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

Welcome, everyone, to the 40th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Priyanka Grover, [ Malcolm Kuno and Chattle Smith ] from the team. Our next presenting company is BridgeBio. Presenting on behalf of the company, we have CEO, Neil Kumar. I want to remind attendees to us to Ask A Question feature in the portal. And if you put more a question in there, I'm happy to ask on your behalf. With that, Neil, take it away.

Thanks, Anupam, for that introduction, and thanks to the Phil and the entire JPM team for the opportunity to present today. I'll refer to slide numbers as I move through here for those of you following along at home with the presentation. Despite some meaningful progress against our pipeline and portfolio in the early stages of 2021, importantly, with our proof-of-concept data in ADH1 as well as our first 2 drug approvals, we ended the year in disappointing fashion for our investors as well as for the patients that we hope to immediately serve with ATTR cardiomyopathy. I want to talk today about the road back both for our company as well as for acoramidis. This isn't the first time we've experienced a setback, and we'll try to employ some of the same strategies we've used in the past, but still is in good stead as we come back, namely: number one, acknowledging our new circumstances and making the appropriate operating changes; number two, hewing to the core principles that we've founded this company on; and number three, being transparent with investors as to what those selling changes are and when we're going to make them. I'm going to move to Slide 3, which is the first real slide in the presentation, and this is all about our new circumstances. 2022 will be a year of focused execution for BridgeBio. We already have a great deal of potential in the pipeline that we've assembled to date, and our intent this year is to put some good, clean wins on the board for patients, especially focusing on our 5 proof of concepts, potential proof of concepts that we can read out this year and doing so with a reduced burn profile. To that end, we hope to enter 2023 on the doorstep with 2 important Phase III readouts in ATTR-CM as well as with ADH1 with a progressing pipeline and a solid balance sheet. The way we intend to do this is by sticking to the core principles as shown on Slide 4 that we started the company with. Certainly, a readout like Part A and attribute CM can shake you to your foundational core, but upon reinspection, we continue to believe that targeting well-described diseases at their source and trying to connect all the dots from genetic algors to therapeutic intervention to clinical outcomes will continue to buy our portfolio in a positive direction. Nevertheless, there's quite a bit of uncertainty in this game and diversification is and will continue to be an important part of the company where we're putting together. Moving to the next slide, Slide 5, one can see that we've already been doing this over the course of the last 6 years, we've been around with 2 approved products, 2 Phase III products shown here are Phase III ready products with an additional 1 in oncology that's partnered with [ Helsen ] and a number of Phase II readouts, as I'll discuss throughout the course of my talk today that are set to deliver over the course of the next 12 to 18 months. While interesting that, we also have several other programs that will either move into the clinic or are in Phase I clinical trials today that we will be reading important data out for over the next 12 to 24 months. And we'll be able to do all this, as shown on Slide 6, with the $800 million plus of cash we have on our balance sheet, which can be extended by a few hundred million dollars over the course of the next 12 months in ways that are obvious as we'll discuss at the very end of this talk. So we have the capital to advance this pipeline and we believe we have a pipeline that can continue to deliver for patients. I want to spend the rest of my talk speaking about specific value drivers within our portfolio. I'll start with acoramidis, I'll then move to infigratinib for achondroplasia, and I'll stop with encaleret for AEH1. I'll briefly touch on the remainder of the clinical catalyst to date. And then I'll talk a little bit about some of the exciting research we're doing in our RAS franchise, which ultimately will be clinical medicine in about 12 months from now. All right. Let's start with acoramidis or ATTR-CM on Slide 7. As a reminder, as many of you know, acoramidis is potentially a best-in-class small molecule stabilizer for use in a very large and also devastating disease, ATTR cardiomyopathy. On Slide 8, we lay out the clinical trial that's being used to interrogate Phase III acoramidis usefulness within this community. We just read out the Part A results, as I alluded to at the outset of my talk, and we continue now with a median of about 20 months in to interrogate the drug in Part B, where we'll have the hard outcomes on both mortality and CV hospitalization reading sometime in the first half of next year. Flipping to the next slide, we lay out the disappointing results of our Part A readout. As I've alluded to and as we went into a great deal of detail on in an investor call about 2 weeks ago, we missed our 6-minute walk endpoint. What we saw there very perplexingly, was a simple lack of any deterioration on the placebo arm. This was inconsistent with anything we've seen in natural history studies or randomized control trials in this population to date and not consistent with the baseline characterization of our patients. Nevertheless, we saw a great deal of opportunity and hope against almost every other measurement that was made. We saw positive improvement in the quality-of-life questionnaire. We saw a reduction in NT-proBNP effectively flatlining it in terms of its median. We saw a positive improvement in TTR levels, some 45%, greatly in excess of what I would have expected based on our Phase II data. And we saw that the drug was safe, well tolerated. And we saw an imbalance in treatments favor for AE-driven death, although those ends were quite small. So lots of encouraging data, but a miss on the primary endpoint. As we proceed to the next slide, we started asking ourselves the question as to, was this spurious outcome just a result of something around the 6-minute walk test? Or did it have to do with a healthier patient population? And as we evaluate that, there are 2 roads we could walk down. One is to really understand the baseline characteristics of the trial; or two, is to understand how the characteristics of patients change over time. Against the baseline, again, I'd encourage you to go back to our investor call about 2 weeks ago. We looked at the great many number of potential differences. The trial was designed to be very similar to ATTR-ACT. And as you can see, it was with median 6-minute walks, almost on top of each other, percent of last 2, 3 patients, very similar, although fewer Class III patients and fewer V122I patients in our trial. The new data I'll highlight today on the baseline NT-proBNP numbers, baseline KCCQ numbers and serum TTR numbers. As you can see, importantly, on BMP, we were at around 2,800 and the track was around 3,000. On KCCQ, we're at 71.4, they're at 66.7, and on serum TTR, we were both in the low 20s. So again, against these 3 critical baseline characteristics, you can see the absolute magnitude of the starting block being around the same, further suggesting that we should have seen a deterioration in health over the course of time that we have been observing these patients. If one looks at the rate of change over time, obviously, if you look at 6-minute walk, you see almost no rate of change. But when you look at BMP elevations, 25% is observed in our trial, it's relatively consistent with what we saw with ATTR-ACT, with the KCCQ decline of minus A, that's relatively consistent with what we saw in ATTR-ACT placebo of minus 10. And again, if AE-driven death is about half of all death or rate of about 5% comports quite nicely with what we saw with the ATTR-ACT about a 10.2% death rate at 12 months. So unlike 6-minute walk, it seems as if this population continues to evolve in a way that's consistent with a slightly healthier patient population than what we saw in ATTR-ACT, which gives us some confidence that we should have a baseline of deterioration against which to resolve a signal for this drug in Part B. Moving to Slide 11. I just wanted to quickly address some of the questions that have been coming up over the course of the last 1.5 weeks here post our last investor call following this trial. There were some hypothesis around whether or not technician standing played a role in the different types of population here, even if they were the same class, same proponent level, same BNP, same diastology baseline et cetera. And as far as we can tell that some 25% of patients in our trial that were biopsy confirmed, seem not to have performed any differently, either in terms of baseline characteristics or progression then technician scan positive patients most -- with a large majority of those scan patients were grade 2 or grade 3. The variability seems relatively consistent with the track. Our standard deviations were 60 placebo on treatment in terms of the change in about 100 at baseline, which is consistent with what you saw in ATTR-ACT. And then the third question, I think, is a very key question, which is has the standard of care itself change over time? So as the ecosystem within which we understand these changes or the baseline characteristics change, there, we believe it has changed. We see increasing use of diuretics, and we see decreased use of rhythm patrol medicines that could be effectively counter indicated for ATTR-CM patients, the degree to which this is the case and the degree to which this would affect various outcomes like hospitalization or 6-minute walk we have yet to ascertain. And some of that work will come along when we look at the blinded, blended rate within our trial, and I'll get to that in a moment. The final piece -- the final set of questions that we've been getting is really around trial conduct and operations, and it has to do with tafamidis usage and discontinuations or drop out given the negative part A result. In terms of tafamidis usage, what we know is that the patient populations that we are partnered with here generally don't have access to tafamidis for other financial reasons or geographic reasons. And therefore, we would expect and have seen a limited amount of tafamidis drop in. So again, with a median of 20-month progression into this trial, we're seeing only about a 3% use of tafamidis in Part B. And in terms of discontinuations, we continue to track to at/or a little less from what ATTR-ACT has seen. We are closely partnering with our physician partners on this trial as well as patient advocacy groups to ensure the fidelity of Part B. We continue to believe that this drug is pharmacologically active, safe and potentially be a great option for patients in this space. And so far, the physicians and patients we partner would believe that. And so we're hopeful that we'll get to the end of this trial without a massive amount of discontinuations so that we can get the correct answer for this drug. Next step here for ATTRibute-CM are shown on Slide 12. I think the most important additional piece of information to note here is that we are in constant contact and are asking the agency and our DSMB whether or not we can look at the blinded, blended, both hospitalization rates and more all-cause mortality rates so that we can make an assessment as to whether or not the trial has a robust number of events so that we can leave it at its 30-month fixed duration or if we need to make a change to that duration, we'd like to make it within the next 2 months. So in the next 2 months or so investors can expect from us a decision as to whether we elongate the trial or we keep the trial the same based on as much information as the agency will allow us to look at so that we can figure out if there's a baseline of deterioration against which to resolve this drug signal. Are we going to move from acoramadis onto infigratinib, low dose infigratinib for achondroplasia? As a quick reminder achondroplasia is a condition that affects some 55,000 folks between the U.S. and EU. It's one of the most monogenic the mendelian diseases we work on. So 90% of patients with the same single point mutation in a receptor called FGFR3. And what we have is a potentially best-in-class in terms of efficacy intervention that targets the disease at its source. And also the only oral intervention that we think will be the most convenient administration for parents and children that are working with this condition. On the next slide, or Slide 14, we lay out the pathomechanism of the disease that's well understood. The most common of the point mutations, again, in almost 90% of the patients that G380R mutation leads to about a 30% elevation in signaling through 2 key effective pathways, the MAPK signaling pathway as well as the JAK/STAT signaling pathway, which respectively, are involved in chondrocyte differentiation and proliferation. Our aim by targeting [ GDH ] source is to ameliorate that elevated signaling through both of the pathways, which would be unique from the standpoint of the other therapeutic interventions that are available in this space to CMPs that just target the MAPK signaling pathway and do so to a lesser extent than would direct inhibition of FGFR3. So the potential here, hopefully, is to impact all aspects of the disease by taking the abnormal signaling and returning it back to normal as quickly as possible and as early as possible. In a mouse model [indiscernible] lab, one could see that we were able to have a more profound effect on bone growth as well as effects on things like foramen magnum areas in L4-L6 site. Hopefully portending the ability for us not only to have impact on AGV, but as well on things like proportionality, spinal stenosis and other pieces of this condition that these sometimes struggle with. The way we've been thinking about convenience is shown here in the HCP study, where if you take 1 step back and say if we deliver the same AGV data as some of the other competing agents in this space, might one still want to take an oral medicine. We think it's important in terms of formulation to have it easy-to-use sachet that one makes in with your food, that's easily administrable over time because many of these titles might want this drug from an early onset all the way until [indiscernible] process. You can see on Page 17 that we're dosing this drug well lower than any of the doses contemplated within the realm of adult oncology where this drug is also approved for second-line cholangiocarcinoma and it's being trialed in a variety of other indications. The reason for this again is that we're not looking for a cytotoxic effects, but rather, we're looking to ameliorate slightly elevated amount of signaling. And so we're dosing almost tenfold lower than where we started to see a hyper-fast which is the FGFR1-driven toxicities that we saw in the adults. So we've been dosing low, and we've been dosing slow. And I think one of the things that we find most hardening is that we must go to the DSMB after a month of dosing before we progress to the next dose in each one of these cohorts, and we're up to our fourth cohort where now we're in that range of 8 to 10 nanomolar where we should have a reasonable amount of inhibition on the key causal pathways, and we've been able to do so thus far safely. Just a review of the overall PROPEL 2 clinical trials that we'll be reading out mid this year. We took a 6-month baseline on AGV, and we'll be comparing that to 6 months on therapy to get our annualized growth velocity. You can see the doses that we've been interrogating here on this slide. We've got a separate cohort of folks that we've been doing some intensive PK on, and we would aim to review all of that data with investors sometime in the July time frame or mid this year. That's exciting progress on infigratinib for achondroplasia. I'll close the more detailed loops with the work we've been doing with encaleret for autosomal dominant hypocalcemia type 1 or ADH1. This is a disease that's uniformly driven by hyper activating mutations in the CaSR or calcium sensing receptor, sub-70 odd mutations that span extracellular transmembrane in intracellular regions, all of which could potentially be addressed by encaleret, which is an antagonist for the CaSR. So again, targeting a well-described disease at its source. When you have hyperactivity mutations at the CaSR, you can think of the CaSR is almost a thermostat for calcium. And what happens is you have a low amount of serum calcium and a high amount of urine calcium. Flipping to Slide 20, what one can see is that almost all of the clinical manifestation or symptoms that present here is a direct consequence of either low serum calcium in terms of things like seizures, tetany, muscle cramps, et cetera, or high urine calcium, where you have things like nephrolithiasis and chronic kidney disease. This is a significant subpopulation of chronic hypoparathyroidism, some 12,000 patients between the U.S. and EU, 70% of which we'll present with mild, moderate or severe symptomatology, which we think could be interesting, should [ in-tolerate ] demonstrate and continue to demonstrate promising results. So this is an overview of the disease and its symptomatology, an overview of the clinical trial in which we're interrogating the usefulness and the tolerate can be shown on Slide 21, where we have 3 periods against which we're -- we've been variabilizing dose. We've been variablizing inpatient versus outpatient setting and the individualization of the dose. We're at period 3, and we expect to present that data sometime in the first half of this year. As a reminder of what we've seen through the first 2 periods of data on Slide 22, you can see that encaleret has been a well-tolerated drug. That's important because of doses at which we're using ACSR antagonists are higher than has been previously used for that same mechanism in osteoporosis. And what you can see is a 100% response or an ability effectively to normalize all patients in terms of both blood and urine calcium. This stands in contrast with the standard of care, which effectively is vitamin D and calcium supplementation, which can sometimes move patients toward rectify serum calcium levels but often times obviously exacerbates urine calcium levels. And so this is the first of its class in terms of a compound that can address both of the key issues here associated with the disease. And the path forward is shown on Slide 23, which is that we expect to have an EOP2 meeting with the FDA sometime early this year and to then initiate our registrational study this year with a readout for next year. So that's encaleret for ADH1, another exciting program. The remainder of the clinical catalysts that are large right now is shown on this next slide here. I won't touch on all of these in detail just given the timing today. Now I might make mention that our congenital hyperplasia program is likely to get through the first 2 or 3 cohorts by the end of the year. Again, this is another very large Mendelian disease, some 75,000 people affected between the U.S. and the EU, maybe the second or third largest gene therapy market. And here, we're uniquely putting back the enzyme that's missing with the hope that we see and promote endogenous cortisol production in a dose-dependent manner. So by the end of the year, certainly [ at 3 -- either the 13 doses ], we would expect to start to see endogenous cortisol production and concomitant depression in some of the biomarkers like 17OHP. Our Limb-Girdle Muscular Dystrophy Type 2i program. Obviously, people are familiar with the Limb-Girdle Muscular Dystrophies from some of the gene therapy work that's been ongoing in that space. For us, we have a simple substrate replacement plan here where we'll be trialing and hopefully announcing data in the first half of this year. What we'll be looking for there is a replacement of the glycosylation that's lacking in the -- of the alpha-dystroglycan complex as well as effects on creatine kinase, which is a good measure of the muscle damage that's occurring. So expect that data sometime first half of this year as well as our dystrophic epidermolysis bullosa data that we would announce at a conference like SID sometime in the first half of this year. All right. So maybe I'll close the talk with a little bit of science. We've been talking about the RAS programs since we started this company. It's something that we've invested a great deal of time and energy in. Have been very privileged to be working with folks like Frank McCormick, Eli Wallace, Pedro Beltran and others on this project. The menu of approaches that we've employed is shown on Slide 26. We have what we believe is a first-in-class direct inhibitor of GTP-bound and GDP-bound G12C KRAS, that is very close to a development candidate sometime in the first half of this year. We have a relatively independent approach in breaking the PI3K RAS interface, which as I'll talk about in a few moments or in a few slides, is promoted by Julian Downward's work showing that the RAS PI3K alpha interface is an effector pathway in the context of tumor-driven cells, but probably not in the context of a normal cellular signaling. So that presents an opportunity to break up that PI3K alpha effect without directly inhibiting the kinase and getting the associated toxicities with it. We have a, I would say, a competitive G12D program where we're looking for -- all about the oral bioavailability, but have some very, very promising cellular data. We have a pan not RAS, but KRAS inhibitor, and then we have a G12R program because we don't think the pan-KRAS program will actually get after G12 [ more ] specifically, and that is quite a bit earlier in lead generation. I'll talk a little bit about some of the exciting signs behind the G12C inhibitor first, and then I'll touch briefly on the PI3K alpha breaker since I see we're running a little short on time here. You can see here with our compound, in terms of percent modification in the GDP- or GTP-bound state, we're almost on -- we're at 100%. And you can see that very quick levels of inhibition in terms of [ ADN polarizing 50 against fossil work ] are achievable here. What this means is not only are we obviously able to block oncogenic signaling in the GTP-bound state, which is not possible given the first generation of inhibitors that target the GTP-bound state, but one might also be able to prevent resistance from residual GTP active signaling in the context of many of these cancers. And I think that, that could be very, very important not only in the context of some of the resistance mutations that affect cycling time and upstream mutations, but also in the context of some of the mutations that are directing the binding site as we showed in our recent R&D Day. You can see on the next slide, Slide 28, the workhorse, MIA PaCa model demonstration of our drug's effects. Very, very promising almost tenfold potency of what we see with the Amgen compound. And we continue to work on some of the PK properties of this drug. We believe we'll have a development candidate again sometime in the first half of this year and then be in the clinic sometime early next year in 2023 with this program. The PI3K alpha program is something slightly different. Obviously, people are thinking a lot about PI3K alpha and specific inhibition, we've been thinking, as I mentioned at the [ outside ] here, about just breaking up the interface between RAS and PI3K, I don't have time to go through all of the various science here. But one of the things that stands to reason is shown on Slide 30 is that with this approach, one should be able to decrease in the tumorgenic context fossil AKT down to the same levels or something like alpelisib would be able to, but spare the increase in blood glucose. And so you don't see the hypoglycemia that's observed with something like alpelisib, even at very similar levels of AKT signaling knockdown. And you can see that here on Slide 30. So this is a very exciting program, both for RAS-transformed cells as well as eGFR-transformed cells, and we expect, again, to have a development candidate against this program sometime this year for entry into the clinic sometime next year. So maybe I'll stop there. I think I'm right up on my time here. I'll just make mention that we do believe we are well capitalized to deliver against many of the POCs and the Phase IIIs that I highlighted today. And we thank you, the investors and those of you listening for your partnership over time. And with that, I'll take any questions from Anupam and others.

Yes. [Operator Instructions] We have a broad question first from the portal which is with the new variant, the new COVID variant, is there any risk to your readouts that you outlined for 2022?

Yes, it's a great question. All of the ways that COVID is impacting functional outcomes, it's really hard to know. For instance, would COVID impact something like average growth velocity? I can't immediately think of how or why, but we certainly don't have enough data to know whether or not that's a firm yes or no answer. That's why I do think the measurement of critical biomarkers is becoming even more key because one doesn't know how the ecosystem is shifting around us. I can't think of immediately how or why COVID would affect -- it certainly wouldn't affect the outcomes from ADH1 because that's serum and urine calcium nor endogenous cortisol for CAH. And I can't immediately think of how it would affect AGV. Certainly, it could affect hospitalization rates in Part B of the ATTRibute-CM trial, but shouldn't affect mortality rates. So I think -- yes, that would be my best guess there.

I think the question was more related to, is there a time line risk because of enrollment and things like that? So yes.

We haven't seen that as much mostly because we're dealing with outside of the gene therapy, oral medicines and pretty devastating diseases. So we've been able to move relatively quickly. I'd say the gene therapies of the space where we've saved some delay just because we're reliant on the NIH in one case for opening that trial site, and they've been a little bit delayed given some of the COVID stuff they're dealing with.

Yes. Just on your comments on ATTRibute-CM, I think you said you were meeting with the regulators in the next 2 months, and you would give this treatment update on -- I guess maybe walk us through the outcomes there, which is keep it at 30 months or extend the study? Is there a risk, though, that maybe the FDA is like, I don't know if we're going to see separation, we should stop the study? Is that -- or how do we think about that?

No, I think -- well, that was what we asked the DSMB to look at after the result of Part A. So I don't think that there would be a risk that the agency would look and stop the study. I think the appropriate decision that we would make is, well, number one, can we look at all of the blinded, blended data. We would then do some simulations based on the FS approach, the statistical approach that we're using to try to understand whether or not we're in good shape, which I think we very well could be. Again, on 6-minute walk, everyone behaves if they were healthy, even if the AE-driven death was the totality of death that's on the trial, which it obviously isn't. Still, a 5% death rate over 12 months is abnormal. You would not expect to see something that high amongst a [ 78-year-old age match ] population. You would expect something more like 1% to 2% maximum, probably 1.5%. So my expectation is that blinded, blended data, we'll continue to track with a baseline of deterioration against which we could resolve the signal. But if it doesn't, then I think we could contemplate -- or if it's not enough, such that when we do our models, we think we would be in better shape extending the trial 6 to 12 months, we would want to know that in the near term. So then I guess the key decision that people would know about is to say, "Okay, we've either elongated the trial or not." And if we're able to, we would certainly disclose of whatever we're able to see on blind and blended rates as well, so everyone can make that same analysis.

There's a question in the e-mail portal, which is, if you -- we assume that the patient population is slightly healthier, is there a concern that the final readout might also be impacted? And I guess, to your point, Neil, the placebo and control arms needing longer to separate.

Well -- I mean -- so when I said slightly healthier, I meant there's a slightly fewer of the Class III patients and slightly more of the Class II patients. And then there's probably slightly healthier based on a slightly better standard of care. I still wouldn't make -- so I would expect there to be fewer events, but I would expect the impact of our drugs to potentially be even larger, both because it's a more potent drug. And secondly, because the hazard ratios were better in Class II versus Class III as you look at ATTR-ACT. So I think all of those things put together, I would expect that the ratio, which does drive ultimately the p-value in an FS-like analysis could be just the same, if not better. Again, maybe another way to put that is, I'm not as worried as obviously, we observed a 6-minute walk that there would be some healthy baseline against which the drug could not demonstrate its efficacy.

A question here is the organization currently is current -- very science-focused, what are the most near-term potential revenue drivers we should be thinking about?

The nearest-term revenue driver past the already 2 commercial products that we have would be ADH1 or acoramidis, but those are 2 -- sort of head-to-head in terms of timing, both reading out their Phase IIIs in -- next year in 2023. And past that would be infigratinib for achondroplasia.

Okay. Maybe a quick scientific question and a couple of financial ones. So the science question here is, what are the implications from a safety perspective from continuously locking RAS PI3K signaling?

Well, if one -- it's a good question. If one just breaks up that effector, ostensibly what's been demonstrated, at least in the tumor models that we've seen to date, is that it wouldn't affect normal cells whatsoever because generally, the PI3K pathway is not activated through RAS in a meaningful way. It's obviously affected through the more economical PI3K signaling path. So the long-term effect should be, hopefully, cytotoxicity in the context of the tumor and not much else in the context of normal cells.

Another question in the portal here. BBP-681 was not mentioned in the presentation, do you see a commercial opportunity with a topical application of PI3K alpha inhibitor for lymphatic or venous malformations?

Yes, we are certainly -- so there were several programs, and I'm glad they -- this person pointed that out. There are several programs as I alluded to on, I think, it was Slide 3 or 4, that are continuing to progress in the clinic that are a little less the focus of the investors but still a focus for BridgeBio that will be reading out clinical data this year or next. And certainly, our topical PI3K alpha for VM continues to be of interest. We continue to be optimistic on that program because we're getting quite a bit of drug, like micromolar levels of drug to the VMs. And if you just sort of back calculate from some of the [ Appalachian ] work in the close condition, and we should be able to see effect at the doses that we're able to get to in that trial to date. So yes, that one, obviously, [ our go eye ] for PH1, our program for pantothenate kinase deficiency in organic acidemias and there are a few others that are ongoing, either in the clinic or about to be in the clinic. We just don't have the time to highlight them nor I don't think are they NPV focus areas right now for investors.

A couple of financial questions. Does your cash runway to 2024 assume you draw the additional $300 million? Or could you get to 2024 with the $800 million you have on the balance sheet now?

Yes, it does assume that we would draw the $300 million to get to 2024 with a reasonable number of dollars on the balance sheet. I think we will dramatically reduce our burn this year, the extent to which you would do that to not be able to draw the $300 million and still get comfortably into 2024, it would be, I'd say, in that $300 million range, which is doable. $300 million to 400 million range is doable depending on some of the tougher decisions we need to make in terms of portfolio prioritization.

Another financial question which is, what are your plans on the $2 billion of debt you have?

Yes. So just as a reminder, we have a couple of convert tranches that are 6 and 7 years out and then we have a senior secured that's 5 years out, that's a little under $500 million to service those, obviously, and that's why I made mention of the risk-adjusted revenue. You would need at least $500 million, $600 million of revenue, which we think we have good line of sight for over that 5- to 7-year time frame. Certainly between CAH, infigratinib, ADH1 and acoramidis, we feel good, plus all of the rest of the already approved programs plus some of the later-stage programs in smaller markets. We feel pretty good about our ability to service that debt.

Okay. I don't see any more questions in the question queue. So with that, Neil, I want to thank you so much for a super productive session.

Thanks, Anupam. Appreciate it.

Thanks, everyone.