BridgeBio Pharma, Inc.

day all lines have been placed on me to prevent any background noise after the company's remarks there will be a question and answer session if you would like to ask a question please press star followed by the number one on your telephone keypad if you would like to withdraw your question please press star one again thank you before we begin i would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities laws including but not limited to statements about Bridge Bio's future operating and financial performance, business plans, and prospects and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward-looking statements. For a discussion of these risks and uncertainties, Please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. With that completed, BridgeBio, you may begin your conference.

Good afternoon and thank you for joining BridgeBio's Q1 2025 Earnings Conference Call. This is Chinmay Shukla, VP of Strategic Finance at BridgeBio. Today we will discuss our financial results for the first quarter of 2025 and provide an overview of how we measure success in our business. We'll provide insight into the early results from the launch of a Truebee, as well as provide an update on our pipeline, which has three phase three readouts expected in the next year, including our efforts in expansion indications, such as in chronic hypoparathyroidism. Today's call will feature Neil Kumar, Chief Executive Officer, Matt Houghton, Chief Commercial Officer, and Tom Tremarcki, President and Chief Financial Officer. For the Q&A portion of the call, Anant Sridhar, Chief Operating Officer of BridgeBio Cardioreno, and Justin To, Chief Executive Officer of BridgeBio Scheduled Dysplasias will also join. Following the remarks by our team, we will open up the call for Q&A. With that, I'll turn the call over to Neil.

Thanks to everyone on the line for the time, and welcome to our first earnings call. We're grateful to open up another dimension of our dialogue with our investor partners. You've collectively allowed us to deliver for the patients we serve, and we look forward to your feedback on how to continually improve our discussion in this setting. Today, we know the star of the show is the Atruby launch. And the good news is that the brand is delivering for patients and the business. $36.7 million in revenue this past quarter suggests that clinicians and patients are resonating with our differentiated clinical efficacy, safety, and accessibility. We continue to educate on our therapeutic impact, which comes as early as three months, with a 42% relative risk reduction on cardiovascular hospitalization and mortality at 30 months, including a 50% reduction in cardiovascular hospitalization at that same time point. All these best-in-class point estimates are available at the lowest price point in the marketplace. There's much to like there. And we're aware that there's much work yet to be done. You'll hear about some of that work today as it pertains both to commercial tactics and further development work. We add to a Truby's good news the continued progress across our pipeline of three additional blockbuster products. Our trials in limb, girdle, muscular dystrophy type IIi, achondroplasia, and ADH1 remain on track with low dropout rates, frequent data collection, and positive site audits, all in preparation for an efficient NDA submission should the data be positive. Furthermore, key additional markets are being opened up. Our hypochondriplasia trial enrolled with incredible speed, and we now have first patient in there. Our work within CALERIT in the hyperparathyroid setting positions it well for a registrational trial which, if successful, could pave the way for the first oral compelling solution in that space. Before we move to discussion into further specifics regarding the business, and since this is our first time hosting this type of call, I wanted to briefly address how we measure the performance of our business on an ongoing basis. It's nice that this quarter was a success, but there will be harder quarters, I am sure. And through it all, you should expect for us to communicate consistently and in terms of net gains or losses in NPV. For instance, in this last quarter, our NPV increased by 9% given changes in the following variables. Number one, the time factor of money, especially given the late stage of our portfolio. Number two, a higher in anticipated revenue driven by a faster uptake of a true B than we anticipated, and likely a slightly higher peak year share by volume than our market research had projected. Third, the success of our small study in HP and other sponsor setbacks in the space of oral HP medicines. Fourth, the early enrollment of our run-in of our hypochondriplasia study, moving our timelines in for that program. And fifth, a slight decrease in our model cost of capital given our recent convertible offering. There were MPV drags, most prominently including tariffs. However, these have a close to negligible effect at less than 1% of our overall MPV. Stepping back from MPV, and as a reminder, our overall objective here at Bridge Bio is simple, to maximize the positive change we can have in terms of quality-adjusted life years for the patients that we serve as quickly as possible. We do so by creating as many meaningful medicines as quickly as possible within three constraints. The first is that each program must have beautiful science, which in our vernacular means a high POTS driven by understanding a mechanism of disease optimally paired with a therapeutic mechanism of action that targets a well-described genetic condition at its source. These types of programs historically have a three to four times higher probability of technical success than all-comer drug R&D efforts. Over time and many programs, this elevated probability of technical success moves us from being a speculative lottery ticket to being something akin to an engineering company. The second constraint is that we strive for each medicine that we make to be first in class or best in class. Determining best in class can be tricky in the absence of double-blind head-to-heads, but we approach this using a straightforward Bayesian approach. For instance, in TTR, if faced with the decision as to what drug to use, a logical person would first interrogate the salient endpoint, death and hospitalization, at a common time point. In this case, at 30 months, a relative risk reduction of 42% is a better point estimate as compared with any of the other products in this marketplace. You would then ask, how quickly does each drug take action? And you would find that the three-month beginning of separation between placebo and active is the earliest point estimate of timing of impact in this field. So logically, LaTruvi is at worst no worse than other medicines. You would then look at safety. Here you would find little difference between small molecules, but would observe that they do not have the safety signals some knockdowns have. Vitamin A deficit, which by the way turns knockdowns into a once daily pill regimen, Injection site reactions, the absence of impact on AFib, whereas both small molecules had meaningful reductions there, the imbalance of cardiac SAEs as observed in the IMPATRO study, and the as of yet unexplained imbalance in death on the REVIEW-SERAN trial. You couple that with the overall finding that across multiple studies, TTR is a cross-species conserved protein, and that ever higher levels of TTR lead to ever longer lives and less disease over time. So, logically, small molecule stabilization from these data is the safest approach. Finally, the logician might look at price only to discover that a true read has the lowest price point. We believe, given all of that, the choice is clear. We apply similar reasoning in other competitive spaces like achondroplasia. Our final constraint is that each program we work on should be NPV positive to ensure firm level sustainability. We use all available levers during the R&D stage to optimize NPV, including time, cost, cost of capital, and probability of technical success. The better our model is at generating economic value from projects, the further we can push into markets where others cannot extract adequate value, in addition to being a better owner of obviously NPV-positive projects. The fact that we will spend well under $100 million per program to get each one of our potential blockbusters from the preclinical stage through proof of concept sets us up well for future growth that is economically attractive. Okay, so that's our overall objective function with its attendant constraints. And you heard the first and most important frame that we use to think about the business, which is MPV. There are other frameworks that we also use to look at the business, understanding the business by staging capability, research, development, and commercial, understanding the business in the context of the overall ecosystem, and understanding the business program by program. Using the buy stage framework first, and as I mentioned earlier, we are pleased with the ongoing progress of our commercial launch and the building of a sustainable competitive advantage there, which means, of course, that our group is able to extract more profit from the asset than another would be able to. I've also touched already on our ongoing development wins. On Discovery, our bread and butter, We continue to advance programs in genetic dilated cardiomyopathy and ADPKD. We also hold significant stakes in bridge bio-oncology therapeutics and gondola bio. In the latter, we expect phase two data in our EPP program later this year, and we expect to generate up to six development candidates in 2025. From an ecosystem framing, the substrate for making genetic medicines remains incredible. We see that in the progress Gondola is making, and more broadly, with the depth of genetic disease starting points being produced and accessible at low price points. Finally, at a program level, Matt will have more to say about a commercial launch of a Truby. Our goal there, as a reminder, is $4.3 billion in peak year sales, or about 30% of a $15 billion marketplace. That gets delivered against approximately $380 million of spend on the brand per year. Almost 25% of current spend is on further research and development activities like Act Early, which we think could continue to improve our medicine's positioning and its ability to help patients in later years. The product of this spend also includes salient results like our variant data, where we obtained a hazard ratio of 0.41 with a p-value of less than 0.02, in the sickest of patients, and new work we are doing regarding AFib, which is an emerging marker of disease progression, the first result of which we plan to present at ESC later this year. For infragratinib, a first-in-class oral FGFR3 inhibitor in development for both achondroplasia and hypochondroplasia, the pivotal Propel 3 Phase 3 is fully enrolled, and we expect last participant, last visit by the end of this year. We have also reached regulatory alignment with the FDA on our clinical development plan for infragratinib in children with achondroplasia from ages zero to three, and we expect to initiate clinical development in this important age range by the end of the year. Excitingly, we have also enrolled the run-in for our phase two hypochondroplasia trial well ahead of benchmarks. For Encallerate, a negative allosteric modulator of the calcium sensing receptor, our phase three Calibrate study is fully enrolled. We expect last patient, last visit, and top line results in the second half of this year. In parallel, Encalerate is also being studied in hyperparathyroidism, and we announced today positive POC data for Encalerate in this key expansion indication. Preliminary evidence in the ongoing POC study has demonstrated that 78% of the first nine study participants were able to achieve normal blood and urine calcium levels within five days of Encalerate administration. Moving to BBP418, an oral first-in-class disease-modifying therapy in Phase III development for treatment of individuals living with limb-girdle muscular dystrophy type IIi. We have fully enrolled Fortify, a Phase III registrational placebo-controlled study, evaluating the safety and efficacy of BBP418. The study includes a planned interim analysis of 12 months focused on assessing a surrogate endpoint biomarker, glycosylated alpha-dystroglycan, to support accelerated approval in the United States. We anticipate top line readout from that phase three interim analysis second half of this year as well. Finally, BBP812 is an AAV9 gene therapy in development for Canavan disease, an ultra-rare neurodegenerative disease that usually leads to death in the first two decades of life. Here, we are pursuing an accelerated approval approach using a single, seamless registrational trial to bring this potential therapy to children with Canavan as quickly as possible. A meeting this month with the FDA reinforced the validity of our approach, which centers around the use of urine NAA in tandem with other clinical measures and the suggested BLA filing that we have laid out by end of 2026. While this is not a very prevalent disease, we believe it's a great example of our model, targeting disease at its source and operating leanly to enable us to go after a well-validated condition in an NPV-positive manner. Okay, that's the final framing. To wrap up my comments, Bridge Bio is executing well and importantly possessed of a tremendously strong foundation for the future. Number one, an unmatched collection of late stage genetic disease businesses with favorable economic prospects. Number two, a cadre of outstanding managers that are dedicated to their specific assets business and to Bridge Bio. Number three, a diversity of stakes including wholly owned assets and significant stakes in gondola bio and bridge bio-oncology therapeutics. Number four, first choice ranking with many academics when seeking a partner to discover and develop new medicines. And number five, a culture that is distinctive from most biotechs I have seen, and that is decentralized, independent thinking, and lives the value that every minute counts for the patients we serve. We're excited to work with you, our investors, to continue to build this company and to keep you up to date on our progress for patients. With that, I'll hand it over to Matt to walk through Atruby's commercial performance in more detail.