Bioteg71 schreef op 26 februari 2019 11:19:
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Morgan Stanley 27 november 2018
Galapagos NV (GLPG.O)
Bus Trip and IPF Symposium Takeaways
Stock Rating Overweight
Price Target $131.00
We hosted investors in a meeting with Galapagos mgt. in the company's office in Basel, Switzerland, following which we attended a symposium the company coordinated on idiopathic pulmonary fibrosis (IPF) and their efforts in the space. Overall, we believe these discussions helped clarify mgt.'s key considerations regarding next steps with filgotinib, outlined the opportunity/unmet need in IPF, and provided further detail on ISABELA trial design. We provide key takeaways from both events below.
Mgt. meeting takeaways (CEO Onno van de Stolpe and CMO Walid Abi-Saab): The discussion with mgt. covered several aspects of the company's pipeline, but focused primarily on filgotinib and GLPG1690 in IPF.
Filgotinib: (1) Regarding the MANTA male toxicity study for filgotinib, mgt. clarified that regulators in Japan have not asked for data from this study for filgotinib regulatory filings, that discussions are needed with regulators in the EU to better understand their requirements, and that the FDA does want the data from MANTA included in filgotinib U.S. regulatory submissions; (2) Mgt. noted that the MANTA study is being conducted in ulcerative colitis (UC) patients because the FDA was concerned about the risk/benefit of JAK inhibitors in healthy volunteers; (3) Mgt. anticipates that there will eventually be ~200 patients on drug in the MANTA study, and the company plans to discuss further specifics regarding the FDA's stance on MANTA and regulatory submissions once data from the PhIII FINCH1 and FINCH3 studies of filgotinib in RA are available in early 2019; (4) Mgt. believes that the FINCH1 data will be important, and that filgotinib will have to demonstrate superiority to Humira in this study in order to match the data generated by AbbVie's oral JAK inhibitor upadacitinib (AbbVie is covered by David Risinger); (5) Mgt. does not see a promising risk/reward profile for oral JAK inhibitors in addressing atopic dermatitis (AD), as recently approved agents as well as selective agents under development (including IL-17C antibody MOR106) will not leave enough of an unmet need to warrant the use of global immunosuppression.
IPF: (1) Mgt. estimates that there are ~80K new patients with IPF every year, and that the market opportunity is multiple fold greater than the ~$2B in sales currently generated by the two approved therapies (pirfenidone and nintedanib); (2) IPF patients experience a yearly FVC loss of ~250 mL/year when untreated, and a loss of ~125 mL/year when treated with current SOC; (3) The two PhIII ISABELA studies of GLPG1690 in IPF are powered to detect an 80 mL FVC difference vs. placebo. Mgt. noted that an 80 mL separation was targeted based on clinician input that this improvement level would be clinically meaningful; (4) Patients in ISABELA will be stratified by their current SOC, as either pirfenidone (1/3 of patients), nintedanib (1/3), or no treatment (1/3); (5) Mgt. clarified that while the ISABELA SAP includes pooled data across both studies, the primary endpoint is change in FVC at 1 year in each of the studies. Therefore, if one study were to fail, all pooled data would technically become exploratory; (6) GLPG1690 is not being evaluated in patients refractory to SOC drugs because mgt. believes GLPG1690's safety profile is better than that of pirfenidone and nintedanib, and therefore GLPG1690 should not be relegated to a second-line position assuming positive efficacy data; (7) The PhII PINTA study of GLPG1205 in IPF is recruiting patients in different countries from the ISABELA program, and mgt. estimates that 50% of patients recruited will be on background therapy whereas 50% will not. This is different than the ‘1690 PhII study where no patients were on background therapy.
IIPF symposium: The symposium included an IPF disease overview, a GLPG1690 status update, a discussion on the role of mesenchymal stem cells in fibrosis, and a look into Galapagos' preclinical fibrosis discovery efforts. Key takeaways include: (1) The incidence of IPF in the U.K. has increased from ~2.5K cases/year in 1990 to ~6K cases/year in 2010, and ~1/100 deaths in the U.K. is now attributed to IPF; (2) An average patient loses 10% of their lung function every 12 months, and lost lung function is never gained back. Median untreated survival time is ~3 years post diagnosis; (3) IPF patients who experience an acute exacerbation die in a median of 30 days following the exacerbation episode; (4) Approximately 20% of patients cannot take currently approved drugs due to their poor side effect profiles, and lung transplants - while they can be effective - are only viable for a small portion of patients (~350 performed every year in the U.K., versus an IPF incidence of ~6K cases); (5) The first patient has been screened in ISABELA, and both studies are ready for enrollment; (6) While the work cited is highly preliminary, early data suggests that lung-resident stem cell derived conditioned medium reverses the pathology of fibrosis; (7) In its preclinical discovery efforts in fibrosis, the company is studying the MKL1 pathway, which the company believes is a central pathway in fibrosis. Systemic sclerosis and NASH were highlighted as two areas where Galapagos aims to further its efforts.