mRNA Hot Takes: Ghost Peppers & Global R&D

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 continue to be stunned at the sheer bravery of the two ladies that are joining me for this ongoing journey into spiciness: Sophia Lugo, CEO of Radar Therapeutics, and Michelle Lynn Hall, general partner of the VC firm, Entrée Bio. Woo-hoo, right? You guys are so excited for today.

Michelle Lynn Hall: Oh, so excited.

Welch: We are back to talk about the scientific and business world of mRNA. But those of you who have tuned in before will know that we don't just have a basic discussion. We handle these very serious conversations while also setting our mouths on fire with hot peppers.

In the past few weeks, we have tackled the jalapeno, the serrano, the Thai chili, and the habanero.

But ladies and gentlemen, we are not going to be messing around here today. This week, we are taking it about a million steps further up the Scoville scale, literally. That's right — this week, we are going to be tackling the infamous ghost pepper. For those of you keeping count, the ghost pepper comes in at 855,000-1,041,000 Scoville units compared to the habanero, which is now just a meager 100,000-350,000 Scovilles.

Now, if I had been truly smart when designing our Hot Takes journey, I probably would've filmed this during the summer when we actually had access to fresh peppers so that you would be able to see us eating a normal ghost pepper.

But as it is January, I made it completely impossible for us to continue down this spicy path without having to gravitate towards hot sauces. So, I've supplied us each with a ghost pepper sauce called Zombie Apocalypse by Torchbearer Sauces, and the main ingredient of the sauce is ghost pepper, but it does have some habanero.

Hall: Let's see. Ingredient number one is something I can't pronounce, which is translated as Ghost Chili.

No mercy ingredient number two is habanero, so…

Welch: There are also some carrots and mandarin oranges, tomatoes, garlic, and the usual. 

But yes, we're going to embark on this journey for those of you who are watching. So, you're welcome in advance. Our pain is for your pleasure?

Hall: Schadenfreude?

Welch: Sure. Yeah. So, we are going to be trying our luck with the sauce while we tackle our question this week. I'm going to start us off because I've gotten us into this journey. I'm going to pour a little bit of this sauce into a spoon because again, purity is everything in this world. Alright, I've put maybe a little dollop in there.

Hall: Bold.

Welch: Thank you. Thank you. I like to live boldly.

Sophia Lugo: Good luck!

Welch: Thank you. Here we go. Here goes nothing.

Hall: We believe in you.

Welch: There it is. There it is.

Hall: I'm not doing a dollop. I'm doing a dot.

Welch: Okay. I'm going to try to read this question, though my mouth is watering insanely. So, I'm going to start with you, Sophia, and then we'll jump to you, Michelle.

Lugo: No, that means I have to have the hot pepper sauce first.

Welch: I'm surviving, guys. I'm surviving. This is good. I may have more; I may be a little bit of a glutton for punishment.

But the question for you today, Sophia: If we want to do good science in the mRNA field, should we be staying in the US or should we be looking and working elsewhere?

Bottoms up.

Lugo: All right. Here ... [Holding up spoon of sauce]

Hall: Oh my god, that’s a lot.  

Welch: That's a healthy serving.

Hall: She's good at this.

Lugo: It's not that bad, actually. It's quite delicious. Free advertising for Torchbearer Sauces here.

Welch: I was going to say, I like the flavor of it. Michelle, you might be surprised.

Hall: We’ll see if I survive.

Welch: I mean, then again, you did choke up on a Jalapeno…

Lugo: Okay. So, good science in the mRNA field: I think that good science in the mRNA field is, thankfully, already geographically distributed. So, I imagine that the origin of the question is that the US seems to be…  

Hall: Go on, Sophia — What is the US doing?

Lugo: This is where it’s best that Michelle says the obvious things that the US administration is doing, but I think it's been very clear that the current US administration is not so interested in funding work at the academic level, which is typically where innovation surges. Certainly, innovation will surge from companies. So, if we think about Moderna, there were a slew of labs that sprung up next to Moderna headquarters in Kendall Square where a lot of good science was being done. Typically, this is the way that things happen. The communities of knowledge have to emerge, and typically it's universities that are good at it. And then there's a company that is headquartered and that will increase demand for a specialized skillset in this area. So, thankfully, this had already been geographically distributed. As we know, CureVac and BioNTech were in Germany, so there's already communities of knowledge there.

There was also a strong community in Boston. Some of those people from Boston have now emigrated to San Francisco and San Diego, and many of the companies that did big deals last year were actually in San Diego. So, I think currently in the US it's distributed, and there are many good places you can do science. In Germany, that was already the case, and, thankfully, it was already the case in the pandemic that other countries were taking bets on this.

So, on the science side, China has already been investing a lot of money, obviously, and I'll make some more comments on China, but China has already been investing since the pandemic. I think a question that often comes up is: How did China not invent the mRNA vaccine itself during the pandemic? I can't answer that question, but I do know that they paid attention to how powerful the mRNA vaccine was and invested a lot of money into it. So, funding has surged year over year for mRNA research initiatives in China. There are now billions of dollars allocated to mRNA research in China, and I think they even did a billion-dollar collaboration agreement with Moderna. That might be more on the manufacturing front, but it’s clear that they're really interested in mRNA research and have now allocated billions.

Singapore had already launched a Biofoundry in 2024, and the idea was: Through their nucleic acid therapeutics initiative, could they start to prepare for new mRNA vaccines and new mRNA therapeutics? And so, the idea was, can we have good research and good ability to manufacture anything that's coming for our local market?

And then last year, Singapore launched a national initiative for RNA biology. Singapore is already a country that includes the top university in Asia for biological research, which is the National University of Singapore, and you can tell that they've made a concerted effort. It's about $130 million going into mechanistic understandings of different modalities of RNA. So, I think they're interested in RNA modifications and how they affect immune responses. They're interested in particularly Asian genetic diversity, interested in RNA delivery and distribution within cells. I've also met with a party from the Western University of Australia who's really interested in getting Australia to pay attention to the importance of RNA and being on the forefront of both RNA biology and having manufacturing capabilities set up.

So, I think regardless of what the US is doing, it's like a global phenomenon that people understand the importance of RNA. Even developing countries understand that what they saw was vaccine timelines getting…I think it was more than half — I think it was like one-seventh the time of a normal vaccine. You can really shorten the time of vaccine development, and a lot of these developing countries have needs for new vaccines. Let's think of the rabies vaccine; there’s not enough of a population in the US. We probably won't see a US company work on it unless there's an incentive to do that. mRNA vaccines now allow for that. So, I think that developing countries understand, developed countries also understand, and while the US has more of a chaotic situation, other countries have made more investments in buckling down in the mRNA space.

So good science is being done everywhere. If it's going to be choosing between the US or another country, I think one thing to note is that I do not foresee the Chinese government suddenly becoming immigrant friendly. They have an issue with population decline, and they're doing basically everything to combat that issue and prepare except for being open to immigration. So I think this is where the US has traditionally been good — Let's disregard what's going on right now. Traditionally the US has been good at trying to attract the best talent in the world irrespective of nationality or gender. Singapore has been doing this, as well, with the resources that they have. China does not do this. It is not irrespective of nationality. I don't expect that to change. It’s Han Chinese first and Chinese national focused. So, I think if you're in the US and you're wondering where to do good science, there will be more labs that are globally distributed and countries trying to get you there.

When I was recently in Singapore, it was clear that ASTAR NUS had been purposefully opening more faculty positions trying to attract top talent from US labs that had struggled with funding in the current environment, and they were doing it successfully. They had dozens and dozens — up to hundreds — of applications for each position from really good scientists. Many are capitalizing on the shifts, and I think that, thankfully, I'll put it this way, if you're doing good science, there should be an opportunity for you.

I think for the first time, these opportunities are going to be attractive enough to not do them in the US.

Welch: I think there's a positive light to this, too, in the sense that we talk about RNA being something that is necessary around the world; we want it accessed; we want that science to be accessible to different nations that may not necessarily have always been able to have access to it before. I've heard that there is more push towards South America; we’re tech transferring manufacturing processes down there to start developing vaccines. I've been watching the work that's being done in Singapore quite excitedly, actually, and now that I hear more about some of the work that they're doing in terms of understanding the mechanisms behind how it performs, that's the foundational information that we absolutely need. We often just push forward quickly, but we need to understand that foundational science really, really well still to this day.

Lugo: I'll add one thing, and I'll earn my addition by having one more little spoon, but —

Hall: She’s just showing off.

Welch: I've taken three spoonfuls. It might not have shown, but…

Lugo: Michelle, here you go. [Shows spoon]

Hall: I knew you were tough. You didn't need to prove it.

Lugo: At some point I'll be just drinking from the bottle.

Welch: I know. It's good though, isn't it? It's actually a really delicious sauce.

Lugo: What I'll note is that when we talk about what is good science — there's a spectrum of things that are good science, but doing the frontier science, science where no one's gone before, high risk science, the US is still very special in being risk friendly. This is both from a company and company formation side and from a scientific institution side. This is still the environment where scientists are willing to do science where no one has gone before. I think the pseudo-U modification Nobel Prize to Kariko, specifically, I think that story was said over and over on how she wanted to take a bet in something no one believed in. The US still has opportunities to do that. I don't suddenly see other countries becoming super risk-friendly. I still see this when we talk to VCs from different geographies; that's like a cultural undertone that you can always tell. At Radar, we're doing frontier stuff. We have reason to believe it's going to work; no one has made it work before. And I do see when we talk to Japanese funds, European funds, UK funds, even Singaporean funds, they're almost not used to seeing frontier science — or their bar for data is so much higher. Or they'll ... We get asked right away, "What's our GMP manufacturing strategy?" And I'm like, "Ah, let's reassess."

Hall: It’s way too early for that.

Lugo: Exactly. I can tell you one, but that's not the crux of what you should be hearing in the presentation. So, I still think that when it comes to those parts of the value chain, the US is very risk-friendly. In phase one, we're seeing other countries be more risk-friendly and taking innovation forward, but this is on the science side.

So, I hope that good science doesn't just become the “de-risked” science over and over. So, it's great that more countries are interested in mRNA, but the US has a special role to play, and we should be proud of that, and that's what we need to remind the administration. We should be proud of all the Nobels we have and the high-risk science that was done in university and then at companies; that is an American aspect. We should be proud of it and investing in more. It's clear that good science does follow dollars invested. So, that's what I'll say there. We cannot expect to have that suddenly form in other parts of the world.

Welch: That's a beautiful point.

Michelle, your time is nigh. I want to hear your take on this question. I thought Sophia's point about some of the funding trends that she's noting were interesting. So now that you are on the VC side of things —

Hall: And an international one, no less.

Are you ready?

Welch: We're ready. [Hall swigs directly from the hot sauce bottle]

Lugo: Oh no. Now it's a competition.

Hall: Holy hell.

Welch: Ladies and gentlemen, she just drank from the bottle.

Hall: It is pretty good though; you're not wrong.

Alright. So, first, I'm dying. Second, what do we mean by good science? So just for the framing of the discussion: If we're talking about translational and clinical, I would argue if you want to do good science, every bone in my body would be ecstatic to see better and more extensive deployment of mRNA vaccines for novel infectious diseases in low- and middle-income countries at the point of emergence. But I'm going to assume that for the sake of discussion, we're talking about basic preclinical research.

Welch: Yep.

Hall: Okay. That was to gain me a little bit of time.

Alright. So, first, unless you've had your head in a hole in the ground, you may have noticed that things around here seem to be getting weird — and, by around here, I mean in the US. So August, the US canceled 500 million of mRNA research. So here we're basically chipping away at mRNA research. Meanwhile, Sophia already told you about Singapore, which is great. Also last year, Australia, the government of New South Wales, announced six million Australian dollars in RNA pipeline grants, specifically for RNA therapeutics, vaccines, and related tech. So, it's almost like the US is like, “Yeah, basic research, especially not mRNA, no,” whereas other countries are saying, “Absolutely yes.”

It would be reasonable for you to take those data points in isolation and say, holy crap, we got to get out of the US if we want to do basic preclinical research in mRNA.

But let's look at the full picture. So, mRNA does not exist alone. mRNA has to come with typically a nanocarrier, as well as different therapeutic disease area biology expertise and clinical expertise. So that's where I think it's really interesting to look at different international hotspots. So, the UK, for example, has a really strong infrastructure for bench to bedside; the NHS and the MHRA are super supportive. So, if you were looking to take your mRNA quickly bench to bedside, that would be a cool place to work. Germany and Switzerland have fabulous manufacturing. Maybe to Sophia's earlier point, these are also the VCs who are going to ask you about your GMP, and also the Swiss Franc is infamously the most stable currency during geopolitical turmoil. So, there's like a cultural fabric that's embedded in how the VCs invest, how the country thinks about their monetary policy, and then how their science evolves.

So, UK, Germany, Switzerland, Canada, especially around the University of Toronto, top-notch for computational biology. So, if you were thinking, “I want to crank out an mRNA engine that leverages a lot of computational biology infrastructure,” you would do it in Canada. Australia: Phase one clinical trials. And then I'm a little biased given that my fund’s anchor LP is in Israel, but Israel and South Korea are also really interesting because those are countries that spend greater than 5% of their GDP on R&D, where Israel in particular is really strong in genomics and AI and South Korea in particular is really strong in material science. Now, that volume-wise is still less than the US and China spend, but it is still a much greater fraction of the GDP than we spend in the US, which is like 3.5% on R&D and China, which is 2.5 %.

So, there's lots of areas you can go depending on what you want to do with mRNA research. And so, I think that's sort of the question. I personally know people who have immigrated from the US to those other countries specifically because they thought that they could do more of their research there. But zooming out and giving even more context to this: The US is still the single largest global R&D budget in the world, and that's written largely by the private sector. So even if RFK Jr. Goes on a tear again and decides to eliminate all NIH funding further — which, by the way, he is attempting to pass 40% budget cuts for the NIH budget this year — Congress is pushing back; write your Congress person. So, even if he goes on a tear, the large majority is still privately funded.

Now, China is catching up. They're a close second, and again, notably, their growth rate is much higher. So, it's reasonable to assume that the US and China will soon be neck and neck in terms of R&D spending.

However, the US is still also the largest market. So, your average American, for better or for worse, pays five to nine times the cost for our drugs that other countries do. Obviously that's been in the headlines recently with Donald Trump talking about negotiating drug prices. And so what that means for us in our industry is if we know the customer and the payer is going to be in the US, it behooves anybody who's making a product, be it a drug, be it a computer, to be closest to the patient for all of the reasons that you can imagine. So, I still think we are far away from the imminent decline of the United States biotech market, even in the much maligned and ill-informed, I should add, mRNA space.

And then I’m going to say one more thing since y'all got me on my soapbox and I survived my pepper bottle. Y'all know my feelings on RFK Jr., and they aren't warm or friendly, but I am not alone. So, between June and October, his disapproval ratings skyrocketed from 43% to 60%. So, America has gotten the memo and recalcitrant though he is, he is capable of changing his opinion. So, February when the measles outbreak started in West Texas, and he was downplaying it, well, April, he came around and was like, "Yeah, actually maybe we should get MMR vaccines." So, I hope, I pray this is temporary, and I do believe the US will continue alongside China to be a dominant place where biotech and basic research, preclinical research in mRNA, RNA, and genetic medicines can flourish in spite of everything we're seeing now.

Welch: I was going to say, I feel like headlines ... Oh, there's pepper. Okay. There it is. It's the whole throat clearing thing. That's where it's getting me. Also, my lips are on fire.

But no, I was going to say, especially coming out of JPM last week, which you both were at, I feel like I was seeing a lot of talk about China on LinkedIn. We continue to hear about the problematic approaches that are being taken in the US, and so this was at the base of my question. But it does seem, if you look at headlines, we are at risk of being annihilated. So, I really appreciate your take that we're still in this game.

Hall: I mean, there's lots of things that are very worth criticizing, like our science R&D budget versus our military budget. These are all very valid criticisms, but I think our demise is far from imminent, and I'm not trying to suggest complacency, just trying to suggest perspective.

Welch: Yes, yes, which is very healthy.

Lugo: I’m going to take another little sip because I wanted to add something. I'm just going to confirm what Michelle said, but I just want one more sip because I'm competitive now.

Hall: I love it. I love it.

Welch: I’ve created monsters.

Lugo: I think the habaneros were worse. This is quite tasty though.

Welch: I know. I'm wondering if fresh peppers would be better.

Hall: I will tell you, I'm a Cholula purist and even I like this sauce.

Lugo: I was going to say that it is very important to dissect what part of the value chain you're talking about, like Michelle noted. All innovation, even the surge of IIT trials in China or Phase one studies in Australia or UK or Europe, all the countries competing for Phase one and China competing for IIT and other countries competing for manufacturing: All of them are competing for the US market. So that is like Michelle said, still the case. What is a threat there is, of course, talks on pricing right now. So, MFN pricing: Some companies decided to make a deal with the president that aligns with MFN. The president is now pushing for Congress to make a law around MFN pricing. And that is going to be much worse for companies because you can't get away with whatever under the table commitment was made on a company—

Hall: Sophia, for people who don't know: Will you explain MFN?

Lugo: So, that's a good question because every company has defined MFN differently, but broadly: There's a developed country list — I think it has about eight countries on it that the administration has printed — and the US should be the second lowest pricing. I think that's the current broadest definition of MFN pricing.

Hall: MFN stands for Most Favored Nation?

Lugo: Thank you, yes. Most Favored Nation pricing. Essentially, we should get our drugs cheaper than others. Of course, because we are a large market that prices innovation in an upfront way, eventually it stops becoming exclusive. It’s kind of like a mortgage on a house. You have to pay upfront to own it, and then once you own it, the benefits are distributed to society. That's been the way that the US has funded this innovation. We do pay more upfront than other countries. We also get it first.

Hall: And we get more subsidized.

Lugo: Yes. So that's the way the US has done that. MFN really is particularly worrisome for companies that have a lot of their revenues from Medicaid. So, we're talking about government payment, which is really important to pricing. That’s why you see Pfizer going at it first because a lot of their revenue is not from Medicaid. But if a broader definition were applied, that becomes very difficult for companies. MFN pricing could make the industry rethink where it markets first. I think the US still will always have a large advantage because China has a drug pricing list that's pretty strict, and they're probably not going to come off of that.

You basically are on the drug pricing list and the idea is the Chinese government subsidizes a lot of drug creation and, therefore, people should get it cheaply. That's great, but companies don't want to launch there. The US is the other large market. I just don't see a place where the US is not the best market to launch, but we might have fewer drugs be Net Present Value [NPV] positive, so be worth the launch.

So, I'll note that, and that will also change the risk profile and the types of medicines that VCs are willing to fund. And so, VCs keep changing their minds. Is it rare drug or is it something that affects the broader population? And what age group: Young or old? Pediatric to geriatric. That actually matters. Those decisions do matter on what kind of innovation gets prioritized.

Welch: Interesting. But that does tend to flip-flop quite a bit, though. I feel like every couple of years we do that swap. Things become more risk averse. We're looking at larger populations or things become more specialized, tailored to smaller, orphan patient populations. It's fluid it seems.

Lugo: Yes, it's certainly fluid. And I think right now it's hard to make decisions. There's a bit too much turmoil. That's on the market side. If we look at the previous part of the value chain on, what does the FDA like to see? — that's also a place where, right now, it's hard to make decisions.

Welch: Well, I want to help cool us down a little bit. Now, I don't have milk, so I might drink more of my zombie apocalypse sauce — mostly because both of you drank it straight out of the bottle, and now I have imposter syndrome, so I feel like I have to do it. But this is noted. We're just going to drink straight out of the bottle next time.

Both of you did a beautiful job of pointing out what different nations are doing, some of the developments or ways that they're approaching drug development that is particularly helpful for advancing science. But if you had to pick one specific development that you've been watching take shape in another nation overseas that you're finding truly exciting in this space and worth watching, what would that be, and what makes it so exciting to you? What gives you hope for us as a global RNA industry?

Let's go with Michelle. Michelle, take us away.

Hall: Thank God. I feel like I've been running around waxing enthusiastic about Australia for a number of reasons. Number one, it feels like home. Certainly Northeastern Australia feels a lot like Texas, but with all the politeness of the Brits; it's really a magical, wonderful place, and I would very happily immigrate. Please dear God take me if the United States implodes.

Welch: If anyone from Australia is watching this, Michelle wants to move.

Hall: I've been very clear that I'm happy to move. But also, I just really love what they're doing in clinical trials. Clinical trial enablement, just everything the government itself is investing in, matching dollar for dollar investments with various consortia, and also all of the tax rebates and incentives for doing research there. I love it. Now, they're not unique in doing that, but what's really handy about Australia, if you are doing what Sophia mentioned which is thinking about commercializing in the US market, is Australia has a very similar population demographic to the United States. So, it is — one hopes, one expects — relatively facile to run your Phase one in Australia and then show that to a hopefully rational FDA and get approval for continuing Phase two over here in the US. And so, I love it. I think there's a really strong scientific talent base there, and they’re continuing to build infrastructure and support all the way up to the government level. That is something I'm really excited about.

Speaker 2 (33:54):

Welch: Their university system is pretty incredible too. They publish a lot of RNA research. They've been building a big RNA ecosystem that I've been watching over the past couple of years.

Hall: Well, because they learned. With COVID, they were not able to get the vaccines. They did not have sovereign manufacturing. And good for them, they said, "We're never going to do that again. We're going to build sovereign manufacturing, and we're not going to stop at manufacturing. We're going to build the research infrastructure as well." And of course, there's obstacles in the way, including a 12-hour time zone difference from, let's say, Boston and New York, and a 36 to 48-hour journey to get there.

Welch: They're hardcore though. I mean, I've had people from Australia on panel discussions at 2:00 AM their time. They don't mess around.

Hall: Yeah, so I'm really excited about what I see there.

Welch: That’s a great response. Alright, Sophia, what are you most excited about or heartened by that you're seeing?

Lugo: I'm going to go for more hot sauce instead of milk because it's actually pretty tasty. I like to brag too.

Welch: You can go to your next meeting and tell people, “Yeah, I just drank half a bottle of ghost pepper hot sauce.”

Lugo: Yeah. So, my vote right now is on Singapore. I think that it's helpful, too, that Singapore has a proximity to China where there's a lot of innovation on the “get in humans fast” and manufacturing and particularly what I call “innovation on the edges” — So something where you can just really engineer something to perform better than what's available. I think they're getting very good at that. It also has easier access to Australia. It's kind of interfacing Korea, Japan. It's already a place that has been super focused on bringing in the best talent. And so, if you visit NUS or ASTAR, there are researchers from India, from China, from US, from Australia, they're there. So, I like that concept. We should bring in the best talent from all over the world and they buy into that. So, I've liked that.

I also do like that there's a concerted effort on mechanistic understandings of RNA. And, what I like too is, I think China did a great job of this idea of we're going to form special economic zones where similar companies come together, and if you are missing a reagent, you can go next door and get it. And we're going to really invest in a particular type of expertise to exist in a certain place. So chemical manufacturing is the first attempt for Shanghai, and now that's become drug manufacturing, but this idea that you should physically co-locate communities of talent and nationalize materials. Singapore is trying to do that. Of course, they're much smaller, but they have this biopolis where essentially they have an incubator that they've built for their companies there. They have universities surrounding the biopolis. They have an office for their regulatory body there. The idea is, a startup should be able to walk down the street and walk in the door and ask a question. It's not like the FDA where you have to really plan for your one question session you get in your FDA Interact. You should be able to walk down the street and ask a question, and then it's not far from a clinic. So, the idea of, can we actually co-locate a lot of the value chain?

And, if you go to Singapore, it's easy to meet everyone in charge of every part of it very quickly. Obviously, it's a smaller country and they know that their patient population is not very large and might not be representative of every disease. But they're trying to make sure that they take in the best of all worlds.

Obviously, they're more politically derisked than China, and they understand that a traditional weakness they've had is taking the great foundational research they have and making it translational. There’s an effort being spearheaded by Gene Yeo at UCSD to get them to understand: How does foundational research become translational research? And he's somebody who's been involved in many, many companies. So, there's a concerted effort there to try to get their researchers to work with companies to get research out of university into the translational side.

So, I think that they're doing a great job, or they've at least noted what they have to work on.

Welch: Beautiful.

Well, ladies, we are out of time for today but look at you: Both of you have drunk from the bottle. You have survived the zombie apocalypse, which I believe was supposed to eat our brains. I think we all still have a brain, right? So, we've succeeded. Go forth and prosper with your new hot sauces. Please enjoy them. It's fun for the whole family.

And for those of you still watching, thank you so much for joining us. You know where to find us. We'll be back. We've got one more challenge facing us. So, stay tuned for the excitement. Thank you for watching, and thanks to Sophia and Michelle for being such willing participants in this challenge with me.