ALX Oncology Reports 2025 Results, Advances Evorpacept and ALX2004 Clinical Programs

ALX Oncology Holdings Inc. reported fourth quarter and full year 2025 financial results on February 27, 2026, announcing that clinical development for both evorpacept and ALX2004 remains on track following strong 2025 execution. The company completed a $150 million registered offering of common stock and pre-funded warrants, extending cash runway through the first half of 2028 inclusive of key clinical program milestones for evorpacept and ALX2004.

The Chief Executive Officer said the company's priority remains execution and positioned 2025 as a year that generated extensive evorpacept clinical data to refine development strategy. The company has treated more than 750 patients with evorpacept to date. Management reiterated its objective to advance both evorpacept and ALX2004 to a stage "ready for pivotal studies" by the end of next year, while emphasizing that clinical development timelines remain on track.

Evorpacept biomarker strategy validated

The evorpacept biomarker strategy was validated by data from both the Phase 2 ASPEN-06 gastric cancer trial and the Phase 1b/2 breast cancer trial, independently suggesting CD47 overexpression is predictive of evorpacept activity and drives durable benefit in HER2-positive cancers.

Data from a pre-planned exploratory analysis of the Phase 2 ASPEN-06 clinical trial in gastric cancer showed that CD47 overexpression is a key predictive biomarker for evorpacept response and durable benefit in patients whose tumors have retained HER2 expression. Retained HER2 expression is defined as tumors that are HER2-positive following HER2-targeted treatment, as assessed by either a repeat tumor biopsy or HER2 gene amplification in circulating tumor DNA. These data were highlighted as part of a poster presentation at the Society for Immunotherapy of Cancer Annual Meeting in November 2025.

In patients with retained HER2-positive and CD47-high gastric cancer (n=43), evorpacept plus trastuzumab, ramucirumab and paclitaxel generated a 65.0% objective response rate versus 26.1% for the control arm. The duration of response was three times longer in the evorpacept arm relative to the control arm in these patients. Evorpacept generated a median duration of response of 25.5 months versus 8.4 months for the control arm. Treatment with evorpacept resulted in a median progression-free survival of 18.4 months versus 7.0 months for the control arm, with a hazard ratio of 0.39. Treatment with evorpacept resulted in a median overall survival of 17 months versus 9.9 months for the control arm, with a hazard ratio of 0.70.

A phase 1/2 study conducted with partner Jazz evaluated evorpacept in combination with zanidatamab in HER2-positive metastatic breast cancer patients who had progressed on prior HER2-directed therapies and had all received ENHERTU. Among nine late-line patients with confirmed HER2 expression by central assessment, the response rate was 56%, with duration of response ranging from 5.5 to nearly 26 months and median progression-free survival of 7.4 months. The company concluded CD47 biomarker analysis in January 2026, finding that responders were "predominantly restricted" to patients with CD47 overexpression. Full biomarker analysis from the Phase 1b/2 evorpacept-zanidatamab combination trial was accepted for poster presentation at ESMO Breast Cancer 2026 Annual Congress. Full biomarker results are expected at the ESMO Breast Cancer Conference in the second quarter of 2026.

ASPEN-09-Breast trial expansion

The company provided an update on its ongoing phase 2 ASPEN-09-Breast study evaluating evorpacept with trastuzumab and single-agent chemotherapy in HER2-positive metastatic breast cancer patients who have progressed on ENHERTU. The company has decided to expand the study from 80 to up to 120 patients to increase the number of patients with CD47 overexpression and to help define an optimal CD47 cut point. The company also updated the primary endpoint to response rate in patients with high CD47 expression, with a key secondary endpoint tracking response rate by HER2 status informed by circulating tumor DNA.

The Phase 2 ASPEN-09 breast cancer trial is currently enrolling patients and will evaluate evorpacept efficacy by CD47 expression levels, with topline data anticipated mid-2027. Management confirmed it is now guiding to a top-line readout from 80 patients in mid-2027, rather than an interim look sooner. The first patient was enrolled in January and global site activations are progressing on plan. The company expects to share "meaningful efficacy and safety data," including response rate, biomarker results, and early durability trends, by mid-2027.

The company observed roughly 40% to 57% CD47-high rates across cutoffs in its gastric study, and expects about half of patients could be CD47-high in breast cancer based on literature, while acknowledging the cut point and expression profile may differ by tumor type.

ALX2004 dose escalation continues

The Phase 1 trial evaluating ALX2004 continues to enroll patients in the third dose cohort. Safety data from the dose-escalation phase are expected in the second half of 2026. ALX2004 is a novel EGFR-targeted antibody-drug conjugate with a differentiated mechanism of action. ALX2004 has successfully cleared the first two dose cohorts in the ongoing Phase 1 trial.

Leadership appointment

Dr. Barbara Klencke, who joined in an interim capacity in September 2025, will remain as permanent Chief Medical Officer. She has prior Chief Medical Officer experience at Sierra Oncology and senior roles at Onyx and Genentech.