Welcome, everyone. I am Josh Schimmer from the Cantor Biotech Equity Research Team. I am very pleased to introduce from BridgeBio, we have Chinmay Shukla, immediately to my right, SVP of Investor Relations and Strategic Finance. Next to Chinmay, we have Anna Wade, Chief Operating Officer of BridgeBio Neuromuscular. Beside Anna, we have Julie Miller Everett, not Everett Miller, because I think we caught that, Chief Operating Officer of BridgeBio Skeletal Dysplasias. So great to have the team with us. Chinmay, maybe you want to kick things off, give us a quick snapshot of where BridgeBio is today and where the company is headed.
Yeah, happy to do that. First, Josh, thank you for hosting us, and thank you to all the investors for joining us here, and as well as on our one-on-ones. BridgeBio today is at an inflection point. We have $8 billion in post Phase III peak year sales assets. The first of that is Attruby, which is launched, which we think is a $4 billion drug. Globally, it was already annualizing to over $1 billion in 2Q, so we are building on our strength there. Right after that, we have three launches upcoming very shortly now. I think the first one, limb-girdle, is going to be in November, and then we expect a launch in achondroplasia as well as ADH1 early next year. So that is where we are at. All those four indications put together are $8 billion in peak year sales.
What is very exciting is that right behind that, we have an expansion indication in hypoparathyroidism, which is probably worth another couple billion dollars, especially when you put it with the depleter antibody, which is in early stage in ATTR-CM. That is not it. I know, Josh, you have always liked for us to think more holistically and think more broadly about genetic diseases and helping patients who are suffering with these diseases. We have a sister company, GondolaBio, where they have a late-stage EPP program, as well as some 16 or 17 very early-stage assets, which are all very exciting. So there is a lot happening. We are trying to do a lot for patients, and my hope is that over time, that value is going to accrue to shareholders also.
Excellent. All right. There is a lot to get through, so we will see how much we can get through in the next 27 or so minutes. Why don't we start with the Attruby? Remarkable drug, remarkable progress, and yet still seems like a long road ahead to achieve what that drug should achieve. Why don't we begin with some of the takeaways after the CARDIO-TTRansform data presentation and how you think that these incremental pieces of information help position Attruby in the competitive TTR landscape?
Yeah. Happy to do that. I think CARDIO-TTRansform was, I would say, the last big data event, which has now really clarified a lot of the picture for us in ATTR-CM. Where are we today? I think the first thing to realize is that stabilizer therapies, there are two main types of therapies, stabilizers and knockdowns. Stabilizer therapy, which is the type of therapy that Attruby is, they are going to be the treatment of choice for frontline ATTR-CM patients. If a new patient comes in, which is a vast majority of patients today, they are going to be put on a stabilizer therapy. The knockdown therapies take about a year and a half to work, whereas Attruby takes about a month to work.
And then you also have to take into account that combination therapy, which some people had hopes for, was proven decisively to be inefficacious in CARDIO-TTRansform. I think the second thing which we learned is that the two knockdown agents are more similar to each other than different. If you look at the placebo-adjusted knockdowns in the Gilmore et al paper, you saw that the two knockdown percentages adjusted for placebo were very similar. And then that translated to monotherapy hazard ratios for the two knockdown agents to also be about 0.67 and 0.7 respectively, so very similar. And then the third thing which I would say is we were very encouraged to see that clearly there is room to do more beyond VYNDAMAX, which is the first generation old stabilizer, which is where Attruby, which is our second generation new stabilizer, has a unique differentiated edge.
And so we do think that having that near-complete stabilizer in Attruby, it confers a very unique kidney protective effect. We also see the fact that it has much stronger effects on hospitalization as well as time to separation, hard outcome separating as early as one month. So we think that that is where Attruby is positioned. Today we have more than 25% share in frontline patients. We have said that our goal is to be at 30%-40% at peak. We are doing market research to refine that, and my expectation is that 30% number will probably move up on the bottom end of the range at least. And then the last thing which I would say is, in our experience, it takes a little bit of time for all this data to really get out there in the field.
We have noticed that it takes physicians multiple visits explaining the data carefully, that these are nuanced data sets. As we do all of that, I think it takes about a year or so for these amazing data sets for Attruby to translate into script growth and then ultimately revenue growth. So near term, we expect about a $25 million to $30 million quarter-over-quarter sales increase for the next three or four quarters, which should then start to accelerate as you get into calendar late 2027 or early 2028.
Okay. Given the claims data analysis you've been able to generate, it seems to be really differentiating versus tafamidis and resonating. I'm surprised your goal is that 30%-40% range, not 2x that or more.
Yeah. That's a great question. We think that Attruby is the best drug for ATTR-CM patients, and we do think that everyone should be on Attruby. Actually, in Europe, more than 50% of new patients are on Attruby, especially in Germany, which is where the drug was first launched in Europe by our partner, Bayer. Why is it that I'm saying that our goal in America is 30%-40%? Well, I think there are a few reasons for that. The first reason is I don't think most investors believe 30%-40%, so let's start there so we can sort of walk them through it over time. Second of all, I think that there are some unique differences in our healthcare system, such as the buy-and-bill economics and things like that, which do impact prescribing on the edges.
In an ideal world, it wouldn't, and I know the government's thinking about that, but it does right now, and so we have to be realistic about that. But what I would say is we have built a very strong foundation of evidence now that Attruby is a differentiated stabilizer. It's not just another VYNDAMAX, it's a much better stabilizer. That started with the label. As you remember very well, Josh, we're the only agent in the field which has the verbiage near complete on our label. Beyond that, what I would say is we've then built upon that to say that that near complete stabilization is correlated with a decrease in all-cause mortality. Then we've built upon that with subgroup analysis, whether it's the AFib patients or the variant patients.
Yes, now we are expanding upon that with a unique kidney protective effect, which Attruby has, as well as the claims data which you're saying, although the claims data is maturing. So my expectation is we'll see more independent studies come out at HFSA. We are always excited when an independent person looks at Attruby versus VYNDAMAX because we feel so good about our profile.
What should we be looking for at HFSA in terms of additional claims analysis that could either bolster the case for Attruby or not?
Thus far, we've done analysis from our own phase III trials, whether that's looking at Attruby versus VYNDAMAX in the trial, and we've also looked at subgroup analysis. I think some people have also done some comparisons of Attruby versus VYNDAMAX on serum TTR in real-world settings. I think what the field is looking for is clinical worsening outcomes. What do I mean by that? Things like diuretic intensification, hospitalizations. Those are hard outcomes. It takes a little bit of time for this data to mature, but I think we're almost two years into our launch. I know that there are some systems which have been looking into this, and my expectation is that people publish what they've found on Attruby versus VYNDAMAX.
That clinical worsening outcome should drive additional behavior with cardiologists, though I will caveat the fact that it takes six to nine months for all of that data to get in the field and then start to get reflected just because we have to go and educate people on it.
What's your confidence then, when it's all said and done with all the claims data analysis, at the time the generic tafamidis enters, that you'll have built such a strong case for Attruby's differentiation that generic tafamidis is not going to be a problem?
Well, first I will answer that by saying our confidence is extremely high. That is the simple answer, and let me build upon that. I think that we already have built a solid foundation of evidence. I think that the earliest that a VYNDAMAX generic could enter is mid-2031, so we have another four or five years before that. I have been saying it takes about nine months, maybe 12 months to have this material educated to the physician. So we do have significant time. The second thing which I would say, which is a little underappreciated by investors, is if you look at the channel dynamics here, it is really a channel which is dominated by specialty pharmacies and institutional specialty pharmacies. The stakeholder dynamics there are such that branded drugs are preferred more.
The last thing which we would say, and we have updated our corporate deck with some of this material. If you look at any pharmaceutical category, when a first to market, less potent molecule goes generic, the second to market, more potent molecule, their sales keep going up. I think the best example of that, which interestingly investors have inbounded into us and told us to talk about it, is Gleevec as well as the next generation TKIs, which came in after Gleevec went generic.
Yeah. Okay. Excellent. Anna, why don't we come to you? CEO of BridgeBio Neuromuscular, that is going to be BBP-418. Are there any other programs within neuromuscular at this point, or is that yet to come?
That is yet to come, but it is definitely something we intend to continue to evaluate. Chinmay might speak to some of the programs within our sister company, GondolaBio, later, which includes some in the sort of neuromuscular space.
Okay, got it. For BBP- 418, I expect you have had your mid-cycle review now with the FDA.
Right. Yeah.
How are you feeling about approval prospects and/or need for ad com or other considerations?
Yeah. We are feeling really good about our approval prospects. To take a step back, our PDUFA is on November 27th of this year. In our data set that we announced last October, we saw clinical benefit on functional outcomes. We basically saw improvements in pulmonary function as well as ambulatory measures, and that data as well as the full data set that the agency has seen, it really is supportive of an approval in November, and they are also still considering traditional approval as the most appropriate path, which would not have any sort of further commitments to do a sort of confirmatory study.
Okay. I think the estimate is around 4,000 patients in the U.S. total with limb-girdle 2I or R9 with 500 identified. Is that correct? Maybe talk a little bit about the cadence of patient identification and what the addressable market you expect will be.
Yeah, absolutely. We estimate there are about actually 7,000 in the U.S. and Europe, and within the U.S., it's about 2,000 to 2,500, of which we currently have identified around 500 patients, where we know where they are, and they are genetically confirmed. We are continuing to see growth there as we ingest more sort of genetic testing data. We have people out in the field, and they are sort of profiling accounts, and we continue to sort of add patients, on a sort of monthly basis through that. As well as we actually got a unique ICD-10 code that came in in October of last year, so it's still not particularly mature, but we are seeing current use of it, and it is growing on a month-by-month basis as well. We're continuing to see sort of momentum there with the increase in patients we've identified to date.
Do you expect all 500 patients identified are good candidates for 18?
Yeah. We do believe that the majority of patients are really good candidates for therapy, and that's driven by a few things. First off, if you look at the clinical trial inclusion criteria from both the phase II and the phase III, that it's very broad. It includes both genotypes, it includes ambulatory and non-ambulatory patients. So a variety of different functions. I think the only sort of potential narrowing of that population is just based on the age. Basically, we were studying 12 and up, in the phase III trial. Also, there's a body weight limit basically based on our current dosing. We dose 9 g twice a day for 30-kg patients and then 12 g twice a day for 50-kg patients and above.
We wouldn't anticipate that those lowest body weight, youngest individuals right now would be candidates for therapy, but pretty much everyone else should be. The HCP market research we've been doing has shown really strong adoption across all of those different patient segments that I mentioned.
Are there useful pricing benchmarks you have in mind?
The most useful pricing analogs that pay is always referred to are the exon-skippers, in DMD. Obviously, that's a very similar disease. It's sort of similar prevalence as well. I think the main thing to consider when you're looking at those analogs is that those analogs really were just based on biomarker data and didn't have functional outcomes. When we have been doing payer research, the fact that we have these functional benefits that are seen in our data set means that we potentially could price at a premium to those.
How should we think about ex-U.S. commercial plans? That may actually be a good opportunity to talk about the MFN agreement that BridgeBio recently forged with the White House.
Yeah. Maybe I'll give a few general comments, and then I might ask Julie to talk about a little bit more because obviously infigratinib is at the cutting edge of ex-U.S. for BridgeBio right now. Our base case plan is to commercialize globally with the next three products, whether that's BBP-418, encaleret, or infigratinib. Really that comes down to a few different things. One is, we are in an MFN world right now, and we're very happy with our agreement with the government and partnering with the government, which I can touch on in a minute. But you never know if you look 10, 15 years out, this is now part of the biotech business, and so we have to think very long-term and strategically about these transactions.
I think the second thing is these are going to be significantly more focused launches, ex-U.S. also because the patients are congregated at a small number of sites of care. We already have presence in these countries through clinical trial sites as well as deep relationships with KOLs. I think about the fact that while these things are capitally efficient launches, we also now are in a better capital position. We had about $1.7 billion of cash on our balance sheet as of July 1 pro forma. So that makes me feel better about our ability to actually invest properly in these geographies and get the right value out of them. Now, look, having said that, if someone comes along and makes an offer which fits our better on our hypothesis, the phone's always open and we're always happy to engage.
But our base case plan, given all of these considerations, is to commercialize ex-U.S. on our own. We have made good progress already. We're being lean about staffing ex-U.S., but we've already made very good progress on the regulatory front and some senior international hires. Maybe I'll let Julie comment on it for a minute or so.
Sure, yeah. Very briefly, I can add, I actually just flew in yesterday from France for the ESPE conference, and I was with the international team there. We feel really good about putting the right people in the crucial first roles as we expand. So at this point, we have hired our commercial and medical leadership team for the international organization. So we have people in place for commercial field, country managers, market access, which as everybody knows, is crucial for speed of uptake as well as overall price potential in Europe. So really have a solid market access team in place at the portfolio level and then also now at the product-specific level.
So we've got our medical team sized and deployed there to initiate those discussions with customers, as Chinmay mentioned, and a really solid handoff from our clinical development organization, who has deep, rich engagement already given the development programs that we've had in Europe. We've started the relationship handoff from clinical to medical to start engaging in that dialogue to that scientific exchange. So we feel very good about knowing who the customers are, where they are, how many patients are treated at which center of excellence, and how we want to size and deploy the international resourcing to accelerate uptake. So I would say very quickly, we feel very confident in our ability to execute ex-U.S. from regulatory standpoint, medical standpoint, commercial standpoint.
And then maybe coming back to the MFN agreement and how that affects the portfolio in total for BridgeBio. And does this supersede any potential down the road MFN rules and laws enacted for the broader biotech community?
Yeah. So I think we're one company, so I wouldn't talk about the broader biotech ecosystem. I'll let you guys who are closer to more companies talk about that, Josh. For us, really, it's a partnership, right? We're very excited that we've been able to expand access to Medicaid patients with, for Attruby, which is obviously our only big commercial product right now. So, that's what we've agreed to with the government. I think that, as we mentioned in our 8-K, our expectation is that this partnership will mean that we're able to get good price elsewhere so that we can take the revenues and invest it into making more medicines for genetic disease patients. And we're excited to work in partnership with all branches of the government to do that.
Okay. Why don't we come to infigratinib? And Julie, I guess the competitive landscape is evolving a bit. We've got combination data from Yuviwel with SKYTROFA, and Yuviwel itself is off to a good start. We recently had some data from BridgeBio for infigratinib framing, I guess, otitis media and sleep apnea. As you look at all the moving parts here, where do you see the real points of differentiation for infigratinib beyond being an oral drug versus injectables?
Yeah, thank you for saying that. I think everybody knows that there's extreme injection burden, whether it's a daily injection or a weekly injection. These families just don't want to have to take an injection. Just being the first and only oral agent is very profound for this community. But clinical points of differentiation, we actually are just coming off of the ESPE, the European Society for Paediatric Endocrinology conference this week, where we are the first and only company to show clinically meaningful benefits beyond height within 52 weeks. We just presented, Dr. Julie Hoover-Fong shared yesterday that if you look at sleep apnea, I don't know how many people, either yourselves or your children, suffer from sleep apnea, but very debilitating condition that can truly impact many aspects of your life, right, with chronic fatigue and other implications.
We demonstrated within 52 weeks that in the overall infigratinib population on the apnea-hypopnea index, the infigratinib population only showed a 10% increase on that scale, that apnea scale, whereas the placebo population showed a 49% increase within 52 weeks. But even more profound, when you look at the children ages three to less than eight, that earlier age population where you can initiate intervention sooner, the infigratinib population saw no change in their sleep apnea, where the placebo saw a 63% increase in the severity of their sleep apnea. That is incredible. Let's talk otitis media, which is ear infections. Again, not sure how many of you have children, but if you have ever had a child who has had an ear infection, this is a miserable experience. You have doctor's appointments, missed school, childcare implications, antibiotic use, chronic antibiotic use.
This is, again, very impactful to functionality in daily life for these families. We showed a 37% reduction in the event rate of ear infections in the infigratinib group versus the placebo group in the overall population, but a 47% reduction in the patients aged three to eight. Again, in that younger population where infigratinib is started sooner, almost half the number of ear infections. We're demonstrating this within 52 weeks. No other product has been able to show benefits like this within the randomized, double-blinded, placebo-controlled portion of a study. Clinical differentiation, not only do we show the greatest benefits on height, the only product to show statistically significant benefit on proportionality within 52 weeks, but now also these meaningful benefits beyond height, both of which are resonating well with the HCP prescribing community as well as the patient community.
Do you have objectives in terms of either new patient share at certain benchmarks or the ability to claim share amongst patients who are already treated with their
I have objective. No, I'm just kidding. We feel very confident, especially with the data that we've seen at this point within 52 weeks and some of the longer-term data. I feel very confident that we will be able to achieve absolutely majority market share at peak. We actually think it could be a high majority market share, and I just walked you through why we believe that from a clinical points of differentiation. But also the oral is just a very compelling kind of proof point for families and why they would like to request infigratinib. What we're actually seeing in our market research, we do market research with both prescribers as well as families. We're seeing source of business across all of the patient categories. Those who are currently treated with VOXZOGO or Yuviwel today, high willingness to switch.
In those families who have not considered treatment previously, there is a large portion who are now saying, with an oral option that is far less invasive, that benefit-risk profile is much, much stronger than with the CNP therapies. That is actually, Josh, the segment I'm most excited about, is not just cannibalizing from the competition, but we very firmly believe that there will be an overall market expansion here in the total number of patients who are treated today, especially in the U.S., where we believe there's only about a 30% overall treatment penetration today, so much room to expand the treated pool. Then finally, the third category is those who have either been on product before and discontinued or who have actually decided that treatment is not for them.
Okay. Excellent. What should we be looking for in the upcoming hypochondroplasia data?
Yeah, so I think everyone's familiar that the phase II program in our hypochondroplasia program is a dose-finding study, so you should be prepared to hear further updates regarding what dose we will continue to explore in the hypochondroplasia program.
Just to build on a couple of things Julie said, I think really the market expansion potential in NF1 is In Europe, about three-fourths of the children are on an intervention. In America, only about a fourth to a third of them are on an intervention. I think that it is very clear that we can triple the market in America, and of course, that would be of significant value. Just to build on the HypoCon answer from Julie, maybe I'll just mention a couple of things. Just I know investors are aware of this, but just as a reminder, we started the HypoCon phase II dose exploration study before the PROPEL 3 phase III results from achon were available. We were testing two doses, the achon phase III dose and a dose lower than that.
I think people know that there's a different mutation which causes HypoCon, compared to achon. So I think what's important for us is going to be able to find the right dose. Of course, given the pristine safety profile of achon in phase III, there is some discussion of potentially expanding and increasing testing a slightly higher dose also. So look for us to provide an update on that. I think that our expectation is that that dose-finding study will continue for a little bit of time.
I've never seen a case where the FDA switched a standard review to accelerated review in the midst of an application. So what happened with that with encaleret, and how did all the timelines adjust accordingly?
Yeah. Happy to-
Priority review, not accelerated review. Just-
Yes
I am sorry, correct.
No, it is okay. Just to clarify. Yeah.
It's okay.
Yeah.
I think we're very excited about encaleret. I know, Josh, you're very excited about encaleret, too. I think that if you look at the phase III data, first of all, let's start with the disease. ADH1 is a devastating disease. The effects on patients are severe. We've had patients come to our patient days and talk to the company, and really, as you hear what their day looks like, the need to go to an ER at short notices, the need to take injections, the need to take lots of medicines, even in young children. The burden here is extremely high, and there is no option for these patients right now. In that context, encaleret delivered really astounding data.
I think actually for both encaleret as well as BBP-418, it is rare to see molecules like in encaleret, we had 76% resolution of both blood and urine calcium, which is basically a resolution of the disease, which is not something which you normally see with medicines. You see a halting of the disease or a slowing of the decline. Here, we are showing with one drug resolution of the disease. With another drug, we are showing reversal of function and gain of function. Really, the profile for encaleret's clinical efficacy was also extremely powerful. We felt like we had a very, very good case for priority review. We submitted the package to the agency expecting priority review.
Unfortunately, it came back as standard review, and we felt like in this situation, for the patients that we are hoping to serve, it would be prudent for us to go request the agency to reconsider, just look at all the facts again. As we talk to them, like we've mentioned, we have a good partnership with the government, and we're working closely with them to bring medicines to patients. As we did that, they have decided to reconsider and changed our review from standard review to priority review. The PDUFA date has not changed, so my base case expectation is still approval by PDUFA, but we will certainly be trying to work as quickly as possible to get the drug available to patients sooner because there is a desperate need in this condition.
It is more of a philosophic approach than a technical timeline difference.
That is correct.
That made. Yeah. Okay.
For now, that is the case.
Okay. For the broader hypoparathyroidism indication that you're pursuing, are you able to address the entire population or do patients need to have some baseline PTH level to qualify for the drug in that program? If so, what kind of percent of the market could you address?
Yeah. We think that encaleret will work for all chronic HP patients, whether they have residual gland or whether they don't have residual gland. I do think that that's the case. I think it is very interesting to notice that in our phase II study, we did look at patients who had no PTH gland activity, and we were able to show a resolution on blood and urine calcium even in those patients. We feel confident about that. I think that I would strongly encourage folks to listen to our CEO, Neil Kumar's prepared remarks on our Q2 earnings call, where he went into the mechanism of why encaleret should work in HP. We don't have enough time to get into that right now.
There are multiple threads of evidence now to suggest that this drug should work, and I actually think it's a pretty high probability of success trial. It's a huge indication, and the trial's probably going to read out late 2027 or late 2028, so it's coming very soon.
One of the many parts of BridgeBio that are generally underappreciated by the investment community. Thank you to the BridgeBio team for coming out to join. Thanks, everyone, for tuning in.
Thanks, Josh, for hosting us.
Thank you.
Thank you.