TNO155–Ribociclib Combination for Extended Tumor Control
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Solution Overview
Problem
Current treatments for cancers such as esophageal, head and neck squamous cell carcinoma, colorectal, ovarian, pancreatic, non-small cell lung cancer, and renal cell carcinoma are limited in efficacy, with existing therapies often leading to disease progression within a year.
Innovation Solution
The combination of TNO155, an allosteric inhibitor of SHP2, and ribociclib, a CDK4/6 inhibitor, is administered to target the SHP2 and CDK4/6 pathways, thereby inhibiting cancer cell proliferation and halting cell cycle progression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If single-agent therapy is used, then treatment simplicity is maintained, but efficacy is limited and disease progression occurs within a year
Solution Approach 1:
The patent combines TNO155 (SHP2 inhibitor) and ribociclib (CDK4/6 inhibitor) into a fixed-ratio combination therapy, merging two distinct molecular mechanisms to achieve synergistic anti-tumor effects. This combination targets both upstream (SHP2) and downstream (CDK4/6) components of the RTK-RAS-MAPK and cell cycle pathways, thereby improving treatment efficacy while managing complexity through fixed-dose formulation.
2Reliability
If combination therapy is used, then efficacy is improved, but treatment complexity increases
Solution Approach 1:
The patent develops a fixed-ratio combination product that integrates TNO155 and ribociclib in predetermined proportions, allowing simultaneous administration of both agents in a single therapeutic regimen. This approach simplifies the operational aspects of combination therapy by eliminating the need for separate dosing schedules and administration procedures.
3Duration of action of moving object
If existing therapies are used, then treatment accessibility is maintained, but time to disease progression is short
Solution Approach 1:
The patent employs preliminary action by inhibiting SHP2 upstream in the signaling pathway before it can activate downstream effectors including CDK4/6. This preemptive inhibition of the phosphatase activity prevents full activation of proliferative signaling, thereby extending the time to tumor progression and improving treatment effectiveness.
Solution Approach 2:
The patent segments the anti-cancer therapy into two distinct but complementary mechanisms: SHP2 inhibition (upstream signaling blockade) and CDK4/6 inhibition (downstream cell cycle blockade). This segmentation allows each component to address specific nodes in the cancer signaling pathway, achieving more durable disease control than single-agent therapy.
Data Source
AI summary
The present invention relates to a pharmaceutical combination comprising TNO155 and ribociclib; pharmaceutical compositions comprising the same; and methods of using such combinations and compositions in the treatment or prevention of conditions in a SHP2 inhibitor combined with CDK4/6 inhibition is beneficial in, for example, the treatment of cancers.