Multispecific Antibody Dosing Regimen for BCMA Targeting
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Solution Overview
Problem
There is an unmet medical need for BCMA binding molecules with an improved safety profile that reduces cytokine release syndrome (CRS) while maintaining high efficacy in treating cancers such as multiple myeloma, and there is a need for proper dosing to minimize unwanted side effects.
Innovation Solution
A BCMA binding molecule, referred to as BSBM3, which is a multispecific antibody that targets BCMA-expressing cells and engages T-cells by binding to CD3, administered at varying doses from 0.25 μg/kg to 1200 μg/kg, potentially combined with side effect reducing agents like acetaminophen and glucocorticoids, and gamma secretase inhibitors, to treat or prevent cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BCMA binding molecules (such as CD3 bispecific molecules) are administered to treat cancer, then anti-tumor efficacy is improved, but cytokine release syndrome (CRS) occurs as a harmful side effect
Solution Approach 1:
The patent applies parameter changes by systematically varying the dosage of BCMA binding molecules across multiple levels (0.03 mg/kg, 0.3 mg/kg, 3.0 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg) to identify the optimal therapeutic window. This dosage optimization resolves the contradiction by finding conditions where anti-tumor efficacy is maximized while CRS is minimized or avoided
Solution Approach 2:
The patent introduces side effect reducing agents as intermediaries to mitigate CRS. These agents act as mediators between the BCMA binding molecule and the immune system, allowing the therapeutic molecule to maintain its anti-tumor efficacy while the reducing agents prevent or lessen the harmful cytokine release syndrome
2Productivity
If higher doses of BCMA binding molecules are administered to enhance therapeutic effect, then treatment efficacy is improved, but side effects including CRS increase
Solution Approach 1:
The patent systematically changes the dosage parameter to resolve this contradiction. By testing multiple dosage levels and evaluating both efficacy and side effects at each level, the patent identifies an optimal dosage range that maximizes treatment efficacy while keeping side effects within acceptable limits
Solution Approach 2:
The patent applies partial action by using side effect reducing agents at specific dosages that are sufficient to mitigate CRS without completely blocking the therapeutic effect of the BCMA binding molecule. This allows partial suppression of harmful effects while maintaining useful therapeutic action
Data Source
AI summary
The present disclosure relates to dosing regimens, formulations, and combinations comprising a multispecific antibody having at least binding specificity towards B cell maturation antigen (BCMA) and a T-cell engaging arm; and methods of using such multispecific antibodies in the treatment or prevention of disease, such as, cancer.