Goldman Sachs: het geheel.
De updates van GS laten zich wat lastig delen. Ik heb dus de tekst gekopieerd. Daardoor ziet het er wat rommelig uit
R&D Update key takeaways
Coming out of the R&D Update, the below captures what we found to be key
takeaways:
On current progress: Since the last R&D Update last year, new targets have been
identified in inflammation, metabolic disease, fibrosis, and OA (with several new lead candidates specifically called out, see below), while several new POC’s have been initiated (PINTA for ‘1205 in IPF, and NOVESA for ‘1690 in systemic sclerosis), as well as a new Phase 3 program, PENGUIN 1 and 2 for filgotinib in psoriatic arthritis.
In terms of where GLPG spends on R&D, not surprisingly, the majority goes to
inflammation and fibrosis (together, 57%), while we were surprised to hear that 18% goes to R&D on metabolic diseases (such as diabetes), 5% goes to polycystic kidney disease (new to us). We’ll continue to monitor the situation closely. We note that GLPG discussed GLPG4059, noting that it featured a novel MOA that does not hit triglycerides, and preclinical data demonstrated lowering of blood glucose, with favorable effects also on hemoglobin HbA1c and body weight.
On Toledo: This represents GLPG’s biggest program in terms of the discovery and early development efforts. The MOA is novel, and as stated earlier, GLPG did not reveal any specifics at the R&D Update, and instead plans to disclose further details in 2020.
However, of particular interest, GLPG disclosed the following about its now three Toledo compounds:
n ‘3312 (first generation) is a pan-TOL compound, hitting what was referred to as TOL1, TOL2, and TOL3 n ‘3970 (second generation) hits TOL2 and TOL3 (i.e., is TOL2 and TOL3 selective); a Phase 1 started in 2019, and a broad Phase 2 development program (will include multiple Phase 2 POC studies) will begin in 2020; potential trials to begin in 2021 exploring utility beyond inflammation
n Newly disclosed ‘4399 (third Toledo candidate) is TOL3 selective
Exhibit 1: New preclinical candidates: GLPG’s potential next wave of innovation
Candidate Comment
GLPG4059 Novel MOA for Type 2 diabetes, will enter Phase 1 in 2020
GLPG4124 Novel MOA for fibrosis
GLPG4259 Backup for inflammation
GLPG4399 3rd Toledo compound
GLPG4471 Also a backup compound
Future directions: In what we found to be an intriguing discussion, GLPG announced plans to expand its list of potential targets from the current 6,000+ that are druggable by small molecules to 20,000+ that are encoded by genes by 2025. It intends to do so by
(1) expanding its scientific interests to pathways and more broadly networks, (2) layering
in a greater reliance on patient data and new technology (such as single cell
sequencing); and (3) using newer modalities. Here, in addition to its traditional small molecule approaches, GLPG will also now look to develop oligomernucleotide (i.e.,RNA-based) candidates in order to knock down levels of aberrant protein expression and also a novel PROTACS (proteolysis-targeting chimeras) candidates which are small molecules that can induces rapid degradation.
It remains unclear to us whether GLPG will be successful in its endeavor to develop RNA-based approaches, but we note that given the company’s previous interest in hepatitis B and current interest in NASH (where the target organ for both is the liver, where RNA-based approaches appear to have some modicum of success), we’re eager to see what emerges over the next several years, and we await next developments to be able to assess the feasibility and tractability of
GLPG’s efforts going down this road.
Filgotinib and operational update: GLPG reminded of its ambitions for filgotinib
beyond the initial indication of rheumatoid arthritis (RA):
n Ulcerative colitis (UC): Top-line Phase 3 data in 2Q20
n Crohn’s disease (CD): Phase 3 still recruiting (we believe this program is running at least one year behind that of the UC program)
n Psoriatic arthrits (PsA): the Phase 3 PENGUIN 1 (patients with inadequate response to methotrexate/MTX) and PENGUIN 2 (patients with inadequate response to biologic agents) studies are just beginning to enroll and will explore two doses (100/200mg)
Ankylosing spondylitis (AS): preparations to initiate a Phase 3 pivotal program are underway . Other indications also being explored.
GLPG reminded us that the global inflammation market is large (expected to be $65bn by 2027, according to their estimates), with indication beyond RA expected to comprise c.60% of the market. Beyond that, however, we learned little new about filgotinib, and further when asked about the status of the ongoing MANTA and MANTA RAy studies and what would be submitted to support the expected new drug application (NDA) for filgotinib, GLPG (perhaps given that partner GILD controls official communications) added little, if anything, new. That said, we believe it is nonetheless key to remind that safety data from neither MANTA and MANTA-RAy are needed to support the NDA filing.