Dive Brief:

• An antibody drug from Spyre Therapeutics fell short of the company’s expectations in rheumatoid arthritis, showing signs of activity in a mid-stage trial but not enough to justify further investment. 
• Spyre tested two different doses of the drug, “SPY072,” in a placebo-controlled study of people with the inflammatory disorder. While SPY072 met multiple study objectives and displayed “proof-of-mechanism” in rheumatoid arthritis, it didn’t meet the company’s “internal bar” for prioritizing further development as a monotherapy, Spyre said. 
• The company will focus on advancing SPY072 as a therapy for other autoimmune conditions, and will report data in psoriatic arthritis and axial spondyloarthritis in the fourth quarter. Shares tumbled by 13%, erasing more than $1 billion in market value. 

Dive Insight:

Drugs aimed at an immune-regulating protein known as TL1A have garnered the attention of many drugmakers. Study results have indicated TL1A-targeting therapies might be more potent than existing therapies for inflammatory bowel disease, leading to a string of big-ticket deals from Merck & Co., Sanofi and Roche, among others. 

Spyre has been one of the beneficiaries of that interest. Formed by company creator Paragon Therapeutics, the company went public via a reverse merger in 2023 to pursue development of multiple drugs targeting TL1A as well as other proteins implicated in IBD. Prior to its stock slide Wednesday, Spyre had a market value north of $9 billion. 

The newly disclosed results were from a key test of whether a TL1A-targeting drug might be useful elsewhere. At a healthcare conference in June, Spyre CEO Cameron Turtle noted that SPY072 had the chance to be the first in its class in a rheumatic disease. But those expectations were dampened by the findings, which suggest the drug might be best positioned as a “combination component” or geared towards other autoimmune diseases, the company said in its statement. 

The Phase 2 trial randomized 143 patients to receive one of two SPY072 doses or a placebo for 12 weeks. The lower dose hit statistical significance on the study’s main measure, reducing by 1.9 points on a test used to evaluate disease activity. Those on a placebo had a reduction of 1.3 points. The high dose wasn’t as impactful and missed its primary objective, according to Spyre. 

Spyre said the side effects observed were “consistent” with the TL1A drug class. Rates of adverse events were “comparable” between drug and placebo recipients, and were generally mild to moderate in severity. Infections and infestations were the most common side effects reported. 

The results represent a “disappointing outcome,” wrote Leerink Partners analyst Thomas Smith in a Wednesday client note. But the company’s “core IBD combo thesis” is still “intact.” 

Stifel analyst Alex Thompson wrote that the findings “do lend support” to the idea that TL1A drugs could be useful in other indications, an “important broader theme in the space given the mechanistic and genetic rationale.”