BridgeBio Pharma, Inc. (BBIO) Earnings Call Transcript & Summary

Okay. Welcome, everybody, to [indiscernible] Virtual JPMorgan Healthcare Conference. My name is on Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan, I'm joined by Matt Bannon and Tessa Romero for the team. Our next presenting company is BridgeBio. On behalf of company, we have CEO Neil Kumar. Before I turn it over to Neil, I just wanted to highlight 2 things really quickly that, number one, we are restricted on BridgeBio. And number two, I also wanted to highlight those on the webcast, please submit a question via the ask-the-question portal -- the feature in the portal. Neil, take it away.

Thanks, Anupam. I'll set the timer and refer to the slides as I go through here. And thank you so much to the JPM team for the opportunity to present and to support over the years. I was just talking to Phil Ross this morning about the first time, I spoke with the Anupam and Phil about the BridgeBio hypothesis, it was probably 6 years ago and I was still employed at Third Rock Ventures, along with several of our other founders, and we just come off setting up MyoKardia. And the question at that time that we had was how do we do what we just did, set up entities that target well-described genetic diseases at their source, hopefully providing profound value for investors and patients alike. But how do we do it at scale, taking advantage of the ever-growing pool of innovation within genetic and genomic medicine. A few months later, BridgeBio Pharma was born. And as Anupam remembers, that first year was incredibly fraud. We were constantly dealing with the mortality hypothesis, barely had enough money to finance our operations and pull together those first few pipeline programs that went on to define what are now our series of lead programs. And in subsequent years, we would always say that first year was by far and away, the most important in our corporate trajectory. We made certain design decisions and reviewed ourselves with certain characteristics that would go on to define us as an entity. And that's been true up and until this year. There is no number of our management team that doesn't feel that 2021 is going to be, by far and away, the most consequential year for BridgeBio to date. And I want to spend the next 20 minutes or so telling you why that is to provide you the context for 2021 and tell you a little bit about our product platform and pipeline, which makes us bullish on what we can deliver this year. And ultimately, to drill into the 4 key catalysts that we'll provide over the next 12 months that will come to define our company for many years to come. So as I mentioned, I'm going to refer to slides as we move through this presentation, we'll begin on Slide 4, which is entitled our 2025 vision. And this is the first slide that tells you what our company could look like should 2021 bear fruit. This is our 5-year vision, and it's quite simple. Our aim is to be a leading player in the space of genetic medicines. What does that mean? 4-plus NDAS, some of which would be a blockbuster markets with the commercial apparatus, a busy pipeline of 30-plus platform projects across a wide variety of therapeutic areas, diseases and modalities, all best-in-class or first-in-class programs helping to serve patients, we really want to serve in this genetic disease area. And importantly, employing our product platform, which is discover, create, test and deliver and increasing returns to scale so that we can match the increasing returns to scale that are incurring in academia and elsewhere. Speaking of returns to scale, which is something that we've talked about over the years, I want to then flip to Slide 5, which is the first piece of context for 2021. I suppose, much like evolution, companies grow in its state of punctuated equilibria. You start, you start setting things up. There's somewhat some linear or linear growth. And then after a while, especially in a decentralized company like ours, the various nodes of the company start to become productive onto themselves. And you start to see super linear growth. We saw glimpses of that in 2020, with 2 NDAs filed from our group and accepted for priority review with 8 new clinical trials initiated with 12 new programs announced with 5 INDs submitted, et cetera. But 2021 will really be the test as to whether or not we continue to exponentially grow. You'll see things like our first 2 commercial launches, several proof-of-concept readouts, several new programs entering the clinic. And most importantly, key data delivered against the 4 key problems, we'll talk about today in TTR (sic) [ ATTR ], in achondroplasia, into general genal hyperplasia and an ADH1. Flipping to the next slide. This is the part of the context that actually never changes. This is very similar to a slide that I presented last year and hopefully, similar to a slide, I will present next year. And so I hope that the column of approved drugs will continue to grow. The opportunity is large to help patients in the genetic and genomic medicine space. There are some 8,000 rare monogenic diseases, over half of which are understood in terms of genetic etiology, and yet, there are just over 50 approved therapies within this space. So any way you cut it in terms of number of diseases, number of patients or the impact of these diseases, there is a huge opportunity to help patients here. A question we often get is, well, in the rare genetic disease space, are you ever actually going to be able to build a large market. And for a small company like ours, you can see alone in our pipeline, 8 individual programs that are playing in blockbuster $1 billion or larger market. So these markets can also be quite large. They are very profound and the opportunity to serve patients is profound. And the opportunity is that way because of the next slide, Slide 7, and I can spend all day on this slide. This is the most exciting slide in our whole presentation, which is our belief that it's still day 1 for innovation within genetic and genomic medicine. For those of you that follow the literature, and this was an extraordinary year, but the themes are the same, ever-increasing genomic and excellent sequencing across broader and broader populations, owing to lower cost and greater availability. A better ability to pair that genomic and molecular information together with symptomatic information, and indeed, together with network signaling information so that we can better understand these complex biologic problems and reduce them to engineering problems that have a higher probability of technical success. And then finally, more and more modalities that allow us to target these diseases at their source in ever increasingly innovative ways, leading to 16 new FDA-approved therapies this year and we hope to be part of the increasing number of approved therapies in this space as we move forward. The next slide, then transitions from context to why we believe we can productively play within this space of innovation. And it starts with our product platform. We call it discover, create, test and deliver. And the discovery piece is really the key part. We are always constantly seeking great programs and great diseases that are very well described, where we can target them at their source and hopefully make a found difference in patients' lives. When we started, as many of you will recall, we had a mapping of the 7,000 or so monogenic disease space to say which diseases were tractable, where there wasn't a lot of [indiscernible] or modifiers and where we could go after the diseases with something that targeted at its source. Beyond that now, we have a series of collaborations with universities, over 20 partnerships that our business development team is set up. And a great statistical genetics group that is mining the data that's being put together in the UK Biobank, in Fingen and databases in Pakistan and Africa and elsewhere, discovering the next great targets, either through ultra-rare variants or through novel cause variants that we're discovering or that others are discovering in Academe. Once we discover or bring on a new program, we put it in the hands of a very talented set of drug discovery folks that can design the best solution for the marketplace and the unmet need, working backwards from that and not necessarily just having a single hammer of we're just an ASO company or we're just an SI company. If we can go broadly using a small molecule, when it's necessary, using a protein therapy when it's necessary, using gene therapy when it's necessary and the like. Once these programs progress into the clinic, we have 18 ongoing clinical trials. We now have a clinical apparatus that spans over 100 countries, over 7 CROs and a number of institutions across the world, making us a reasonable owner of development programs, so that we can, as quickly as possible interrogate these through Phase I/IIs and understand whether or not each 1 of these programs can provide benefit for patients. And then the final piece of the product platform is deliver, which we hope to prove out this year, it's commercializing these products, not taking advantage of traditional economies of scale like call point, but rather seeking to be patient-centric and access forward and working on things like market access, LDMs, patient hub services so that we can be the white blood service providers of our drug products, should they work to patients and therefore, maximize the value of each one of our programs. The next slide, Slide 9 lays out what underlies all of this platform activity, which is really the people in the process at Bridge. I feel very privileged to be continuing to learn from many of my scientific heroes and mentors shown on the high row here, Charles, Frank, Richard, Len and Phil several others that help us to identify new programs. And once those new programs come in, we put it into the hands of the team that's extraordinarily accomplished and sliding the details of moving drugs forward people like Uma and Robert, Eli and Pedro and Susan have over 25 NDAs and over 100 INDs to their name. And they, alongside our 400 colleagues at BridgeBio, continue to be very active in pursuing new programs and developing the existing programs we have just as quickly and efficiently as possible. So what does all that result in? I'm going to talk about our product pipeline, but I'm not going to flash up the 32 row Gantt chart today because we haven't found that to be all that productive. We're going to talk about 2 aspects of our product. Platform or product pipeline today. The first are new programs. So as you recall, last year, we talked about specifically 4 new programs that we added to the pipeline. One of those programs, by the way, is ADH1, which is one of our key catalysts for this year. So you can see the addition of new programs over time can very rapidly integrate itself and become important to the company. This year, we have 12 new programs that we add to the pipeline, as I mentioned earlier. There'll be a forum for going through each one of those programs today is in that forum. But I'll just make a couple of mentions. Number one, you're seeing us push into new modalities. We're doing that carefully. We're doing that on the modality has already been proven out. But there's no question in our mind that antisense oligonucleotides for use in diseases of apple insufficiency, and in some cases, we use where you want to knock down, let's say, a toxic aggregation in the cytoplasm, like in the case of TDP-43 associated ALS are here and now. And so you're seeing us push into that space. You're seeing us build upon expertise that we've already established in certain areas. For instance, in achondroplasia, where we have an expertise in the network in skeletal dysplasias, we're now pushing into diastolic dysplasia, which is a disease-related co mutations in SLC26A2, last sulfate inside of the cell, we're using a prodrug approach to provide reduced resisting so that we can elevate the amount of sulfate in the cell. And then the final piece is building around modality expertise. Our gene therapy group, we believe, is one of the premier groups out there, obviously, in a very competitive space, and we've added a series of new programs, including we're very privileged to partner with Sandra Brakefield on her work in tuberous sclerosis, both looking at a mini-gene for tuberine as well as a gene therapy for [indiscernible]. So those are all exciting advances, and we want to talk about those as we move forward. We also want to be very clear about the fact that in certain cases, programs that we work on will fall out of our risk reward profile. And that's true for our programs in RPE65 associated retinal dystrophies for our program of Leber's congenital optic neuropathy and for our previously unannounced program in Huntington's disease, which we are working on with a very, very talented investigator out of Canada. All of these programs, we will provide more detail on in the future forum and hopefully find partners that may be wanting to move them forward for the patients that we desire to serve them. So that's one way to think about product pipeline, which are these new programs and the evolution of programs that are either parked or moving or new. The other way to think about it is just the shape of return that we can provide to patients and investors alike. And that's shown on Slide 11 here. We think that our pipeline actually provides a fairly unique profile for folks within the biotech space. And what I mean by that is you have a layer of derisking, you have a layer of NDAs that have been filed, that hopefully will lead to a small amount of revenue this year in second-line cholangiocarcinoma and MoCD Type A. That's the proving ground for a team that's been very talented and has filed a series of NDAs now and knows what to do in terms of commercial launch. On top of that, that our 4 key catalyst. Late stage, high probability of technical success in big market programs in TTR (sic) [ ATTR ], ADH1, achondroplasia and CAH, and I'll talk through each 1 of those programs. On top of that, you have a lot of upside. 2021 could just be the first of many years where we have a significant number of catalysts reading out. And we bucket that upside in 2 forms: number one, our targeted oncology portfolio, where we have in pivotal trial, our Phase III FGFR3 inhibitor for adjuvant urothelial carcinoma, where we have SHP2 inhibitor in the clinic. And where we have a very interesting KRAS franchise that's ongoing. And then the second bucket is the common and dealing in diseases that we're working on that are in the clinic already. Limb-Girdle Muscular Dystrophy Type 2i should reach proof of contract sometime late this year or next year. dystrophic epidermolysis bullosa, the same and venous malformation, which is quite a common genetic dermatologic disease, same thing there. So these are diseases that are in the clinic already, programs that are in the clinic already, where we hope we can provide significant upside to patients and hopefully, investors alike. All right. So now I'm going to transition to the specific 4 catalysts that we have upcoming. I note that I'm at almost 14 minutes. So we will touch on a few of these, and then we can address the remainder during Q&A. We thought about this year as kind of a -- we call it the gauntlet year, but I suppose you could call it the mountain year based on this slide. On the Y-axis, you can see increasing value to investors and patients and on the x-axis is time. And these are the 4 catalysts that will come to define the future of our company. I'm going to start on the left-hand side with our program in ADH1, which is a significant subpopulation of hypoparathyroidism. It's disease that not as many people have heard us since there's not a lot of competition in this space, but it's quite common and at least in very dramatic morbidity. The goal here, the specific hurdle is a 50% or more responder rate in terms of normalizing the disregulation associated with this disease, which is low serum calcium levels and high urine calcium levels. The next read out is our better understood readout in ATTR cardiomyopathy, which should be towards the end of the year where we're looking for a greater than 50% benefit against 6-minute walk. And we'll walk through exactly how we intend to do that. And why that 50% benefit is important. The third readout is in our program in achondroplasia, where we hope to deliver for these kiddos, something that is actually beneficial in terms of AGV something greater than 1.3 centimeters per year in terms of what we saw with BioMarin against placebo. And importantly, something that is a safe oral option for these children that potentially in inhibiting both the causal pathways, hopefully not only address AGV, but things like spinal stenosis, pain, infection in many of the other aspects of this disease, that can be more troubling and [indiscernible]. And then the final program, last but not least, at the very end of the year or maybe Q1 of next year, certainly within this 12 to 14-month time period is our gene therapy for the general genal hyperplasia, where we hope not only to affect the top end of the pathway in antigen flux, but also to uniquely, in providing that what's missing there, which is the 21-hydroxylase enzyme, encourage the production of endogenous cortisol. And the bar there is 5 per deciliter or greater production of endogenous cortisol for many of these children who have close to 0 on an incoming basis outside of exogenous steroids. All right. So let me take a couple of minutes on ADH1, and I'm flipping to Slide 13 here. ADH1 is a remarkably prevalent disease for the lack of attention that it has. 12,000 to 13,000 carriers in the U.S. alone, got 13,000 carriers in the U.S. alone, 3,000 to 4,000 people that have already been identified as we go across the health care system. The disease reminds one from a prevalence standpoint of SLH or in the case of a disease that we work on ATTR polyneuropathy. So it's a large disease in terms of number of patients. It's also a very morbid disease. The downstream clinical sequela associated with lack of serum calcium and increased urine calcium, which stem from both those things very specifically are as follows: seizures, muscle cramps, brain fog in the former case of serum calcium lowering and nephrolithiasis and downstream renal disease in the case of increased urine calcium levels. And our hope is in target this disease at a source, we can rectify all aspects of this disease, and I'll tell you how in a moment. I want to flip to Page 14, though, before we do that, just so that we can talk a little bit more about the patient population. This is something we get asked a lot and what the current unmet need is. Recall that the standard of care in this disease is calcium supplementation, which obviously doesn't address urine calcium levels and Vitamin D supplementation. You can see even on top of the current standard of care, almost 60% of patients have or are symptomatic for this disease. With 1/3 of them being severe, meaning they actually are having seizures. And so the unmet need that remains here and the ability to take one off of those supplements and hopefully provide them with something more profound to rectify all aspects of this disease is launched. How do we do that? That's described on the next slide, which is an outline of the molecular pathophysiology of this disease. It's remarkably straightforward. 70-odd hyper activating mutations occur in a GPCR, called the calcium sensing receptor, they incur either the transmembrane region or they occur extracellularly. And you can think of the CaSR as kind of the thermostat of calcium in your body. And with the hyperactivated mutation on board, it's reading 70 degrees, but it's really only 65 degrees in the room. And so unfortunately, you have lower serum calcium, you have higher urine calcium, you have lower PTH levels. And our approach is very simple. We're taking a small molecule to target these hyperactivated CaSRs and bring them back to normal fleet in terms of signaling. And in doing so, we hope again to rectify all the molecular signatures of the disease as shown in the middle panel of this slide, which should in turn lead to rectifying the symptomatology associated with the disease. And the good news, as shown on Slide 16, is that we've already seen in 1,200 patients at the compound that we're using, which we in-licensed from Japan's backup is safe and actually increases serum calcium levels. It was just done in the context of an osteoporosis trial. The other bit of good news is with an 86 nanomolar long half-life product like we do have, we've been able to fully rectify the disease phenotype in a mere model. So lots of hope here, this is an ongoing Phase II clinical trial that should read out sometime in Q3 of this year. I've got about a minute left. And so instead of speeding through all of these programs, let me just highlight what the design criteria are, Anupam said I could take a minute more if I wanted. And then we'll wrap up and go to Q&A. The second program, just in terms of temporal evolution is going to be our program in ATTR, where, again, the design criteria suggests that the more stabilization, the more better for patients. And what we're trying to do is to preserve this critical protein transthyretin and even elevate it as serum ATTR levels or the most important univariate of morbidity and mortality within this. We showed in our Phase II OLE data that we can do something hopefully more profound than what current stabilizers can do, doubling almost stabilization levels as compared to tafamidis. And on Page 18, what we're showing is that we have an ongoing clinical trial that's overenrolled that will help us to understand the clinical benefit of these elevated levels of stabilization. Importantly, now being part of the BridgeBio ecosystem should allow us to run critical Phase IIIb and Phase IV clinical trials that allow us to move a shape small molecule should it be that, that's effective earlier in the treatment algorithm, and this is a mass disease as well as interrogating it in key subpopulations to further demonstrate its advantages versus current standard of care. I'll very briefly touch on our FGFR inhibitor for achondroplasia, it's again the only agent that I think is targeting the disease added source, inhibiting both causal pathways and the hope is that we provide benefit, as shown on Page 20, for these kiddos that spans both growth as well as spinal stenosis and some of the other symptomatology that's being seen. We're looking critically for a safe administration at 140th of the adult oncology dose of this drug that provides this type of benefit for children. And then finally, on Page 21, the final readout, which is, I don't know, general genal hyperplasia program, again, replacing a siP enzyme, the thing that is missing in this disease hopefully showing, as we've shown on Page 22, durable and high level protein response so that not only can we adjust 17 OHP and antigen flux, but also we can impact endogenous cortisol production productively. So let me wrap up on Slide 23. This is going to be a busy year, as I mentioned, it's going to be an important year. And with your support and health, hopefully, we get through import to the other side of the year where we can go on to have a big impact for patients with genetic disease. And we've got the cash to do it. I know that's going to be the first question from Anupam as he comes back up on the screen here. We've got the cash to read out all 4 of these key catalysts with $711 million in cash and cash equivalents as of September of 2020. And with that, I'll thank you all and take any questions.

Neil, maybe quickly, do you want to introduce your -- the broader team on the line from...

Yes, that's great. So alongside of me, I've got Christine Siu, our COO in Residence. I've got Cameron Turtle, our Chief Strategy Officer and Head of all of our cardio renal activities; and I've got Tom Trimarchi, who is our Senior Vice President of Product.

Okay. Maybe we'll start out with the ADH1 program. In your presentation, you talked about a 50% responder rate, but you also mentioned kind of multiple potential important biomarkers to monitor. So maybe help us dig in a little bit about how you're defining that response rate? What are the 2 markers, 3 markers and how are you defining "response"?

Sure. And I can take that one, Anupam. So really, the 3 things that we're looking at are the measures that Neil was mentioning as the primary drivers of disease manifestation in ADH1, which are first and foremost, serum calcium levels, secondarily, urine calcium levels; and then finally, parathyroid hormone levels. And if [indiscernible] works the way we expect it to, across all of those, we should see improvement even when you're removing calcium and Vitamin D supplementation from these patients. In terms of what we're defining as a response, I mean, we're actually just looking at the normal lab values in terms of the upper and lower limits of normal for each of these measures. So in serum calcium, 8.5 to 10.5 mgs per deciliter, and if we can get people who typically are going to start quite a bit below that level into the normal range on serum calcium, drop their urine calcium level from far above the normal range to at or below the normal range. That would be a kind of home run scenario in as many patients as we can.

And you mentioned this compound has been studied in osteoporosis in 1,000-plus patients. Anything on the safety profile that we should be kind of aware of?

Yes. So the dose-limiting toxicity in osteoporosis was hyper calcemia, right? So they saw dose-dependent increases in serum calcium levels in those studies, and that's what was dose limiting. So in fact, that's what we're trying to see in the ADH1 patient. So certainly, that's not what we expect to be dose limiting. It may be the case that there are other toxicities, but that's -- it's been in over 1,200 patients, as you mentioned. And so something that hopefully we'll see the same level of well tolerability in ADH1 patients. And we'll also see the same increase in serum calcium levels that was a toxicity and osteoporosis, but is what we're shooting for in a ADH1.

Got it. Maybe switching gears a little bit to the ATTR franchise. The slides, Neil talked about a 50% benefit on 6-minute walk distance, I believe. So I'm assuming that's relative to placebo. And then, I guess, the question would be, what would be meaningful benefit to relative to tafamidis?

Yes. So I think the bar that Neil set there is exactly what we've seen with the other agents. So for both Part A and Part B, we know exactly what we're shooting against and you've seen in how we designed the study that we're looking for a relatively similar patient population based on the inclusion criteria the study looking for a comparable patient population. So the bar for success in our mind is to have an outcome that is superior to what was observed previously. That's certainly what our hypothesis is, based on what we've seen in the in vitro data and clinical data to date with acoramidis, and so the goal is to beat what was demonstrated previously on 6-minute walk. So a better than 50% slowing of 6-minute walk test decline. And on mortality, the effect that was observed was a 30% reduction in mortality, and we would hopefully beat that as well. In terms of the -- what would be considered superior. We typically hear 10% to 15% relative risk reduction seems to be where we hear physicians and start to say that's where it looks superior if the populations are comparable. But it's -- yes, so we'd expect 10% to 15% on both of those outcomes is where you'd start to see it.

Yes. Yes. Maybe a quick question on attribute PN study. What's the latest on the polyneuropathy efforts?

Yes. So I think you may have seen at the end of last year, we started adding sites for that study. So the site has sites that are actively enrolling, and you'll continue to see updates there this year. We're not guiding yet to time lines for enrollment of that study. It's still early days in terms of enrollment, but we'll provide updates as we start to get better visibility in terms of when we think that study will finish.

Got it. And then I guess when you think about ATTR like market dynamics, just broadly speaking, you've got the knockdown agents. You've got a stabilizer in the market. You've got next-generation knockdown agents coming. What are the push-pull levers for market share here in a situation that there are multiple stabilizers available in their knockdown agents available where you could be dose quarter type of situation?

Yes. I guess maybe the first statement here is that in the markets of this size, we don't know any markets of this size where one agent is the right answer for all patients with the disease. This is a not that rare disease, as we've discussed previously, and the diagnosis rate continues to increase pretty dramatically. So we expect that to continue to be the case over the upcoming years as multiple agents come to market. And -- but when we think about market share in this disease, as in most diseases, it's 4 factors and roughly declining order of importance from safety and efficacy first as the first 2. Ease of use, and then pricing as the last of the 4. And as we -- as Neil alluded to in his presentation, and the first question out of here for you was on the safety and efficacy side, that's where we hope to differentiate. We think that's what's most important. But we think an oral agent makes a lot of sense. And we ultimately think the pricing for this disease category should get better over time as multiple agents come to market and the number of patients diagnosed improves as well.

I guess another question that we have here is Neil, you talked a lot about kind of the near term here, but one thing we -- maybe the KRAS and SHP2 programs and latest updates there?

Yes. Sure. So on the KRAS program, I think that the -- we made exciting advances in 2 aspects of it. Number one is we were working on that H95 approach, targeting the bolt histamine in the context of GTP mutant KRAS. There, we're making good advances. We've got the structure. We've got chemistry now in the hundreds of nanomolar range that's active and cellular assays. That's also true, by the way, in the [ PHK ] breaker program. Where we have a crystal structure of the interface between KRAS and alpha. We've got some very, very interesting chemistry. So that's why I say I'm pretty confident that we'll get to a development candidate here. Sometime either late this year or sometime next year early. On the C185 approach that we highlighted more during our IPO, that one has been a little slower going in terms of finding a drug-like compound. So that's kind of where the KRAS franchise sits. We're super excited about it. Still, it's by far and away, our biggest investment preclinically with 40-odd scientists, a huge amount of both structural work going on. As well as modeling work. So still excited there. SHP2 is an interesting one, right? I mean it's -- strategically, I think we probably -- well, we'll find out. I mean we're in the clinic, we hope to have an advantaged PK profile. We think that SHP2 is going to be most interesting, not in the context of monotherapy, but rather in combination. And strategically, we made a choice to basically move this thing forward on our own. Hoping for a future state where either we could combine with osimertinib, which is -- or an EGFR inhibitor that's commercially available. But also, I think the G12Cs will be available sometime late this year. And so if they are, we've got to SHP2 to that we can actually run in combination with G12Cs if the Novartis Mirati data prove out to be interesting, which we think it very well could be, SHP2 to being potentiated for G12C inhibition. And in the context of all that, we're pretty excited about the program. I don't think many people give it much of a thought in our pipeline. And nor do I ask you right now, we're running the clinical trial. But I think if the PK ends up being interesting and we're covering target. We're showing those dependent decreases in Phosphor, et cetera. I think this can be a very interesting program for us. Okay. I don't know if you'd add anything to that.

No, I think you did it.

A program that you -- Neil, you mentioned very briefly was the recombinant collagen VII program in RDEB. Based on much known about that program so far from some of the data, what are your expectations for the 2021 update?

Yes. So as you recall Anupam, in the last 12 months, what we showed was dose-dependent increases in collagen VII and that actually, the data were very encouraging there, but also a little strange in that for some patients, collagen VII went out immediately. In other cases, there was a little bit of a delay. So we have to figure that out. But the most important piece of it, I think, was that the highest doses were safe, tolerable and functionally leading to collagen 70 corporation versus NT1 or using NT1 or NT2 staining and also, in some cases, leading to angry and fiber formation, et cetera. So really the hope here and this year is we've now fully enrolled our Phase II trial at that high dose, 3 mg per kg, and we're going to take patients out to 12 months. And my hope is that not only do we see rectification of movements in that. We drive some modeling analogous to what's been seen with some of the gene therapies, but that we also see some effect on the systemic aspects of the disease. The whole point of having a systemic collagen VII approach here is that you could do hopefully something more profound than just a topical approach. So that's the hope, and we'll find out at the end of this year. I think the biggest challenge there was trying to understand whether or not circulating levels of collagen VII would incorporate, it seems like they are. So then the next challenge is how long do you need to be in that wound to have a durable response, but we'll find out.

Got it. It doesn't look like there are any questions in the portal and because you made fun of me for asking cash position question. So I want to thank you, Neil, and Cameron and Christine and Tom, so much for taking the time and going through some of our questions and having a productive session here.

Thanks, Anupam. Appreciate it as always.

Thanks, Anupam.

Thanks. All the best.