BMS-986466

P1, N=4, Terminated, LianBio LLC | Phase classification: P1a/1b --> P1 | N=52 --> 4 | Trial completion date: Jul 2026 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Mar 2024; Business reason

P1, N=7, Terminated, LianBio LLC | N=28 --> 7 | Trial completion date: Sep 2024 --> Mar 2024 | Recruiting --> Terminated; Business reason

P1/2, N=5, Terminated, Bristol-Myers Squibb | N=410 --> 5 | Active, not recruiting --> Terminated; Business objectives have changed

P1/2, N=410, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting | Trial completion date: Jul 2029 --> May 2024 | Trial primary completion date: Aug 2027 --> May 2024

P1, N=130, Active, not recruiting, Navire Pharma Inc., a BridgeBio company | Recruiting --> Active, not recruiting

In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors...Furthermore, the combination therapy of compound 4b and KRAS inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells...Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRAS mutant non-small cell lung cancer.Communicated by Ramaswamy H. Sarma.

P1/2, N=410, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

P1/2, N=410, Not yet recruiting, Bristol-Myers Squibb

P1, N=130, Recruiting, Navire Pharma Inc., a BridgeBio company | Trial completion date: Oct 2023 --> Feb 2025 | Trial primary completion date: Apr 2023 --> May 2024

Pharmacologic targeting by SHP2 inhibitors TNO155 or IACS-13909 as well as dual SHP2/JAK2 targeting was evaluated in MPN cell lines and primary MPN patient cells. Our findings suggest a relevant role of SHP2 in MPN given enhanced MAPK pathway suppression and correctiveeffects when SHP2 is targeted in MPN cells, mouse models and primary patient isolates. Further studies will delineate the involvement of SHP2 phosphatase vs. non-phosphatase functions and detail the potential of JAK2/SHP2 inhibition as therapeutic approach in MPN.

P1, N=45, Recruiting, Navire Pharma Inc., a BridgeBio company | Initiation date: May 2022 --> Oct 2022

P1, N=28, Recruiting, LianBio LLC

P1, N=85, Recruiting, Navire Pharma Inc., a BridgeBio company

Further study showed that PTPN11 interference and specific inhibitors IACS-13909 abrogated the discrepancy of self-renewal ability, proliferation, migration and tumorigenicity capacity between miR-6071 overexpression HCC cells and control cells. Clinical cohort analysis revealed that HCC patients with high miR-6071 expression got more survival benefit from postoperative lenvatinib treatment than patients with low miR-6071 levels. In conclusion, our study demonstrated a regulation mechanism of LCSCs, a target against LSCSs, and a biomarker for postoperative lenvatinib treatment.

P1, N=45, Recruiting, Navire Pharma Inc., a BridgeBio company

P1, N=130, Recruiting, Navire Pharma Inc., a BridgeBio company | N=60 --> 130 | Trial primary completion date: Jul 2023 --> Apr 2023

P1, N=60, Recruiting, Navire Pharma Inc. | Not yet recruiting --> Recruiting

In EGFRmut osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation in vitro and caused tumor regression in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFR inhibitor-resistant NSCLC.

P1, N=60, Not yet recruiting, Navire Pharma Inc.