ALX2004

A Highly Differentiated Antibody-Drug Conjugate

ALX Oncology’s second clinical pipeline candidate, ALX2004, is a novel epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate (ADC)

EGFR is a highly actionable cancer-therapy target given its prevalence in non-small cell lung cancer, colorectal cancer, head and neck cancers, and other solid tumors. ALX Oncology scientists applied the company’s proprietary platforms, informed by learnings from earlier-generation ADC programs in the field, to create the EGFR-targeted ADC ALX2004. Built with best-in-class components, ALX2004 has demonstrated potential to deliver the full power of ADCs to EGFR-positive tumors.

Abstract 3D molecular structures in purple and blue tones.

Designed to Maximize Potential for Success

ALX Oncology’s protein engineers designed ALX2004 to optimize all mechanisms of ADC cancer-killing while also maximizing dosage and safety (i.e., the therapeutic window).

The investigational therapy uniquely employs a matuzumab-derived antibody stably linked to a topoisomerase I inhibitor (TOP1i) payload.

EGFR Antibody

Matuzumab-derived EGFR antibody selected to minimize off-tumor skin toxicity and to maximize therapeutic window. Epitope distinct from that of FDA-approved EGFR antibodies.

Proprietary Linker-Payload

Lysosomal cleavage like deruxtecan ADCs with improved linker-antibody stability to minimize off-tumor payload release.

Proprietary TOP1i Payload, DAR 8

TOP1i with similar direct cytotoxic potency and enhanced bystander activity compared to deruxtecan

This unique, highly purpose-driven design has demonstrated multiple potential advantages, including:

More payload delivered to tumor

Less drug delivered to off-tumor, off-target tissues

Broad applicability in EGRF+ tumor types

“Given the promising preclinical findings we have seen to date for ALX2004, which demonstrate a favorable toxicity profile and potent anti-tumor activity, we remain very optimistic about the potential success for this approach in treating EGFR-positive tumors.”
Jason Lettmann, CEO, ALX Oncology

Demonstrated In Vivo Anti-Tumor Activity

Extensive preclinical data support the potential of ALX2004 to break new ground in ADC innovation in the EGFR-targeting class.

ALX2004 demonstrated potent, dose-dependent, anti-tumor activity in in vivo models with differing levels of EGFR expression and varied mutational status across the EGFR signaling pathway. Additionally, preclinical data suggest that ALX2004 has the potential to overcome the toxicity challenges associated with earlier generation EGFR-targeted ADCs. These data support a favorable preclinical safety profile at clinically relevant doses, including no skin toxicity or interstitial lung disease.

View the ALX2004 Data

Scientist in a lab coat reviewing data on a tablet in a laboratory setting.

We are further exploring the potential of ALX2004 to transform the treatment of EGRF-positive tumors in an ongoing clinical program, starting with a Phase 1 trial evaluating the safety, tolerability, and preliminary efficacy of ALX2004 in patients with advanced or metastatic solid tumors that are known to express EGFR.

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