... one of the Bank of America Healthcare Conference. I'm Greg Harrison, one of the biotech analysts here at B of A. Today, we're lucky to have Sangamo Therapeutics with Sandy Macrae, Chief Executive Officer. Thank you for joining us. Let's move right into Q&A. Please. The Fabry program and the ongoing phase 1 to STAAR study. For those new to the story, maybe you could review the current status of the program and how your treatment could be differentiated compared to the standard of care. Well, we're really excited about the Fabry program. We're best in class, first in class, and now only in class as the other gene therapies have all dropped out or disappeared. We've dosed 20 patients now, both in the dose range finding and in the extension part of the study, and we're planning to go to the agency in the summer to confirm the design of the phase three. Our intention is to initiate the phase three at the end of this year and dose the first patients in the first part of 2024. It's really important because Fabry is a relatively common, rare disease. The patients on ERT have to go every second week for infusions that can take them up to five hours, and they're not getting all the satisfaction they're seeking. It's fascinating when you look at the patients in our study who were on ERT, how much better they feel once you add in the gene therapy, how their SF-36, how they feel scores go up, how they stay off of ERT once they're off of ERT. Then those patients who hadn't had treatment yet, the naive and the pseudo-naive patients, are noticing for the first time a real benefit to their condition. It's an important condition. It's a condition with morbidity, mortality. It's a condition that ERT has been a great solution up to now. With gene therapy, I really think there's a future for these patients that is very exciting. Okay. That's great. Now you're looking to go into phase three soon. Yes. What would your ideal phase 3 program look like? When will you provide an update on your interactions with FDA? We would love to share details of the phase 3, I think until we go to the agency and have that conversation with them, it wouldn't be fair. We spoke to them last year got some really deep, thoughtful feedback from them, one of which was, "Come back once you've seen a certain amount of time on the dose you're going to take into phase 3." That's what's gating our going back. Phase 3s have two components to them. It's how can you get registration as quickly as possible, how can you ensure as many patients as possible are contained within whatever label you get. That's what our design is focused on. It's making sure that Sangamo gets this medicine to patients as quickly as possible, it hits all the groups that are requiring it. You know, in the U.S. and Europe, there's different treatment modalities. There's men and women. There is patients with cardiac disease, with renal disease. Fabry is a really eclectic group of a condition. We want to make sure as many patients as possible get benefit. Got it. now looking into, you know, entering the market after the phase 3, what aspects of the treatment do you think you would like to emphasize through the phase 3 that would put you in the best position to be competitive compared to standard of care at launch? By standard of care, you mean the ERT? ERT. Yeah that you get every second week where you have Sure ... to get a five-hour infusion. Mm-hmm. That's the most interesting thing about this journey. Mm-hmm. We haven't yet understood how fundamentally different genomic medicines are. It isn't a case of do you want the blue tablet or the red tablet? Do you want something that you take twice a day versus three times a day? It's something that you go in for a single infusion, and that's your treatment. Mm-hmm. We would hope and expect you then get long-term, years' worth of benefit from that treatment, as opposed to your life being decided by having to go in every 2nd week and have that long infusion. If all we did was replace the convenience for the patient, I'm sure they would embrace this and endorse it. The results we've seen thus far in the study for patients that were already on enzyme replacement therapy, they're getting more. They're feeling better than they did. They're suddenly sweating. They're feeling better and reporting that. I think you need to listen to the voice of the patient. The fact that patients that were on ERT have come into a study for a genomic medicine says they're voting with their feet. They're saying, "ERT doesn't solve my problems. I'm looking for something better and something more." I would then refer you back to the patients in the hemophilia trial, where the benefit that they get and the difference in their lives is not blue pill versus red pill. It's a fundamental change. They no longer have to worry about factor, about bruising. They feel different, and that's what we, I think, in all the genomic medicine companies will offer them. Yeah. That's great. How do you think about durability of the treatment and, you know, what would, what would your target be as far as durability that would, you know, make you know, excited about the profile of the drug? The truth is as long as possible. We have patients out, I think it's 22 months was the last result that we've shown, and there's no sign of a decline in durability. There's a debate that has been engendered by the hemophilia data that from both BioMarin and Sangamo Pfizer that suggests that there is something different about hemophilia A. The assumption always was shows that this is not what you see for Fabry, and there's nothing like it in Fabry. All of the patients, both the naive and those on the ERT, have flatlined benefit with their alpha-Gal A. There is no sign of a decline in it. The patients that are off ERT have now been off for months, almost a year now, and they show no decline in the benefit. What do the patients want? In the hemophilia trial, they've said, "Give me 5 years. Give me 7 years," and the benefit risk works. I think what Fabry offers is a lot more than that. If we can do that, and they don't have to go for those infusions every second week for 5 to 7 hours, we offer them a real patient promise of a future. Now, when we come back here 10 years from now, we won't be talking about gene therapy. We'll be talking about editing. Mm-hmm. We're talking about new technologies that will fix the gene that the patient has. I'm absolutely confident of that. I see the gene therapies as a bridge to that future and a solution for patients that are eagerly looking for something more than ERT. Great. That's super helpful. Let's move on to the CAR Treg program. Could you just talk about the unmet need in the kidney transplant space and how TX200 could be a novel way to address this? In 2018 we acquired a company in France called TxCell that is an expert in Tregs. We've now dosed 3 of the 3 patients with TX200, which looks at patients with an HLA-A2 mismatched renal transplant and creates CAR-Tregs for A2, which we then give back to the patient. The only place that they have HLA-A2 is in their transplanted kidney. The hope is that it will go there, and it will control and suppress inflammation and eventually allow them to back off on their immunomodulation that they get as part of the transplant. There's great animal data that shows that this works. There's great data in humans already in the one study where they use polyclonal Tregs, and they show that expanding a patient's Tregs simply and giving them back suppresses that inflammation and allows them to back off immunomodulation. We're really excited to show data later on this year from this study. Now, I want to be absolutely clear. In the initial doses, we'll be showing safety because many people thought are Tregs safe, and we've shown that up to now they're very well tolerated. Secondly, can we show target engagement? We're not going to show at the end of this year that the patients are off all of their medicines. This is a journey, and the renal transplant study allows us to biopsy the kidney and see that target engagement in a way you couldn't do easily with multiple sclerosis. Mm-hmm. It's a model, but we also feel it's a model for a transplant area where there hasn't been any great development recently. Patients want to not take the various immunosuppressants that they do. It's a bit like the story around the Fabry or around the hemophilia. They're looking for some way to walk away from their disease and live as normal life as possible. We feel that the Tregs offer that possibility. Behind renal transplant, we have programs in multiple sclerosis and inflammatory bowel disease with near-term INDs that are in large indications. It's a strategic choice we made at Sangamo to move from niche rare diseases, which is a very specific space, to larger high on medical needs where we can make a difference to patients and hopefully a much more sustainable commercial model. Mm-hmm. Okay. Great. Where would you see this treatment fitting in the landscape in something like MS? Let's wait and see what the results are. I mean... Fair enough. ...to be very candid, MS is a space with several medicines that provide benefit. Mm-hmm. They're medicines each that come with their baggage and have to be given on an ongoing basis. What we are looking for is something that tolerizes the patient to whatever it is that's causing the MS and gives them a long-term solution from a single injection or very few injections. That's the experiment that we need to do. We have so much incoming interest from a whole range of companies on our, on our Treg program. They see the science as cutting edge and exciting. They like what Sangamo's done, that we have GMP manufacturing, we have editing capability, we understand how to do INDs, and they want to know how they can get involved. There are 15 Treg companies now, and we're the only one in the clinic. We're the only one with GMP manufacturing. We're the only one with an experience in INDs. I really think that future. For Sangamo, the challenge is, with all the interest in Tregs, how do we help people invest in our Tregs specifically and drive that program forward? Okay. Great. Well, just a few minutes left, I wanted to make sure and discuss the program you announced recently, which is the Nav1.7 program for chronic neuropathic pain. Isn't that exciting? It is. Yeah. I mean, it's interesting the approach here because, we've seen, you know, other attempts to go after this target and, you know, not a ton of success with blocking it. Your approach is very different. Absolutely. They are not comparable. Yes. You know, having been in this industry for 25 years and done small molecules for a lot of that, the problem is specificity. Nav1.7 looks like Nav1.6 or Nav1.8. If you, if you block Nav1.7 with a small molecule, you end up with cardiac side effects that have meant that despite all the efforts of many companies, they've not been able to find a drug. We go completely in a different direction. We go to the gene, and the gene doesn't look like Nav1.6 or Nav1.8. We're able to target a specific bit of DNA that's unique. It's the only part in the genome that the repressor goes to, and we turn off that gene. We feel that we can deliver it intrathecally. We can deliver it specifically. We have the specificity of the vector, of the promoter, and of the repressor. We get triple lock on specificity only for that gene. If we can do that, we can go into patient populations. There were 40,000 patients with the very specific form of neuropathic pain that we're targeting first. We will give them relief from what is a life-altering, in some cases, life-ending form of illness. That is the most specific group. There's a whole rings of patients with similar conditions that once we find if this works in that subgroup, we can move into others. We're targeting an IND next year with treatment soon afterwards. We have great results that we're gonna show at ASGCT, and it uses the zinc finger platform that's been the core Sangamo for such a long time. Great. What other areas, you know, could you go into with this approach of the, you know, epigenetic regulation in neurology, down the road beyond pain? There are so many areas that will be unlocked by successful delivery to the CNS. We have shown repressors for tau, for alpha-synuclein, for Parkinson's. We have beautiful data that we're going to show at ASGCT on prion disease. There are just a series of diseases that with the right vector... I want to get people's head around the idea that it's vectors for courses. It's not one vector will solve everything in the CNS. There'll be some that go for deep brain delivery, some for cortical delivery, some that will do better at the basal ganglia. With the group that we have in Sangamo, we're evolving those vectors. We're talking to other people who have got other vectors as well. We see there being a kind of Venn diagram of vectors and targets that will completely unlock the CNS in the very near term. Great. Well, just about half a minute left, but I wanted to, you know, touch on something you mentioned, which is ASGCT coming up. You guys have a ton of abstracts. We have 14 abstracts reflecting the strength of the science in, at Sangamo. If I had to direct you to 3, it would be the Nav1.7 presentation, which really shows the remarkable signs that we're betting on. The prion disease, which shows that mice live normal lives that would die otherwise from prion disease, and the capsid evolution from David Agüer a and his team that I think is the future of CNS delivery. Great. Well, with that, our time's up, but I want to thank you, Sandy, so much for joining us. My pleasure, Greg. Hi, everyone. Welcome to day one of the Bank of America Healthcare Conference. I'm Greg Harrison, one of the biotech analysts here at Bank of America. Today we have Liquidia Corporation, represented by Michael Kaseta, Chief Financial Officer. Thanks for joining us. Hey, thanks for having me, Greg. Do you wanna start off with maybe quick opening remarks, and then we'll jump into Q&A? Yeah, that'd be great. I mean, first of all, I just wanna thank you for having us. It's really a great time for Liquidia. We think we're nearing the completion of our patent litigation with our competitor. We are laser focused on commercial readiness for launching YUTREPIA, you know, by the first half of 2024, if not earlier. You know, we're really excited to treat the patient populations of PAH and also the emerging population of PH-ILD, which we believe is gonna be a multibillion-dollar opportunity. Great. For those new to the Liquidia story, maybe you could just review quickly the current status of the legal proceedings, and what's left to achieve before you can launch YUTREPIA in PAH? Absolutely. Just to give a little bit of history, back in June of 2020, United Therapeutics asserted three claims against us related to our 505(b)(2) submission of YUTREPIA. As we stand right now, only two patents are remaining. We have rulings in lower courts that if all are affirmed during the rest of 2023 as appeals are ongoing, that we will have freedom to operate and we'll be able to apply for full FDA approval at that point. Great. With the approval or the full approval and the launch in PAH upcoming, you know, potentially early next year or maybe later this year, where are you at with preparation for commercialization? Yeah. you know, as I said, we're laser-focused. you know, we were ready to launch this product in Q4 of 2022 when the initial U.S. District Court ruling was made. We built, we received tentative approval in November of 2021. We focused most of 2022 building commercial supply. We've continued those efforts in 2023. What I can also say is we're now currently and actively recruiting both our medical affairs teams, our sales force. When we get that clearance to move forward, we will be ready to launch and execute. Okay. What patients do you think would be best for treatment with YUTREPIA? Where do you see it fitting into the PAH paradigm now and as the market evolves? You know, PAH is a well-defined market. We have a tremendous amount of experience from our leadership team. We also are currently and have been promoting generic treprostinil injection for several years. We have, you know, key relationships with doctors, with KOLs, with payers. You know, from a patient point of view, we feel that YUTREPIA is gonna do really well in the market in the sense that, you know, we have a convenient device. We have an ability to try to titrate to high doses, because I think, you know, the feeling with treprostinil, the higher you can go in dose, the higher you can titrate is better for patients. You know, the convenience, the low resistance device that we have and that ability to titrate, I think is going to play very well. Okay. Yeah, that was, that was one thing I wanted to touch on as well is, you know, it's an inhaled dry powder formulation of treprostinil similar to the TYVASO DPI. I don't think you guys view it as an equivalent product, right? Maybe you could talk a little bit about the differentiation that you see versus TYVASO. Yeah, absolutely. you know, as I said, we have a device. It's a device, it's a plasti-appli device that is manufactured in the millions. It's been well received in the PAH community, globally, in the COPD community here. It's a low resistance device. you know, tolerability is critically important for these patients. Our device is the closest thing that these patients are going to get to a nebulizer. That ability to be able to increase those, to titrate to higher doses, with a device that provides the lowest resistance, we feel is really going to be effective for PAH and especially in PAH-ILD. Great. And, and how are you looking to raise awareness of YUTREPIA upon approval? You know, how do you educate physicians as to the difference here? And would you expect to see, you know, switching or is it more of a new patient type of market? As I said, we're actively recruiting to expand both our medical affairs team and also our sales force. We're gonna use that as an opportunity to spread that word and to educate. I think what's important is we're gonna have two companies, both United Therapeutics and Liquidia out educating, and especially in ILD. ILD is an indication and a disease that up until last year had no approved treatments, now has one approved treatment in TYVASO DPI. We will be the second who get that approval. That education, you know, frankly speaking, you've seen this in other disease states where there's no treatments, it's very much underdiagnosed. Now that there are treatments, a treatment that we feel that we can be differentiated in from TYVASO DPI. You know, a combination of all of that we feel is very important and, you know, like I said, execution is gonna be critical for us and we're gonna do everything we need to do to get there. Mm-hmm. What have you learned so far from, you know, the launch of an ILD from United? Does that tell you anything about, you know, the market and your, you know, how that would impact your strategy going forward? Yeah, I mean, we think, you know, ILD is very much an untapped market. I mean, we've done our own research. We believe that there are 60,000 patients out there to treat. You know, we feel that again, trying to understand how the TYVASO DPI launch is going, we're less concerned there. I think we realize is that, you know, ILD patients have, you know, severely compromised lung function. Those patients with compromised lung function are going to require a lower resistance device. We feel our ability to have a lower resistance device to be able to titrate, you know, in our clinical trials, we got up to the equivalent of 27 breaths of TYVASO. We really feel confident and, you know, that once we get out to the market, once we get ILD in our label, that we will really be able to expand the market and- Mm-hmm. you know, increase patient share considerably. Okay. 60,000, that's a pretty big number relative to, you know, how many patients are on, inhaled treprostinil currently. You know, how should people be thinking about what portion of that market is really addressable and how far you could penetrate into that? If you just compare it to PAH. PAH, we believe, has roughly 40,000 patients treated. About 15,000 patients are treated with prostacyclins. You know, a little less than half of that is currently treated through inhaled treprostinil or TYVASO. When you look at the opportunity, that 60,000 is obviously a large number. It's, you know, very much been an underserved patient population. Tremendous amount of education that we'll do, especially at the launch, with our sales force and with our medical affairs team. We really feel that we are positioned nicely to be the prostacyclin and a first choice, both in PAH-ILD and PAH. You know, frankly speaking, especially the ILD market as a multibillion-dollar opportunity- Mm-hmm. a multibillion dollar market that we're, that we're gonna be launching into. Okay. You kinda see that whole 60,000 as, you know, patients for your treatment. It's not a subset of... Absolutely. I mean, it's always gonna be a subset. Sure. You're never gonna get all of the patients. Of course. You know, we're gonna learn a lot. We've learned a lot about ILD in the last couple of years. I think we'll continue to learn more, and as voice gets out and education gets out from literally the only two companies that will have products to treat this, you know, this terrible disease, we feel that the opportunity is really, you know, is a great opportunity, you know, most importantly for patients to have an option and to have a treatment for this debilitating disease. Yeah. Okay. Now you recently had oral arguments in the appeals. Can you give us an update of where the legal process stands and outline the different scenarios that would affect the YUTREPIA launch timing? Absolutely. It can be somewhat nuanced, but, you know, to really break it down, you know, we've been guiding for several months that we expect a launch to occur sometime in the first half of 2024, if not earlier. There's two paths that we're going down. As I said earlier, there are thretwo patents that were asserted against us, only two remain. There was the Hatch-Waxman trial in U.S. District Court in Delaware last year. There were two rulings given there. One on the '066 patent, we won. On the '793 patent, we lost. Both us and United are appealing those rulings, actually, oral arguments on that appeal occurred last week. We were very happy with how the oral arguments went. We would expect to hear a ruling, between, you know, somewhere between one and three months. The third ruling that is outstanding is the PTAB. The PTAB invalidated their '793 patent in July 2022. They denied a rehearing request in February 2023, now we are in the briefing process for that appeal, which we expect to be heard and oral arguments to occur sometime towards the end of this year or early next year. I think if we're able to be victorious on the Hatch-Waxman appeal on '793, we could theoretically be able to seek full FDA approval in one to three months from now after that ruling is given. If those original rulings are affirmed and we get to the PTAB appeal that will occur later in the year, if that ruling is affirmed in our favor, we would be in that first half of 2024 range. We're very, you know, we're very excited. We're, like I said, we're focused on getting ready for commercial launch. We're preparing for launch. We're spending to a launch right now and investing into the launch, and, you know, we feel really excited that whenever that time comes, whether it's in Q3 of '23 or the first half of '24, we will be ready. Okay. Great. Can you remind us of the cash runway and plans for funding the YUTREPIA launch? Back in January, we entered into an important transaction with HealthCare Royalty. We did a revenue interest financing agreement, where it was a $100 million facility. We received $32.5 million upfront. There are 3 additional tranches. Tranche two is an additional $7.5 million if we do a business development transaction. There's a $35 million tranche at the time that we clear the legal risk. Again, it's not at FDA approval, it's not at first commercial sale. It's when we get the order to allow us to go to the FDA for approval, we get $35 million, and then there's an additional $25 million tranche that is at the mutual option of both parties. It was an important transaction for us. HealthCare Royalty is a great partner, a reputable firm. We feel that it really validated both our legal case and also our commercial thesis here. You know, as we've talked about ranges of timing of when we could launch sometime in the back half or back third of 2023 or into 2024, we feel confident that if we could do it on the early end of that range, that our current capital could actually get us to profitability. At the very least will be able to take us through launch and achieve all of our priorities to get ready for that launch. Okay. Great. Speaking of profitability, what, you know, what is the way to think about the launch of YUTREPIA and just the trajectory that you would expect, you know, as far as uptake? Listen, we're very excited. It's a product, you know, that most importantly, patients need. Patients haven't had a choice in this space in 20 years. For us to be able to give that choice is gonna be very important. You know, we've said and we believe that we could be cash flow positive as a company within two or three quarters after launch. As I said earlier, when you look at the current PAH market with the 40,000 patients treated, 15,000 on prostacyclins, and the ILD market, which is largely untapped right now, you know, we feel that, like I said, the overall market opportunity is a multibillion-dollar market. For where we stand right now in ILD, there are no other treatments coming on the horizon in the short term. We feel a real opportunity and an opportunity to compete and ultimately win and become the prostacyclin of first choice in both PAH and, you know, definitely in PAH-ILD. Okay, great. Well, less than a minute left. You mentioned BD. How are you thinking about that and, you know, what opportunities are there down the road? We're focused now. First and foremost, we're focused on getting YUTREPIA approved and launched. At the same time, we're building a best-in-class commercial organization, a best-in-class R&D and medical affairs organization. We're always looking for opportunities for molecules, for products that could complement YUTREPIA and generic treprostinil. You know, while our focus is really on launching YUTREPIA, we are absolutely evaluating every opportunity, and if the right opportunity comes up that we feel is in the best interest of our shareholders, we'll absolutely look to do that. Okay, great. Well, with that our time's up. Michael, I'd like to thank you for joining us today, and thank everyone out there for listening. Thanks so much.