1.Project Profile

(1) Asset type: Molecular Inhibitor

(2) Indications: Solid tumor (ALK+ NSCLC)

(3) Dosage form and administration: Oral, Once Daily

(4) Research phase: PCC

(5) Cooperation demands: License-out

2.Strategy of Design

Huge Unmet clinical need
Activity against oncogenic ALK alteration (EML4-ALK fusions, activated point mutations)
Treatment -emergent drug-resistant ALK mutation (single or compound treatment-emergent ALK mutations)
Sparing tropomyosin receptor kinase (TRK) family, minimizing off-target CNS adverse events
TRK kinase is related to neurological events and dose-limited toxicities. Avoiding inhibition of the structurally-related TRK family
Activity in CNS
Inadequate control of brain metastases (40% of ALK+ NSCLC patient present with brain metastases).
The 3^rdALK TKI, lorlatinib, showed excellent efficacy. However, CNS related adverse reactions, mutation and resistance has emerged in patients
It is urgent need to develop the next generation ALK TKI.

3.Highlights

Asset shows comparable Kinomescan hit number, Kinase activity, and cellular activity to NVL-655.
In vivo ALK mutations xenograft Model.

Asset shows comparable TGI to NVL-655