ALX Oncology Receives IND Clearance From FDA for a Novel EGFR-Targeted ADC

ALX Oncology Holdings Inc. recently announced receipt of US FDA clearance for the Investigational New Drug (IND) application for ALX2004, the company’s potential best- and first-in-class antibody-drug conjugate (ADC) for the treatment of epidermal growth factor receptor (EGFR)-expressing solid tumors. Based on this clearance, ALX Oncology will initiate a single-agent dose-escalation and expansion Phase 1 clinical trial for ALX2004 in mid-2025.

“Clinical advancement of our first ADC and the first drug candidate developed on our proprietary linker-payload platform is an important milestone in our mission to deliver breakthrough therapies that will help transform the future of cancer treatment,” said Jason Lettmann, Chief Executive Officer at ALX Oncology. “We meticulously designed all aspects of ALX2004 – the antibody backbone, linker and payload – to optimize the targeted delivery of a powerful chemotherapy payload to tumor cells while minimizing systemic toxicity. The resulting, highly differentiated molecule has demonstrated potent anti-tumor activity in preclinical models and is a strategic addition to our clinical pipeline, which also includes multiple trials evaluating our lead therapeutic candidate, evorpacept.”

EGFR is a transmembrane protein located on the surface of cells that regulates cell growth; overexpression occurs across various tumor types, including breast cancer, colorectal carcinoma, head and neck squamous cell carcinoma and non-small cell lung cancer. EGFR is clinically validated as a therapeutic target with several FDA-approved targeted antibodies and small molecules. However, there are currently no approved EGFR-targeted ADCs. Early-generation attempts to develop EGFR-targeted ADCs were limited by drug design, on-target off-tumor toxicities and toxicity of older generation payloads.

Utilizing the company’s proprietary, highly differentiated topoisomerase I inhibitor payload platform, ALX Oncology scientists designed ALX2004 to optimize ADC-based mechanisms of anti-tumor activity and improve outcomes in patients with EGFR-expressing tumors. The ALX2004 molecule, created entirely in ALX Oncology labs, comprises an antibody backbone engineered to optimize anti-EGFR activity, a linker with enhanced stability and a proprietary topoisomerase I payload that can generate an enhanced bystander effect.

ALX Oncology plans to conduct an R&D call focused on ALX2004 in Q2 2025 and to initiate a Phase 1 clinical trial of the investigational therapy in mid-2025.

ALX Oncology (Nasdaq: ALXO) is a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives. ALX Oncology’s lead therapeutic candidate, evorpacept, has demonstrated potential to serve as a cornerstone therapy upon which the future of immuno-oncology can be built. Evorpacept is currently being evaluated across multiple ongoing clinical trials in a wide range of cancer indications. More information is available at www.alxoncology.com.