The Friday Biotech Perspective #30

The curious case of Eidos

As BridgeBio Pharma, Inc. (NASDAQ:BBIO) awaits next month’s FDA decision to approve its transthyretin amyloidosis cardiomyopathy (ATTR-CM) drug acoramidis, the company’s early investors may be less anxious than one would expect.  If approved, the acoramidis timeline from discovery to approval would be ~10 years. Very much in line with industry standards. Acoramidis, however, moved forward as the cornerstone to catalyze the company’s pipeline growth and equity growth.

Acoramidis originally was developed by Eidos Therapeutics (former ticker EIDX), following the discovery of the molecule by researchers from the University of the Pacific (Stockton, California), Stanford University and the Scripps Research Institute in La Jolla, California. Eidos listed in June 2018; at the time, the Eidos’ shares primarily were owned by soon-to-be investors in BridgeBio. Thirteen months later in July 2019, BridgeBio listed.

In between, Eidos reported strong, promising phase II data for acoramidis, then known as AG10. The phase II success enabled BridgeBio investors to advance the company’s promise that it could collect assets selectively and build value quickly. Eidos, in effect, always was a proof-of-concept exercise through which BridgeBio could leverage the uptick in value from acoramidis data to build its pipeline while reducing the dilution inherent in a traditional IPO.

Not surprisingly, MIT professor Andrew Lo sits on BridgeBio’s board and is a guiding hand of the company’s strategy. Lo is director of the MIT Laboratory for Financial Engineering and a principal investigator at the MIT Computer Science and Artificial Intelligence Laboratory. In addition, BridgeBio co-founder and CEO Neil Kumar is an MIT grad and worked at Third Rock Ventures and as a consultant to McKinsey & Co. before transitioning to a biopharma executive, first at MyoKardia and then as CEO of Eidos.

Five years after listing, BridgeBio is on the cusp of approval for acoramidis data and owns a pipeline of five clinical stage drugs to treat genetic diseases. The company claims more than 10,000 diseases caused by a single genetic mutation, which in total affect tens of millions of people. However, less than 50 FDA approved therapies exist to treat these conditions. The clinical stage drugs include treatments for  autosomal dominant hypocalcemia type 1 and limb-girdle muscular dystrophy type 2I/R9. Both conditions affect less than 25,000 people worldwide.

ATTR-CM notably afflicts ~450,000 worldwide with three distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM) with ~400,000 patients, mutant ATTR cardiomyopathy (ATTRm-CM) with ~40,000 patients , and the smaller ATTR polyneuropathy (ATTR-PN) group consisting of ~10,000 patients. BridgeBio expected to make a big splash quickly in ATTR-CM.

Pfizer, Inc.’s (NYSE:PFE) Vyndaqel family of drugs were approved as ATTR-CM treatments in 2019. Thanks to broad consumer advertising and direct marketing to physicians, the Vyndaqel family produced $1.1 billion in sales in 1Q 2024, placing the drug on track to $4 billion in annual sales. Acoramidis, Eidos and BridgeBio were not supposed to miss out on the market explosion.

Patients with ATTR-CM produce a mutated version of the protein transthyretin (TTR). Healthy TTR normally helps transport vitamin A around the body but the mutant version results in misfolded clumps of the protein, leading to pain, organ failure (in the heart, liver and nerves) and early death. Acoramidis and Vyndaqel are supposed to stop the TTR protein from misfolding.

Eidos’ data in 2019 was compelling but after being moved into BridgeBio acoramidis flopped in a phase III trial, sending BridgeBio’s stock down ~75% in one month. Part of the phase III problem was BridgeBio selected the 6-minute walking test as a key endpoint to measure the effectiveness of acoramidis.

Patients in the phase III trial who received a placebo performed better on the walking test than past results from ATTR-CM patients had indicated. BridgeBio attributed the strong placebo performance to better all-around care people with the disease now receive compared to historical data. BridgeBio regrouped and ran a longer trial to detect a benefit for acoramidis. The company also designed the trial to measure how acoramidis extended lives and kept people out of the hospital – the same endpoints used by Pfizer for Vyndaqel.

BridgeBio reported strong phase III data for acoramidis in January 2024. Was the observed 80.7% survival rate at 30 months in the treatment arm more compelling than Vyndaqel, which has been on the market for five years? BridgeBio believes so and it may have a good argument. However, convincing physicians to convert when physicians are still learning about ATTR-CM and Pfizer owns a strong first mover advantage may be very difficult.

When BridgeBio bought the 36.3% of Eidos it did not already own in 2020, Eidos shareholders had the option of receiving 1.85 shares of BridgeBio stock or $73.26 per share in cash. Eidos originally listed at ~$18 per share in 2019.

BridgeBio’s stock traded this week between $25 per share and $30 per share. Should acoramidis be approved, BridgeBio’s board would appear to be at biopharma’s classical intersection: Sell the company to a Big Pharma to market acoramidis effectively or continue with its long-term financial engineering strategy. Stay tuned.

FULL DISCLOSURE: The author owned shares in Eidos but did not accept the offer of BridgeBio stock.