ALX Oncology Q1 Earnings Call Highlights

Key Points

• Evorpacept data presented at ESMO indicate CD47 expression may predict benefit — centrally confirmed HER2‑positive patients with CD47 ≥20% had a 100% ORR, median DOR ~20.2 months and median PFS ~22 months versus 3.4 months in CD47‑low patients, consistent with ASPEN‑06 gastric results.
• ASPEN‑09 is a single‑arm phase 2 (up to 120 patients) targeting the CD47‑overexpressing subset, with interim top‑line data from ~80 patients expected by mid‑2027; ALX says a ~30% ORR and DOR ≥6 months would be considered a compelling outcome versus historical ~15% post‑ENHERTU response rates.
• ALX2004, the company’s EGFR‑targeted ADC, remains in dose escalation with enrollment progressing and an initial safety readout expected in the 2H 2026 timeframe.

ALX Oncology NASDAQ: ALXO executives used the company’s first-quarter 2026 earnings call to highlight new clinical data for its lead CD47 blocker, evorpacept, and to provide updates on its EGFR-targeted antibody-drug conjugate program, ALX2004. CEO Jason Lettmann said the quarter featured “continued good execution,” including a February financing and the addition of Jeff Knight as chief development and chief operating officer.

ESMO Breast dataset highlights CD47 as a predictive biomarker

Lettmann said the company was “very excited” to share data presented at ESMO Breast Cancer 2026 in Munich from an analysis of a phase 1b/2 trial evaluating evorpacept in combination with zanidatamab in heavily pre-treated HER2-positive metastatic breast cancer. He said the analysis “clearly showed again that CD47 expression is a key predictive biomarker for increasing durable clinical response,” and characterized the findings as consistent with prior results in HER2-positive gastric cancer from the company’s ASPEN-06 trial.

Fred Hutch Cancer Center’s Dr. Sara Hurvitz, a steering committee member for ALX’s ongoing ASPEN-09 breast cancer study and an investigator on the zanidatamab plus evorpacept trial, described the post-trastuzumab deruxtecan (T-DXd/ENHERTU) setting as an area of unmet need. Hurvitz pointed to observational and retrospective datasets suggesting median progression-free survival (PFS) “under 6 months” after T-DXd, and referenced a figure showing “median progression-free survival of only 4.1 months” following prior ENHERTU treatment.

Hurvitz said the exploratory biomarker analysis covered 24 patients from the dose-escalation cohort and cohort 1, noting the group was “extremely heavily pretreated,” with all patients having received prior T-DXd and a median of five prior lines of HER2-targeted therapies. Patients entered based on local HER2 testing of archival tissue, but most had fresh baseline biopsies with retrospective central HER2 assessment, and tumors were also tested for CD47 expression.

Response rates improved in centrally confirmed HER2-positive patients

Hurvitz reported that in the full 24-patient intent-to-treat population, the confirmed objective response rate (ORR) was 33%, with a median duration of response (DOR) of 20 months and median PFS of 3.6 months. In the subset of 10 patients with centrally confirmed HER2-positive disease, ORR increased to 60%, with median DOR of 20.2 months and median PFS of 8.3 months. Patients without centrally confirmed HER2-positive disease had a lower ORR of 14%, according to the presentation.

Breaking the centrally confirmed HER2-positive group down by CD47 expression using a retrospective cutoff of at least 20% total membrane staining, Hurvitz said all five patients who were HER2-positive and CD47-high responded (100% ORR) with a median DOR of 20.2 months. Among four centrally confirmed HER2-positive patients with CD47 expression below 20%, one responded. A Kaplan-Meier analysis presented on the call showed median PFS of 22 months in the CD47 ≥20% group versus 3.4 months in the CD47 <20% group, though Hurvitz cautioned the numbers were small and said she hoped to see the findings confirmed in a larger study.

Chief Medical Officer Barbara Klencke added that an IHC assay quantified CD47 total membrane staining and that a “positive result was defined retrospectively as a score of 20% or higher.” She said all five CD47-high patients responded, including one complete response, while four patients without CD47 overexpression included one responder, and one additional patient was unevaluable.

Company draws parallels to ASPEN-06 gastric cancer study

Klencke emphasized what she called consistency across two independent HER2-positive cancer studies. In ASPEN-06, a randomized phase 2 trial of evorpacept added to trastuzumab, paclitaxel, and ramucirumab versus the regimen alone, she said response rates in the evorpacept arm were 41% in the intent-to-treat population, “over 49%” in patients who retained HER2-positive disease, and 65% in tumors that also expressed CD47. She noted ASPEN-06 enrolled 127 patients.

She also highlighted durability metrics in CD47-high subsets, citing DOR of 20.2 months in the breast study and 25.5 months in ASPEN-06. For PFS, Klencke cited a median of 22.1 months in the breast CD47-high cohort versus 3.4 months in CD47-low, and in the gastric CD47-high subset, a median PFS of 18.4 months in the evorpacept arm with a hazard ratio of 0.39.

ASPEN-09 enrollment progressing; companion diagnostic work ongoing

ALX’s ongoing ASPEN-09 phase 2 breast cancer study will evaluate evorpacept plus trastuzumab in patients previously treated with ENHERTU. Klencke said the single-arm study will enroll up to 120 patients and has a primary endpoint of response rate in the subset that overexpresses CD47. The company said it remains on track to provide interim top-line data from approximately 80 patients by “the middle of 2027,” with Lettmann separately noting an expectation to read out 80 patients “mid next year” in prepared remarks.

In response to an analyst question on what would be compelling ASPEN-09 outcomes, Klencke said available therapies after ENHERTU “are not producing very good outcomes,” adding that “much of the data suggests that the response rate may be 15%” with trastuzumab plus chemotherapy alone. She said a 30% response rate would represent a doubling versus that expectation, and that “anything north of 30% would be a very, very good outcome” with DOR of six months or more. She said DOR may be preliminary at the 80-patient mark and that PFS could be too immature to report, depending on follow-up. Hurvitz said she would view “anything around 30% objective response rate and a PFS of 6 months” as important in such heavily pre-treated patients.

On biomarker implementation, Hurvitz said if CD47 is validated as predictive, she would expect work toward a companion diagnostic, though she said it was “too little data at this point” to be definitive. Klencke said Ventana is the company’s partner on companion diagnostic development, with a goal of having an assay and cut point set by the time ASPEN-09 is complete to potentially enable patient selection in a phase 3 study.

Asked about the prospect of accelerated approval, Klencke said the company’s “base case is that a phase III trial will be required,” citing regulatory challenges for single-arm combination trials and “retrospective application of a companion diagnostic.” She added the company would discuss accelerated approval with regulators if the response rate were “extraordinary.”

ALX2004 EGFR ADC continues dose escalation; safety update expected in 2H 2026

ALX also reiterated progress with ALX2004, its in-house EGFR-targeted ADC. Klencke said the molecule was designed to minimize off-tumor skin toxicity, target a distinct epitope from approved EGFR antibodies, and use a proprietary linker and a proprietary topoisomerase-1 inhibitor payload with an antibody-drug ratio of eight. The phase 1 study includes dose escalation, exploration, and expansion cohorts in lung, head and neck, colorectal, and esophageal cancers.

The company said enrollment is progressing and reiterated it remains on track to report initial safety data in the second half of 2026. Klencke noted the company had previously disclosed dose escalation from 1 mg/kg to 2 mg/kg and then to a 4 mg/kg cohort, and said ALX is now shifting away from granular dose-escalation updates until the initial safety report.

Closing the call, Lettmann said the company believes the new dataset adds to evidence across two HER2-positive cancers that evorpacept can deliver meaningful benefit and that a CD47-targeted approach “can drive transformational benefit to patients.” He added that the company’s balance sheet was strengthened by the February financing and said ALX expects “additional updates very soon.”

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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