Galapagos avoids 'complete whiff' as key anti-inflammatory drug fails to beat placebo in midphase trials

Galapagos CEO Onno van de Stolpe (Galapagos)

After talking up its anti-inflammatory therapies for years, Galapagos is switching gears to preclinical SIK inhibitors after the lead compound in the critical program delivered underwhelming midphase data.

The Belgian biotech is advancing other molecules against a target that has become vital to its future as other pipeline prospects have flamed out.

Leaders at Galapagos have talked up the importance of the Toledo program for several years. The program, which Galapagos later disclosed is focused on salt inducible kinases, has now advanced to the point that Galapagos has clinical efficacy data in several indications. In keeping with the rotten run Galapagos is on, lead Toledo compound GLPG3970 failed to live up to expectations. 

SIK 2/3 inhibitor GLPG3970 was no better than placebo in a phase 2a rheumatoid arthritis trial in reducing disease activity and most other efficacy endpoints. Similarly, GLPG3970 failed to best placebo in reducing the severity of ulcerative colitis trial in a phase 2a trial.

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Galapagos saw some evidence of endoscopic improvement in the ulcerative colitis trial and found four out of the 13 psoriasis patients who received GLPG3970 had at least a 50% improvement in the severity and extent of their disease. The biotech hailed the results as early clinical activity but is switching its attention to earlier-stage SIK inhibitors. 

The company is ham strung by previous undisclosed preclinical evidence on dose-limiting toxicities, meaning they cannot up the dose in future trials in an effort to boost the drug's effect, analysts at Jefferies wrote in a note to investors. This is why Galapgos is pivoting to "back-up SIK2/3 compounds" GLP4876 and GLP4605, which are from different chemical families. Jefferies said both are in preclinical testing with plans to move into human testing next year. 

RBC Capital Markets analysts said the results were not great, but avoided a "worst-case scenario of a complete whiff," according to a Wednesday note. 

Shares in Galapagos fell 12% to around $58 apiece in the wake of the news. Galapagos suffered the decline despite sharing the SIK update alongside a more upbeat release about a phase 1b trial of TYK2 inhibitor GLPG3667 in psoriasis. The 31-subject study found 40% of patients on the high dose of GLPG3667 experienced a 50% or greater improvement in the severity and extent of their disease at week four.

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Galapagos aims to start a phase 2b psoriasis trial next year on the strength of the data and plans to develop the candidate more broadly in inflammatory indications. However, based on the available data, it is unclear whether Galapagos has a compound capable of competing with Bristol Myers Squibb’s near-approval TYK2 asset and rival drugs in clinical development at Nimbus Therapeutics and Ventyx Biosciences. Specifically, it remains to be seen if Galapagos can match the specificity of the allosteric domain inhibitors and thereby avoid the toxicity associated with JAK inhibitors.

The importance of the SIK and TYK2 programs to Galapagos has ratcheted up as other programs have run into difficulties. Filgotinib now looks highly unlikely to live up to expectations, and other assets have either failed in the clinic or been culled in a cost-cutting drive.

Editor's note: This article was amended at 9:48 a.m. ET on July 15, 2021, to add analyst commentary.