STING Agonist Intravesical Therapy for Bladder Cancer Recurrence

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Solution Overview

Problem

Current treatments for Non Muscle Invasive Bladder Cancer (NMIBC), particularly BCG-unresponsive cases, have high recurrence rates and significant morbidity, necessitating the development of new therapies that can induce long-lasting immune responses against bladder cancer and solid tumors.

Innovation Solution

Administration of a STING agonist compound, specifically a 4,9-dimercapto-tetrahydro-19H-3,5,8,10-tetraoxa-4,9-diphospha-1(8,9)-purina-6(4,2)-furanacyclododecaphane 4,9-dioxide, via intravesical route to elicit immunological memory and minimize systemic exposure, combined with anti-PD-1 therapy for enhanced efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If BCG therapy is used to treat NMIBC, then established treatment protocol is followed, but high recurrence rate and treatment failure occur in 50% of patients

Engineering Contradiction:

Improvetreatment efficacyVSAvoidrecurrence rate

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent changes the therapeutic parameter from BCG (a bacterial immunotherapy) to a small molecule STING agonist compound. This parameter change targets a different immune pathway (STING pathway versus BCG-mediated macrophage activation), thereby overcoming BCG-unresponsiveness and reducing recurrence in NMIBC patients who fail standard BCG therapy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The STING agonist compound acts as an intermediary that directly activates the STING pathway in dendritic cells and other immune cells, bypassing the need for BCG-mediated activation. This intermediary approach provides a more direct and reliable immune stimulation mechanism that overcomes the limitations of BCG therapy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If intravesical instillation of BCG is administered, then therapy is established, but significant morbidity and quality of life issues arise

Engineering Contradiction:

Improvetreatment establishmentVSAvoidmorbidity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a small molecule compound that can be administered as a single dose or limited course of intravesical instillation, replacing the need for repeated BCG instillations. This disposable approach (single-use or limited-use formulation) reduces cumulative morbidity while maintaining treatment efficacy, as the small molecule provides sustained immune activation without the ongoing inflammatory burden of repeated BCG therapy

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If STING agonist compound is administered via intravesical route, then tumor-specific immunologic memory is induced, but systemic exposure must be minimized

Engineering Contradiction:

Improveimmunologic memory inductionVSAvoidsystemic exposure

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent utilizes the intravesical administration route to create local high concentration of the STING agonist compound within the bladder, where NMIBC tumors are located. This local quality approach ensures potent immune activation and tumor-specific immunologic memory induction at the treatment site while minimizing systemic distribution and exposure through targeted delivery to the bladder lumen

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11883420B2Sting agonists for treating bladder cancer and solid tumors

Publication Date: 2024.01.30 VENENUM BIODESIGN LLC

AI summary

Methods for treating bladder cancer and solid tumors are disclosed. The methods include administering to a patient a compound of formula 1Pharmaceutical compositions of compound 1 are also disclosed.