mRNA Hot Takes: Fighting Complacency And "Alternative Facts" In 2026

Anna Rose Welch: Hello everyone and welcome to Advancing RNA's MRNA Hot Takes, the show where we talk about serious RNA things, but with a spicy twist. I'm your host, Anna Rose Welch, the editorial and community director of Advancing RNA. And I am once again over the moon to be joined by two leaders in the RNA world who entertained my off-the-wall dreams to make this show a reality. So, a round of virtual applause and my endless gratitude go out to our stars, Sophia Lugo, the CEO of Radar Therapeutics, and Michelle Lynn Hall, general partner of the VC firm, Entree Bio. I will never not be thanking you ladies for joining me. So, thank you, thank you, thank you for joining us and keeping us informed, and I would say just as importantly entertained. You're here to entertain us as well.

So, the concept here, ladies and gentlemen of mRNA hot takes is pretty simple. We'll be talking about the scientific and business world of mRNA, but that's where the normalcy ends. We're going to be trying to carry on these conversations while also seeing how well we handled the heat of a hot pepper. As we learned last time, the jalapeno was a little bit much for one of us...

Michelle Lynn Hall: And I know that one of y'all was trash talking and was spreading rumors about how-

Welch: No, I was going to say, Michelle, not to name names, but you just outed yourself. We crowned Sophia the jalapeno queen. So last week, last episode, we faced down the jalapeno, which, for those of you who are interested in Scoville units, is anywhere between 2,500 and 8,000 Scoville units.

Hall: I argue mine was higher.

Welch: That is what you will always say. You will take that argument to the grave. Meanwhile, Sophia ate half a jar of pickled jalapenos after eating two whole jalapenos.

Hall: It was really annoying.

Welch: Last week, we faced down the jalapeno. This week we have a new contestant on the block, and this is a pepper that clocks in anywhere between 6,000 and 23,000 Scoville units. So that is, ladies and gentlemen, the Serrano pepper. Are you two ready for the Serrano? Michelle's like, absolutely not. This is going to be a disaster.

I feel like I have a surge of confidence that I can handle this and this could be a terrible, terrible idea.

Hall: We'll find out.

Welch: I know. I know. All right. So, are you two ready? Are you two ready to rumble here? Yeah.

Sophia Lugo: I'm ready.

Welch: All right. Well, cheers to you, ladies. Here we go.

Hall: Notice I'm not goading her this time because I've been properly humbled.

Lugo: Just wishing for the best. We won't do the seed check this time.

Hall: Wait, I could have removed the seeds? Let me do that.

Welch: I needed to get some seeds so I couldn't be chastised. All right. So, we're turning it to you ladies as I deal with this experience that's happening right now in my mouth. All right. I'm going to start… Michelle — she's already drinking water — I'm going to start with you this week.

Hall: I'm not drinking milk yet.

Welch: I know that's true.

Hall: Okay. You're going to start with me. All right. But wait — can I introduce my pepper first

Welch: Please introduce your pepper!

Hall: Okay, because I'm really excited about this one. I did not get this one from my local farmer's market here in Boston. My darling husband is New Mexican, and he happened to be in New Mexico, which, if you ask any New Mexican is, quote, the chili capital of the world. Just throwing that out there. And so, he went and got me a pepper from the farmer's market in New Mexico. However, we had to push this filming back by a week, which means that pepper got a little moldy. So, what we have done is cut out the moldy parts to create essentially one full serrano fresh from New Mexico.

Welch: Do you think, Michelle, that mold makes a pepper spicier?

Hall: I think mold is likely to make me sick. Throwing that out there.

Welch: Alright. This is the risk of this show. As you enter into the realm of eating a previously moldy pepper with us, I want you to put on your RNA thinking cap and tell us, if you had to create a wish list of the top two to three developments you want to see happen throughout 2026 in the year ahead, that's going to improve the growth trajectory for the mRNA industry moving forward, what would those two to three very exciting events be, and why?

Hall: Eat first, answer second?

Welch: Eat first, answer, second. I'm going to take another bite. I don't know. I'm not impressed by the serrano. I'm not impressed.

Lugo: We have to move to hot sauces where we know exactly how much spice is coming in.

Hall: There could be batch to batch variability.

Welch: There is. These are biosimilars.

Hall: All right. I'm okay so far.

Welch: Same. Same. Glad I bought a couple of these. I don't know. I'm going to have to try another one.

Hall: All right. There's a bunch of things. Number one: It's starting to hit. Number two: RFK Jr. Immediate resignation. That is the thing I would be the most excited about. So did you all see yesterday — so today's Thursday the 20^th — Yesterday, the CDC website on vaccines was changed. Did you notice this?

Welch: I saw a headline about this.

Hall: Well, in case you didn't, I printed it out.

Welch: Oh, excellent. Please share.

Hall: The CDC — Oh, there it is!

Welch: That serrano is kicking in

Speaker 3 (06:27):

Hall: The CDC website now reads, and I quote, "The claim vaccines do not cause autism is not an evidenced-based claim."

Welch: Oh dear.

Hall: “Studies supporting a link between vaccines and autism have been ignored by health authorities, and the Department of Health and Human Services is launching a comprehensive assessment of the causes of autism, including investigations on plausible biologic mechanisms and potential causal links with mRNA.”

So, the one thing I would be most excited about is the resignation of RFK Jr. I have other things, but that's my spiciest take.

Welch: Yeah, a reversal of that policy change or that text would be exquisite.

Hall: There was one quote that I really, really liked. So, NPR published an article on this earlier today. Favorite quote. Ready?

Dr. Paul Offitt, pediatrician and director of the Vaccine Education Center at the Children's Hospital of Philadelphia said, and I quote, “These are usual anti-vaccine tropes, misrepresentation of studies, false equivalence.” Here's my favorite part. "They might as well say chicken nuggets might cause autism because you can't prove that either."

Welch: They should put that onto a t-shirt.

Hall: Yes. Anyway, that's my favorite.

Welch: That's beautiful. That's beautiful. All right. So, the resignation of RFK. I don't think you're going to be the only person to desire that by any stretch, especially after this. You ate another bite. You're still surviving somehow. Do you have another top two or three that you think for 2026 that you want to get into here before we have Sophia join us?

Hall: I'm dying. Okay. Wait, hang on. Can I have water?

Lugo: The more you wait, the spicier it'll be.

Hall: Wait, really?

Welch: Yeah. Sophia’s the pepper queen. She knows what she's doing.

Hall: All right. So, it would be really easy and obvious to say extra hepatic delivery because that's what everybody says. So, I'm not going to say that.

What I am going to say is global access to mRNA vaccines, especially in low- and middle-income countries, especially point of care manufacturing, miniaturized manufacturing so that we can combat novel zoonoses at the origin before they spread and become global pandemics. That would be number two on my list behind RFK Jr. resigning.

And then number three on my list would be — not to plug Sophia too much here — but I think we have talked a lot about delivery, and I think there's a really long way [panting] for mRNA drug substance to go. I think tuning in specificity at the tissue and cellular level [panting], as well as— I'm like, Oh man, I'm really dying here.

Welch: And she's from Texas!

Hall: Yeah, but I'm a redhead! As well as the durability. I think we were all really excited about circular mRNA, and it has moved the needle, but I think there's still a lot farther to go. If you think about a circular mRNA, it can express for weeks. Ideally, if you think about a DNA, a DNA can be transcribed and translated for years. So, I would love to see us bridge that gap between weeks and years. Have mRNAs that are far more durable or somebody figure out how to do non-viral delivery of DNA that is not immunogenic. So, that's what I'm really excited about.

Now can I have milk?

Welch: Not yet. That's the cool down question, sweetheart. Take another bite. Just keep adding.

Sophia is going to join us now. So, we've had durability, we've got global access. We have the resignation of RFK Jr. These are all on the wish list for 2026. Sophia, what would you be adding to this list? What are your top three? If you had to guess what 2026 is going to bring to the table or what you would love to see happen, tell us.

Lugo: So, I'm not in the chili capital of the world. I'm in London, which is maybe the bland food capital of the world.

Hall: No, they've got a great curry.

Lugo: Except for the curry.

Welch: Curry's great.

Lugo: So, I really tried hard to find a Serrano. I have found chilies that are spicy. Not really sure what they are, but I'll be eating them, as they're spicy.

Welch: Please. I'll take another bite, as well, to join you in this journey.

Lugo: It does look like a serrano. It’s already spicy.

Hall: Watch, she's just eating a Thai chili. No big deal.

Welch: Okay. This one's definitely worse than the first one.

Lugo: I did buy Thai chilies in case these were not spicy, so I was like, okay, I would need to compensate. Yeah. Okay. It goes to the back of your throat very quickly.

Welch: Yes, it does. Oh, gosh.

Lugo: So maybe I'm going to pretend this is the end of 2024, and we are still talking about the excitement behind the platform guidance that had been issued.

So, to me, it is about regulators. We need regulators to, yes, focus on the science, and by science, I mean experts who are actually seeking truth by studying the natural world. So, yes, what I'm going to advocate for are regulators that continue to be focused on the science and that are continuing to embrace this platform model because that was very new. I'm particularly thinking about products with variable mRNA sequences for streamlined entry into the clinic. I don't think we clearly saw that in the platform designation that the FDA sent out in 2024. Obviously, the impact here is trying to shave months off development where it's not needed. And yes, there's been some talk on bespoke therapies, but it doesn't just have to be N-of-1; it's getting a genetic medicine to be as personalized as possible to be effective, and there are going to be different technologies that tackle that in different ways. So, to me, let's continue to build on the conversation that started, but kind of got stalled in 2024.

The UK MHRA drafted guidance for personalized mRNA cancer immunotherapies that would allow for single marketing applications to cover where they might be the same backbone or the same LNP formulation or process, but we'll just look at like there's a different protein produced every time. So, there has been work done.

Again, in 2024, there was a lot of excitement, but I think it was incomplete. Really very strong work with industry earlier in the cycle that looks at what parts of the mRNA are fixed — and I'm focusing on the payload here — but what parts are fixed and what parts are variable? Where can danger actually come from, so that we can minimize the amount of data that needs to be reassessed? That's downtime that doesn't really help patients. I do think you're going to have to actually — which maybe this year's not the right time — but you're going to have to increase regulatory capacity to do that. You're going to have to increase the number of smart people that are willing to talk to companies even earlier.

Welch: I would agree. There hasn't been as much talk this year, at least in 2025, about this guidance. It was hugely celebrated in 2024. We did see Sarepta got awarded a platform designation, which was then taken away as this year has gone on. So, it feels like it's maybe fallen slightly out of favor to some extent in discussion and/or has taken a backseat to all of the policy upheaval that's been shaping our space this year.

Lugo: Right. And we all have to remember: What is the objective? The objective is to get things to patients faster. It's lower cost of drug development. It's speeding up timelines for innovation and to impact. If something is invented today, we don't want 30 years for it to actually produce patient benefit. The FDA has been very focused on patient safety. If regulators actually fell to the urgency of patients and brought clinicians more into this process too, because they see it, there would maybe be a recalculation of the risk versus benefit and a more tailored approach. So yes, it feels like it could be end of 2024 when I'm saying this, but we need to refocus there.

Hall: But your point is a good one, right? And the people running HHS right now are not clinicians. They're not PhDs, they're not MDs. And I'm not trying to say that one must have higher education in order to have an intelligent and informed opinion on this, but to Sophia's point, they aren't intimate with this and so they aren't feeling the impact. I think it's noteworthy that one of the biggest opponents of the FDA upheaval and misinformation has been, notably, a Republican from Louisiana, Bill Cassidy, who is, you guessed it, a physician himself. So, I think to build on Sophia's point, people who are in this who do see patient urgency understand.

Welch: Absolutely. And the MHRA guidance really did hit on focusing on the caretaker and the physician as well. So, if we're looking at that push from other agencies to start focusing the discussion on what that very important audience has to — they have to be included in this discussion as well and be a big part of that moving forward.

Lugo: Yeah. Put patients in patients in every room and the conversation changes.

Hall: But do you think it's just about a lack of familiarity and intimacy, or do you think there's something else going on? I'm asking the question in a leading way, so I'm sure you know my opinion.

Welch: It’s a hot pepper question.

Lugo: In 2018, I was in a room with Dr. Hamburg, who was the former head of USFDA and many Chinese regulators and representatives of pharma from China and the US. This is 2018. And, at the time, China, I think by the end of 2017, China had more CAR-T trials going on in China than the US — and they’d been invented in the US. And so, the conversation then, which echoes today, but the conversation then was the US regulators were trying to harmonize the regulatory approval process, trying to ... If there could be more harmonization, there might be more allowance of Chinese developed drugs into the US regulatory process. And there's of course this political push for China not to get the ... I don't know what is the ... It's really not renowned in CAR T, but it really felt like that for China to slow down and the US needs to speed up. So that's what the conversation was. And the US didn't bring clinicians, but the Chinese did bring clinicians. There were two clinicians in the room trying to describe what their patients were going through, how they could slow down; Why would they slow down? That was the essence of their message.

And so, I'd say that there's a lot of things going on with the Chinese regulatory process; a real focus on slashing downtime for the regulatory process, but there's also a different calculation of risk benefit that's somewhat ... I don't know what ingrains it into the regulators, but it is certainly a different calculation. And I found it quite interesting that there were two clinician representatives there trying to explain what these patients were going through and that these patients really want to take on this risk. And how could they say no? They had nothing else to give them.

Hall: I also think China's been really at the front in promoting investigator-initiated trials, and I don't think we have done as good of a job over here in the West. And I don't think we're going to do a better job of that anytime soon. It's almost like the Chinese government is pushing to decrease regulatory hurdles, speed up clinical trials, speed up access to patients, and we're doing the exact opposite. And so I think it's really interesting to me — and that's great for science that it is continuing to have life and vivacity over in Asia Pacific. But I think it's also really terrifying for those of us doing drug discovery and development in North America watching that shift focus over there and watching the focus shift and knowing this was totally preventable. Sophia's talking about things she saw seven years ago. We don't have to let this situation persist. We can continue to invest in science, in patients, here in the US today.

Welch: My eyes are watering. That’s a new development.

Hall: HA!

Lugo: Well, I'm on Chile number two…

Hall: Oh, she's so annoying. I need

Welch: To be fair. I'm on chili number two as well, but number one was somewhat disappointing. I'm not going to lie. So yeah, these are biosimilars. I'm going to do one more bite here. But as we're thinking through — and I want to be cognizant of time as well — so Sophia, we had a discussion about your hopes and dreams for 2026. Is there anything really quick, top of mind, any other developments that you're really excited to see happen in 2026? I'm sure there are.

Speaker 1 (20:06):

Lugo: Well, I'm a company, and I was just at Jefferies in London, and what a company is looking for is signals of optimism. And so, yes, my wishlist is definitely a resurgence of biotech investments. But for me, we've seen a lot of funds actually raise a lot of money, but I'm really hoping for a move away from the mega rounds and to more distributed bets on very good science.

Hall: Agreed.

Lugo: We need to be making distributed bets on good science. We need to actually hold operators to account for how they efficiently spend that money. You need to see that an operator can learn faster than their burn rate. And to me, different operators, different business models, it is a different way of distributing risk that can help new technologies come forward. We do need operators that are more willing to change how we make drugs, because there is a break in the model right now. China is surging with a new model, and they're, in a way, showing us the way to actually make drugs faster and more efficiently, and we have to learn what we can.

For me, I'm hopeful of a return of generalist investors; that always signals higher market confidence. I think the public markets and biotech have always suffered from low transaction volume. And this is bad because even for ... I'm really interested in platform technologies. The idea is that you can build a backbone infrastructure, a set of assays and protocols that let you develop the next drug faster. Obviously for mRNA, this is a real play for everybody in the mRNA space. And when these platform companies are pushed towards the binary risk, single asset model, one bad data event can knock down so much work that could have had impact on patients because the transaction volumes are so low. So, we need a way to support risky, an inherently risky business.

And so yeah, I think the return of more sizable rounds that distribute bets, and the return of generalist investors would be amazing. Crypto and generative AI: these are deep tech; they're hard to evaluate for non-insiders, and they have a massive amount of generalist investment that also brings with it positive public sentiment — or at least guided public sentiment. People want to learn more. So, I think more measured deployment is good; more break in the business model; more distributed bets; and, generally, more influx of capital that also supports platforms. And by platforms, I really mean allow platforms to actually build deeper pipelines because that's what's going to get us to actually be able to develop drugs faster for diseases that we haven't before been able to do.

Welch: Absolutely. Well, my mouth is on fire. I need to drink milk. So, as Sophia takes another bite of her second pepper — is this one hotter Sophia?

Lugo: No, I actually think I need another green one because this one is not hot.

Hall: Do it. Do the tiny one.

Welch: Do the tiny one.

Hall: Oh my God she did the whole thing. What the — Oh, she's experiencing things.

Welch: Alright. Well, and on that note, for this cool down question, Sophia, as you're digesting that pepper and it sets your mouth on fire… In my cube in the office, I have a statement by Oscar Wilde: A poet can survive anything but a misprint. So, I want to pretend that our buddy Oscar Wilde here was writing about the mRNA industry. So, I want you to complete the following statement for me: “The mRNA industry can survive everything but what?” And why do you feel that way?

Lugo: Complacency. Michelle started this call saying it just right. It is very clear that mRNA is not in a stable place. The public doesn't have a high level of understanding of what we do. I think I've said before that ... See, this one was spicy.

Hall: I'm actually seeing you suffer. It makes me feel a little bit better.

Welch: I’m not going to lie, people, this pepper is toppling the queen!

Lugo: I don't have milk because I didn't think of buying milk while I was searching for actually hot peppers.

Welch: She was so confident. She was so confident she'd be fine.

Lugo: I'm going to make it through this question because suffering is good when you're pushing a boulder uphill, which is what the mRNA industry is doing. It's what we're doing.

The public doesn't have a high level of understanding. And when people don't have understanding, it can create fears or theories that aren't well supported. And governments — particularly our government — it can react negatively to concepts where people don't have high trust. So, I am someone who does not believe the arc of the universe naturally bends towards justice. You have to use collective willpower and force to get it to justice. Anyone who works in innovation, you have to push a boulder up a mountain while walking on glass sometimes, and that's what creates change. And mRNA had a huge influx of capital that got us very excited and made a big leap in the COVID years, but we clearly see that if we don’t put a lot of willpower into making mRNA happen and making innovation happen, it will not happen. We are not in a place of stability. Every company, everyone who has access to regulators and government, and people who have a voice that the general public listens to, we should be motivating everybody to get behind this molecule that really could go after so many diseases at the molecular level.

Hall: And saved many, many lives.

Welch: Michelle, it's your turn.

Hall: I think we can survive everything except the erosion of public trust. To me, it is deeply concerning when you can no longer go to the website for the CDC, who should be the authority on disease control in the United States, and you can no longer trust the information there. I think that puts us in a really precarious situation as a society and as scientists and developers of mRNA medicines. And, so, I know that there's a push, at least here in Massachusetts, to form an alternative to the CDC. Here we go. We're now embracing alternative facts. And I mean, it's terrifying that we have to bifurcate like that. But there needs to be a place where the public can go and look things up and know that what they're looking up is based in science and explained in a way that is accessible and digestible. And, so, I think we can survive everything except the erosion of public trust.

Welch: That's a beautiful response.

Well, ladies, I hate to let you go, but we're at the top of our hour here. So, I want to thank you so much for sharing your thoughts and getting spicy with us.

Sophia, did you win again?

Lugo: I cooled down with the second chili, which had some-

Welch: She cooled down with another chili for God's sake.

Lugo: I love playing games I can win.

Welch: We’re going to have to keep making these spicier. We're just going to have to keep making these spicier.

Hall: Can we do this next time with really stinky cheeses, because I'm very confident I could take y'all.

Lugo: No, that one I cannot do.

Welch: I also can't do the stinky cheeses. But I really appreciate both of you joining me on this lovely adventure. Thank you all for watching with us and experiencing this with us. I can't wait to sit down with you again for our next installment. So, thanks, and we'll see you next time.