BridgeBio’s Pipeline Expansion Continues as Portfolio’s Milestones Approach

Xconomy San Francisco — 

BridgeBio Pharma Inc. is poised to achieve its goal of rapidly bringing treatments for genetic diseases and genetically defined cancers to the market with two different products expected to be submitted to the US Food and Drug Administration before the end of 2021—just four years after the company’s first big funding round.

Palo Alto, CA-based BridgeBio (NASDAQ: BBIO) recently raised $463.7 million in net proceeds from the sale of 2.5 percent convertible senior notes due in 2027 with an aggregate principal amount of $475 million and could net as much as $537 million by the time the debt sale concludes. The proceeds, on top of the $577.1 million in cash on its balance sheet as of the end of 2019, will fund a pipeline of eight clinical-stage programs, including one for which a rolling NDA has been initiated.

BridgeBio was established in 2015 and closed a $135 million venture capital round in 2017 to fund additional acquisitions of drug candidates and ongoing development programs, each of which was housed in a subsidiary set up to focus on moving the individual program forward. (Also see “The Next Roivant Or Fortress? BridgeBio Raises $135m To Spin Out New Companies” – Scrip, 18 Sep, 2017.)

The BridgeBio business model of a big hub with multiple spokes continued to bring in investors attracted to the diversification of the parent company’s portfolio. The company closed a $299 million venture capital round in early 2019 and in June of last year launched an initial public offering, which grossed $401 million and laid the groundwork for the recent sale of convertible notes. (Also see “IPO Update: 28 Biopharma Companies Raise $3bn, Provide An Average 10% Return” – Scrip, 28 Jun, 2019.)

“We thought that this debt financing approach would be attractive to raise funds for the next couple of years and let us get through a couple of the major value-inflection points that are coming for this company,” BridgeBio’s Cameron Turtle, vice president of business development and operations, said in an interview with Scrip.

The cash will help fund completion of the rolling NDA for BridgeBio subsidiary Origin Biosciences’ fosdenopterin (BBP-870) in the treatment of molybdenum cofactor deficiency (MoCD) type A and submission of an NDA for QED Therapeutics’ infigratinib in second-line or later treatment of cholangiocarcinoma by the end of 2020. (Also see “Keeping Track: US FDA’s Rejection Of First RMAT BLA Blemishes Otherwise Positive Week Of Non-Oncology News” – Pink Sheet, 9 Dec, 2019.)

The next two years also will include data from two Phase 3 programs and three proof-of-concept studies, including a Phase 3 clinical trial for the Eidos Therapeutics drug BBP-265 (AG10) in the treatment of transthyretin amyloidosis (ATTR) cardiomyopathy. (Also see “Start-Up Eidos Surfs Crest Of TTR Amyloidosis Wave” – Scrip, 27 Aug, 2018.) The other pivotal trial readout will come from PellePharm’s BBP-009 (patidegib) in Gorlin syndrome; Leo Pharma AS paid $70 million up front in 2018 for an option to buy PellePharm based on this asset. (Also see “Leo Lines Up PellePharm Buy In Rare Skin Cancer Deal” – Scrip, 20 Nov, 2018.)

“It’s really a dense amount of transformational events that will occur for this company, and within three years from now we will be a commercial company with multiple assets past top-line data readouts,” Turtle said. (See table below.)


The company’s subsidiaries have eight clinical- or registration-stage candidates and many more treatments for monogenic diseases and genetically defined cancers in preclinical development.


BridgeBio has more than 20 subsidiary companies and announced four more assets to be housed in additional subsidiaries during the J.P. Morgan Healthcare Conference in January. These new programs included what may become the company’s eighth drug candidate in clinical trials—the Phase 2-ready drug BBP-303 that will be developed by Calcilytix for autosomal dominant hypocalcemia type 1 (ADH1).

BBP-303 is a good example of how BridgeBio’s model works, Turtle said, because it’s a drug that previously was developed unsuccessfully for osteoporosis but was identified as a potential treatment for ADH1 by the National Institutes of Health (NIH). BridgeBio sources its drug candidates primarily from academia, but also from pharmaceutical companies.

BBP-303 “antagonizes a calcium-sensing receptor, so what that causes is an increase in the calcium levels in the serum. It was hypothesized to be sufficient to treat osteoporosis, but unfortunately it wasn’t.”

However, the NIH believes that for ADH1—which is caused by mutations in the calcium-sensing receptor that results in hypocalcemia, or low serum calcium levels—BBP-303’s mechanism matches the need in this disease. And BridgeBio believes it can get to proof-of-concept with this drug fairly quickly.


“We still are planning to add three or so new programs a year,” Turtle said. “There are 7,000 Mendelian [or monogenic] diseases out there and less than 5 percent of those have an approved therapy, so there’s a ton of substrate for diseases that we think need a novel therapy. This approach lets us work with academic collaborators around the world and identify a really tractable drug starting point and put together programs in a quick way and move them forward.”

Turtle said BridgeBio executives frequently are asked, “Don’t you have a huge pipeline already?” But he noted that when the company compares its pipeline to the number of diseases with unmet needs, “I think we’re just getting started.”

BridgeBio has different strategies for taking on different drug candidates, however, based on the size of a disease’s market and the stage of the potential treatment.

“One of the examples of something that would be difficult to go after from the beginning, for instance, is the MOCD type A program that we brought in,” Turtle said. “That’s one of the rarest diseases that we know of that effects likely around 100 people across the US and Europe.”

“That’s a disease that we were comfortable in pursuing and advancing a treatment for because the molecule that we licensed in from Alexion Pharmaceuticals (NASDAQ: ALXN) already had Phase 3 data,” he explained. “And that’s something that would have been very hard to do if, for example, the program was just an idea in an academic center. The amount of R&D dollars it would take to bring it from a preclinical asset to the Phase 3 data, it would be hard to justify spending that much money when the opportunity size is so small on the back end.”

In terms of new drug candidates in very early stages of development, BridgeBio’s ability to take on those programs depend on the level of unmet need, number of patients, severity of the disease, the drug’s potential to be a viable treatment, and its path to approval.

“We’re modality-agnostic at BridgeBio, so we are happy to use small molecules or gene therapies or protein replacements or whatever it happens to be that we think is the best approach for addressing that disease,” Turtle said. “We most often start from an idea that an academic has or at best a dirty lead molecule or an approach that looks like it’s having some level of efficacy, but certainly it’s not a final drug candidate—something that you could put into the clinic.”

“The other thing that matters is what the potential registration path looks like,” he added. “For some diseases, it’s much more tractable, where you have a biomarker that you can look at early and potentially get approval on. [For] others, it’s harder to tell how a disease is advancing and whether the therapeutic is having an effect. That means it might be harder for us to look at a much smaller disease area, if that was the case.”


BridgeBio’s strategy has been attractive to academics as well as investors. Increasingly, researchers are coming to the company in search of a deal, rather than the other way around, because they like the idea of remaining involved in the subsidiaries formed to develop their assets.

“By creating these individual subsidiary companies where they each own a single asset—and these are usually coming out of an academic center—those scientific founders get to play a pretty big role in the advancement of the program, and we pair them with experienced drug developers, and they get to own equity in their program specifically,” Turtle said.

“So, I think that the dynamic has shifted quite a bit, where a few years ago we were the ones walking down the hallways of children’s hospitals knocking on doors trying to get people to give us some time and chat about putting together a company,” he said. “And now, fortunately, it’s shifted a little bit to where we’re getting more inbound requests and spending less time walking through the hallways and trying to get meetings.”

[Editor’s Note: This article was updated on 22 April to note that QED’s NDA for infigratinib will be filed before the end of 2020, not 2021.]

Image: iStock/Yuliia Hrozian