taladegib (ENV 101)

P2, N=200, Recruiting, Endeavor Biomedicines, Inc. | Not yet recruiting --> Recruiting | N=320 --> 200

P2, N=320, Not yet recruiting, Endeavor Biomedicines, Inc.

P2, N=41, Completed, Endeavor Biomedicines, Inc. | Active, not recruiting --> Completed

P2, N=44, Active, not recruiting, Endeavor Biomedicines, Inc. | Recruiting --> Active, not recruiting

P2, N=40, Active, not recruiting, Endeavor Biomedicines, Inc. | Recruiting --> Active, not recruiting

Patient was further treated by vismodegib for 12 months followed by Cemiplimab. For the first time we report here that mBCC patients who were refractory to current standard of care treatments responded to taladegib with a duration of response of around one year with fewer and manageable adverse effects.

Stage 1 (phase IIa) of this protocol will enroll a total of 44 patients randomized between two dose levels. In the presence of acceptable efficacy, stage 2 (phase IIb) of this protocol will expand enrollment using a single dose level.

P2, N=44, Recruiting, Endeavor Biomedicines, Inc. | Not yet recruiting --> Recruiting | Initiation date: Jan 2022 --> May 2022

P2, N=44, Not yet recruiting, Endeavor Biomedicines, Inc.

The value of these WNT pathway genes as predictive biomarkers of patient response to Hh inhibitors warrants further investigation. Impact statement Investigating crosstalk between Hh and WNT pathways could potentially lead to new therapies.

The primary objective was to determine the recommended Phase 2 dose of crenigacestat in combination with other anticancer agents (taladegib, LY3023414 [dual inhibitor of phosphoinositide 3-kinase; mechanistic target of rapamycin], or abemaciclib). This study demonstrated that crenigacestat combined with different anticancer agents (taladegib, LY3023414, or abemaciclib) was poorly tolerated, leading to lowered dosing and disappointing clinical activity in patients with advanced or metastatic solid tumors. NCT02784795 and date of registration: May 27, 2016.

Our results reveal Taladegib as a novel drug in controlling chondrocyte hypertrophy depending on Smo blocking, which plays a vital role in the homeostasis of cartilage and the development of OA. Besides, we found that Taladegib only works in the previous stage of chondrocytes hypertrophy but not in the later of the process.