Cool. All right, we'll go ahead and get started. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Good afternoon, everyone. Thank you very much for joining us at TD Cowen's 45th Annual Healthcare Conference. For our next session, we have a fireside chat with BridgeBio, and it's my pleasure to introduce Neil Kumar, the Co-founder and CEO. Neil, it's great having you here. Thank you very much for joining me.
Thanks for having me here, Tyler.
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Is it on? Can people hear me?
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There we go. Ready to go.
Do it.
If you guys have questions throughout the discussion, feel free to raise your hand, and we'll do our best to get them asked. But we'll start naturally with Attruby. It's been a long time coming with the launch here, and you guys have put out some very early, very encouraging metrics. But before we get into the launch, just wanted to level set everyone and get your high-level thoughts on the label and the pricing decision.
Yeah, sure. Happy to get into that. Thanks, everyone, for taking the time. Maybe even before I get into the specifics around Attruby's label, I'll just say this year, as many of you know, is a really formative year for BridgeBio. We obviously have to execute on the launch that, and we've been thrilled with some of the early numbers that are coming out, but we'll continue to focus there, and we've got three important phase IIIs with last patient, last visit delivering this year, all in billion-plus dollar markets, plus the ongoing Canavan trial, and what we think that does is it sets us up quite nicely for the next three to five years in terms of significant revenue growth and hopefully the growth of our pipeline.
We'll spend a bunch of time on Attruby today, but we're always happy to take questions, especially in and around ADH1 and LGMD2I, which are two programs that should read in the near term here that I think have been a little bit overlooked in terms of both commercial opportunity as well as potential to help patients in terms of probability of technical success. With that being said, obviously our first big informative launch in ATTR cardiomyopathy is happening with Attruby. I'll just remind everyone that the basis of the potential best-in-class theory here was that we were an even more potent stabilizer than obviously our competitor, which is Tafamidis.
And indeed, we are the only stabilizer with near complete stabilization in the label, consistent, I think, with the data that we were able to generate both across in vitro assays as well as in the clinic with serum TTR. And from there stems, I think, the three most important numbers at the company right now, which is 340, 250, all on the label, all on the Kaplan-Meier curve really, which I think is the seminal part of section 14, which is the most important part of any label.
And that is separation as early as three months, relative risk reduction against the metrics that people care about, which is cardiovascular hospitalization and death, 42% relative risk reduction at 30 months, and then a 50% reduction in cardiovascular hospitalization. So those three numbers we think are the best that we've seen in the space and have set the launch up to be, I think, successful to date.
Great. Thank you. And again, for brief background, maybe you could just start by reviewing the launch metrics that you guys have put out launch to date.
Yeah, so I think as of mid-February, it was February 17th, we had announced that we were above 1,000 scripts, unique patient scripts, and I think even more hearteningly above 500 prescribers and with about 77% of our lives at parity with Tafamidis already in the commercial setting. And as we were discussing last night, we've been trying to sort of analyze that in many different theoretical ways. We actually just kicked off something we're calling the Revenue Institute alongside the QLS Institute at MIT, where we've been analyzing 470-odd launches and trying to make sense of what this early trajectory means in terms of future performance.
And one of the things that's really critical in a launch like this, especially when you have 10,000 or so high-volume heart failure practices, is that you get that number of practices up as high as possible. So 500 was well beyond what I thought we might get right out of the gates. And so I think it portends quite well in terms of the theoretical spread of this message.
Great. So you guys have generated a significant amount of goodwill with the 10% price discount to Tafamidis, 28-day free trial for patients as well, given that these are expensive drugs. But even though you guys put up an amazing 1,028 new prescription patient number, some are asking about that conversion to paid prescriptions. So maybe you could talk through what everyone should expect in terms of filled and paid prescriptions, and kind of what the average is that maybe you guys hope to meet or exceed moving forward.
Yeah, I mean, I can't, you know, I think we were discussing this last night as well. I mean, if someone asked me about the probability of technical success of one of our trials, I'll say it's 76% because that's the historical POTS for phase III's in rare. And so I can't really comment on conversion right now. What we're seeing is very heartening, but we'll obviously comment on that in May. The average across those 470 launches we have looked at, that is about 45% all in. But I always encourage our team to do better than the mean, and I hope we do here as well.
Even though it's early, you guys are starting to see refills?
Exactly. Yeah, for those earlier patients, we're seeing refills. You know, I mean, one of the things you mentioned in terms of the free trial is, yeah, there is some goodwill and some upside there. But actually, the biggest thing is we're able to get drug to patients within 48 hours. And you can see from that every minute does matter when you have a life-threatening disease like this.
And so that three-month separation, I think, has been a huge deal as well. And we don't see patients being like, "Oh yeah, I've been on this thing for a month. Now I'll take a five-week delay and transfer over to Tafamidis." Or, "Yeah, I was on it for a month. That was really awesome, but let me drop off and just do my normal stuff." This is not that type of condition. So I would expect conversion rates, compliance rates, things of that nature to be parallel that type of unmet need, put it that way.
In terms of the patients that are coming on therapy, is it kind of what you expected, more new patients versus TAF switches, or what are you seeing there?
Yeah, we don't have the precise data yet from our SPs as to what the blend of switch to naive is, but it is majority naive. And I think one of the things you can see is that there's continued growth of the Tafamidis franchise as well. So that just means we're diagnosing a lot of new patients. There's probably a super- linear diagnosis rate that's ongoing right now. And I expect that to continue, obviously, as new sponsors come onto the playing field. So yeah, more naives than switches, but obviously there's a good chunk of patients that don't respond well to existing therapy. So we've been able to pick those up as well.
Okay. And what's the latest on the reimbursement front? And I guess the goal is after they're done with the 28-day free therapy to have them obviously be covered for the refill. Have you guys been successful with that so far?
Yeah, that's been, I think, one of the things that was really helped by the fact that we were able to start payer discussions six months before the launch. And one of the things that we found was that 50% reduction in hospitalization alongside a lot of the programs that we've put in place has resonated quite well, both with commercial payers, Medicare Advantage plans, and then traditional Medicare is fairly straightforward.
So I think either if it's prior auth or if it's medical necessity, we've been able to get people on drug quite easily. And the forms, like we've paid attention to every moment of kind of what that physician prescribing or patient prescribing or patient getting script journey looks like, and down to just the length of the forms, which is about half that of our competitors right now. And I imagine they'll match us, and then we'll have to go even leaner. But it's a fairly seamless process once people start to do it.
So I imagine most people in the audience are not super familiar with your specialty pharma distribution strategy. So I wanted to ask you just to take a moment to describe that and how it's being executed.
Yeah, I mean, I would just say at the highest level, we've learned obviously from our colleagues in the rare space and also learned a bit from the launch of our drug product in Molybdenum Cofactor Deficiency Type A , which obviously wasn't a big deal for investors, but a big deal to the children that we serve there. One of the things in rare is you always want that white glove service coming from your SPs or PANTHERx Rare. It gives a very different LDN than what you see, obviously comprised at our next nearest competitor. Probably going to be similar for the knockdowns would be my guess. One of the important themes there outside of obviously a direct physician and patient service,, is also flexibility.
If you have a capitated SP, like many of the major institutions that we serve do, then they're able to be flexible. They can use those SPs or they can actually just hold and actually own their scripts where they're making some money there as well. I think that's been important to the customers.
Amvuttra, Alnylam , [Zembutra] should be approved later this month. Does your launch strategy change at all once Amvuttra is on the market, or how are you thinking about that?
Our launch strategy won't change actually because we continue to view 340, 250 as those paramount numbers that will continue to be best in class in this space. And we continue to view the real battle for us as the frontline oral stabilizer battle. I think orals will maintain their frontline status. We'll have to see where Amvuttra prices. There will be a little bit of that, but I could even imagine there being some steps associated with it if prices kept at the same level. But I think the important message is one actually an ex-FDA regulator just said the other day. It's kind of like if you're just looking at it and you're not an expert in the space, obviously the point estimates at 30 months are better with the oral stabilizers. I'll just use them as a class, obviously.
I like our data, and then you move to safety, and you see that obviously there's the vitamin A deficiency, there's injection site reactions. That's just in this trial. There's an imbalance of AFib on knockdowns that you don't see with the small molecule stabilizers, and 10%-15% of our patients or more have AFib involvement. And then you move obviously the Onpattro trial where you saw an imbalance in cardiac SAEs. You move to the Revusiran trial where we still don't have an adequate explanation as to what happened there in terms of imbalance of cardiovascular death.
And then you move to the Levin paper that just came out three months ago suggesting ever higher levels of TTR over the course of a lifetime are statistically significantly connected with greater degrees of longevity, lower levels of cerebrovascular disease, neurologic disease, and cardiovascular disease for obvious reasons. I think if you put all that together, you would say, wow, okay, point estimates are better on efficacy, but let's say that's a wash. Clearly, a small molecule that retains the tetramer is a safer first step, and then ultimately, if they're also cheaper, I'm not really sure why you're going with knockdowns first.
What about Part D versus Part B? I think there's a lot of people that are not familiar with how it works, and I've been doing a lot of learning in recent months, but are there any key distinctions to call out, you know, pros or cons with the Attruby versus say like Amvuttra, a Part B drug?
I mean, the lowest, if all the medicine you were ever taking from a patient perspective, let me start there, were simply these medicines, it's still more expensive on B versus D. I think there's a mistake there because it's about $217 per month for supplemental insurance and it's $167 a month given IRA for part D copay. But you can build it up. I mean, from there, I mean, your average Medicare Advantage patient is effectively about $10,000 of copay on the B side. And again, it's $2,000 on our side. So there's almost no circumstance in which I could, sorry about that, in which I could see there being an economic advantage to patients B versus D. Now you can move to insurers.
And on the Medicare Advantage side, it's actually a significant disadvantage for B versus D because of the fact that we're picking up 20% of the bill given the IRA redesign. So they're 100% on the hook for that. And they do cross BD management in Medicare Advantage, which is obviously a majority of the Medicare lives. I think for traditional Medicare, you might say, well, you know, that's a little different, but that's not cross-category managed B versus D. And taxpayers on the hook. So I know people have made a lot of ASP + 4%. I'm not meeting a lot of cardiologists that are telling me that ASP + 4% is going to be a material part of their business.
And that's really the only economic advantage I can imagine for a higher- price drug that again has all of the attributes that we just discussed. So again, I think there's no part of the system that should promote starting with those drugs. I think those drugs could be very meaningful for those that aren't responding well to oral stabilizers.
That's great. So Attruby called now Beyonttra in Europe is approved. Maybe you could talk about why you selected Bayer as a partner, your confidence in them launching it, when you expect those sales to start or revenues to start to contribute, obviously since you've got a really impressive 30% tiering upward royalty rate.
Yeah, well, maybe I'll start with the, I think the opportunity in Europe is quite important and got ever more interesting given the fact that, remember, recall European regulators will do and reimbursement authorities will do cross-trial comparisons. And so our hospitalization data, I think especially as it will compare to some of these new entrants in the marketplace, will dramatically, I think, impact both pricing and our ability to distribute the drug effectively there. So I think it's a super exciting space. We should see sales as early as sort of mid to late March here. And how Bayer will do with the launch, I mean, we selected them because number one, we love the deal. We own a good chunk of the profits as we've discussed in the past. Number two, their experience with Xarelto was quite impressive.
They're already calling on a lot of the doctors and physicians that are important to us, and so we'll have to see. I'm banking on them doing well, but they're going to have to prove it. We've done it here in the U.S. They should be able to do it over there.
Great. So to wrap up the Attruby discussion or acronym, should I say, what's your latest thoughts on how big the ATTR cardiomyopathy market on a global basis could be? And how do you think that changes with the Tafamidis LOE?
I mean, I think as sort of the back- of- the- envelope math suggests, this category could be extremely large. I mean, if prices stay where they are today and there truly are 250,000 patients in the U.S. alone and additional hundreds of thousands of patients worldwide, this is easily a $20 billion category. I think we've said 20 billion because that kind of makes sense to me over the course of the next decade or so, and we're finding patients in a seamless manner now given the 16,000 technetium scanners that are out there, so I feel like the market is large and I feel the market will continue to grow.
I'm not going to make comment on TAF LOE. I think people know where we stand on that and everyone has access to lawyers, so I'd encourage you to talk to your IP lawyers and chemists. I'll just say from our perspective, our IP estate goes out to 2040. We're going to be investing in this space for a long period of time, including double-blind head-to-heads, including switch studies and the like. So we view Acoramidis, Attruby, and beyond, and whatever cool names that we come up with as a lasting option here for patients that should serve them well on the front line.
I'm not convinced the broad investor audience is spending money on lawyers when it comes to the TAF LOE, but I guess at least in the next year or two, we'll get some potential trial dates, right? And things will start to progress. Okay, let's move to the pipeline. So,, Encaleret and Limb-girdle phase III's are reading out by the end of the year. Next thing in your stock for those two indications, I think a lot of people need to be educated and learn about those opportunities. So can you briefly discuss both of those and when we might get data from each if one's coming before the other?
Yeah, well, I mean, maybe timing-wise, they're likely to be right on top of each other second half of this year or pretty close as folks come back from their summer breaks, and maybe I'll just start by reminding everyone of the severity of the unmet need here. These are relatively large conditions, at least in the context of the types of disease we work on. For ADH1, the prevalence in the United States could be as large as 12,000 patients in the U.S. alone is what we see in StatGen databases. Although there's some 4,000 or so patients already identified, there is an ICD code. So we can find those patients. On the Limb-girdle side, 7,000- 8,000 patients between the U.S. and EU for LGMD2I, and probably an additional 2,000- 3,000 for the related conditions that affect enzymes in the pathway that ultimately affect α-dystroglycan glycosylation.
Both very large markets, all bigger than the Exon 51 DMD market, easy to get to the types of numbers we talk about well over a billion if indeed these drugs are proven to be beneficial, and I think in both cases, really high probabilities of technical success in the sense that phase II showed dramatic improvement over standard of care and all the sort of connect the dots in terms of what we were able to measure from biomarkers ultimately to the primary endpoints of both trials resulted in P values that were vanishingly small.
What do you need to show in these phase III's to be successful and file for approval?
Yeah, so the primary endpoint in terms of the ADH1 trial is normalization of serum and urine calcium. I just remind everyone that the disease uniformly arises from gain-of-function mutations in the calcium- sensing receptor. And what the agency had asked us for was to show that we can bring people back into that serum calcium level of 8.5-11 or so and bring down urine calcium below 250 or so a day. And in both cases, in the phase II, which we published in the New England Journal, we did that in about 70% of patients as compared to, if you look at natural history, about 2% of patients that are able to manage that with standard of care. And even then the 2% seems a little high because standard of care is vitamin D and calcium, so it should be exacerbating the urine calcium phenotype.
So basically the drug needs to do what it did in phase II or it could do even worse. And I think it would be a meaningful improvement for the patients that we serve there. In terms of Limb-girdle muscular dystrophy Type 2I, just as a reminder, this is an accelerated approval that we've agreed to with the agency on increase in α-dystroglycan glycosylation as measured as a continuous variable. And we saw an approximate doubling in both of the key patient populations within that phase II, the two being basically the homozygous population L276I and the compound heterozygotes. So again, the drug needs to do, it doesn't need to do what it did in phase II, it could do half of that, and I think it still hits the primary endpoint.
Importantly, in the phase II and what I was referring to earlier, we also saw concomitant reductions in CK. We also saw, albeit in an open-label study, so I take this with a grain of salt, improvements which we've never observed in natural history studies in measures of ambulation. So I think there's a lot to be hopeful for in that trial, but the primary endpoint again is going to be ADG increase.
Okay, great. Let's move to infigratinib. So the launch of BioMarin's Voxzogo has gone quite well. Maybe you could think about or talk about the positioning of infigratinib relative to Voxzogo or Ascendis TransCon and how large you think the achondroplasia, hypochondroplasia, et cetera market could be?
Yeah, I mean, maybe just starting with the unmet need in this case, maybe around 10,000 kiddos in each of those indications that you spoke about. And I think that the Voxzogo and obviously the impending or ongoing Ascendis launch has done a nice job of starting to tap that unmet need. I mean, I know everyone says that that's a great launch. I think in part it's been a pretty high price. So it looks like a good launch, but there aren't that many children on drug right now, especially for the number that are frankly identified.
And a lot of that has to do with the needle phobia. A lot of that has to do with the lack of efficacy outside of change from baseline and annualized height velocity. A lot of it has to do with the relatively mediocre impact on that variable itself. So long story short, I think an oral that's safer and with better efficacy has a chance to open up that marketplace in a meaningful way.
What about your existing phase II data gives you confidence that you can meet or exceed what those two other candidates have shown in phase III?
I mean, I think, so I don't ever look at one parameter really in the clinical studies. I think it is all of the dots connecting from the fact that we target FGFR3 uniquely, that we turn down those two effector pathways as we can measure in the clinic using a variety of different measurement techniques. I think it goes through all of the different ways we measure efficacy, including a change from baseline that's in the 2.5 range, which is well above what's been delivered by CMP analogs. But importantly, responder rates, importantly, obviously in order of magnitude, better impact on proportionality in the first statistically significant result there at 18 months.
I think also in every animal predictive model, the ability for us to correct not only height and proportionality, but some of the other impacts of the condition that we hear from this community are important to them. I think all of those things. I have yet to see a data point that suggests to me inferiority or even stasis.
Great. And data still by early next year, the phase III readout?
Yeah, last patient, last visit will be end of this year for sure. That kiddo can come two weeks early, then maybe we have a surprise earlier, but I would say, yeah, that's Q1 of next year would be fine.
Okay, so in the limited time we have left, I wanted to ask you about the recent convertible offering you did. So cleaning up the balance sheet, the mic's going in and out here, but maybe you could just talk about the convertible offering, why you did it, and how it went.
Yeah, the convert offering was really the first part of a liability management campaign from us. We have a lot of interest from that marketplace, and we were dealing with a senior secured facility that was right for us at the time that we implemented it, but was quite expensive going forward. So we were able to obviously push out the duration of our liability with this convert offering, get a number of great investors in, and I'll comment on that in just a moment.
But importantly, to dramatically reduce both the interest payments that we have and the amort payments that we have, so meaningfully extending our runway as well. So I think we say we have access to like $900 million of liquidity that's inclusive of the milestone that's coming and inclusive of the decrement in interest payments and not inclusive of any revenue that comes in. So we feel pretty good about the balance sheet at this point.
Okay. To close out, what do you believe is the most underappreciated aspect of the BridgeBio story by investors right now?
I would continue to focus people, if they have time, on ADH1 and LGMD2I. I think these are two molecules that I know they're first in class, so it takes a little bit of time to kind of come up to speed on the marketplace, but there truly is no competition in the space. That's the added benefit. You can make a really meaningful difference for patients, and I think these are marketplaces that are durable and quite large. So we've been trying to, whenever we can, get people to do a little bit more work there.
Wonderful. Neil, thank you very much for your time.
Thank you.