Spyre Drops SPY072 in Rheumatic Disease After Mixed Phase 2

The Tip Desk · November 3, 2026 · 3 min read

Pro forma cash reached $1.47 billion after a $400 million October raise as Spyre pivoted SPY072 toward a hidradenitis suppurativa pivotal program.

Spyre Therapeutics (SYRE), a clinical-stage immunology biotech, said it will not advance SPY072 in rheumatic diseases after the anti-TL1A antibody showed statistically significant benefit in a rheumatoid arthritis Phase 2 sub-study that did not meet the company’s internal bar, and missed primary endpoints in psoriatic arthritis and axial spondyloarthritis.

The company instead initiated SKYLIGHT, a Phase 2 trial of SPY072 in hidradenitis suppurativa (HS), and raised more than $400 million in gross proceeds from an October underwritten offering to fund a pivotal HS program with SPY072 as a potential best-in-class TL1A monotherapy.

In the SKYWAY RA sub-study, both doses of SPY072 showed statistically significant benefits versus placebo on one or more of the primary DAS28-CRP, key secondary ACR20, and exploratory ACR50 endpoints, and the drug was well tolerated. Spyre said the magnitude of benefit was insufficient to prioritize advancement in RA. In the PsA and axSpA sub-studies, SPY072 was well tolerated but did not meet its primary endpoints of ACR20 response and change from baseline in ASDAS, respectively.

SKYLIGHT, started in September 2026, enrolls subjects with moderately to severely active HS who are initiating bimekizumab. The company described it as a surrogate proof-of-concept study for its internal SPY772 combination of SPY072 and SPY007, a long-acting anti-IL-17A/F. Topline Week 16 results are planned in late 2027 or early 2028.

In inflammatory bowel disease, Spyre announced positive topline induction data for SPY003 from Part A of the Phase 2 SKYLINE trial, completing proof-of-concept for all three monotherapies. SPY001, SPY002, and SPY003 achieved their primary endpoints with statistically significant reductions in the Robart’s Histopathology Index of 9.2, 10.7, and 10.0 points, respectively. Clinical remission and endoscopic improvement rates were 40% and 51% for SPY001, 33% and 42% for SPY002, and 20% and 30% for SPY003. Modified Mayo Score changes at Week 12 were -3.7 for SPY001 and SPY002 and -3.5 for SPY003.

SKYLINE Part B, the randomized placebo-controlled portion, is enrolling ahead of schedule, enabling an increased enrollment target. Topline induction results for three potential best-in-indication combinations are expected in the third quarter of 2027. Chief Executive Officer Cameron Turtle said the combination portion is enrolling faster than expected and that the company plans to deliver topline data in Q3 2027.

Research and development expenses were $89.2 million for the three months ended September 30, 2026, versus $45.2 million a year earlier, which the company attributed primarily to higher manufacturing costs and clinical trial expenses. General and administrative expenses were $16.6 million, versus $11.6 million, driven primarily by increased headcount and professional services fees.

Net loss widened to $96.1 million from $11.2 million a year earlier. Total other income fell to $9.6 million from $45.7 million, primarily due to changes in the fair value of the contingent value right liability in the prior period. Net cash used in operating activities was $77.5 million in the third quarter.

Cash, cash equivalents, and marketable securities were $1,071.9 million as of September 30, 2026. Pro forma cash of $1,467.9 million also reflects $378.0 million in net proceeds from the October offering and $18.0 million in October at-the-market sales. The company said it expects runway into the second half of 2029.