AerialPerspective Works
Last time I covered BridgeBio Pharma, Inc. (NASDAQ:BBIO) was in June, when BBIO stock was trading down after a critical phase 3 trial failure. BridgeBio Pharma, which has one approved drug in a rare disease and an interesting business model, failed a phase 3 trial in transthyretin amyloid cardiomyopathy (ATTR-CM). The molecule, besides having a poor safety profile, failed to adequately differentiate itself from placebo. The company called foul, claiming a strong placebo effect; however, the damage was done, and the stock fell.
BridgeBio’s hub-and-spoke business model is interesting. BridgeBio is like an umbrella company consisting of a number of private and public companies and a long pipeline of some 20 product candidates. Two of these are in the commercial stage, two are in phase 3 development, and two more in phase 2. The two approved products are Nulibry for the treatment of an ultra-rare, life-threatening disease called molybdenum cofactor deficiency (MoCD) Type A, approved in March 2021, and an accelerated approval for Truseltiq, targeting previously-treated, locally advanced or metastatic bile duct cancer with an FGFR2 fusion.
One of the subsidiary companies used to be Eidos, which was spun out of BridgeBio to develop acoramidis or AG10, also known as BBP-265, for the treatment of ATTR-CM. Two years ago, BridgeBio was in the news after a persistent effort to acquire the remaining 33% of Eidos became successful. Last year, however, BridgeBio was again in the news because this asset, BBP-256, failed a phase 3 trial, dragging the stock down with it. Not only did the molecule not meet the primary endpoint, but it also had a poor safety profile. The trial will, however, continue to the Part B readout at 30 months, “where we will see the effects of acoramidis on all-cause mortality and cardiovascular hospitalizations,” noted Prof. Daniel Judge, who is involved with the trial.
There was more bad news in 2022. Helsinn used to be the company’s commercialization partner for Truseltiq worldwide excluding Greater China. In October 2022, in an SEC filing, BridgeBio Pharma, Inc. disclosed that Helsinn has decided to discontinue selling the drug because ongoing distribution is not “commercially reasonable.” This also affected LianBio, which had rights in Greater China. LianBio, too, decided to pull the drug. BridgeBio shut down a phase 3 trial for the molecule in cholangiocarcinoma, as well as other oncology indications.
In the past few months, the company presented data from the following programs:
Preliminary data from the Phase 1b trial of VT30 topical gel (BBP-681) in patients with venous, lymphatic and mixed venolymphatic lesions of the skin
Positive Phase 2b data of encaleret in patients with autosomal dominant hypocalcemia type 1 (ADH1)
Pharmacodynamic data from the first two participants dosed in CANaspire, its Phase 1/2 clinical trial of BBP-812, an investigational intravenous (IV) adeno-associated virus serotype 9 (AAV9) gene therapy for the treatment of Canavan disease
Positive Phase 1 data for BBP-711 in healthy volunteers, supporting the development of the investigational therapy for patients with primary hyperoxaluria type 1 (PH1) and recurrent kidney stone formers
Positive interim results from PROPEL 2, a Phase 2 trial of the investigational therapy infigratinib in children with achondroplasia
12-month data from the Phase 2 study of BBP-418 in patients with limb-girdle muscular dystrophy type 2i (LGMD2i)
Of all these data readouts, the important ones are for encaleret in ADH1, infigratinib (Truseltiq) in achondroplasia, and BBP-418 in LGMD2i.
“ADH1 is a rare genetic form of hypoparathyroidism associated with lifelong abnormally high urine calcium and low blood calcium levels, sometimes leading to severe consequences such as seizures, heart rhythm abnormalities, muscle cramping, and breathing difficulties,”
said Rachel Gafni, M.D., senior research physician and head of the Mineral Homeostasis Studies Group of the National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIH). She continued:
“Current management with calcium and vitamin D supplements is inadequate and may exacerbate high urine calcium levels, which can cause kidney complications. These 24-week outpatient data, evaluating an investigational calcilytic in a precision-medicine approach, demonstrate that encaleret has the potential to restore normal calcium and phosphate metabolism in individuals with ADH1.”
The above quote says it clearly. On the four mineral biomarker metrics on which the company provided data, encaleret was able to normalize (homeostasis) every one of them with high statistical significance, at both day 5 and 24 week intervals. That shows that encaleret was not only able to quickly reduce/normalize these values in patients, but also sustain that effect for a period of 6 months.
There are 12,000-200,000 patients in this indication. A phase 3 trial has been started.
Achondroplasia affects approximately 55,000 people in the U.S. and EU. The importance of this trial is in that it is a sort of resuscitation attempt for the molecule infigratinib, which has not done well in oncology trials. Even worse, the molecule, in “earlier cohorts in PROPEL 2, did not achieve the target efficacious exposure as suggested by our preclinical data and no dose response was observed.” So it was interesting to see that:
At the highest dose level evaluated to date (0.128 mg/kg once daily), mean increase in annualized height velocity (AHV) was 1.52 cm/yr over baseline (p=0.02, n=11) for all follow-up data available at time of data cut in children 5 years of age and older. In this group, 64% were responders (defined with a strict criterion of an increase ≥25% in AHV from baseline) and the average percent change from baseline in AHV was 60%.
Financials
BBIO has a market cap of $1.3bn and a cash reserve of $558mn. Despite nominally having two approved products, last quarter revenue was only $0.34mn. R&D expenses were $93mn, and SG&A was $31mn. That gives them a cash runway of 4-5 quarters. However, the company made some restructuring efforts last year, which should improve the runway.
Bottom Line
BridgeBio Pharma, Inc. is a complex company with a lot of trials, couple of approved products, decent cash balance, but no solid revenue stream as of now. I once invested, and made some money in, BBIO shares. However, the complexity of the offering worries me. There are a lot of things going on, and it looks a lot like “bill padding.” I will wait for one or two products to stand out and produce strong data before I form an opinion on BridgeBio Pharma, Inc.
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