QXL-138AM

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• Why Interferon Alpha 2? Interferons have direct anti-tumor activity as well as being master regulators of both innate and adaptive immune responses. IFNα induces tumor cell-specific cell death as tumor cells are more susceptible to IFNα induced apoptosis. IFNα also causes activation of NK cells and induces synergy of anti-tumor antigen antibody-dependent cell-mediated cytotoxicity. 

• Why target CD138? Multiple Myeloma and many solid tumors express a CD138 receptor.  Tumor antigen targeting enhances tumor retention and localizes the fused cytokine to the target cell surface.  By fusing an anti-CD138 antibody to the MIC, the antibody binds to its antigen on the tumor cell surface (where the proteases are located) providing an enhanced opportunity for cleavage.  Thus, Nammi’s MICs retain full potency vs non-masked controls in preclinical studies.

• Mask rationale: The mask prevents systemic IFN receptor binding while maintaining anti-tumor activity. The masks are attached through a peptide sequence that is sensitive to cleavage by tumor-selective proteases; thereby allowing activation of the IFN selectively within the tumor environment.

• Target Indication:  Multiple Myeloma and solid tumors expressing a CD138 receptor include Hepatocellular, ovarian, breast, prostate, bladder, Gastrointestinal and head and neck carcinomas.  QXL138AM was granted FDA Orphan Drug Designation for the treatment of Multiple Myeloma and Pancreatic Cancer. ​