ALX Oncology (NASDAQ:ALXO) outlined progress across its two core programs—CD47 blocker evorpacept and EGFR-targeted antibody-drug conjugate ALX2004—while providing updated clinical timelines and financial runway during its fourth-quarter and full-year 2025 results call.
Leadership update and execution focus
Chief Executive Officer Jason Lettmann said the company’s priority remains execution and positioned 2025 as a year that generated extensive evorpacept clinical data to refine development strategy. ALX also announced that Dr. Barbara Klencke, who joined in an interim capacity in September 2025, will remain as permanent Chief Medical Officer. Lettmann highlighted her prior CMO experience at Sierra Oncology and senior roles at Onyx and Genentech.
Evorpacept data: CD47 as a predictive biomarker
ALX emphasized CD47 expression as an increasingly validated biomarker for response to evorpacept-based combinations in HER2-positive cancers. Lettmann said the company has treated more than 750 patients with evorpacept to date and is increasingly confident about where the drug works best.
Klencke reviewed results from a randomized phase 2 HER2-positive gastric cancer study presented at SITC in November 2025, focusing on patients whose tumors were HER2-positive and overexpressed CD47. In that subset, she said:
- Response rate was 65% in second- and third-line patients receiving evorpacept plus a trastuzumab-based regimen, versus 26% in the control arm.
- Median duration of response was more than two years and more than three times longer than in the control arm.
- Median progression-free survival was 18.4 months versus 7 months (hazard ratio 0.39).
- Median overall survival was 17 months versus approximately 10 months (hazard ratio 0.7).
She said the findings support CD47’s potential as a predictive biomarker and strengthen confidence in ongoing breast cancer development.
Separately, the company discussed a phase 1/2 study conducted with partner Jazz evaluating 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. Klencke noted ALX first presented data from this trial at the San Antonio Breast Cancer Symposium in December 2024, reporting that 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 PFS of 7.4 months. She said the company concluded CD47 biomarker analysis in January 2026, finding that responders were “predominantly restricted” to patients with CD47 overexpression. Full biomarker results are expected at the ESMO Breast Cancer Conference in Q2 2026.
ASPEN-09-Breast: trial expansion and updated endpoints
ALX 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. Klencke said 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 ctDNA.
In the Q&A, management confirmed it is now guiding to a top-line readout from 80 patients in mid-2027, rather than an interim look sooner. Lettmann described the shift as an effort to provide more “robust” and “meaningful” data, including sufficient representation of CD47-high patients. Klencke said investigators have expressed enthusiasm for a biomarker-driven strategy.
On expected prevalence, Lettmann said ALX 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. Management also cited literature suggesting CD47 overexpression may rise after ENHERTU exposure.
Enrollment remains early, with Klencke noting the first patient was enrolled in January and that global site activations are progressing on plan. ALX said it expects to share “meaningful efficacy and safety data,” including response rate, biomarker results, and early durability trends, by mid-2027.
ALX2004: dose escalation and safety data timing
ALX also highlighted progress for ALX2004, its EGFR-targeted ADC, noting the challenge of developing EGFR ADCs due to a narrow therapeutic window. Klencke discussed preclinical attributes, including broad antitumor activity across models and the absence of EGFR-related skin toxicity and interstitial lung disease (ILD) in GLP toxicology studies in non-human primates. She said the ADC uses the matuzumab antibody, described as having an affinity-tuned epitope, combined with a proprietary topoisomerase I inhibitor linker-payload designed for stability and bystander effect.
Clinically, the company has cleared the first two dose cohorts and is enrolling patients in the third dose cohort at 4 mg/kg after seeing no dose-limiting toxicities at 1 mg/kg and 2 mg/kg. Klencke said ALX believes 4 mg/kg may be at the lower end of the therapeutic range and expects smaller incremental escalations from here. The phase 1 trial is enrolling patients with non-small cell lung cancer, colorectal cancer, head and neck cancer, or esophageal squamous cell cancer.
Management guided to providing ALX2004 dose-escalation safety data in the second half of 2026. In Q&A, Lettmann said the timing reflects a focus on delivering a more complete dataset, and indicated it is reasonable to expect up to four dose levels may have been tested by the time of disclosure. Klencke said ILD monitoring includes regular CT imaging per protocol and that skin toxicity will be assessed at clinic visits, while noting matuzumab was selected in part for lower skin toxicity compared with other EGFR antibodies.
Financing, cash position, and outlook
CFO Harish Shantharam said ALX ended Q4 2025 with $48.3 million in cash, equivalents, and investments prior to a February financing. The company closed a $150 million financing with $140.4 million in net proceeds after underwriting discounts and offering expenses. Following the raise, Shantharam said ALX believes its cash and investments are sufficient to fund operating expenses through the first half of 2028.
For the quarter ended Dec. 31, 2025, ALX reported a GAAP net loss of $22.8 million, or $0.42 per share, compared with a GAAP net loss of $29.2 million, or $0.55 per share, in the year-ago quarter. Shantharam attributed the year-over-year decrease primarily to lower stock-based compensation, lower personnel-related costs, and lower preclinical costs following pipeline prioritization.
ALX’s guided milestones include the ESMO Breast Cancer biomarker presentation in May 2026, ALX2004 dose escalation safety data in the second half of 2026, and ASPEN-09-Breast top-line data from 80 patients in mid-2027.
About ALX Oncology (NASDAQ:ALXO)
ALX Oncology, Inc is a clinical-stage biopharmaceutical company headquartered in Redwood City, California, focused on developing next-generation immuno-oncology therapies. The company’s mission is to harness and amplify both innate and adaptive immune responses to improve outcomes for patients with a range of solid tumors and hematologic malignancies.
The lead candidate in ALX Oncology’s pipeline is evorpacept (ALX148), a high-affinity CD47-blocking Fc-silenced fusion protein designed to enhance macrophage-mediated phagocytosis of cancer cells when combined with standard therapeutic antibodies or immune checkpoint inhibitors.
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