ALX Oncology's Evorpacept: A High-Conviction Biotech Play in CD47-Expressing HER2+ Cancers

In the evolving landscape of oncology therapeutics, ALX Oncology's Evorpacept has emerged as a compelling candidate for targeting CD47-expressing HER2+ cancers. With recent clinical and financial milestones, the company is positioning itself at the intersection of innovation and unmet medical need. This analysis evaluates the near-term catalysts driving ALX Oncology's value proposition, focusing on the therapeutic potential of Evorpacept and the company's financial resilience.

Clinical Catalysts: Evorpacept's Progress in HER2+ Cancers

The Phase 2 ASPEN-06 trial has delivered groundbreaking results for Evorpacept in HER2-positive gastric cancer patients with high CD47 expression. According to a report by ALX Oncology, the combination of Evorpacept with trastuzumab, ramucirumab, and paclitaxel achieved an objective response rate (ORR) of 65%, significantly outperforming the 26% ORR in the control group. The median duration of response (DOR) was 25.5 months versus 8.4 months, while progression-free survival (PFS) and overall survival (OS) also showed marked improvements, as detailed in the ALX Oncology Holdings Inc. to Present Updated Data from Phase 2 ASPEN-06 Trial. These findings, presented at the SITC Annual Meeting in November 2025, underscore Evorpacept's potential to redefine treatment paradigms in CD47-high HER2+ cancers.

Building on this success, ALX Oncology is advancing to the ASPEN-09-Breast Cancer trial, a Phase 2 study evaluating Evorpacept in HER2-positive breast cancer patients who have previously received ENHERTU®. The trial is designed to assess efficacy based on CD47 expression levels and is on track to begin enrollment in Q4 2025, with interim data expected in Q3 2026, as noted in the ALX Oncology Reports Third Quarter 2025 Financial Results and Provides Corporate Update. This trial represents a critical next step in validating Evorpacept's broad applicability across HER2+ tumor types.

Financial Resilience and Strategic Milestones

ALX Oncology's financial position provides a stable foundation for its ambitious clinical roadmap. As of Q3 2025, the company reported $66.5 million in cash, cash equivalents, and investments, sufficient to fund operations through Q1 2027, as noted in the ALX Oncology Reports Third Quarter 2025 Financial Results and Provides Corporate Update. While the quarterly adjusted loss of 41 cents per share exceeded analyst expectations, as reported in the ALX Oncology Holdings Inc. reports results for the quarter ended September 30 - Earnings Summary, this reflects the capital-intensive nature of late-stage trials and the absence of revenue-generating products-a common challenge for pre-commercial biotech firms.

The company's near-term focus remains on advancing its pipeline. The ASPEN-09-Breast Cancer trial and the Phase 1 ALX2004 trial (a novel EGFR-targeted ADC) are key drivers of value. ALX2004, currently enrolling patients in its second dose cohort, is expected to deliver initial safety data in the first half of 2026, as noted in the ALX Oncology Reports Third Quarter 2025 Financial Results and Provides Corporate Update. These milestones, if successful, could attract partnerships or accelerate regulatory pathways, further bolstering the company's financial outlook.

Risks and Considerations

Despite the promising data, investors must remain cognizant of risks inherent to biotech development. The ASPEN-09 trial's success hinges on replicating ASPEN-06's outcomes in a different tumor type, a challenge given the heterogeneity of HER2+ cancers. Additionally, competition in the CD47 space is intensifying, with players like Amgen and BeiGene advancing their own programs, as detailed in the ALX Oncology Holdings Inc. to Present Updated Data from Phase 2 ASPEN-06 Trial. However, ALX Oncology's focus on CD47 expression as a biomarker stratification strategy may differentiate Evorpacept by identifying a subset of patients most likely to benefit.

Conclusion: A High-Conviction Play

ALX Oncology's Evorpacept represents a high-conviction opportunity for investors seeking exposure to next-generation immuno-oncology therapies. The ASPEN-06 results have validated the therapeutic potential of targeting CD47 in HER2+ cancers, while the ASPEN-09 trial and ALX2004 program offer clear near-term catalysts. With a robust cash runway and a pipeline anchored by biomarker-driven trials, ALX Oncology is well-positioned to deliver value acceleration in 2026. However, success will depend on the execution of its clinical strategy and the ability to navigate competitive and regulatory challenges.