Sionna Therapeutics Inc at Citi Global Healthcare Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Yeah. So welcome. I mean maybe just to kick it off, Mike, just give us like the two-minute type of elevator pitch. I mean I know the category, you guys do, too, but I think for those on the webcast, maybe for a bit of a background.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Yeah. Let's take a step back before we start talking about the pipeline and the mechanism and obviously, the CF population, the sort of technology platform, the kind of the R&D platform. Talk a little bit about how you think Sionna is doing something unique and NBD1 focus is unique, but the kind of the discovery engine that you could backfill a number of assets in the pipeline with?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : One of the first approach is adding on to standard of care. So talk a little bit about what you guys view as the unmet need or the opportunity to further expand standard and then we'll talk about you and your individual assets.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : That makes sense. Have you guys done market research in terms of the patients that are on a modular today, the ones that are suboptimal responders or the dropout of therapy, the reasons why and maybe that could help guide kind of how your product portfolio going forward?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : No, it's just interesting that you have all the Phase 3 data for, say, Trikafta and for ALYFTREK, but in the real world, may have a different experience. And you just don't hear about that, right, from a lot of pulmonologists that maybe for various reasons, like patients can't tolerate the highest dose, so they don't get the FEV1 that was promised. So Charlotte, you mentioned sweat chloride, so is that becoming more of a metric like in the community to help sort of put a patients kind of where they are from a maintenance perspective?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : That makes sense. And Mike, you talked about the strategy here with the add-on and then the ability to move up on the efficacy and improve the profile. So talk a little bit about the selection process between 719 and 451? What attributes of the compounds kind of drove your decisions of one path versus another?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Yes. Let's talk about that a little bit. So 719, the timeline for data and then maybe -- and you guys view like what does success look like that maybe will inform your decision to raise capital and to go into a larger study?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : In sort of the stability the patients on Trikafta, I'm assuming that they have to be on drug for an extended period and maybe they can't have a lot of sweat chloride variability from like timepoint? I just -- maybe help us with like kind of the lead into that.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Just given your experience with these compounds, is there a direct correlation between whatever points of sweat chloride could translate to X points of FEV1? Is it -- if you had 10 or 20, does that mean like a 2 or 3 points of FEV1?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : I mean, CF drugs used to be approved on a 2% FEV1, right, so prior to Vertex. Yeah. Let's talk a little bit about the dual combination. So just give us the timelines for maybe a proof-of-concept. What are -- maybe -- and also what are the challenges of developing that in the context of kind of accepted standard of care today?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Can you look you know, OUS, in areas maybe where Vertex is not well adopted or maybe not reimbursed. I mean because I think initially, there is a long -- you probably know this better than anyone, the hesitation from -- in the UK, right? I mean there's a three-year negotiation where everyone was jumping on clinical trials there because you had an identified population, but they weren't on drug. But that's less the case now, right? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 04, 2025 / 2:45PM, SION.OQ - Sionna Therapeutics Inc at Citi Global Healthcare Conference

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : And maybe at a higher level, where do the assets from AbbVie and Galapagos fall into your priority list?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : And so the capital that you have now, though, you can develop both strategies, right? But then how do the assets that you in-licensed kind of fall into that in terms of the -- maybe the R&D spend?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Would you say that in-licensing more compounds is maybe less of a priority? You just have to figure out the assets that you have today and the --

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : In CF, would there be any emphasis, so Mike, on adding drugs for ex-mutation, premature stop? I know that that's a different mechanism, not NBD1 related and there's a whole like cats and dogs of technologies that have used in that. It's been not easy, right, of a population.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Makes sense. Let me ask you just about the economics of it, right? So the comment we always hear is all these drugs are expensive to begin with. So if you can improve FEV1 on the back of a $250,000 therapy, right, so what does the value of that -- like have you guys done any payer studies or things like that? What does that mean to eventually a patient outcome or it's not just quality of life, right? I mean legitimately like you're improving the pathophysiology of disease.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Yeah. The dual.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Right. Yeah. It does seem like when you look OUS or our geographies, US, Western Europe, Australia or the kind of the core Vertex markets, but there are many others you don't hear anything about, Eastern Europe, Middle East, like South America, Latin America overall. Like so there are pockets of, I think, around the globe where this is truly a global market, probably ex-Asia. But my point is that like there are many avenues you could -- there are many different payer discussions you have depending on where you are in the economic spectrum.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Yeah. So I guess the follow-on to that is that, okay, if you look forward into -- I know, I mean, Charlotte did me a Phase 3, it's what -- let's get to the proof-of-concept first. But when you start to think about how that could -- what would be the theoretical design of that, that's probably maybe in the back of people's mind, like, all right, like that's not an easy trial to run. But it could be something where if you had a strong argument and a proof-of-concept to switch for a much -- for a step-up in therapy, then that would be a very straightforward trial to run. So I guess, obviously, data-dependent. But get your perspective on maybe what would a pivotal down the road look like.

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Right. And if you go back to the proof-of-concept studies, Mike, I mean, are you -- you're pretty confident in the predictability. I guess you mentioned the HBE assays, I think, for Vertex that was the -- so the [CELIA B] frequency assay was predictive of clinical but then HBE was predictive of that. So the -- are you pretty confident in what you have that could predict good proof-of-concept data?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : And as you move to Phase 2 and then eventually Phase 3, are there disease sort of biomarkers that maybe Vertex didn't look at that you could add? I'm just trying to think of like how you could further differentiate yourself to present the best efficacy. It's not just about FEV1 and sweat chloride, there are other pathophysiology kind of markers?

Question: Geoffrey Meacham - Citi Infrastructure Investments LLC - Analyst : Okay. Guys, thank you very much. Great conversation.