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Toledo Demonstrates POC, But Next Compound Needed For Higher Doses; TYK2 Advancing
Stock Rating Overweight
Price Target $118.00
Matthew Harrison, Connor Meehan
July 15, 2021
Mgt. presented data for both '3667 (TYK2) and '3970 (Toledo) today. Both assets showed encouraging initial efficacy signals in Psoriasis (stat. sig. for '3970), and were safe/tolerable. Additional Toledo data will be presented later this year, and mgt. will advance '3667 into a PhIIb study by 2022.
Galapagos' TYK2 inhibitor GLPG3667 advancing into PhIIb: In PhIb, 31 patients were enrolled and treated with high or low dose '3667, or placebo. In the high-dose cohort, at week 4, 4/10 patients achieved PASI 50, vs. 1/10 in the placebo group. No patients in the low dose cohort achieved PASI 50. Improvements in other efficacy signals in the high dose cohort included Body Surface Area and physician and patient global assessment, versus placebo at Week 4. On safety, the drug was found to be well tolerated, with only one patient in the low dose group pausing treatment (for one day) due to psoriasis exacerbation. The majority of AEs were mild in severity and transient, and no SAEs were observed during the study. On next steps, based on the initial efficacy signal, mgt. has indicated it plans to initiate a PhIIb program in psoriasis during 2022 to continue the development of GLPG3667. We see this result as encouraging, but expected, given competitive successes with TYK2 assets in the treatment of psoriasis.
On the Toledo program GLPG3970 demonstrated proof-of-concept but mgt. believes higher doses are needed: Galapagos is running a number of proof-of-concept studies for the Toledo program, which includes a number of assets targeting the salt inducible kinase (SIK) mechanism, such as GLPG3970. The drug is currently being investigated as part of five separate proof-of-concept studies; data from the first three were presented:
CALOSOMA - PhIb study in moderate-to-severe psoriasis (n=26): At week 6, 4/13 patients (~31%) achieved PASI 50. These results were statistically significant vs. placebo (p=0.002). Benefits in other efficacy endpoints, including Body Surface Area and physician and patient global assessment, were also observed.
SEA TURTLE - PhIIa in biologic-naïve, moderate-to-severe ulcerative colitis (n=31): At week 6, no difference in the drug arm (vs. placebo) was observed in the primary endpoint (Change From Baseline in Total Mayo Clinical Score at Week 6). There were, however, observed improvements in some parameters, including endoscopy, histology, and fecal calprotectin. Additionally, 7/18 patients treated with GLPG3970 at Week 6 met the criteria for Endoscopic Improvement on the endoscopic response score vs. 1/9 patients on placebo.
LADYBUG - PhIIa in MTX-experienced, moderate-to-severe rheumatoid arthritis (n=28): At week 6, GLPG3970 did not show an improvement in any efficacy endpoints, including the primary endpoint (DAS28).
On safety, GLPG3970 was found to be generally safe and well tolerated, with discontinuation rates similar to placebo. No deaths or SAEs were observed, and the majority of TEAEs were found to be mild or moderate in severity. In the CALOSOMA study, 2/15 patients discontinued treatment with the drug arm (for COVID-19 and pruritus) vs. 1/11 on placebo. In the SEA TURTLE study, 1/21 patients discontinued treatment with the drug arm (COVID-19) vs. one of 10 on placebo (QT abnormality). In the LADYBUG study, 3/16 patients discontinued treatment with the drug arm (COVID-19, ALT increase and physician decision) vs. 2/12 on placebo (COVID-19).
Data suggest activity, but a new chemical series is needed for higher doses to broaden activity; we expect next-gen Toledo to advance into the clinic in 1H22: While we believe the demonstration of activity is important, the lack of robust activity across diseases is likely to temper investor enthusiasm. We would expect the next-gen molecules to have data in late-22 or early-23.