JP Morgan Healthcare Conference 2021 analyst call
Management remarks
JAK1 inhibitor, Jyseleca on the market in Europe and Japan. New agreement with GILD in EU transfers full European rights to GLPG at end of this year. European P&L share (50% cost share) continues until end of ’21. Once profitable in ’24, GLPG will pay GILD royalty of 8-15% with no EU milestones. GILD to pay €160m for development work from RA studies. GILD will retain ex-EU and royalties are unchanged at 20-30%. Broader R&D collaboration is unchanged.
Jyseleca peak sales guidance of €0.5bn, which assumes 8-12% market share. EU5 inflammation market is estimated at €5.7bn (RA: €3.2bn, UC: €0.8bn, CD: €1.7bn). Patent exclusivity until 2035. Jyseleca in RA is differentiated by its fast onset of action, ability to use as monotherapy, lasting activity, and safety profile.
GLPG3667 TYK2 added to portfolio. Reversible kinase domain inhibitor that has shown PK profile that allows for once daily dosing and good PD activity in P. Currently being evaluated in PsA.
PHASE3 ISABELA 1&2 studies have currently recruited 1300 patients to date (target for both trials is 1500 pts). Expect recruitment to complete in summer with data in 2022. Also expect outcome of futility analysis in summer.
TOLEDO programme: novel SIK target with dual action on inflammation; suppressing pro-inflammatory and stimulating immunoregulatory cytokines. Five PoC studies currently ongoing investigating ‘3970 with topline data expected in the middle of 2021.
Gild-GLPG R&D collaboration (10 years) provides access to compounds, assays, libraries, technical capabilities and expertise. GILD has option opportunity after P2B.$3.95bn upfront plus opt-in fees & milestones, $1.5bn equity investment (25.5% share), and 20+ % royalties US/RoW, while GILD retains full European rights.
2021 cash burn to increase by around €50m due to SG&A launch costs related to Jyseleca launch. Reminder that 2020 guidance for R&D spend was €520m and expect this to remain flat for 2021.
2021 newsflow: Re filgo: Filing UC in Japan, MANTA/RA-y outcome, CHMP opinion UC EU, approval decision UC EU, DIVERSITY recruited CD.
Other programs: ISABELA futility IPF ziritaxestat, Toledo PoC read-outs in Pso/RA/UC. ‘3667 read-out (TYK2) Ph1b Pso, and Read-out of ‘555 (JAK1) Ph1b OA.
Jyseleca opportunity in IBD: uncertain in IBD, especially in UC given FDA requirement to have 52 week follow-up based on MANTA/RA-y, which would delay filing though this is less of an issue in CD which is yet to read-out.
Key TOLEDO read-outs: ‘3970 PoC studies reading out topline data in psoriasis, UC, and RA mid-2021. SLE and Primary Sjogren’s syndrome are 12-week studies and will see if showing directionality on efficacy. Study outcomes will determine which indications should be pursued. Do not believe that 6 weeks of data is sufficient to estimate full therapeutic potential. Running trials in 5 PoC trials, but not expecting a strong response across all five indications.
GLPG3970 preclinical toxicity: Less immunosuppressive vs. JAK inhibitors, so will be better tolerated.
GLPG3667/TYK2 differentiation: Strong PD effects noted in phase 1 especially on interferons and IL-6. It’s an ATP competitive inhibitor, which is selective for TYK2 and doesn’t hit JAK1. Low dose achieved full efficacy on interferon blockage in P1.
GILD opt-in rights: GILD have opt-in rights on all molecules that reach end of P2b including ‘3667. The asset was discovered and developed in-house at GLPG.
Jyseleca initial launch feedback: Approval was granted end of September. Positive signal seen in Germany with good physician feedback and initial uptake in line with expectations. Pleased with depth and breadth of prescriptions.
Olumiant as proxy to Jyseleca launch trajectory: Olumiant had very strong launch (one of best in RA in past 5/6 years) which is evidence of the need for JAKs. Competitive field and pricing has changed since Olumiant launch but GLPG has been looking at both Xeljanz/Olumiant launch trajectories, but is confident in Jyseleca profile.
TYK2 selectivity vs. JAK1: ATP competitive inhibitor with TYK2 selectivity that is 20-fold greater than JAK1-inhibitor. Achieve full inhibition of interferons at a low dose and does not hit JAK1.
ISABELA update and interim: ISABELA 2 has finished recruiting ahead of ISABELA 1 with the latter trial still needing to recruit 200 subjects- anticipated to complete by summer with results expected ’22. Interim read-out is driven by both trials (waiting on ISABELA 1). Aim was to get approximately 30% of patients in trial to cross 52-week line in order to model patients at earlier stages of the study to determine change after 1 year. The totality of 70% would then enable a call to be made on whether ziri would be superior to PBO on primary endpoint.
GLPG555 economics: partnership with GSK was terminated, so now fully owned by GLPG.
NOVESA primary endpoint: SSc suffers from endpoint and patient selection. Pleased that NOVESA trial investigating zirtaxestat was able to show a statistically significant change from baseline in mRSS given it was a small trial. Confident that ‘1690 is active in demonstrating anti-fibrotic activity in another indication. Once ISABELA results are made available, the plan would be to broaden indication to include PF-ILD and systemic sclerosis linked ILD, which is 60-65% of all SSc patients.
MANTA study primary endpoint: Don’t think outcome from 52 week will be of any value after what was seen in double blind clinical trial. Study was designed purely in collaboration with the FDA. Looking at sperm levels is problematic from a technique and analysis perspective given how count is highly variable in healthy individuals. As such, it is unknown how this will play out in patients with chronic inflammatory conditions on background therapies. Think this will be the most informative database on sperm health in IBD and rheumatology and study has enough patients to show if filgo has effect or not on sperm health.