incentives “poison” the discussion because prices must keep rising on the holder’s timetable.
3. Strong annual activity coexists with a difficult quarter
Garabedian reconciles Endpoints’ optimistic sentiment readings with today’s difficult market through survey timing. Every constituency was well above the index’s 100 level, but fieldwork ran from mid-August through September 15, reflecting a strong Q2 for M&A, IPOs, and XBI. He notes that the Fed raised interest rates immediately afterward. Q3 subsequently brought weaker M&A, flat XBI performance, and questions about whether the IPO window remained meaningfully open.
His prediction is a return to a healthy market, rather than the beginning of another prolonged downturn. “Modulate our expectations” quarter to quarter, he urges: reverse-merger PIPEs, IPOs, valuations, and acquisitions still make this one of biotech’s best years in a long time. A co-host who had just attended Forbion’s 20th-anniversary gathering in Amsterdam adds its 2.3 billion raise and an engaged LP audience as evidence of interest in science, while noting that wars, energy issues, tariffs, and MFN create external volatility.
Zohar says bankers and senior pharma executives continue working on deals, including a couple of potentially substantial announcements: it is “not pencils down by any means.” Her caveat is that falling share prices can leave boards seeking premiums buyers will not pay. She cites Stifel’s projection that 2026 could become biotech’s second-most-active M&A year, behind 2019’s two mega-mergers, with an unprecedented patent cliff sustaining pipeline demand.
4. Silence’s sale followed painful decisions and a decisive indication switch
Mortazavi joined Silence around mid-2012 at a £5 million AIM market capitalization, betting on foundational siRNA-chemistry IP. Alnylam’s human proof of concept with patisiran, and the roughly $600 million market-cap increase he recalls that day, supplied fortunate validation. By 2015, Silence raised £50 million, an astonishing UK financing in his telling. His advice about the journey: “Don’t try this at home, kids.”
His family’s experience of leukemia treatment and stem-cell transplantation sharpened his objection to advancing Atu027, a pancreatic-cancer program already in Phase Ib. Despite preparations for manufacturing and Phase II, he stopped it: patients deserved the best chance. Silence then benchmarked Alnylam’s GalNAc delivery, rejected its own lipid-nanoparticle approach as unworkable, and rebuilt around LPA and TMPRSS6. The share-price collapse made this “the ultimate game of Snakes and Ladders.”
To extend runway, Silence bought 10% of Arrowhead in 2016 after its shares fell roughly 90% and traded at a 70% discount to cash. Mortazavi believed Arrowhead’s GalNAc technology was a couple of years ahead. Selling at a profit funded survival, although he reckons retaining the stake would have made it worth $900 million within around four or five months. “Would I do that today? I’m not sure.”
Mortazavi credits Laura Rocco Alonso, Ian Ross, and subsequent management, especially whoever redirected TMPRSS6 from MDS and beta thalassemia into PV. That was “one of the best biotech corporate decisions ever made,” he says, and probably explains most of Merck KGaA’s announced 1.3 billion cash acquisition, at approximately a 130% premium. His account ends with a “team effort,” rather than a single-founder victory.
5. Execution drives progress while public CEOs shape the industry’s reputation
Mortazavi notes that Silence had no CEO in the year before the sale and calls platform biotechs “hedge funds in disguise.” Gline says a CEO could be dispensable: biotech is a “game of inches” driven by people close to the work. His “wood chipper” comment came in a STAT discussion with Adam Feuerstein about AI’s eventual impact on pharma; his point was how hard development is. He cited a viral report of a weak scorpion-antivenom binder and a post saying an actual treatment could still be ten years away. Garabedian framed the metaphor as a warning to younger tech-bio entrants not to assume drug development will be easy.
Gline praises Dave Ricks’ direct participation on Twitter, while allowing that he could be wrong in thinking Ricks writes the posts himself. Loncar says he can confirm that and that neither lawyers nor communications staff review them. His Ricks interview drew two dominant reactions: he seemed nice and knew the technical material. Ten to twenty minutes of video made an executive people knew by title feel like a person.
Loncar calls compliance excuses for avoiding public engagement “total nonsense” and wants more executives participating. Another co-host agrees that direct engagement can humanize pharma, but calls social media a minefield, including legal considerations and the risk of being dragged into exchanges. The point is practical: show that pharma leaders are ordinary people who care about patients, counterbalancing advertising and negative headlines.
Gline estimates Abivax chatter on Twitter outpaces discussion in his private investor settings “100 to 1.” He calls its IBD data “unquestionably super impressive,” but focuses on the unresolved launch question if acquisition never comes. Management, pharma buyers, and public commentators may assess independent commercialization very differently. Ricks’ joke about tracked pharma jets captured how acquisition speculation dominates that public conversation.
6. Tango’s pancreatic-cancer results stand out despite the share-price reaction
Schmidt highlights Tango’s PRMT5 inhibitor in very refractory third- and fourth-line pancreatic cancer: an 82% response rate and 88% non-progression rate at nine months. The relevant MTAP-deleted population is a subset, perhaps 30–40% of patients. He calls this “some of the best data I’ve ever seen” in his years covering oncology and a massive potential change for patients with that mutation.
Shares nevertheless fell. Schmidt attributes that entirely to “sell on the news,” connecting the reaction to the earlier discussion of market dysfunction. He considers it a “short-term blip” within a positive long-term trajectory.
7. China licensing could strengthen pharma’s advantage over venture formation
Garabedian cites Roche’s China deal at 400 million upfront and 15 billion in “biobucks,” alongside rationalization of its earlier pipeline and emphasis on Phase III assets. Gilead announced 1.3 billion upfront for an oral-peptide IL-23 drug; Lilly also licensed oral-delivery technology. His point is the continuing intensity of pharma’s direct China activity, despite the surrounding policy uncertainty.
The proposed Treasury language, still subject to public input, appears more punitive toward venture investment and China-derived new-company creation than direct pharma licensing, Garabedian argues. That asymmetry could advantage multinational buyers such as Roche and Novartis. The investment question remains open: will pharma “bypass biotech” and source directly from China, reducing its reliance on acquiring US companies? The eventual details matter.
8. The Sabatini discussion centers on reputational damage before disputes conclude
Garabedian reports a $6 million defamation judgment for Sabatini against Knouse after institutional claims were dismissed on all sides. He says Knouse plans to countersue and appeal, so the dispute remains unresolved: “There are no winners in this.” Garabedian also says Sabatini was recruited by a female NYU faculty member, but public feedback was so strong that the move did not happen. His reason for revisiting the story is that audiences often retain the original headline without following subsequent proceedings.
Zohar recalls Ram Sasisekharan as another case in which, in her account, damaging accusations proved untrue. She urges institutions to be careful about public statements before allegations are established, given reputations built over decades. Garabedian extends the caution to listeners: avoid quick conclusions and retain the principle of “innocent until proven guilty.”
9. The next cycle’s bets combine commercial discipline with new delivery technologies
Schimmer’s biggest change is biotech offering generalists real profitability and bottom-line growth, helped by higher launch prices; Gline likewise celebrates successful independent launches. Garabedian highlights replacement capital from Forbion, Catalio, and corporate venture investors as crossover financing receded. He also sees broader acquisition participation and therapeutic coverage, plus healthier cost discipline through leaner teams, fractional executives, and outsourcing.
Schmidt is surprised by the speed of the asset-centric shift. Five years ago, platforms and internal research dominated discussion; now, among drug-focused companies, he sees “almost none” doing truly innovative in-house research, with molecules sourced from pharma or China. His forward hope is commercially successful genetic medicine through better delivery, cost, convenience, safety, and efficacy, first with AATD and Beam’s program.
Fazeli expected COVID to encourage anti-infective investment; it went “completely the opposite direction.” For 2031, he hopes for progress in difficult cancers, including GBM, and neurological disease. Loncar singles out brain shuttles for more efficient brain delivery and degraders as a “whole new mega class of medicines.” Kymera’s STAT6 program excites him, but his bet spans the modality.
Garabedian expects 2031 biotech to remain recognizable, with AI not fully meeting current hype; Gline jokes it will still be “about to change biotech.” Mortazavi’s competing vision is living-room GalNAc-siRNA design, Claude or ChatGPT target selection, and connection to WuXi in China. If hypotheses become abundant, he thinks clinical operations become the key asset: “do the trial on time, right patient population, get the result.”
Full transcript
I’m Daphne Zohar, and my co-hosts today are Matt Gline, Eric Schmidt, Chris Garabedian, Brad Loncar, Sam Fazeli, and Josh Schimmer. We’re also joined by special guest Ali Mortazavi, former CEO of Silence Therapeutics, which was in the news this week.
Today is the 200th recorded episode of Biotech Hangout. The first recorded episode was five years ago, in December 2021, with Chris, Brad, and me hosting. Looking back on that day, John Maraganore joined the show after announcing his transition from Alnylam, and we had Damien Garde and Adam Feuerstein of STAT talking through the reporting on Biogen’s Aduhelm, which was one of the big stories of the year.
But that actually wasn’t our first episode. Biotech Hangout, which was formerly on Clubhouse, began as a closed-door session in January 2021 after the first virtual J.P. Morgan conference. I don’t think I was at that one, but I joined soon after. Since then, we’ve had more than 60 news-making guests, and our top episodes have had more than 15,000 listeners tune in across platforms.
Hangout is basically the watercooler for what the industry is talking about and thinking about. What our listeners may not know is that it’s entirely unscripted. We schedule the hosts and then agree on topics a few days before the show. Our hosts prep their own topics, but it wouldn’t be possible without Shannon Costello and Daniella Spector, who do everything before, during, and after to make sure the show runs smoothly and the episodes are available to everyone.
We’re going to go around quickly with some thoughts on Hangout, what makes it unique, and what you’re hearing from listeners. I’ll start with my Hangout co-founders, Chris and Brad. Chris, start with you.
Yeah, great. Well, Daphne, congratulations to you as well for taking that initial idea on Clubhouse, which was a little bit more of a party line. People could come on and ask questions. It was a little bit of a free-for-all. That was kind of the Clubhouse format.
When you moved it over to Twitter, now X Spaces, you made the really good decision to broaden the co-hosts, right? Have a rotating group of folks who could talk about any topics, still have guests on occasion, like Ali today. It’s amazing that we’ve been running strong for five-plus years.
It does take a lot of work. I think when Brad and I took a little bit of a back seat from being involved week in and week out, it was because it was a lot of work and a big commitment. Shout-out to Brad, who started BiotechTV. I have my BioVenture Voices podcast, and we’ve all amplified these social media vehicles in ways to help the industry.
It’s really fun to be part of this milestone episode. I’d love to hear from Brad.
Yeah. Congratulations to everyone. It’s cool to see how far it’s come. I travel all the time, and people come up to me at conferences and medical meetings saying that they listen to this and appreciate it. I hear that constantly.
The most important thing is that a lot of people listen to it. It’s become both an educational and a very important business tool, and people really appreciate it. I think that’s the key to success, of course. I’m glad to see that it’s contributing as a true service to the biotech industry.
Yeah, I’ll just add, Daphne, that we all know and follow the news pretty closely—the co-hosts and a lot of others. But what I think we’re really trying to do is reach people who are earlier in their careers and want to learn more about the hot topics. What should they be paying attention to? What’s relevant, as we see it, as longstanding, experienced operators, bankers, and the like?
The more we can raise all boats with knowledge and awareness of the issues at hand, hopefully the better it makes our whole industry. People have a resource like this, and like a lot of other media outlets, to keep everybody on a level playing field and help them understand the core data readouts, regulatory issues, and policy matters we should be paying attention to as an industry.
Great. We’ll come back to everyone at the end and talk about how our industry has evolved over the last five years. One thing that hasn’t changed is the outsized impact of Moderna on industry sentiment. Back then, it was a household name because of COVID. In recent weeks, Moderna’s cancer vaccine data prompted tweets from the likes of Elon Musk, a short squeeze that had a broad impact on biotech stocks, and then yesterday’s leak.
Sam, before the leak, you commented that Moderna’s market cap was $10 billion higher than Sanofi’s. Tell us a little about what’s happened since.
I looked at the market cap a couple of days ago, before getting ready and warming up for ESMO, where I am. I think Josh is here, and I know Eric is somewhere in the area as well. The market cap was just shy of $100 billion. That’s a big number for any biotech company. There are some great biotech companies with market caps like that and above, of course, like Amgen and Vertex.
The comparison is a bit weird because those are large pharmaceutical companies. Sanofi was around $90 billion; I looked at GSK, too. We were sitting here with revenue of, what, $2.2 billion, $2.3 billion this year. The amount of hope the market has pumped into this story for the cancer vaccine is incredible. I don’t know what multiple of sales people look for, but it was looking pretty strong.
Then, of course, I landed here last night, and the news broke with the leak. At first, we all thought it might not be right or might be random. Then I quickly talked to some of my contacts, and they all said, “We’ve known for a while that it was a hazard ratio of such-and-such.” It’s been quite an interesting ride with this story. Over to you, Daphne.
Why do you think it dropped so much?
I’m still discussing this with investors. I’m sure Eric has points on this, and I’m sure Brad’s held a lot. Let’s start with the valuation. It was getting to a point where you needed absolute perfection.
I’ve heard a lot of reasons. I’m worried that people are looking for reasons to explain the drop other than traveling and arriving, which is a really boring thing to say when it comes to the stock market. It just sounds like you’re throwing your hands up in the air. But the reality is, it suddenly dawned on people—something we’d been going on about for weeks, months—that there are regimens for treating early melanoma, meaning neoadjuvant, or presurgery treatment.
In particular, there’s one called NADINA, which uses ipilimumab and nivolumab, or Yervoy and Opdivo. Two cycles, and you’ve got a better reduction in the risk of disease recurrence than you see in this trial. That’s not new. We’ve known that. It’s a regimen that is included in guidelines in the U.S. It’s becoming reimbursed in Europe, even though Bristol Myers Squibb has never filed it.
That’s not new, so why did people suddenly start clutching onto this? I think it’s because everybody was thinking, “Okay, so I’ve got my data. What do I do now?” The rubber has hit the road. Now folks are looking for kidney cancer data coming up, and we just had some pancreatic cancer data in a poster. ESMO somehow magically put all the posters out today, so that’s ruined all our dinner plans.
In that pancreatic cancer study, 19 out of 20 patients showed an induction of T cells. It’s supposed to be a cold tumor, right? There are angles here, and we can talk about this more. I’m not saying that’s a big, big win. I think all that’s gone on here is people have tried to find a reason to take profit on something that’s gone up, I don’t know, 200%, 300%, 400%, depending on where you measure it from.
Mm-hmm.
Yeah, I would jump in and say, your question, Daphne—why did it fall so much? I almost dispute the context of the question and the way it was reported yesterday. That’s how it was reported everywhere yesterday: “Moderna falls.” I think one news organization even said, “Moderna crashes after data comes out.”
But when this news came out in mid-August that the trial succeeded, it traded at $150 for an entire month. So where it’s trading on any given day, and the fact that it went up to $250 the day before this news came out, is almost irrelevant. If you think of it in the context of it trading $50 higher and being tens of billions of dollars higher than before, when we knew the magnitude of the success, then this is clearly above what people thought this could do.
If you take a step back and look at it through a wider lens, as opposed to looking at what it was trading at the day before, clearly the stock got ahead of itself in the day trading it was doing. But in the context of whether this is a medical success and whether this is going to be a big seller for the companies, now that we know the data, the answer is a stronger yes than it was 2 months ago, when we knew this was some kind of success to begin with.
It really bothers me how the world, our industry, and the media report on these things. If you weren’t paying attention, you would have read this news yesterday and thought, “Wow, what a disappointment. The stock crashed,” or something. It couldn’t be farther from that. Are you looking at it from where the stock was trading yesterday, or in the context of the bigger picture of what’s going on here?
Yeah. One of the things I heard was “sell the news,” and I think we’ve seen that in other cases. I’d love to hear from Josh and Eric. What do you think is going on with this market right now?
1. Biotech’s Bearish Market Tape
It’s a bearish biotech tape. I think it’s been a little bit masked by the performance of Moderna.
Some diagnostic companies in the XBI are also meaningfully outperforming and masking the true bearish nature of the tape. You’ve heard tons of different explanations as to why things have rolled over: interest rates, upcoming midterms, some threat from AI, lack of M&A, or a string of negative catalysts. There are all sorts of possible explanations to attribute it to.
Overall, it suggests that generalists have rotated out of biotech and, to some extent, tech. They’ve also rotated into Moderna and a couple of AI names. It’s a unique setup for the XBI, but certainly a tape that feels like one of the most challenging bear tapes we’ve seen in a while: risk-off, buyers’ strikes, et cetera. Underneath it all, the fundamentals still seem really strong.
As long as the midterms don’t uncover more questions, concerns, and political rhetoric around drug pricing, the sector itself is incredibly well positioned: increasingly profitable, increasingly revenue-generating, and increasingly appealing to the things generalists really care about, which are profitability and growth.
Mm-hmm. Chris, I want to come to you about the Endpoints Biopharma Sentiment Index. But before I do, I want to hear from Matt. He had a really great quote, which I think reflects a lot of the industry sentiment: biotech is like a wood chipper that eats your soul, or something like that. Matt, can you talk a little bit about that? You also had some feedback for investors.
Thanks, Daphne. Can you hear me okay?
Yes.
Great. I got a bunch of wellness checks after that quote. People were like, “Is he doing okay? He sounds kind of down.” Look, you succeed in this industry, and we’ve had a tremendous run at Roivant over the last 12 to 18 months. One of the things that stands out is that you feel like you’ve overcome pretty long odds, and you look around at everyone else and at your own future, and you’re like, “Yeah, it’s a tough business.”
The specific context of that quote: I was at a STAT event with Adam Feuerstein, and we were talking about AI and how I thought Dario or Anthropic would eventually impact pharma. Apropos of nothing, there was this viral thing where a research firm found a weak binder for scorpion antivenom and was talking it up. There was a post about how it’s 10 years from this to an actual scorpion antivenom. I think that’s sort of the point, right? You live in this industry and realize it’s just really hard to get anything done. That was the nature of the quote, and it really did seem to strike a chord.
I think a lot of people in biotech feel like our industry is a long-odds kind of industry. It’s fun when it works, but it’s tough when it doesn’t. From an investor’s point of view, listening to the conversation about Moderna and Brad’s commentary was interesting. You asked at the beginning about reflections on Hangout. I think one thing that’s interesting is that Hangout is an open-door space in an industry with a lot of closed-door spaces, and a place where you can hear from people who aren’t public.
If I go to investor conferences, there’s an elaborate conspiracy theory about what’s happened in the last 2 months. A bunch of shorts got blown up when Moderna traded up. Those firms had to significantly reduce both their long and short exposure. They sold “good stocks,” bought more Moderna and other things they were short, and that drove prices further apart. Then Moderna wound up large in benchmarks, and long-only asset managers had to buy it, increasing their exposure and driving the price up further.
It was an entirely technical explanation for what had happened, with relatively little to do with either Moderna’s actual value or anybody else’s actual value. That’s a narrative. I don’t think anyone will ever know how true it is as an explanation, but it’s certainly widely discussed at investor conferences. Yet you read the news coverage of Moderna’s stock price, and it’s all “Moderna crashes on cancer data,” which isn’t at all about market technicals. It’s about the idea that investors are keeping Moderna’s price relevant to what they actually think of the data.
My message to investors is that it’s not great if what’s actually happening is this complicated technical back-and-forth. I thought it was maybe not great that investors weren’t able to keep prices reflective of their belief about fair value. That noise adds to all the many challenges that make biotech a wood chipper as an industry.
Many investors reached out to me and pointed out that their job was also difficult. I agree; their job is difficult. They point out all the ways in which our difficult job is tough sometimes. I’m just pointing out one way in which their job is tough. But that was another thing that came out of that discussion.
If I could just add on to Matt, I’m glad he brought up this topic, and he’s 100% correct. This is what folks are discussing in the back rooms of investor meetings these days: just how much the sector may be technically challenged because of the massive preponderance and growth of platform funds, of long-short funds that don’t necessarily add capital but are neutral-weighted, yet swing these stocks around massively on a daily trading basis. They also tend to be a little shortsighted and groupthink in their mentality.
To my observation, this is the first time in the history of the industry that we’ve ever talked about this.
Degrossing is having a very real, and maybe tangible, impact on the sector. Like Matt, I don’t know if it’s true, but it certainly feels like it. To me, it’s the best explanation we’ve heard for why the group has gone through this tremendous swing in valuations—not just Moderna, but Iovance and other heavily shorted names like Twist going up. Conversely, everything that the pod funds had long went down and was fundamentally repriced, which might be attractive.
We may have to deal with this as the amount of capital dedicated to our sector from these long-short funds continues to increase. I don’t think it’s had a down year in the last 10 years, and now it’s reached maybe a breaking point where the structural issues are potentially more of an impact than the fundamental issues. So, for all these folks working in these very difficult jobs trying to pick stocks, this is another consideration to keep in mind.
Yeah. Chris, tell us about the Endpoints survey.
Yeah. Just to comment on Matt’s wood chipper comment, I think you said this, Matt: the clash of titans I see coming is between the new tech-bio, Silicon Valley AI optimism coming into the old-guard sector, where they haven’t gone through what we all know about how difficult this area is. So this idea that it’s just going to be simplified and easy—I think that was your main point. The wood chipper comment was like, “Hey, the wise, older, experienced person trying to advise the younger, new person in their career: Be careful about how easy you think this is going to be.” I appreciated the metaphor there.
On the sentiment, I think there are a couple of themes I pulled out of it.
So first of all, Endpoints is a quarterly biopharma sentiment survey. It’s actually pretty good because they’re getting more longitudinal data, and they take a forward 12-month look. This was, again, moving in the right direction. From their Q2 survey, all constituencies are now well over 100, which is their index. The 12-month forward look is even more optimistic. I was scratching my head because this was just released this week, and all I’ve been hearing in recent weeks is how difficult the market is right now.
And that’s true. I think we have to hold the mid- to long-term view in the same hand as the short-term view. In the short term, we have some real challenges. I looked at when they made the survey, and they did it from mid-August to September 15. Literally, I think it was the next day that the Fed raised interest rates. There were bond-yield discussions, and that put a chill on things. They were also interviewing folks who had just had Q2 data. By all measures, Q2 was a great quarter: M&A, XBI movement, everything was working well, and there were IPOs.
So I think the Q3 sentiment survey, conducted from mid-August to mid-September, really reflected coming out of a very strong Q2. In Q3, the reality is that M&A fell off and the XBI was flat. People are questioning whether the IPO window is open right now, or how robust it is. Right now, we’ve got an election year coming up, and that’s not even mentioning the China-Treasury stuff. We’ve got a lot of things that have changed.
It’s similar to Brad’s comment on Moderna: you have to look at when that first announcement was made, where it’s trading now, and whether that value reflects the data that was just released—not just whether it dropped. You have to look at it the same way when considering the major bull run we had from 2014 to 2021. We had some ups and downs, some tough quarters or tough halves, but overall it was going well. I’m of the sentiment that more things are working right now, and although it’s been a tough quarter, I’m predicting that we’ll resume having a healthy market. It’s not the beginning.
The thing that surprised me most is how quickly industry experts and novices were saying, “Oh, is it over now? Is this going to end soon? Did we get ahead of ourselves?” After about 3 quarters of good news, we’re already talking—
Yeah.
—about another downturn. So—
Mm-hmm.
—I think we need to modulate our expectations a little bit quarter to quarter, and really look at the overall picture. Even if you were to cut off everything right now, this would be one of the best years biotech has had in a long time, with reverse-merger PIPEs, IPOs, valuations, and M&A. I just don’t want us to lose sight of that because we’re in a very tough quarter right now.
Mm-hmm. Mm-hmm.
Yeah. Daphne?
Yes.
Can I just add a little bit here? I just came back. I had the privilege of being at Forbion’s 20th-anniversary gathering in Amsterdam. They just raised 2.3 billion. This is a European VC, and 2.3 billion is a big number for a VC, right?
Mm-hmm. Mm-hmm.
I think the people I saw in that room—the LPs—were clearly interested in hearing about all the things going on in science and everything else these guys are looking to invest in. The fundamentals, as everybody has said, are fantastic and strong. The problem is that we have a very volatile world around us, and it’s not biotech’s fault or biotech investors’ fault. It’s just volatile. We have wars, energy issues, tariffs, MFN. Everything you can think of is happening at the same time, so I’m not particularly surprised that we’re having these soul-searching moments.
From what Josh said, I think the generalists probably came into the sector for about 5 minutes. We were only talking about whether they would come in, probably at the beginning of the year.
Right.
But it is difficult. It’s difficult for them. It’s not smooth sailing, and I don’t think we should do too much soul-searching here. The fundamentals of the sector are phenomenal.
Yeah.
Overall.
Yeah.
Hey, Daphne, I want to ask you about something because you created some news of your own: “Hey, I’m hearing from the bankers that there’s a good pipeline. We can expect more M&A.” I’m paraphrasing here. You had a lot of comments, with a lot of people speculating on names that might be acquired. People said, “Hey, you should ask Eric Tokat if that’s true or not,” and all of that.
I think you were sending an optimistic note because we all talk to bankers, and they’ve been very active recently. Do you want to comment on that and share that sentiment?
Yeah. It goes back to Matt’s comment about closed doors, space, and back rooms. I’d been hearing—and I’m still hearing—from people on the banking side, but also from senior people at big pharma, that there are deals in the works. People are working on deals. I was hearing that a couple of substantial deals could get announced.
One caveat is that when stock prices drop, there can be a disconnect between board expectations and the premium an acquirer is willing to pay, and that can cause deals to fall apart. But as recently as a few days ago, I was hearing that it’s not pencils down by any means.
On the positive side, according to Stifel, 2026 is on track to become the second most active year in biotech M&A history, second only to 2019. In 2019, there were 2 mega-mergers, and we can’t forget that pharma companies are continuing to replenish their pipelines ahead of an unprecedented patent cliff.
We also have Ali here, and we did have an M&A transaction this week: Merck KGaA announced it would acquire Silence Therapeutics for 1.3 billion in cash, about a 130% premium over the last closing price. It took me back to that first episode 5 years ago, when we were talking with John Maraganore about Alnylam and how it took 16 years from founding to first approval. There are some parallels here, with both companies going through the peaks and valleys of RNAi. Like many biotechs, both are overnight success stories that take decades.
Ali Mortazavi was the CEO of Silence when it was a £5 million market-cap AIM-listed company. Ali, I’d like you to tell us about the history briefly, and please don’t forget to mention why Hikaru Nakamura was wearing a Silence shirt at a chess tournament.
Okay. Thanks for having me on, guys. Peaks and valleys? A lot of valleys. I’m going to give you a compressed version of the Silence story. The actual story, as I tweeted last week, would be a Hollywood blockbuster movie, but that’s too crazy to do. Let’s start around mid-2012, when I joined Silence. Don’t try this at home, kids, is my advice. The biotech space has changed so much.
RNAi was such a privileged IP space, and little old Silence, with a £5 million market cap on AIM, had a foundational patent in siRNA chemistry. I guess my big bet was on RNAi. As the hands of fate, destiny, and luck came in, around mid-2012, I think Alnylam announced that patisiran was the first proof of concept in humans for RNAi. I remember their market cap going up $600 million that day. That was a stroke of luck: “Okay, this modality really has some legs. It’s early days, but it’s still got some legs.”
Rushing through, Silence was, as you can imagine, a £5 million market-cap company. We had a program called Atu027, a pancreatic cancer drug. In the glory days of siRNAs, when we were looking for oncogenes, this was a program that I was really worried about from the get-go. I was thinking, “I’m just not sure about this program,” but we had a Phase Ib trial running. Let’s go and see the data. Let’s march through to 2015.
We raised £50 million, which in the UK was an astonishing number, to be honest with you. A couple of strange things happened to me. I had a personal tragedy: the mother of my children was diagnosed with leukemia, so I spent many years in real hospital settings, acute settings, stem cell transplants, and experimental treatments. I had a visceral reaction. I didn’t want to be that biotech company that went with a drug they didn’t really believe in. I think patients deserve to have the best chance.
It was one of the most painful corporate decisions because everybody was getting geared up for manufacturing and a big Phase II trial, and I just said, “No, we’ve got to stop this.”
“This is not going anywhere.” At the same time, what I saw was the remarkable work of Alnylam and John Maraganore. Frankly, they were the frontrunners. We were the underdogs. In some ways, we copied them. We benchmarked against them and saw this GalNAc technology, which is frankly remarkable. We take these things for granted now.
We thought, okay, this was a big, big setback. You can imagine the share price collapsed. It really wasn’t a very good few months. But I thought, look, this is the only thing that works. These lipid nanoparticles, which were the cornerstone of siRNA drug delivery, were just no good. We just couldn’t possibly work with them.
We were behind, but something worked. We had an IP position in GalNAc. We worked so hard to get up to speed, and we went after 2 targets. We were playing the ultimate game of Snakes and Ladders. We went right back to the beginning, and it was a long, long wait. It wouldn’t be Silence. We couldn’t be waiting around doing nothing.
There were some quite frankly staggering things. We took a 10% stake in Arrowhead in 2016 when their share price fell, I think, 90% or something crazy, and they were trading at a 70% discount to cash. I felt that their GalNAc technology was frankly a couple of years ahead of us. I thought, “Look, we have to deploy capital.” Would I do that today? I’m not sure.
The horrifying part is, if we’d kept the Arrowhead stake, it would have been worth $900 million within around 4 or 5 months. But the board and us, in our infinite wisdom, decided to sell it for a good profit, which kept the runway going. This is the sort of crazy stuff I’m talking about.
Mm-hmm.
We were in merger discussions with Arbutus, where we were looking at their lipid nanoparticles, which, believe it or not, were ultimately used in the Moderna vaccines. Again, another case of Silence: close, but no cigar. We had deep merger discussions with Dicerna when they were in litigation with Alnylam, to basically merge with them, because I thought we had a lot of work on their legal case and on their IP. I thought, “Look, we could basically form an alliance.” That fell apart at the last moment.
In any case, the trials and tribulations of drug development: our 2 targets were LPA, which is another story in itself, and another gene target in hepatocytes called TMPRSS6. We were going to the clinic. I left in mid-2018. When I say “left,” I didn’t necessarily leave. That’s another fantastic Silence story for another day.
New management came in, and, to be fair, a lot of different people have got to take credit for Silence. One of them is Laura Rocco Alonso. I think none of Silence’s achievements over the years would have happened without her. She’s now the CEO of Tangram Therapeutics. I actually introduced Ian Ross to the board and said, “Look, he should be involved.”
Mm-hmm.
That man has been through hell and back.
Mm-hmm.
One crucial decision was made outside of me and everybody else: TMPRSS6, our target. We were going after MDS, myelodysplastic syndrome, and beta thalassemia. Someone at Silence—I don’t know who—decided to switch to PV. Honestly, that’s probably one of the best biotech corporate decisions ever made.
Mm-hmm.
That’s what divesiran is. It’s probably most of what you’re seeing in the Merck takeover.
Mm-hmm.
It’s shown such incredible clinical activity. Let’s call it a team effort, if you like, right?
Huge, huge congrats to you and to Ian and to the rest of the team.
Thank you.
Maybe another time we can hear more about your experience as a chess—I think you’re a chess master, right? I mean, you’re not a grandmaster.
Apparently.
But anyway, I look forward to watching the movie when it comes out, so thank you.
No, we—
Yeah.
Actually, one thing I think would be interesting for discussion: Silence hasn’t had a CEO in the last year.
Right.
So actually, it got sold—
Mm-hmm.
—with no CEO. I’ve actually begun to really wonder: What is the structure of a biotech in the new world of AI?
Mm-hmm.
Let’s say intelligent systems can come up with ideas, target-indication pairs, literature searches, or whatever they’re going to do. In the end, you’ve got to nominate a target, and you’ve got to go and do your preclinical cascade.
Mm-hmm.
My sneaky suspicion is that biotechs, especially platform biotechs, are actually hedge funds in disguise.
Yeah. Well, let’s actually pick up on that because it’s an interesting hypothesis. Do we even need CEOs? Matt, I’d love to hear your thoughts on it, and maybe we can talk about a CEO who’s made quite an impact on biotech: Dave Ricks. Go ahead, Matt.
Can you hear me okay?
Yes.
Great. I think many biotech CEOs would say the same thing when asked: “I think you could absolutely do it without us.” There’s no question. I think the people around me do so much more good for Roivant than I do every day.
Ultimately, it’s an industry that’s a game of inches, propelled by the people on the ground doing the work. As a CEO, I often feel impotent to drive the business forward relative to the day-to-day work. There are moments when, not even speaking about Roivant, you see leadership taking companies in directions, and I think that’s super helpful. But those moments are few and far between. Most of the successes every day are driven by individual decisions made by people who are ideally—and often—close to the thing. So I buy that.
You were asking about Dave. I wanted to say—I don’t know if he’s listening or not—but one of the things that’s been fun to watch recently is that Dave Ricks has shown up on Twitter. I still say Twitter, I’m sorry.
Yeah, me too.
Dave Ricks has shown up on Twitter, and he’s been a really great presence. I think I could be wrong, and maybe I’m not cynical enough, but it really feels like he’s writing the tweets himself. He’s engaging with people, and it’s something I’ve tried to do over time. Obviously, I’m here in this space. It’s hard to do well, honestly. It takes a lot of time and effort, and you can get yourself into some weird loops. There are a lot of weird people out there listening and interacting with you, so I want to applaud it.
I think there’s a school of corporate PR. There’s this woman, Lulu Cheng Meservey, who talks about going direct. I feel like Dave’s trying it. I’m interested to hear from him at some point why he’s doing it, but it’s been interesting and fun to watch. I’m curious what his experience will be in the coming months as he participates in our little echo chamber, such as it is.
Yeah. I think you need a certain type of authenticity to do it well and naturally. Otherwise, some CEOs would be better off letting the communications group do their tweets. But I think he definitely has the right instincts around it. Brad, you did an interview with Dave Ricks, and it captured a lot of attention on BioX or BioTwitter.
Yeah, I can confirm 100% that it’s him, and I think that’s what’s successful about it, just as you said, Daphne. I think it’s a good thing for our whole industry that somebody like him is out here putting a face to our business, especially in such a positive way.
The biggest takeaways from the comments and feedback we received from our interview, by a landslide, were, “Wow, he seems like a very nice guy,” and, “Wow, he really knows the technical stuff.” I’m biased, but I think that’s the magic of video. People literally knew his name for decades, and knew his job and how important it was, but didn’t really know him as a person. Then they saw him in this video for 10 to 20 minutes and felt like they had a better sense of who he was. They were impressed by it.
I would just say we need more of that. There are a lot of other big pharma CEOs and biotech CEOs who are equally impressive. Our industry is so misunderstood and, sadly, so hated by the general public. If it were better understood, and we were more authentic and showed the people behind it, that would be a good thing for all of us.
One thing I hear all the time when I visit companies is the CEO will say something like, “Yeah, I see you on Twitter,” or, “My lawyers—I wish I could…” They always have some chummy comment about their lawyers holding them back.
Whether that’s true or not, credit to you, Daphne, for how long you’ve been on Twitter and how much you share. Credit to you, Matt, for doing it too. My message to everybody out there is: if the CEO of the biggest company in our entire industry can do it, then you can too.
Though I can tell you with firsthand knowledge that his tweets aren’t reviewed by a comms team or lawyers or anything like that. He’s just out there being himself, and that’s a good thing. Any excuse about compliance and everything, I think, is total nonsense. I would love to see more Dave Rickses jump into the conversation, because that would be good for all of us.
Mm-hmm.
Yeah, I just want to add—
Vas was on—
Yeah.
He’s on here as well, but he hasn’t posted anything in the last few years. Vas from Novartis. But go ahead.
I was just going to add that I agree with everything and all the sentiment that’s been shared. It’s great what Dave Ricks is doing. The thing that makes me nervous is that, as one of the most hated industries out there, pharma has a really prominent spokesperson. There’s a double-edged sword to that.
We may all agree with everything he says, but there’s also the idea that, as the first trillion-dollar-valued pharma company, anything—a missed tweet, a misperception, or being tone-deaf to the general public—could potentially become an issue. I think it’s great. We’ve lacked pharma leaders stepping up and trying to provide a narrative around our industry. I think biotech is almost different in terms of what we do and how we operate in the ecosystem, but it also comes with scrutiny. We all know there are a lot of folks on social media, and they may not be representative of the broader sample.
I’m rooting for him, and I hope he doesn’t run into any of that. But we need more voices than just Dave Ricks to represent the larger pharma landscape.
And speaking of Dave Ricks, people on X viewed his recent post as referring to Abivax. Matt, do you want to talk about Abivax’s data?
Sure. I don’t know how qualified I am to talk about this, but Abivax is a name that gets a lot of attention. The noise about Abivax on this platform outpaces the noise about Abivax in the other, less public rooms I’m in by about 100 to 1. At investor conferences, there are names that get talked about an enormous amount. Abivax is on the list; it’s a relatively well-held stock at this point. But some days it feels like 80% of the comments on Twitter are about Abivax.
There was a whole thing about the Eli Lilly jets and various other pharma company jets being followed, which is a thing outside of Abivax too. But Dave was absolutely poking fun specifically at that. Abivax had some more data at an academic conference this week that looked good.
One thing I’ve found interesting about the biotech Twitter debate about Abivax is watching the question of its ability to go it alone if it doesn’t get acquired. That’s been a big part of the public story about the company for at least the last few months on Twitter. What can they do alone? What will that look like?
As someone launching a product, it’s interesting to watch people on Twitter discuss how easy or hard that might be, and to think about the competition with big pharma companies and the differences between a launch in IBD versus some of these other indications. Abivax’s data is unquestionably super impressive. We used to be in IBD ourselves, but it’s fun to watch the public debate and think about how that feels to the Twitter commentariat, the Abivax management team, and what a big pharma company might think about Abivax’s ability to launch the product on its own. It’s interesting to consider how that debate must sound in all the different rooms where it’s taking place.
By the way, now that I’ve said Abivax on this space, I’ll get about 600 random outreaches from people on Twitter about something I’ve just said. I’m looking forward to that too.
Matt, really quick. I want to tie what you’re talking about back to our discussion about whether we’re in a good market or a bad market. One thing that I think poisons the discussion—and I don’t think biotech CEOs understand this or think about it enough—is that, especially from a retail trader standpoint and in what you see on Twitter, too many people own options and not stocks. Because of the time premium, which erodes over time, they need stocks to only go up.
That’s why, when stocks take a totally normal breather, people react the way they do. The XBI started the year at 108, and it’s at 150. By any measure, this is literally one of the best biotech markets of all time. The reason so many people are calling it over, doom and gloom, and all of that is that too many people own options that are going to expire worthless because of the time premium.
That’s how a stock like Abivax gets totally out of control: everyone’s betting on which month it’s going to be acquired. If it doesn’t get acquired by then, you literally lose everything. So you have a stock that may be the most successful stock in biotech over the last year, and people panic and overreact because they’re losing all their money on one of the biggest success stories out there. They’re playing options that erode, eventually evaporate, and blow up over time if a buyout doesn’t happen.
It’s fundamentally an unhealthy thing, and it poisons and distorts the discussion about companies like that and our sector in general, because too many people need things to keep going up or they get in big trouble.
Daphne.
Yes.
Can I just add something on Dave Ricks?
Okay.
I think there’s a discussion in the UK and Europe about how politicians should learn to use social media so they can connect with people. The new Prime Minister of the UK, Andy Burnham, has certainly mastered that, and he had mastered it a long time ago.
What pharma needs is to prove to people that the folks who run it are normal human beings and that they care about patients. Most of the time, people’s contact with pharma is either the advertising on television, at least in the United States, or the negative news that comes out. I was really pleased to see Dave join in and do this.
I just wish more pharma CEOs would do it. It is a minefield, and you need to be careful about how you get dragged into it and what you do from a compliance and legal perspective. But the more these people can engage with ordinary people, some of whom are on Twitter or X, in the social media world, the more I think we can try to address this idea that pharma is evil.
Yeah.
I just wanted to add that.
That’s a great point in terms of our general reputation as an industry. We only have about 11 minutes left, and we have some data from conferences. I’m going to have Eric choose the ones he feels are most important and highlight those.
I want to talk about China for a moment. I think Chris wanted to talk about the Sabatini verdict. Then we’re going to wrap up at the end. I’m just going to tell you what we’re asking so you have a moment to think about it. To wrap up our 200th episode, I’m going to ask each of you to think about answering one of these questions: What has surprised you most in the industry over the last 5 years? And if it’s 2031 and we’re recording episode 400 or whatever, what do you think we’ll be talking about then? Think about that, and we’ll come back to it.
Eric, over to you. I think you wanted to talk about a couple of things going on at ESMO and United European Gastroenterology Week.
I’ll be really quick. Thank you, Daphne, because I know we want to spend some time on the good stuff and our backward-looking thoughts on the industry. I’m curious to hear what everyone has to say.
2. Tango’s Pancreatic Cancer Data
The only comment I want to add about ESMO is the phenomenal data that Tango presented this morning in pancreatic cancer. It’s a subset of patients, maybe 30% or 40%, who have MTAP deletions that make them amenable to its PRMT5 inhibitor. We just saw game-changing data: an 82% response rate and an 88% non-progression rate at 9 months in very refractory third- and fourth-line pancreatic cancer patients.
This is perhaps some of the best data I’ve ever seen covering the oncology space in many, many years, and it’s going to be a massive game changer for patients who have this mutation. It highlights the innovation that’s coming out of the world today and our sector, and all the good that we can do. Apropos to our earlier discussion, shares are, of course, down on these data. Nothing to do with anything other than selling on the news. There’s some funky stuff going on in the stock market, but this is a short-term blip on an otherwise long-term positive trajectory. I’ll stop there.
Great. Matt, I know we were going to give you an opportunity to talk about some of your recent data, but I think we’ll just suffice it to say that you’ve been on a total roll lately and you keep putting out great data. So congratulations. I don’t know if you want to say anything about it, but we can move on.
No, look, we were excited about the data we put out this week, but all good. I get to talk about my data all the time. Thank you.
Okay.
Yeah. Congrats, Matt. As you know, Perceptive is a proud investor, so we’re all pleased at our firm.
3. China Deals and Sabatini
China deals are continuing to happen. Roche did a big deal: $400 million upfront, $15 billion in biobucks. This is in concert with Roche communicating that they’re going to rationalize their earlier pipeline. They’re promoting their Phase III programs, so they’re going through a reorganization of their drug strategy. This China deal is a bit of an exclamation point on that. Gilead just announced another China deal yesterday, with $1.3 billion upfront for an oral peptide IL-23 drug. Lilly also did another China deal—they’ve done some in the past—on an oral drug delivery technology. There was a smaller deal with MediLink. The main point is that pharma is still very active in dealing with China, and we’ve all talked about this: Are they going to bypass biotech and just start doing deals directly with China so they’re less reliant on acquiring U.S.-based biotechs?
This comes against the backdrop of the Treasury proposal, which has an open public hearing period. But the current language is pretty onerous in terms of how it would chill venture investment and new companies started from China. It seems more punitive to venture capital investment and company creation than to a direct license from pharma. That could give pharma an advantage, particularly multinational pharma like Novartis and Roche. Anyway, I think it’s something to keep an eye on. It doesn’t look like we’re going to be able to eliminate this, so it’s really going to come down to the details.
We often hear headlines, make up our minds, and fixate on them without knowing what happens afterward. We all know Sabatini was dismissed about five years ago for violating a relationship policy at the Broad—or, I’m sorry, the Whitehead Institute, Howard Hughes Medical Institute, and MIT. There have been many court battles along the way from both sides. His accuser, Kristin Knouse, who’s still an MIT professor, had all of the institutional claims dismissed on all sides. So it came down to the final he-said-she-said, and it was Sabatini against Knouse. Sabatini won the judgment: $6 million, a pretty sizable settlement, over five years. It was ruled that her defamatory claims hurt his career and his income.
He was even recruited by a female faculty member at NYU, but the public feedback was so strong that it never happened. Hopefully, he has a path forward. There are no winners in this. Knouse is going to countersue and appeal, so it’s not like she’s going to be out $6 million in the near term; she’s going to appeal that. I just think it’s important to understand these bigger, broader issues in the culture. We don’t like when they infiltrate our industry, but this one did. If you want to learn more about it, 2 proponents of Sabatini were Bill Ackman, the hedge fund manager who writes what are like mini-novels on Twitter—
Yes.
—he posted something in October—and Jeffrey Flier, the former dean of Harvard Medical School, has been a strong supporter of Sabatini. I just wanted to highlight that.
Yeah, Chris, it also reminds me of the situation with Ram Sasisekharan. There were accusations that he was stealing IP or something like that, and he was ostracized. It turned out that it wasn’t true. I think that case was at MIT; in this case, it was Whitehead, which is also affiliated with MIT. I really think these institutions should be careful about what they say about people before things are proven. These are reputations built over many, many years, and until something’s proven, we really need to be careful.
And all of us need to avoid jumping to quick conclusions. We used to have a feeling that you’re innocent until proven guilty, and we’ve culturally moved toward, “You’re guilty, and now prove you’re innocent.” Anyway—
Yeah.
—but I think your point’s well taken, Daphne.
All right, let’s wrap up this episode by answering these questions. I’m going to start with Josh. What has surprised you most over the last 5 years, and what do you think we’re going to be talking about in 2031?
For me, it’s the fact that biotech has never really cared about offering investors traditional business models with real profitability and bottom-line growth, for pretty much the history of the sector, except for a couple of moments. But that’s changed quite dramatically, thanks to much higher launch prices and companies vaulting into profitability in the sector, becoming far more investable for a generalist audience.
Okay. And 2031?
Too far away to predict, but the innovation that we’re seeing is phenomenal. As long as we don’t have new drug-pricing rhetoric get in the way of the sector, it’s going to be an incredible ride.
Great. Whoever wants to go next, just unmute and go.
I’ll go. Historically, what surprised me is that I thought going through COVID would make people more amenable to anti-infectives. There would be a realization that we need to invest more, but it’s gone completely the opposite direction. I was a bit surprised. And the resilience of biotech—we’re here on another upcycle. Those are 2 things.
For 2031, I can say what I like because I’ll probably be retired by then. Let’s say I think oncology will again be solving all the diseases that are difficult: GBM, potentially some of the smaller indications. I think we’ll see a lot of progress there, and a lot of people living with cancer as opposed to dying of it. In neuroscience, I’m really looking forward to neurological diseases finally being cracked open and treated. I don’t know where we’ll be on the cycle, but that’s what I’m looking forward to. Over.
Yeah, I’ll go next, Daphne. Three quick things for me. The crossover financing kind of ceased during the downturn, and we saw new funds step up, like Forbion, Catalio, and corporate venture capital. It was a newer mix of investors who were willing to lead and co-lead rounds, even in the downtimes.
Number 2 is the breadth and diversity of M&A—not only from the acquirer standpoint; it’s not just big pharma and big biotech, but mid-size biotech too. We’re also seeing activity in a range of therapeutic areas. Even if you remove Lilly from the equation, M&A has been very robust over the last 2 years. Third, I think we’re seeing more discipline in the cost structure of biotech, leaner teams, some fractional C-suite roles, and a lot more outsourcing. I think that’s overall healthy for the industry.
For the 2031 outlook, I think we’re going to look more like we do today than like a vision where AI changes drug development forever and the industry becomes unrecognizable. I think it will be more recognizable in 2031, and AI isn’t going to fully live up to the current hype.
Maybe I’ll chime in. In terms of what’s surprised me most, I think we’ve moved toward this asset-centric business model much, much quicker than I ever would have thought. Five years ago, we were still talking about platforms, science projects, research, and development. Now there’s just so little of that going on. Some platform companies are still doing internal R&D, but when you think about how many drug-focused companies are doing truly innovative research in-house, it’s almost none. Everyone’s grabbing their molecule from pharma, China, or some other source and trying to develop it for a quick fix. So that’s probably what’s changed most, in my opinion.
Looking forward, I’m at least hopeful that genetic medicines are going to be commercially successful based on our ability to achieve favorable delivery, cost, convenience, safety, and efficacy. I think that’s going to happen, and I think it’s going to happen first with AATD and Beam’s program.
Matt?
In terms of the last 5 years, I don’t know if I’d say it’s been surprising. This dovetails with what some other people have said, too. It’s been really satisfying to see biotech companies do such a good job launching products for a wide variety of reasons that we could have a whole discussion about. I think that’s been relatively new in the last 5 years, at least in the recent arc of history, and that’s been great to see.
In terms of what I think we’ll be talking about in 2031, I hope we’re talking about the next rise of Roivant. But practically, I think we will also—
That’s important.
…be talking about how AI is about to change biotech in an enormous way in 2031. I look forward to having that discussion in 2031.
Great. Brad?
I would say what I think is changing, and what has surprised me, is just how much more aware the general public is of the things our industry is working on, ever since COVID. To this day, I’m still shocked when my parents know the word Moderna or mRNA. To me, that still feels like a technical thing that, before COVID, was our secret.
I think an end result of that is that our industry is becoming much more consumer-oriented. The glaring example is the GLP-1s, and how you’re literally seeing Instagram ads about how to get a GLP-1 without a doctor’s visit. I think some of that is a little concerning, but that’s the way the world is headed, and I think you’re going to see more of it in other areas of medicine.
In the future, I’ll echo Sam. I think neuroscience, and specifically brain shuttle technologies, are going to revolutionize neuroscience because they’ll totally change the efficiency of how drugs get into the brain. I think that’s going to have a big impact on a lot of different things.
The other thing is, if I could only place one bet today, I would probably bet on degraders. I think degraders are going to be the next mega class of medicines, so I would watch that space very carefully. Right now, I feel like we’re focused on individual programs because it’s such a nascent industry, like Kymera’s STAT6, which is certainly exciting. But I would think of it from a much bigger perspective. I think it could be a new class, just like antibodies and small molecules, which they really are. I think it’s going to be a whole new mega class of medicines that’s going to change a lot of areas of our business.
Great. And Ali?
Yeah. I’m going to try and wrap up a bit controversially. I think in the age of AI, the whole of biotech infrastructure and what a biotech is are at play. I’m going to give you a controversial example. I’m sitting in my living room right now. I could very easily design a drug on my computer, an siRNA conjugated to a GalNAc, and I’m connected to WuXi in China. I choose the target with my Claude or ChatGPT. The question is: What is a biotech company? Where is the value of a biotech company? Is it in the clinops?
I think that’s basically what’s going to happen: almost anyone can do a clinical trial. Let’s say OpenAI or Anthropic. That’s basically what they’re doing. Their machines are going to be generating hypothesis after hypothesis, and they’re basically going to go to China and generate. And then the clinops is really the key asset in biotech.
Mm.
It’s like, do the trial on time, with the right patient population, and get the result.
Okay. Thank you. I want to take this opportunity to thank this community of co-hosts and the people who engage with us. It’s really amazing, and I’m really thankful to be part of it, especially since I haven’t been able to be on as often. I think I was on twice in the last 8 months or so. This is a really great opportunity for everybody to learn from each other and share the learning. I really appreciate it, and thanks for joining us for this 200th episode.
Thanks, everybody.
Thank you.
Thank you.
Good stuff.