Jef Akst: Hello, welcome back from the holiday weekend. You guys do anything fun?

Annalee: literally just garden. I mean, it's not a holiday here in Canada, but like I did get to enjoy a day off. I went golfing and then I was finally able to plant out into my garden. So busy, busy weekend.

Jef Akst: I love that. How about you, Gabby?

The Weekly 5.12: Yeah, I went on a 10 mile bike ride. was super nice. It rained a little bit and I got extremely sunburned. I was like, how is this happening? it was overall good.

Annalee: It always, it always takes me like three or four sunburns before I finally get the point and start wearing sunscreen every year.

The Weekly 5.12: Yeah.

Jef Akst: And those overcast days will trick you. You think that you're in the clear and those are the worst.

Annalee: Yeah. been doing sunscreen on my face, but like I'm really working on my farmer's tan now that I have my garden. So like I it's looking really nice guys. So.

The Weekly 5.12: Nath, how was your weekend? heard it was someone's birthday.

Jef Akst: Yes, yeah. Today, Tuesday is technically my birthday, but my family celebrated over the weekend. My daughter threw me a cute little backyard party with the cutest fox piñata. I have never had a piñata at one of my birthday parties before, so that was very special. Guess I had to wait till 43 to make that happen. Candy, lots of candy. No, they got Sour Patch because they know I like Sour Patch, among other things. It was good.

Annalee: What did she put in it?

The Weekly 5.12: Yeah.

Annalee: My kids would probably put rocks or something in it just eat the candy. Aw, that's so sweet.

Jef Akst: Well, let's get to our show. Obviously it's Lily, Lily and more Lily, but let's start by introducing ourselves. Lee, you want to go first?

Annalee: Yeah, I'm Anneli Armstrong. I'm senior editor at Biospace and I do the weekly Biofarm executive newsletter.

The Weekly 5.12: And I'm Gabrielle Mason. ⁓ I prepare our weekly brief and then our gene pool newsletter.

Jef Akst: and I'm Jeff Axt, managing editor. Our other senior editor, Heather McKenzie, is out enjoying a little bit of a break right now, but I'll put in a plug for her weekly newsletter, Clinica Space, which normally goes out on Mondays, but should have hit your inboxes today, Tuesday, on this holiday week. So again, diving in to Lily. There are a few different elements of Lily that we'll need to touch on. They have swept the headlines today and after making several headlines last week. But today's big one was their vaccine trifecta. So they made this slew of deals on top of the many, deals they've already been making. Annali, you covered that.

Annalee: Yes, this one was of the crazier deals that I've seen in pharma recently. has bought three separate companies. I had never heard of any of these companies, maybe the last one. So they're buying Curevo, Lima Tech Biologics and the Vaccines Company, the aptly named Biotech. this is... ⁓ Lilly is going to pay a $3.8 billion total. There were upfront fees and some milestones. Those were not broken down. So kind of a small outlay, but a really critical acquisition for Lilly. They are to acquire across this kind of portfolio of biotechs, they're going to get shots for shingles, bacterial pathogens, one for Epstein-Barr Lilly has kind of framed this as a way to prevent diseases that are known to cause long-term complications. Epstein-Barr, for example, has been linked to multiple sclerosis and multiple cancers. This a big cluster of deals from Lilly and suggests that they are moving in this infectious disease trajectory.

Jef Akst: And just to be clear, these are all earlier stage in development or even preclinical. None of these are close to market just yet.

Annalee: Yes, think the late we saw there was one that was phase one, one that was in phase two, we're still trying to actually confirm some of that information. So early early stuff, kind of represents what been doing, which is trying to bolster their early stage pipeline with some of this money that they've made from their GLP ones.

Jef Akst: And then of course, vaccines. We can't talk about this space without talking about Peter Marks, the famed vaccine regulator who left the FDA early in Trump's term after pledging to stay and work with the new administration. And then that was not tenable and he left under not great circumstances.

Annalee: Yeah, so Peter Marks is apparently going to be the leader in charge of all these companies, which is fantastic. It seems like Lilly has essentially bought him a pipeline. couple analysts pointed this out. So he is now going to be in charge of these three companies shaping Lilly's vaccine policy. So pretty cool ⁓ role for as he kind of puts the FDA in the rear view.

Jef Akst: Yeah, and as we kind of commented, you said this morning, think, Annali, kind of explains we were a little confused when Marks first went to Lilly after leaving the FDA, but here we go. Now he's got a pipeline to work with.

Annalee: Yeah. And like, now there's an opinion we should have put out on the podcast. Cause I was like, why is Lily hiring Marks? mean, of course why he's a, you know, a well-known leader in this space. Like obviously he's like the vaccines regulator in here. so it made sense, but it was still just like, well, Lily doesn't really have an infectious disease pipeline. So we wondered if they were going to make an acquisition here they are. We should have put that in public. ⁓ Jeff, we, know, although if put everything in public, a lot of our stuff would be, you know, just.

Jef Akst: Yeah, exactly. We gotta keep some stuff close to the fence.

Annalee: We wouldn't always get it right, but it feels really good. I just want to say that we did call this behind the scenes.

Jef Akst: Yeah, but it's also interesting. mean, one of the reasons, the main reason that Mark cited for his leaving the FDA was challenges in the vaccine market with RFK, a known vaccine skeptic stepping up as secretary of the Health and Human Services Department. that hasn't changed. mean, the vaccine sector as a whole has continued to face headwinds because of this ideology that now sits on top of HHS. And we have watched vaccine makers struggle. We have watched vaccine makers such as Moderna cancel trials. So this is kind of interesting to see Lily doubling down in this space.

Annalee: Yeah, I think deals are really crucial. All of these companies, Sanofi, Merck, GSK, they have all reported declines in vaccine sales that has actually been becoming material their earnings report. So here is Eli Lilly, which is now the biggest pharma company in the world saying, we still believe in vaccines. We still believe in coming up with preventatives for infectious diseases. what is going on in the regulatory environment and maybe some of the vaccine hesitancy does not matter to our future business. that is, I think, a really powerful endorsement of vaccines. They're not alone. Pfizer has done a licensing deal with Novavax. Sanofi acquired Dynavax year. So companies are seeing this as an opportunity right now. And that's fantastic because we do need more vaccines. ⁓

Jef Akst: it Sanofi CEO who said buy the dip or whatever it or something along those lines?

Annalee: Yeah, for sure. Paul Hudson, has now moved on, unfortunately, from Sanofi. But, you know, another thing kind of key about this is Curevo, which is one of the companies that Lilly is buying. They have a shingles vaccine, and Lilly thinks that they can do better on tolerability, which has been a bit of a challenge with GSK's approved vaccine, Shingrix, which is, you know, one of their most well-known products. So there's some real interesting dynamics here.

Jef Akst: Yeah.

Annalee: And I think it's safe to say that vaccines are alive and well in the pipelines of pharma at the

Jef Akst: Well, that's certainly good to hear. We won't get into the public health side of the discussion, but I love hearing the pharma investment and the pipeline continuing to grow there. And of course, these three deals, those are just the most recent of this week. This week alone, we have more Lilly deals. So Gabby, you covered one last week. Why don't you tell us about that one?

The Weekly 5.12: Yeah, it's kind of unbelievable, honestly, but the three buyouts that were announced kind of follow a separate acquisition just last week by Lilly. So in that deal, the pharma offered up to $202 million for a pre-clinical biotech, which is fairly notable, that doesn't have any publicly disclosed pipeline programs, but touts a non-viral DNA delivery platform. The science is supposed to address current limitations in DNA delivery help Lilly bolster its genetic medicine candidates. Somehow that's not the only deal that was last week for Lilly either. They made a nothing

Jef Akst: And that one was EngageBio. You had some good ⁓ puns with that one. I loved it. Lily engaged to a new biotech or whatever it was.

The Weekly 5.12: Yes, that was a really fun one to write. I love when the biotechs have punny names that we can have some fun with in the headlines and things. So yes, that was EngageBio. And then they also made another deal. That one continues their commitment to AI by teaming up with Collaborative Drug Discovery. And they provide data management solutions for life sciences. So that was actually one of three Pharma AI collabs announced last week with teaming up with Anthropic to use Claude among many realms of its business. And then Insight also expanded its relationship with Genesis Molecular AI in hopes of discovering at least five new ⁓ disease So ⁓ it's to see so many deals just in the sector in general. It's been pretty busy. this quarter and this year.

Annalee: Yeah, I think what's key about all of these deals too, is that they're very early stage. We were seeing a lot of ⁓ &A specifically tipped towards late stage. we started to hear analysts say, listen, all the kind of low hanging fruit or like the real, you know, obvious programs have been picked off. But now companies are starting to go early stage, which is exactly what we need to start getting some more innovation into the sector. So it's a really great sign.

Jef Akst: Yeah.

The Weekly 5.12: Mm-hmm.

Jef Akst: Agreed, yeah, those earlier stage pipelines. And then also the continued investment in AI. I mean, it's nonstop, but it's good to understand more about how the companies are using it and we get little peeks and insights with these deals. All right, well, Lily, because of all of this dealing has been placed as Pharma's top dog by Idea Pharma, which for eight years now has been rating drug makers based on how well they can take a small molecule drug, a theoretical small molecule drug, not a specific one, but just the idea of taking the drug. through early and clinical development and then executing a successful commercial strategy. They kind of idea pharma that does this analysis breaks it down into two parts. There's the invention side where you've got the idea and you bring it through early and clinical development. And then there's the innovation part, which is that commercial application part of it. And again, I am a real proponent of... treating these two things differently and looking at them differently after the whole Bluebird bio incident where they got three marketed gene therapies and they can't make ends meet. So I think it's really appropriate to look both at the science and at the commercial prowess of these companies. So Idea Pharma ranks the pharma. They've been doing it for eight years in a row. is at the top, ⁓ just of one, but of both. It's the first time that Idea Pharma has done this analysis and a single company has taken the cake on both sides. It's not a surprise. We started the show, Lilly is stealing all of our headlines. Their sales are surging up almost 50 % year over year. And then of course, this rapidly growing pipeline that they continue to fill with these deals. And then also on top of great deals and a good pipeline, they also have some pretty positive readouts coming on. That pipeline is doing quite well. So that's a little nice transition to another huge Lilly headline in the past week to update you on is their next-gen weight loss asset. So Anneli, tell us about that.

Annalee: Yeah, so the data that we saw for Rettitrutide, which is one of ⁓ next-gen obesity assets, is a really good example of what Idea was talking about. In this latest readout, the drug to weight loss of 70 pounds, ⁓ or 28.3 after 80 weeks, ⁓ which is, believe, the highest that we've seen. This is a drug that Lily has positioned to be used for more severe obesity cases. they also had a low dose group that had really strong data as well. In arm, was 19 % weight loss or 47.2 pounds at that same ⁓ time BMO Capital Markets said that this data point kind of suggests that Reta-Trutide could be tailored to patients. So it's not just for these severe obesity cases.

Jef Akst: So if it's typically for the more extreme though, are there going to be a little bit more flexibility with the tolerability profile?

Annalee: Yeah, so this drug has had kind of an interesting safety profile. ⁓ earlier studies, there were cases of dysesthesia, which is a neurological condition that causes normal sensations to feel unusual or painful. So that was a bit of a weird one that emerged. And I believe it's the first time that some of these weight loss drugs have seen something like that. So the rate of dysesthesia in this latest readout, it did rise along with the dose. So the higher dose group saw more instances of this. So there were about 12.5 % of patients who reported it in that high dose arm. This was, however, lower than the earlier study. And analysts were pretty satisfied with not only the lower side effect rate, but lower discontinuation rates in this readout. So I guess it's just another win for Lily.

Jef Akst: They just keep coming. And then there was another one too, Gabby, Lily. Yeah, no, there's still more. But there's more. Their verve Lily bought a verve last year, but they had a readout recently that, again, another win for Lily.

Annalee: We're not done with Lily.

The Weekly 5.12: Yeah, so they bought VIRB for 1.3 billion, so a hefty chunk of change. And that included the company's gene therapy that's designed to treat a condition that it raises the risk of early heart disease. So now an ongoing phase 1b trial has shown that the base editor lowers bad cholesterol or LDL cholesterol levels. So a single dose was actually seen to lower LDL cholesterol levels by 62%. So that billion dollar buy seems to really, really be paying off.

Jef Akst: Interesting to see gene therapy applied to cardiovascular. It'll be, I mean, there's a lot of options currently on the market, but I've heard a lot of chatter about moving more and more toward those preventive therapies. And I wonder if this could maybe fall into that category or at least just be less chronic treatment than we currently see.

The Weekly 5.12: Yeah, you don't see that a lot at all and you don't really see gene therapies as preventative either. So really interesting on all aspects.

Jef Akst: early stage, but one to watch for sure. All right, well, long last, I do think we've wrapped up most of our Lilly headlines there. course, we'll have more for you on that, whatever giant is doing next week. I'm sure they'll make more headlines throughout the week, but let's pivot now. So another company we do wanna touch on today is Moderna. So Moderna, I mentioned them earlier in the show when we were talking about the vaccine space, well-known company in the vaccine space having brought COVID-19 vaccines to market and... the company kind of skyrocketed in the pandemic heyday, has struggled though since then, of course, as many vaccine makers have, they have actually canceled a lot of their ⁓ stage vaccine trials in infectious disease and is more focusing on their cancer vaccines at this point. But we are in the midst of some hantavirus fears. So what's going on there, Annalee, you're gonna take this one.

Annalee: so we had a story that out last week talking about kind of the fear that is happening ⁓ amid this of hantavirus cases that stem a ship. So some scary stuff coming of there. And this is kind of, ⁓ know, renewed interest a little in Moderna specifically, Moderna was the company, remember, like very quickly made one of the COVID-19 vaccines. ⁓ was really developed at lightning speed thanks to Moderna's mRNA platform. So this moment with hantavirus has kind of brought analysts back. And Moderna has experienced a bit of a surprise uptick in their share price recently as this has been going on. Now, Moderna has not exactly come out and said, hey, we're going to develop a vaccine for hantavirus. However, they have some work that they've done kind of with some in the more academic setting. So Analysts don't really expect this to be a major market for Moderna, but this could be a great moment for them to kind of remind the world of what they're capable of. I believe Jeffrey said that this could help them build goodwill amid a general downturn in vaccine rates in the US.

Jef Akst: I think just general sentiment on how this antivirus scare is going to just bring public attention back towards the public health side of vaccines and maybe push back a little bit more about, again, some of the anti-vaccine moves that we've seen in the administration. So specifically are just public health and vaccines broadly. Maybe there's a silver lining to this antivirus outbreak right now.

Annalee: Mm-hmm. Right. And some of these infectious disease outbreaks can be kind of tricky ⁓ biopharmists to navigate. it can be a big risk. So it's not always something that companies want to jump into.

Jef Akst: Yeah. Or it can be like the biggest thing in a hundred years with COVID and then those companies, Moderna, Viontech, absolutely. Yep. Well, also on Moderna and again, getting back to their mRNA vaccines for these infectious diseases, we can all think back to February. We coined it Moderna gate when FDA and specifically former CBA director Vinay Prasad served Moderna with a refuse to file for their mRNA based flu So this is

Annalee: Like Moderna and Beyond Tech.

Jef Akst: Not a rejection. This is a rejection of the application to even review it, which came as a shock. FDA Commissioner Marty McCary was pulled up to Donald Trump's office. And then within a week or so, the FDA did accept that application and it is now under review. But Gabby, give us the update on what's going on there.

The Weekly 5.12: Yeah, I think it's interesting that move was the first time that really prompted focal industry wide backlash under this new kind of administration. And so ⁓ obviously, like you said, the agency reverse course ⁓ they've set up an adcom for the application, which is particularly interesting given the lack of adcoms we've seen under this FDA. So vaccine panel. set to meet on June So that's definitely something we'll be watching very closely.

Jef Akst: Yeah, you're right. We just covered the AstraZeneca adcom just a couple of weeks ago. And that was the first one after a nine month drought of no adcoms at all at the FDA. the adcoms have been a particular focus for former commissioner Marty McCary. One of the first moves he made when he stepped into that role was to limit industry involvement or to make formal rule that if you served an industry, you couldn't serve on adcoms. And this was a bit of a challenge, especially in the vaccine space where so much of that expertise comes from industry. And then the FDA instituted these expert panels, which it was never really clear how they differed from ad coms other than couple that they had before these kind of petered out seemed very stacked. the we got was they were just trying to support a specific agenda. So there wasn't a lot of positive reception to those. And then, like I said, this drought, nothing, no expert panels, no ad coms, and still lot of decisions that industry was questioning. So I'm glad to see ad coms coming back, especially for a controversial decision like this. You need that. external expertise to kind of guide the FDA. And then it will be especially interesting as these ad coms come back, will the FDA follow the ad coms? I know Heather has put together some stats on historically how often does the FDA follow the ad com advice. ⁓ I would be curious to see if that differs as we start to bring ad coms back into the cycle.

Annalee: I have to say from a productivity perspective, I haven't missed all day ad comms, but has really, it's a great picture into the regulatory process that you really, up until, now we're these complete response letters, but previously you really didn't know what the FDA was thinking unless there was an comm held. So it's a really great transparency effort that I think is lacking at the FDA and really always has

The Weekly 5.12: Yeah. ⁓

Jef Akst: you And nowhere do we need more transparency than vaccines and mRNA vaccines specifically, so.

The Weekly 5.12: I do think it's interesting because typically a lot of these ad coms are saved for rare diseases or really therapies gene therapies that aren't tested in a ton of patients. So it interesting to see it in something like a flu shot, which would be a lot more commonplace. I think you're right. It's good to see this transparency, especially around something that has been so controversial with all the vaccine skepticism. ⁓ But yeah, just typically something that I wouldn't consider maybe ⁓ that would go up for an adcom. But think ⁓ in current day and age that we're in, it makes sense.

Jef Akst: Yeah. All right. So we'll watch for that. That's next month. Next, sooner than next month, Friday, all eyes will be on ASCO. So the American Society of Clinical Oncology kicks off May 29th out in Chicago. We have a preview of the meeting out today in Clinica space. ⁓ I'll give you a couple of high points from that as we look forward to that. Revolution, we all were paying attention last month when their investigational pill nearly doubled overall survival in pancreatic cancer. That was really exciting and they have a plenary at ASCO to give more data on that. Experts that we spoke to are really eager for a little bit more information on the depth of the response and the results based on patient-specific mutation. And then also toxicities, Heather has covered this. there has been a high rate around 30 % had serious side effects and even more, vast majority of patients had a rash. I think they're really analysts and industry watchers are really curious to learn more about revolution specific data. And then those companies that are challenging revolution in the pancreatic cancer space or competing with them and bringing new therapies to market are also focused on making that tolerability profile better for patients.

Annalee: ⁓ gonna be standing room only, I bet. It's gonna be hard to find a seat there.

Jef Akst: Agreed agreed another one that might have that same problem another plan area this one was given to a queso which has the summit therapeutics partnered by specific Ivan eskima This is the PD one veg F by specific antibody that has been closely watched since summit ⁓ with a queso and The trial results are ⁓ were primarily coming out of China and this one, you know grew to popularity by being known as the Keytruda killer and outperformed Keytruda in one of these China trials. specifically with progression free survival, really positive data just last October from the European Society for Medical Oncology Congress. So this was all the rage. This is gonna be the next big thing until we started seeing some of the global clinical trials come out. And with a broader patient population, there were less stellar progression free survival results. Still, ⁓ you know, enough to keep moving the therapy forward, but not the key true to killer that the industry maybe had once thought we were looking at. the data that are going to be coming out at ASCO this week are for overall survival, not progression free survival. So this is what everybody's waiting to see. You know, we have progression free survival, but often overall survival lag. So we want to see good data there, but this is another, this is a China trial. This is Harmony 6. And so what a couple of experts that we spoke with were saying is basically you need ⁓ overall survival data coming out of China, if you expect those numbers to drop as you put this into global testing. So everyone will be curious, what is the overall survival data that Akiso can report? ⁓ going to need to be better than you would have wanted to see in a global trial because this is China only data. So that and much, much more coming out at ASCO later this week. We'll be following that closely. So stay tuned to Biospace for that. And then just to wrap up our show, we always do, Anna Lee, what can you tell us about BioPharm Executive this week?

Annalee: Yeah, so we have our annual Executive Compensation Special Edition. So entire ⁓ BioPharm newsletter is going to be about our recent ⁓ compensation analysis. We've been kind of teasing this all month, talking about the stories we've been putting out. So as as you are subscribed to BioPharm Executive, you will get that in your inboxes. ⁓ If you not already subscribed, please do so at the top right corner of our website. ⁓ You will missing out if you don't. ⁓

Jef Akst: Definitely check that out. That's one of my favorite special editions of the year. It's always kind of mind blowing to see what these people make. And I know you put out a number of stories, but having that all pulled together is definitely a good read. So that's it for our show today. Thank you for listening and we'll see you next week. and welcome to Biospaces the Weekly. I'm your host, Jeff Axt, and today is the Lilly Show. This wasn't planned as a special episode, but Eli Lilly stole all the headlines this week with nearly half a dozen new deals to add to its already record-setting year, not to mention benchmark-setting weight loss results for its next-gen obesity treatment. Outside of Lilly, we will touch on Moderna's once-re-buffed mRNA flu vaccine as well as its antivirus vaccine projects, and we'll also provide a preview to the upcoming ASCO meeting, which kicks off this Friday in Chicago. Let's get started.