Ep. 369 - ASCO advances, China innovation & U.S. science under threat

Revolution Medicines continues to impress with more pancreatic cancer data, earning a standing ovation at ASCO over the weekend. On the latest BioCentury This Week podcast, BioCentury’s analysts discuss the detailed data for the company’s daraxonrasib, Akeso’s Harmoni-6 readout, as well as other results from the meeting. BioCentury’s analysts then argue that U.S. biotech executives and policymakers should embrace the challenges and opportunities that come with the rise of innovation in China — rather than sticking their heads in the sand. They also discuss why leaders of the U.S.’s biggest drug companies should use their influence to stop an OMB proposal that threatens the foundations of U.S. science. Plus: takeaways from BioCentury's conversation with Alkermes CEO Richard Pops on The BioCentury Show.

View full story: https://www.biocentury.com/article/659629

#ASCO #PancreaticCancer #BiotechInnovation #ChinaBiotech #DrugDevelopment

00:00 - Introduction
01:49 - ASCO: RevMed
06:50 - ASCO: Akeso
16:33 - China U.S. Biotech Rivalry
24:15 - Science Under Threat
36:29 - Richard Pops Takeaways

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

Transcript

0:00

[Autogenerated Transcript]

Jeff Cranmer: 0:02

RevMed continues to impress with more pancreatic cancer data, earning a standing ovation at ASCO in Chicago over the weekend. We'll discuss the readout on the latest BioCentury This Week podcast. Plus, we'll talk about Akeso's HARMONi-6 data, and Phase II data from another PD-1 VEGF bispecific, this one from BioNTech and BMS, starting to address one of the biggest questions that has emerged for the class over the past two years, whether it beats PD-1 in chemo combinations. And we'll take a moment to look at first-in-human data at ASCO, the big cancer conference uh only comes once a year, And why leaders of America's biggest drug companies should use their influence to stop a ruinous proposal out of OMB, a call to action by our Washington Editor, Steve Usdin. He'll also talk about his conversation with Richard Pops, three decades in biotech. It was a really fun one on our sister podcast. And hey, US Biopharma, take your head out of the sand on China. We'll hear from Josh Berlin, our Head of BD, and Simone Fishburn, our Editor in Chief, who jumped into a hot conversation on the socials last week about the state of competition between the US and China. I'm Jeff Cranmer, host of the BioCentury This Week podcast. Why don't we cut to the chase and bring Lauren Martz right into the conversation. Lauren leads our coverage of product development. She has a passion for new modalities, and she is up to her eyeballs in ASCO data. Lauren welcome back to the podcast. Uh, where do you wanna start?

Lauren Martz: 2:10

I guess we should start with the Revolution Medicine data because that's what everyone is talking about this weekend and today. We already knew that this was an exceptional result. We heard about the overall survival benefit completely unprecedented in pancreatic cancer. What we got over the weekend in the presentation was um just more details about how exactly this was working in this patient population. first of all concerns about safety I think are quieted a bit. It had a, a pretty positive safety profile. there were some original concerns about rash from the Phase II study, and that was consistent um a-across the Phase III study. So there's still a, you know, 14% incidence of Grade 3 uh or higher rash, but that was expected and not worse than expected. What we also learned was sort of a, a little bit about the subpopulations. You know, there was a strong response in the patients with KRAS mutations, with mutations in the G12 part of KRAS, and we know that that was similar to-- the results were similar in that population and the intent to treat population. And I think, I guess the, the takeaway that you get from this data is that it really gives you validation that this RAS on targeting approach is effective. And I think yet to be determined is uh what happens when you also target RAS off. I look at this, and I think a lot of the people who are, are watching this data look at this as, as hopefully a jumping-off point for what we can do by, by targeting RAS um and hopefully what Revolution Medicine will do with the future programs

Simone Fishburn: 3:51

Lauren, you know, you mentioned that we had a lot of this data ahead of time. Fill in for us, is it around the toxicity, sort of color in between the lines a little bit for us about what we specifically learned this weekend. I'm assuming that the standing ovation, I would like to say well-deserved standing ovation, is based on the data that sort of had already come out. Like, we knew this was a big deal already, but where do we actually land, you know, in terms of the advantage that this particular molecule brings?

Lauren Martz: 4:22

Sure. So I think as expected, it was the survival curves that are just shocking for everyone when, when that came up on the screen. And then in terms of the new information that we have, we now know that all of the endpoints were met in this trial, and this is an interim analysis, so there will be additional data coming out. we do know that all of this will go into a submission to FDA. We don't have a timeline for that yet. Again, it's just the information about safety was something that everyone was looking out for. I, I think that's the, the big take home

Simone Fishburn: 4:55

Do we know what's next from RevMed?

Lauren Martz: 4:58

We do. So this was the pan-RAS inhibitor, and the company has a, a pipeline of programs against RAS different ways of targeting RAS. And so they do have a G12D specific inhibitor in development. There's also a G12V specific inhibitor. Yeah, I'm interested to see how, how these mutation-specific programs work from this company that has, pioneered this, pan-RAS approach

Simone Fishburn: 5:26

you know, that, that's kind of interesting because one of the important things is that, that … I mean, there are actually other agents, of course, against the mutations, although maybe not in pancreatic cancer. But the advantage of the pan-RAS is that there are actually so many patients with a non-functional, dysfunctional RAS, but we don't know the mutations. Is that right? How is that strategy, like, in terms of the competitive landscape gonna pan out?

Lauren Martz: 5:52

I, I think that's unclear at this point within the pancreatic sp- cancer space. So we do know that there are a high level of G12D mutations within pancreatic cancer. So the inhibitors that we have approved are for G12C. Those are higher prevalence in the non-small cell lung cancer space. I don't think we have an answer on, you know, within the G12D population where, where I think a decent amount of patients are getting um screened for that specific mutation, I don't know that we have an answer on which will, will be better. You know, I, I-- obviously, I think the hope is that toxicity would be better if you're more selective, but I don't know how, how that would impact the efficacy that we've seen with the, the pan approach. and for all of the details you can see the story from our colleague Tierney Baum, which should come out today. she spoke with the company and, and she, she knows quite a bit about this program

Jeff Cranmer: 6:45

Excellent. well, Lauren uh the other… Well, there's many things that folks are talking about. There's just you know, the usual uh huge amount of news coming out of the conference, but the Summit Akeso data why don't we go there next?

Lauren Martz: 7:00

Yes, this is the other big news coming out of the weekend. We have, again, interim results from a Phase III study. This was the HARMONi-6 trial of ivonescimab. This is the PD-1 VEGF bispecific that everyone's been talking about for the last two years. And I think this data addresses one of the two big questions that we were left with after the first really big head-to-head study against Keytruda in non-small cell lung cancer, which was does the same level of efficacy result when you do a, combination with chemo? So often in first-line non-small cell lung cancer in PD-L1 positive patients, it will be a PD-1 blocker and chemotherapy. In the original study that we- that read out two years ago, there was no chemotherapy in the combination. This addresses that question. these results were positive. There was a statistically significant overall survival benefit at this interim endpoint which is what everyone was hoping to see. This was a study in patients in China, this was like that first Akeso readout where the other big question was, will the results in China translate to the global population? So this doesn't really give insights into that global translation question, but I think it's important that this is kind of a clinically relevant setting for this mechanism and this class

Simone Fishburn: 8:22

Yeah, I mean, that is just a hot company in a hot place. I think we're gonna return to it in the context of another topic in a minute, Jeff. But Bing Wang, who's the CFO of that company, was on the panel and on our podcast, in fact at the China Healthcare Summit last year. And Michelle Xia, the CEO of that company, has… I- I just have to say, you know, they've, they've really put it on the map in a way that's made people stand up and take notice

Lauren Martz: 8:52

A-and I'll a-add to that, that everyone is paying very close attention to the data that come out. So while this is overall incredibly positive there are all these new questions emerging from this data. one of them is, i-it looks like in this study, there was definitely an advantage over the, the PD-1 chemotherapy combination. There are some studies, there was a study of Keytruda, a different PD-1 inhibitor than the one used in this trial in China, where that, that PD-1 combination actually led to longer overall survival in a similar population than the ivonescimab arm of this study. So there are questions, you know, about how the comparator performed. I think it could- performed pretty consistently with how you would expect it to. If you break this down by different age groups, there are questions about whether the performance is the same across those age groups. So this will continue to be something that everyone is watching very, very closely. Um, and there's a ton of, ton of activity beyond this program within this class

Jeff Cranmer: 9:53

And BMS uh and BioNTech had a readout here as well, Lauren

Lauren Martz: 9:59

They did, and theirs was from a Phase II trial. it was in uh sorry, the HARMONi-6 is specifically in squamous non-small cell lung cancer, and uh the BMS was in non-squamous and squamous. So we don't have survival data yet for that Phase II/III study. The other difference between these two studies was that was a global trial. We do know that the response rates that they saw within the squamous population that could, could be compared across the two trials was consistent. So, you know, that starts to address that globalization question which I think is important.

Jeff Cranmer: 10:34

Lauren uh you're gonna have one of those great pieces that you do, the First in Human looking at what is new in the clinic. that's coming out later this week. Any top line on what you're seeing?

Lauren Martz: 10:47

Yeah. Uh, thanks, Jeff. It's an extension of what we saw from this analysis last year. And you have to keep in mind that what companies choose to include uh and present at ASCO and what ASCO chooses to include in this conference sort of bias these results. Um, and I think maybe this is a very innovative representation of what is actually happening in, in the first-in-human space. But it is really, really skewed towards first-in-class programs. there were about 100 first-in-class assets that are being presented in first-in-human studies at the conference based on our analysis, and there were about 40 that were either not first in class or um sort of the first-in-class question wasn't really relevant. Which I think it, it just reflects a ton of um new targets, new ways of addressing old targets. The other thing that I think is interesting is just the dominance of antibody-drug conjugates at this meeting. I think a few years ago when we were looking at deal trends, we were questioning whether this explosion in interest in, in ADCs was starting to die down. Um, but when you look at the results from, from conferences like ASCO, it's, it's just continuing to skyrocket. There were almost as many first-in-human antibody-drug conjugate trials as small molecule trials this year. There were many more ADCs than standard monoclonal antibodies. And then within that ADC space uh some of the trends that we've been talking ab-about quite a bit, the bispecific ADCs, the dual payload ADCs, the degrader antibody conjugates um immunostimulatory ADCs uh show up a few times. It's just a, a very hot space to watch

Simone Fishburn: 12:33

Wow, I can't believe we actually questioned that, Lauren. We probably shouldn't say that out loud. No, I'm just

Lauren Martz: 12:37

mistake. It was my mistake. You know, I, I do think the There were so many deals for, for a while there um especially cross-border deals, that we kind of saw the companies

Simone Fishburn: 12:47

W- well, we got everything else right, you

Lauren Martz: 12:49

ground. Yeah.

Jeff Cranmer: 12:50

Well, I, I like Lauren giving uh giving the word on the deals there. I wanna give a quick shout-out to the dealmakers out there in the world of biopharma. They clearly did not wanna be overshadowed by ASCO. we had David Lee and team at Servier acquiring uh the neurology business from Edgewise in a deal that topped $1.5 billion upfront. Servier our colleague Stephen Hansen tells us, he spoke with David a couple of hours ago. Stephen says Servier leaned on M&A to quickly establish its oncology franchise and is now hoping to replicate that strategy in neurology Edgewise being the first deal. Servier also very active in Asia. I guess this is no surprise, but Lilly had two deals that it announced. Both Asia deals. Um, I guess Asia's sort of the theme uh in biotech these days. Lilly is paying $75 million upfront for rights outside of Korea to a GLP-2 program from Hanmi, it's in Phase II for short bowel syndrome, and then it has a deal with uh Haisco a Chinese, a very large Chinese company. Uh, Lilly's paying $87 million upfront in a five-target small molecule discovery deal, the biobucks in the range of $3 billion. we're gonna take a quick break, and we're gonna talk uh it, it's gonna be BioCentury unchained, where we're gonna get a little opinionated in the second half here. But now this

Voice Talent: 14:34

This episode of BioCentury This Week is brought to you by the second BioCentury Grand Rounds Europe in Amsterdam, September 23rd to 25th. The 2nd Edition of BioCentury Grand Rounds Europe convenes the leaders shaping the future of biopharma. This time we meet in Amsterdam, September 23rd to 25th, gathering academic innovators, biotech CEOs, pharma R&D leaders and investors to debate the translational science that will define the next decade. Grand Rounds Europe focuses on what matters most: Breakthrough biology. Transformative technologies. And how to make early-stage R&D investable. Grand Rounds is where rigorous science meets real-world execution. Join BioCentury and Regional Host Chairs Forbian and BGV, and take a deep dive on translational opportunities in the Benelux region. BioCentury Grand Rounds Europe. Where discovery moves toward impact. Register at BiocenturyGrandRounds.com.

Jeff Cranmer: 15:46

Okay, we are back. very much looking forward to Grand Rounds Europe. Forbion is helping put together the meeting. It will be in Amsterdam, and of course, this week we kick off Grand Rounds US. It's our third Grand Rounds US. Uh, I can't promise you Jon Bon Jovi as we had the first year in Nashville. But I can promise you David Baker, you can go to biocenturygrandrounds.com. Josh, is that right? Biocenturygrandrounds.com.

Josh Berlin: 16:20

That's right, Jeff

Jeff Cranmer: 16:21

Sounds good. We're gonna hear more from Josh in a minute. BioCentury Grand Rounds, and we do reserve a few walk-up tickets. so if you're wandering around Seattle on Wednesday, Thursday, drop on by. All right. Uh, Josh and Simone, you uh you jumped into the fray last week and uh wrote a little piece about uh, China-US biotech rivalry. frenemy-ship. What, what are we calling it here?

Josh Berlin: 16:48

Yeah. So um th-thanks, Jeff, and thanks for having me on. Um, I really enjoyed teaming up with Simone on this piece, which is something that uh she and I have been talking about for many years, and some of our colleagues as well, some of our friends in both the West and uh in China. We felt like, you know, the crescendo of discussion, particularly on social media, has really risen over the last few months uh, particularly as all the deals have happened, and we thought it was time that we sort of said something, a-about it. Um, I don't want to speak for Simone, but I, you know, I've been traveling to China for, twenty plus years now, and I've seen it over and over, people underestimate the ability of China biopharma to innovate, and I think what we are seeing today out of China biotech is only the beginning, and if anything, the innovation is going to accelerate. You know, we're gonna see first-in-class China biotechs. We're gonna see China biotechs that become multinational players and develop drugs for patients everywhere. We're gonna see China fix its reimbursement system, which will reward both China biotechs and Western biotechs with better uh reimbursement for innovation. And as for my money, as long as everyone is competing fairly, that's great for patients. Uh, are some of the b- China biotechs we're reading about today going to fail? Um, absolutely. That's, that's biotech. It's a tough business. are there bad apples in China biotech? You know, absolutely, again, but, you know, we've had a few bad apples in the US biopharma industry through the years as well. I think it's time that, you know, everyone in the West comes to terms with the fact that, innovation is gonna come out of China that's hopefully gonna be helpful for patients everywhere. And BioCentury has been following this for a long time as have others. And we need to um adjust in the US and compete. If we do so, I think it'll be great for patients everywhere.

Simone Fishburn: 18:45

So I'm just gonna jump in. I mean, Josh and I were separately just fuming away, watching all this conversation unfold on different social media and conversations and so on. And so yeah, we got together, 'cause we're very much on the same page. And And I wanna jump back to the Akeso data, the Akeso summit data, because, you know, Josh, in my mind, this is really one of the sort of flexion points or trigger points in this journey in terms of the West. So just to remind everybody, Lauren, was it, like, two years ago, I think, we, when the initial data came out? And they, they did something that no one thought was imaginable, which is that they upstaged Keytruda. This little upstart company from China had data that suggested it could be better than Keytruda. That sort of meant that frankly, people just didn't have their eye on the amount of innovation that was coming out of China and the kind of work that they're doing there, which has only accelerated since then. And the more it accelerates, the more Josh and I hear people say, "Yeah, but you can't re- they're not really… You know, it's not real innovation." What's the latest one?"It's incremental innovation." And all of these kind of, the, what, latest one I've heard is it's peaked. And this is why I really think that there's just a lot of people burying their heads in the sand. And I gotta tell you, America, there's a lot of arrogance going into this. There's a lot of the idea that nobody could really challenge the primacy or supremacy of the US in biomedical science, which goes against everything we know, that scientists are found everywhere, that good science is found everywhere. And, you know, when you, when you enable it and you, Steve is gonna talk about the other side of this coin in a minute. But when you enable it, when you fund it, when you allow it to flourish, it's going to come out and it's going to compete. And so our call is really to people to sort of, you know, there's this idea that only true innovation comes from America. Certainly in biomedical science you hear this. The EV auto industry would tell you differently. Solar will tell you differently. High-speed rail will tell you differently. And so, our question or our position is go find out for yourself.

Steve Usdin: 21:10

so so one, one of the things that's interesting, so you mentioned EV, you mentioned high-speed rail and solar and so on, and that- that's part of a lot of the discussions in Washington now also. And the question is, is the life sciences like those to the extent that Chinese success comes at the expense necessarily of American ability to innovate? Uh, I think the answer is no, but I, I'd be interested in thinking and hearing what you say about that because that has a lot of implications for what the policy responses should be to what's happening in China

Simone Fishburn: 21:46

Well, well let's, let's put it this way. I think um so first of all, no. Medical science is not zero sum, right? First of all, there are patients everywhere. Innovation can come from everywhere. It is not the rise of China that is going to cause the demise in the US or any demise in the US. It is sort of the US held back on EVs, right? It's not that China was the only place that could do it. It's that the US actually just didn't compete except for Teslas, right? But we're not gonna go into all of that. Into every se- e- every other industry. But I think the parallels are more what do you continue to compete on on the merits, and competing on the merits. Medical science is a different thing. It is, in its nature, it is global and collaborative. Almost every drug that's come to market has come about through, you know, international collaboration. You've got to access patients everywhere to test it. I do think you're right to call out some differences, but the differences really are on the side of the consumer or in this case the patient, where it's really in their interest to have the discoveries made wherever they are made and brought globally as fast as possible. There can be no argument against that as far as I'm concerned.

Josh Berlin: 23:04

Yeah, I, I think that- that's right, Simone. And, and s- you know, Steve, you, followed this a long time also. You know, none of this happened overnight. Did it, did it happen quickly? Um, yeah, maybe it happened quickly, but it certainly wasn't overnight. And a lot of what we're seeing now develop and all the news flow about the deals and so forth, well, a lot of it is based off the fact that China made major regulatory reforms over the last, you know, 10 plus years. In many cases, essentially borrowing wholesale policies from the U- US FDA and ICH. The Hong Kong Exchange made major policy reforms, essentially borrowing policies from Nasdaq to allow pre-revenue biotechs to IPO. And, you know, maybe it's now time for the US to borrow a few policies from China, Australia, and elsewhere to help our biotechs get into the clinic quicker to uh de-risk assets for potential partners.

Jeff Cranmer: 24:03

Yeah,

Steve Usdin: 24:03

think that there

Jeff Cranmer: 24:04

Chinese government really takes sort of a holistic approach to developing its industries in a way that might uh you know, stand to benefit the US. Steve, I know um the other piece that I wanted to talk about uh or have you guys talk about today is uh Steve's piece, which it came out of this proposal from the OMB director, which uh frankly was quite shocking. Steve, do you wanna just uh bring folks up to speed who, who haven't, uh, been looped in?

Steve Usdin: 24:35

Sure. I, I I do. Uh, just really quickly, though, on the, the discussion we were just having now, I think one of the most positive and interesting things that's happening out of this discussion about competitional rivalry with China is a, is a really healthy discussion about what the United States needs to do to respond to improve the efficiency of biomedical innovation in the United States. One interesting contribution to that was also in BioCentury recently. David Beier from Bay City Capital had a, a commentary in, in BioCentury with his ideas. We've also, of course, over the years had a, a, a lot of discussion of what the United States needs to do. I even reflect back to the recent BioCentury show interview that I had with Karen Knudsen, the CEO of the Parker Institute, where she talked about her ideas for advancing translational science. But, the first thing we have to do is to stop shooting ourselves in the foot and maybe in the calf and in the knee and other parts of our body that we've been shooting ourselves in um over the last year and a half or so. So what I wrote about on Friday was something that's extraordinary. On Friday morning the OMB published a proposed rule in the Federal Register, whopping four hundred and twenty pages overhauling, proposing that they're gonna overhaul the way that all grants are handled in the United States, including, of course, NIH grants. It says that all-- that senior political appointees would have to review and approve every discretionary grant before their award, applying ideological criteria to individual grants. And it explicitly bars senior political appointees from deferring to peer reviewers. It makes expert peer review recommendations non-binding and says that political appointees can override scientific judgment without cause or findings of deficiency. It refers to a-an undefined standard of gold standard science being what American grants have to meet. It gives NIH and other grant-making agencies the authority to terminate any grant at any time without having any kind of due process, no finding of non-compliance or fraud. They can just cut it off at any time. it says that grant funds can't be used for a variety of of purposes having to do with communications. One of the more egregious things, I think, is that it says that an applicant can be denied a grant if they are affiliated with an organization that's deemed to threaten public safety or national security, which on its face, well, that might sound reasonable, but it doesn't define what threatening public safety or national security is. And the current administration has defined it in very broad ways to include potentially organizations like the NAACP or the Sierra Club. Actually, the way that, that uh the Trump administration has defined it, y-you could even say that Bio or PhRMA you know, being affiliated with those could be construed as being a threat to public safety or national security.

Jeff Cranmer: 27:47

How so, Steve?

Steve Usdin: 27:48

Oh, because both those organizations have advocated uh for actions to mitigate climate change and said that it should be a priority. They've advocated in the past and currently have positions on their websites advocating for diversity, equity, and inclusion in hiring practices and clinical trials and things like that. The rule also basically makes it impossible or extraordinarily difficult for anyone who receives grants in the United States to collaborate overseas, to have any kind of international collaborations on their grants. Also, backing up on the uh criteria for institutions, if anyone at an institution is involved in an activity that the administration finds to be um adverse to the American national interest, then that entire institution can be precluded from receiving grants. So if anyone at an elite university, if that university has a gender studies program or some other kind of program and something involving the Middle East politics or something that's completely unrelated to their scientific endeavors, everybody at that institution could be precluded from receiving a grant. Anyway, I could go on and on. There's a lot of different things that are in this, You know what, w- basically what I said in the commentary, and I believe it's true, is that this is really the biggest assault on American science since the advent of the current paradigm at, at the end of the Second World War.

Simone Fishburn: 29:17

You know, I have to say, I quite often try on this podcast to say, will it happen, or, you know, what's the other side of this point of view? But really on this one, actually, there is, to quote uh Fiddler on the Roof,"There is no other hand here." I think that it's so fundamental to what we do to allow academic freedom, right? That is part of the whole premise. And going back to what we said before, you started this, Steve, with shooting yourself in the foot in terms of science. As China, is accelerating, so we're making it a more hostile place with things like this for researchers. may not happen. We can, we can talk in a minute… Hang on. We can talk in a minute as to whether it will happen or not, but the more you put forward these kind of policies, the more hostile a place you are making this to science, sending out messages which, let, let's just say one more thing. If this comes to pass, it may well be that there are people who agree with this administration's policies and where they draw the line, but the next administration can do it in the other direction, right? You do not wanna politicize science. And so I think people need to be really thinking long-term about the consequences of this and what that would do, and that is one of the reasons why actually it's worked so well in this country to have an apolitical system for handing out grants

Steve Usdin: 30:47

and I think that a couple of things. One thing is to make it clear that what's being proposed is applying ideological and political tests at the level of individual grants. It's not saying, "Here's an overall policy that an administration has, and NIH should support that policy or should prioritize that policy," or something like that. It's saying each individual grant, and it's creating this level of uncertainty because any grant can be canceled at any time. Well, that's gonna have a chilling effect also because then anyone who's received a grant is going to have in the back of their head, well, if they say something or affiliate themselves with a view that the administration doesn't like, their grant could just be cut off and everybody-- their work could be stopped. Everybody who's depending on them for their livelihood and for their scientific careers could be put at risk. It's amazingly chilling. So when we get to the, "Well, is this gonna happen?" So this is a, a proposed rule. There's a forty-five-day comment period on it, and it's something that the administration believes that it can impose without without legislation. My guess is there are aspects of it that will be challenged in court. That's a very uncertain thing. It's very uncertain w-whether litigation would be successful, and even if it is, how long it would take and whether it would be comprehensive. So the, the thing that I called for in my commentary is for this very small group of people who I believe have a great deal of influence over President Trump on this particular issue to step up. And the people that I'm referring to are the CEOs of the largest pharmaceutical companies in the United States, the largest pharmaceutical companies in the world. Many of them have President Trump's cell phone number. They all have his ear. They've all done deals with the administration on MFN. They've done deals on onshoring. They're part of an ongoing dialogue with the administration on um drug pricing, on Trump Rx, and things like that. I think that it's really critical for them to intervene. There isn't time to build uh you know, a massive political consensus, and this isn't the kind of issue that's going to affect electoral policies. It's not something where the Trump administration's gonna look at this and say, "Well, they, they have to calibrate whatever they do with consideration, for example, of the midterm elections. That's not likely. So basically what I've said is that the CEOs of the largest pharmaceutical companies in the world, which have benefited tremendously from publicly funded research and will benefit tremendously from publicly funded research going forward, need to intervene. They have been silent for the entire Trump administration about issues having to do with biomedical research funding. I'm told that there were PhRMA board meetings early in administration where PhRMA CEOs brought up the idea and said, you know, "Should PhRMA as a trade association weigh in on, on this issue?" And there was an explicit vote to say no, that they, they shouldn't because there were other things that were higher priorities to them. I've heard from people who work closely with the CEOs of some of these companies that they've decided that this is an issue that they're not going to expend their political capital on, and that they believe that, for example, because there are universities in many congressional districts that they can do the, the necessary lobbying and things like that. I think that's an untenable position at this point. The other thing that some representatives or some people who work closely with um the CEOs of some of these companies have told me is that, "Oh, well, you know, intervention by the CEOs wouldn't be effective," that um that the administration you know, you can't uh overturn a policy that's advocated by Russell Vought, who's the head of OMB, by the Heritage Foundation, by uh the Silicon Valley techno-libertarians. And I would say that there's evidence to say that that's, you know, absolutely not true. There was a, an executive order that was drafted it circulated around Washington on AI. It was ready to go out and uh and it was held back. The uh the president hit the pause button on that because there were executives, there were leaders of l- the-- some of the largest tech companies in the world and some of the most prominent investors in the world who pushed him to, change the policy, and it worked. And I would say closer to home, you could look at the administration's decision To provide liability protections or extend liability protections for the manufacturer of Roundup, the um the herbicide. That's something that HHS Secretary Kennedy came into office saying that he was going to try to ban um the use of this herbicide and economic and uh economic interests in, the food industry persuaded the uh the president and the administration to take a, step that 180 degrees different from what the HHS secretary wanted and from what um many constituents in the MAHA movement wanted. So it is possible to affect change. It would be possible, I think, to prevent this from happening, and I think that the most effective way for that to happen would be for the PhRMA CEOs they're already engaged in communications personally with the president to intervene

Jeff Cranmer: 36:18

All right. Well, Steve's commentary along with Simone and Josh's and the David Beier piece, which is excellent as well all in front of the paywall. I'll drop links in the show notes. Before we go Steve you had a great conversation with Richard Pops, who he handles negotiations on PDUFA. He's led uh bio. He's uh became a CEO at 28. Any favorite moments of the conversation?

Steve Usdin: 36:47

So it, it was a great conversation. So uh Richard Pops is the CEO. He's stepping down soon as the CEO of Alkermes. He is gonna remain as the chair of Alkermes. It's, it's really gonna be interesting to see what else he does in his kind of post-CEO life there. You know, as you said, first thing I asked him, 'cause I've known him, I've known Richard for at least 20 years, and I've always been meaning to ask him, I never did, was, you know, how does somebody become the CEO of a pharmaceutical company at the age of 28? His first response to that was, "Well, it's ill-advised." But but it's, it's worked out. It's worked out for him. It's worked out for Alkermes. And, and look, this is a company that's been through the whole biotech rollercoaster um an IPO uh near-death experiences, activist investors, complete response letters, setbacks at the FDA, difficulties with PBMs and reimbursement, and a, a great deal of success also in millions of people who have benefited from their drugs. What was really interesting to me about the conversation was mapping how public policy changes have changed the landscape for drug development in a very specific way. How he as CEO had to change not only how he did things, but what he could do, what kinds of drugs he could develop how he would price them, and how he would market them. He's had to continually change that over the decades in response to the changing public policy environment, and it's led him to try to change that public policy environment in ways that he believed would make it possible for him to develop medicines that are gonna be better for patients and um that patients would be able to have access to.

Jeff Cranmer: 38:30

All right. And that conversation, of course, on our sister podcast, The BioCentury Show available wherever you get your podcasts. And if you uh are into the video format head over to our YouTube channel. And if you like what you're hearing here or there subscribe, leave us a comment, and we appreciate you listening. Simone, Lauren, Josh, Steve thanks for all the, the good commentary today. And, and Cole, our production engineer, good to have you back. Kendall Square Orchestra provides the music for BioCentury's podcasts. We will catch you next week