BridgeBio Pharma, Inc. (BBIO) Earnings Call Transcript

Good afternoon. I'm -- The floor is back from lunch. I'm Mani Foroohar, Managing Director and senior analyst here at SVB Leerink, covering genetic medicines, and I'm overjoyed to introduce the Neil Kumar.

That's nice of you.

Of BridgeBio and Eidos Therapeutics. You -- so you're a CEO of 1/7 of my whole coverage universe right now.

I guess that's a good thing.

Do you want to hop through a couple of slides, talk about like, overview of the story?

Sure. Yes. I mean, I think most people in the room, I just see a lot of familiar faces, so probably, I won't overwhelm the intro, but we are -- we consider ourselves very privileged to be in this area of genetic disease where the advances are absolutely insane. I think last year, there were 374 novel disease-causing genes found. When I was in graduate school, it was like 2 a year. So just the pace of discovery -- and I think what's unique right now is actually, we're just getting better at setting these mutations in the right context, do things like saturation mutagenesis and cryptic variation and a lot of which you guys have read. The other thing that's been interesting, and we've seen it in TTR, we're going to see it now. A wide variety of the disease that we work on is identifying subpopulations amongst polygenic diseases of truly mendelian or monogenic populations. I think that's been an ongoing theme in the literature. That's been really interesting. And then you see the continued depression in costs for exome and genome sequencing as well as our ability to do things faster. One of the things that we should talk about at some point is, in our pipeline, there's a variety of different products that are extraordinarily effective, if you can find a child in the first 6 months to a year of life. But after that, they start to have deteriorating effect. And so how do we play a role and others in the industry, in terms of identifying these children early enough? We have the technology to do it. We can sequence in the ICU at 48 hours. How do we start to just roll that technology out more broadly is going to be, I think, a key thing as we get closer and closer to commercial markets. I think you all know that the vast majority of monogenic diseases or mendelian diseases -- and this is not even somatic cancers, have yet to have even 1 approved therapy. So there's a massive opportunity, and that's why we continue to say we're at Day 1 in this space. And we think there's a lot of opportunity for a company like ours, which is laid out on the next page, which has certain attributes that we think allow us to be at scale, one of the better players in the genetic disease space. So we think a lot about the marriage of really good target selection, and we do that with some of the folks I'll mention on the next page, really experienced R&D prosecution, but we marry that with an efficient corporate structure, which is very decentralized. So it's effectively variablizing a lot of the fixed costs you see in single asset or dual asset companies. It allows us to get scale, so we can shut things down that aren't working, and we can learn across a wide variety of different modalities and programs. And the decentralization as well allows us to have focus at the level of each asset. And we've done this -- what, 21x now? If you go back to the Third Rock days, the first 2 programs we set up. Charles set up Global Blood Therapeutics. Charles and I put together MyoKardia. First 2 things we did at Bridge were Eidos and PellePharm. All of those assets are in Phase III now for well-described mendelian diseases, and we have 18 more of those programs coming along. So I think we're learning a lot, and we've obviously made mistakes along the way, too. But in all of this, we've put together a pipeline that I think is pretty diversified and powerful and now, late stage. So maybe I'll stop the intro there, and happy to take product-specific questions or I can keep going.

Let's start the question.

All right.

Let's start with the sort of more -- yes, we talked about -- we still have an ocean of ink, actually. I thought I'll never cover my theme. But let's talk about the cancer side of the story as well. I think people just think about the margin entities, not appreciating the -- near term, you're going to pile up, be a potentially commercial oncology company. And how do that fit into the infrastructure of BridgeBio? And where is that -- where do the oncology opportunity, FGFR, et cetera, fit into your greater corporate strategy?

Yes. Like in many ways, it's not distinct at a scientific level. Obviously, if you have clear genetic driver of cancer, that's very analogous to having a monogenic disease with a clear genetic driver. And in some cases, those drivers are the same. One just happens to manifest during development and the other, later in life, and to different magnitudes. Obviously, we've seen that with achondroplasia and cholangiocarcinoma. So our early-stage programs like SHP2, KRAS, GPX4, I think the only difference there is that those tend to be much more competitive spaces. But a lot of the science and the approach is the same, to really targeting well-described disease at its source. You're right to say, though, that the commercial infrastructure and everything we're building late is totally different for cancer. It's more expensive. It tends to be a little bit more complicated. We're obviously not doing it just for a second line cholangiocarcinoma, because that's a relatively small market, maybe a couple hundred million dollars of sales. But what we're much more focused on are the follow-on opportunities available to us with this FGFR inhibitor. So we, I think, recently -- we're working on starting a trial in adjuvant urothelial carcinoma. Well, we've had some really interesting data from the Phase I expansion cohort that we looked at, up to 50% ORR, which was -- so that's an interesting cohort of FGFR3 mutants. We're running our FGFR Fusion trial. Both of those I expect to kick off in the next week or two. And so those are very large markets where it makes sense for us to start staffing up on the commercial side.

So at what point you start to reach greater maturity? When you've got the couple of food products, you have some commercial infrastructure in place, should that -- will that or should that inform some of your earlier-stage asset in-licensing, where you start thinking about what we have built-out expertise in these markets? Does that change how you think about the risk-reward profile for things you might bring in, in the future?

Yes. That's a great question. I think this concept of the traditional M&A environment in -- or new program environment in pharma tends to focus around call point. So I have a certain call point. I own this physician relationship, and now I'm going to stack a bunch of programs up in that bag. I think that concept is kind of dead in rare genetic disease. The fact that I'm calling on a NICU is MoCD Type A solutions, doesn't mean that I'm just going to focus on the NICU as a call point or even pediatric neurology because these are 2, 3, 4 MSL field-force 20 sales rep-type opportunities, and you can do that in a bespoke fashion across a number of different indications. So I don't see that our commercial infrastructure on the field-force side or the call point side will inform how we pick up new programs. I do think, however, that the distribution of products and our learnings around what moves the needle for physicians, and how large or small a market can be and where we can compete, all of that will help us to inform whether or not we can be in competitive spaces with best-in-class or can we be first-in-class and how small can that really be -- still be profitable. Those things we'll learn more about.

Yes. And when you think about -- all right, another question that reflects really somewhat traditional bio pharma having covered this space. Obviously, you've -- I mean your -- did some attractive nondilutive financing for the Eidos business by partnering Japan with Alexion. Obviously, a large sophisticated rare disease player, robust, established infrastructure into Japan. Japanese commercial infrastructure can be complex and has some unique challenges to build? Does that kind of reflect the long-term, you just don't see value for yourself in building out an independent structure there? Or we should expect that to be sort of a -- part of your Japan strategy across the portfolio.

No. I mean, look, I think we're learning through some of these early partnerships. Our expectation is that we would build our own infrastructure one day as broadly as it makes sense from an NPV standpoint. In this case, we did a partnership, because we felt like we needed to get moving in Japan and need to have a couple of key regulatory discussions that we didn't think we could be the best owners of. But over time, I think that there's no geography outside maybe China that we don't think we can fill. In fact, I just read this book about BioMarin, their early days in their first 2 launches and their second launch, and what they were able to do in Europe with a relatively small team, gives me some confidence that for these really 2 differentiated assets, we can do something special and not just in the U.S. So I think we should stay open to that. I think China has its own challenges, especially in the orphan disease market, maybe less so in cancer. And so, we have been in active discussions around, is there a partnership to be done there, for someone who really knows on the ground game better than we do.

That makes sense. I think one of the other questions through the -- when you started the discussion around doing very high level things, how do you get every sub 6-month old with a genetically-defined [indiscernible] disease, CAH, et cetera? CAH will be a different opportunity. Every one of these very severe rare diseases that are best treated earlier, how do you get them all diagnosed? The sort of conventional wisdom is universal screening. As the cost of screening has gone down, what do you see as the challenges to adoption of universal screening across many of these defined diseases in the U.S. and in Europe and then internationally? And how different are those challenges in each place?

I mean, I would just have to say that for the majority of the diseases that we work in, screening is a nonentity. I mean, CAH is different, as you just mentioned. But the concept of adding something to the tandem mass spec panel right now is still painful. I mean, MoCD Type A is a perfect example of a child is born in uncontrollable seizures. There aren't that many reasons why a child should be born that way. We have a product that where we've filed an NDA, it's going to be a marketed product. You could do a simple sulfide test. You could do a mass spec test very quickly and they either have Type A or Type B. Put them on the drug, if they have Type B. If drug has no MTD, take them off the drug. But -- and yet still, I think it will be a challenge to get to the regulators and the government and you got to go state-by-state. So right now, I think the availability of biochemical or bespoke assays could -- they could be genotypical, they could be a biochemical assay, is the way to go. I think going forward, newborn screening, universal screening is the way. I think, companies like [indiscernible] and others are trying to do that. I just don't understand why it's not more broadly available. I assume it's a price point issue. If it's a couple of hundred bucks, I don't know why a parent wouldn't do it for the most part.

That makes sense to me. So diving a little deeper on that side of the business, on the gene therapy side. Obviously, you and I talked on CAH a few times. But the size of that opportunity is a little unique and that you're not necessarily trying to dose the youngest adrenal gland you can get your hands on. Tell us how you think about developing a gene therapy where people -- where the knee-jerk reaction of everyone is find the youngest baby, you can treat them with a product that explicitly want -- where that explicitly ideally used later in life, when [indiscernible] lowering. How do that change how you think about clinical development? How do that change how you think about the product profile, commercialization, et cetera?

Yes. I mean, this is a lifelong disease. Obviously you're dealing with exogenous steroids, and it's the downstream Cushingoid symptomatology that you're either pushing toward or the adrenal crisis that you worry about throughout the course of those first couple of years of life. So the concept that one would want a dose within that range where the client is actually involuting, I don't think it's that big a deal, quite honestly. I mean, obviously, there is a time in which you'd rather not dose with gene therapy, and we'll have to be cognizant of that. Children will have to be managed through that with alternative resources. But I still think the opportunity is large because after that, you're still using steroid or you're going to be using in the future some sort of -- one of these small molecule antagonist that doesn't affect endogenous cortisol production. So yes. I think it's -- I mean it's just a good -- nice thing there is we're picking the newborns up. We know that they're there. We can manage it to that point, and then we can administer the gene therapy.

When you think about potential study for CAH, would the -- being steroid-sparing is itself inadequate? Like the endpoint, do you think it needs to be an independent serum biomarker?

Well, there's -- yes, I mean, this is going to be a discussion with the regulators. Obviously, 17OHP has been what people have concentrated on so far, Spruce and Neurocrine. But that's just because they can't -- they're not putting 21-hydroxylase back. I think for us, I mean, obviously, 17OHP is interesting, but I think beyond that, actually looking to see whether or not you can improve or de novo-start endogenous steroid production, that's going to be the real key. And obviously, that is sparing by its very nature. Whether or not you bring it up into the total realm of normalcy or whether it's just sparing versus completely taking them off, I don't know. We'll find out as we dose up in the clinic, but we should find that out pretty quickly. We should be able to find that out pretty quickly.