Acoramidis

iStock/ jauhari1 As it nears a crucial FDA action date for its transthyretin amyloid cardiomyopathy candidate, BridgeBio focuses on its late-stage pipeline. Bay area–based biotech BridgeBio, founded in 2015 to be a bridge between promising early-stage academic work and patients with genetic diseases, is now a growing commercial enterprise, with two products on the market and another expecting an FDA decision by the end of November. As such, the company is making strategic moves, spinning out some assets into two new companies, cutting an entire gene therapy program and focusing its remaining resources on its late-stage programs in transthyretin amyloid cardiomyopathy and achondroplasia, which analysts say are key to BridgeBio’s success. “We have the capability, by our tenth birthday, to have had six approved products for a billion-plus dollar market,” Neil Kumar, the company’s charismatic founder and CEO told BioSpace . “So that’s a very, very productive engine.” However, commercial success requires the company to make some adjustments, Kumar continued. “Our investors would like to see us focus our resources to show that we can commercialize,” Kumar said, with a specific focus on the company’s later-stage pipeline. “We’ve shown we can do R&D, but now we have to show we can commercialize and build a business against these products.” To satisfy these investors, BridgeBio has adopted a hub-and-spoke model. In May 2024, it spun out its KRAS-focused cancer portfolio into BridgeBio Oncology Therapeutics , which it endowed with $200 million in initial funding. And last month, BridgeBio debuted GondolaBio to further develop early-stage assets for tuberous sclerosis complex, erythropoietic protoporphyria and alpha-A1 antitrypsin deficiency. Then this week, the company announced that it is discontinuing development of its gene therapy candidate BBP-631 after it failed to show “transformational results” in a mid-stage study in congenital adrenal hyperplasia (CAH). “The data we generated did not suggest that our efforts would result in a meaningful step forward for patients as compared to what we think standard of care will be in the coming years,” Kumar said. “Therefore, we felt our efforts would be better applied to other areas of unmet need,” though the company is seeking a partnership to continue development of BBP-631 and other next-generation gene therapies for CAH. That leaves the company’s two approved products— Nulibry for molybdenum cofactor deficiency type A and the targeted cancer treatment Truseltiq (infigratinib), both approved in 2021—and four assets in late-stage development. First and foremost, BridgeBio is gearing up for a Nov. 29 FDA action date on its transthyretin amyloid cardiomyopathy (ATTR-CM) hopeful, acoramidis. At the same time, the company is continuing Phase III development on three more drug candidates —infigratinib for achondroplasia, BBP-418 for limb-girdle muscular dystrophy type 21/R9 and encaleret for autosomal dominant hypocalcemia type 1. Kostas Biliouris, director of biotech equity research at BMO Capital Markets, noted that the primary interest in BridgeBio is in acoramidis and infigratinib. “The other spinout companies are probably increasing efficiency” for these late-stage products because they effectively remove from BridgeBio’s portfolio “something that investors are not focused on,” he told BioSpace . The Path to Success If approved in November, acoramidis will be going up in the ATTR-CM market against Pfizer’s tafamidis, sold as Vyndaqel and Vyndamax, which Biliouris said is well-established in the market. Like tafamidis, acoramidis is a transthyretin stabilizer. Biliouris said that while acoramidis may be “incrementally better” than tafamidis, it needs to be dosed twice per day, compared to once per day for Pfizer’s drugs, which may limit uptake. In addition, Biliouris said, Pfizer has demonstrated that tafamidis can reduce the risk of mortality, whereas acoramidis did not show a statistically significant effect on this measure. In a survey of 30 physicians conducted by BMO Capital Markets, 50% of doctors said the efficacy is similar between acoramidis and tafamidis, while 40% believed acoramidis to be incrementally better, Biliouris shared. “That’s why it’s not an easy story.” If BridgeBio does secure FDA approval for acoramidis, the company will then need to beat sales expectations in 2025, Biliouris said, estimating these to be about $165 million in the U.S. “If BridgeBio can beat that number, it will be great,” he told BioSpace . “It will help the stock and the story. If not, it will be challenging.” Some of the drug’s success could also be tied to whether or not tafamidis goes generic in 2028 or 2035, Biliouris noted, adding that this won’t be known until 2028. Another piece of the puzzle, according to Biliouris, is infigratinib, which if approved, will go up against BioMarin’s Voxzogo in the achondroplasia space. BridgeBio is anticipating a readout for the drug in late 2025, according to Biliouris. This trial needs to meet its primary endpoint and show a good safety profile, he said. “Usually, this drug treats kids and safety is very sensitive here.” It also “needs to be at least as good, if not better, than its main competitor,” Voxzogo, Biliouris continued, and like acoramidis, will also need to beat sales expectations. Kumar, for one, is confident in BridgeBio’s future success, noting that its ultimate goal is “to serve as many patients as possible across as many indications that effectively allow us to do high probability drug discovery development. What some companies would do [in BridgeBio’s position] is they would push pause,” he said. “But I don’t believe in pushing pause.”

Dive Brief:BridgeBio Pharma plans to trim its spending on gene therapy research by more than $50 million after early-stage study results for one of its experimental therapies failed to meet the companys threshold for additional investment.Disclosed by BridgeBio Tuesday afternoon, the data showed treatment with the companys BBP-631 therapy led to increased production of a key hormone in people with a condition known as congential adrenal hyperplasia, or CAH. No treatment-related serious side effects were reported.BridgeBio claimed its study showed for the first time that people with CAH can make this hormone, called cortisol and necessary for the bodys response to stressors. But data to date are not yet transformational, said company CEO Neil Kumar, so BridgeBio intends to find a partner for BBP-631s development.Dive Insight:BridgeBio isnt getting out of gene therapy entirely. The company has another experimental treatment for a neuromuscular disease called Canavan.We believe that gene therapies have the potential to fulfill a significant unmet need and are eager to work closely with the FDA and the Canavan community with the goal of bringing our therapy to families living with Canavan disease as fast as possible, said Chief Financial Officer Brian Stephenson in Tuesdays statement.But BridgeBio is taking a step back from the field and, moving forward, will be reserving gene therapy for priority targets that we cannot treat any other way, Stephenson said.The effect is a further focusing of BridgeBios pipeline around a handful of later-stage assets, foremost among them acoramidis, a treatment for transthyretin amyloidosis with cardiomyopathy thats currently under regulatory review in the U.S. The company also has medicines in Phase 3 testing for a rare calcium disorder, a kind of muscular dystrophy and a bone growth disorder.The results for BBP-631 came from the latter half of a Phase 1/2 study that enrolled adults with classic CAH. The study found treatment led to increases in endogenous cortisol production in all patients given higher doses of the therapy. Investigators also reported substantial and durable increases in the product and substrate of the enzyme that makes cortisol. This, BridgeBio said, suggested its therapy had successfully delivered its genetic payload into the body.BBP-631 uses a benign form of an adeno-associated virus to shuttle a functional copy of the gene encoding that enzyme to the adrenal gland. By inducing the body to produce cortisol, BridgeBio hoped to eliminate or substantially reduce the steroid treatments that people with CAH currently use to manage their condition. '