BI 905677* is a humanized biparatopic nanobody® comprising two blocking domains for lipoprotein receptor-related proteins (LRP) 5 and 6. BI 905677 binds to LRP5 and LRP6 with high affinity, and prevents them from activating the Wnt signaling pathway that drives cancer proliferation, survival and immune escape.1,2
Clinical trials (monotherapy): BI 905677 is currently undergoing investigation as a monotherapy in a Phase I trial in patients with advanced solid tumors.3
Wnt/β-catenin signaling activation was shown to drive resistance to checkpoint inhibitors through loss of DC function and T cell exclusion, which is blocked by BI 905677. This inhibits Wnt ligand/β-catenin-driven tumor cell proliferation and survival.2,4
Mechanism of action
BI 905677 binds to LRP5/6 with high affinity, preventing the binding of Wnt ligands to LRP5/6 and blocking Wnt/β-catenin signaling that promotes tumor cell proliferation and survival.1,2
RNF43 inactivating mutations and R-spondin 3 fusion transcripts are genomic alterations that are known to drive ligand-dependent Wnt/β-catenin signaling activation in some solid tumors.7,8 Preclinical data have shown that BI 905677 potently and selectively blocks ligand-dependent Wnt signaling and induces tumor growth inhibition in RNF43 mutation-positive and R-spondin 3 fusion-positive tumors.1
Combination therapy
BI 905677 has also shown immuno-modulatory activity through induction of DC activation and T-cell infiltration in tumor tissues, leading to tumor regression when combined with an anti-programmed cell death protein-1 (PD-1) immune checkpoint inhibitor in syngeneic tumor models.1
BI 905667 is currently undergoing clinical investigation as a monotherapy in patients with advanced solid tumors who have failed on, or are not amenable to, conventional therapy, or for whom there is no therapy of proven efficacy.3
More information about Boehringer Ingelheim oncology clinical trials can be found on the MyStudyWindow website. Relevant trials for our Wnt Signaling (LRP5/6 antagonist) include: BI 1401-0001.
| Trial number | Phase | Treatment | Patient population | Status |
|---|---|---|---|---|
|
NCT036044453 (1401.1) A Phase I dose-finding study of a LRP5/6 antagonist in patients with advanced solid tumors3 
AE, adverse event; ECOG PS, Eastern Cooperative Oncology Group performance status; iv, intravenous; LRP, lipoprotein receptor-related protein; MTD, maximum tolerated dose; PK, pharmacokinetics; RECIST, Response Evaluation Criteria in Solid Tumors. |
I |
Wnt Signaling (LRP5/6 antagonist) [BI 905677] |
Advanced, unresectable, and/or metastatic solid tumors |
Recruiting |
Zinzalla V, et al. Oral presentation at AACR-2019 (Abstract DDT01-01).
Fuerer C, et al. EMBO Reports 2008;9:134–8.
ClinicalTrials.gov. NCT03604445. http://clinicaltrials.gov/ct2/show/NCT03604445 (Accessed: September 2021).
Boehringer Ingelheim. Data on file.
Zhan T, et al. Oncogene 2017;36(11):1461–73.
Spranger S, et al. Nature 2015: 523(7559):231–5
Giannakis M, et al. Nat Genet. 2014;46(12):1264.
Seshagiri S, et al. Nature. 2012 Aug 30;488(7413):660-4.
*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
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Page last updated: September 2021
