ALX Oncology Highlights $150M Raise, Evorpacept Breast Cancer Push and EGFR ADC ALX2004 Update

Key Points

• ALX closed a $150 million financing that management says extends cash runway through the first half of 2028 and will fund a concentrated effort to make both lead programs pivotal-ready by the end of next year.
• Clinical data highlight evorpacept’s potential as a CD47-targeted therapy: in the ASPEN-06 gastric cancer subset with retained HER2 and CD47 overexpression it showed an ORR 65% vs 26% (control), a 25.5‑month duration of response and a PFS HR 0.39, prompting ALX to refocus its ASPEN-09 breast cancer study on the CD47‑overexpressing post‑Enhertu population.
• ALX2004 is now in dose escalation (entered dose level three), is an EGFR‑targeted ADC with a TOPO1 payload (DAR 8), and ALX expects additional safety data in the second half of this year while exploring partnering interest pending clear safety/efficacy signals.

Executives from ALX Oncology NASDAQ: ALXO outlined the company’s clinical and corporate priorities at a recent investor event, emphasizing a narrowed focus on two oncology assets: its lead CD47 blocker evorpacept and an in-house EGFR-targeted antibody-drug conjugate (ADC), ALX2004.

Chief Executive Officer Jason Lettmann said the company is “hyper-focused” over the next two years on progressing a breast cancer study for evorpacept and advancing ALX2004 through dose escalation. Chief Medical Officer Dr. Barbara Klencke, who recently joined as permanent CMO, reviewed clinical datasets supporting evorpacept and described early development plans for ALX2004.

Two-program strategy and recent financing

Lettmann said the company recently closed a $150 million financing, which he stated extends ALX’s cash runway through the first half of 2028 and supports upcoming clinical milestones. He described the period ahead as a “big next 18 months,” with an objective of having both programs “pivotal-ready by the end of next year.”

ALX’s primary near-term milestones include:

• ASPEN-09, a breast cancer study of evorpacept in patients who previously received Enhertu, with top-line data expectations discussed by both presenters.
• ALX2004 dose-escalation progress, with additional safety data expected in the second half of this year.

Evorpacept: CD47 blockade with an “inactive Fc” design

Lettmann described evorpacept as a differentiated approach to CD47 that “separat[es] the signaling” by delivering full CD47 blockade while using a “dead” (inactive) Fc region. He said this design aims to block the “don’t eat me” signal without engaging Fc-mediated macrophage activity, and is intended to avoid the on-target toxicities observed with conventional CD47 antibodies that attempted to use CD47 as a tumor-associated antigen. He said those conventional “active Fc” approaches have largely failed or been discontinued due to toxicity and narrow therapeutic windows.

Dr. Klencke said ALX has now presented five clinical datasets supporting evorpacept’s potential, including two in HER2-positive solid tumors and three in indolent lymphoma.

Gastric cancer data: ASPEN-06 randomized phase 2

In ASPEN-06, Dr. Klencke highlighted results in patients with gastric cancer treated in the second- and third-line setting. Patients received a backbone of trastuzumab, ramucirumab, and paclitaxel, with evorpacept added in a 1:1 randomization of 127 patients. She said that 95 patients retained HER2 positivity based on either fresh biopsy (48 patients) or ctDNA assessment, and efficacy analyses emphasized subgroups by CD47 expression.

Dr. Klencke said that in patients who both retained HER2 positivity and had CD47 overexpression, the trial showed:

• Objective response rate (ORR): 65% in the evorpacept arm versus 26% in the control arm, which she described as a roughly 40% delta.
• Duration of response: in CD47-overexpressing patients, a reported duration of response of 25.5 months (over two years).
• Progression-free survival (PFS): a hazard ratio of 0.39 in the CD47 subset, with a median PFS of 18.4 months in the CD47-high, HER2-positive group.
• Overall survival (OS): a trend favoring evorpacept, with a hazard ratio of 0.7.

She added that while the CD47-high analysis was pre-specified, the exact cutoff selection was exploratory, and that the benefit appeared consistent across multiple cut points and endpoints. On safety, she said grade 3 to 5 adverse event rates were “very consistent across the two randomized arms.” She also stated ALX has treated “over 750 patients to date” with evorpacept and has not observed the toxicity profile that led other CD47 programs to be discontinued.

Breast cancer focus: post-Enhertu and a CD47 biomarker strategy

Dr. Klencke positioned HER2-positive breast cancer after Enhertu as a key unmet need, saying that once Enhertu moved into the first-line setting, many subsequent agents have not performed as well as they did historically in patients without prior Enhertu exposure. She discussed results from a study combining evorpacept with zanidatamab (described as a bispecific anti-HER2 antibody), first presented at San Antonio in 2024, in late-line patients with a median of six prior lines of therapy.

In patients with confirmed HER2-positive status in that study, she reported an ORR of 56%. She also said ALX has completed an exploratory CD47 analysis and plans to present data in May 2026 at ESMO Breast Cancer 2026, indicating that responses were “largely restricted” to patients with CD47 overexpression, consistent with ASPEN-06.

ALX’s ongoing ASPEN-09 study is evaluating evorpacept plus trastuzumab and physician’s choice of chemotherapy in patients who are post-Enhertu. Dr. Klencke said enrollment began in January. She added that the company has increased the planned sample size from 80 to up to 120 patients, and refined the primary endpoint to report response rate in the CD47-overexpressing subpopulation, reflecting the company’s view that CD47 is a predictive biomarker based on prior studies.

ALX2004: EGFR-targeted ADC enters dose escalation

Turning to ALX2004, Dr. Klencke described the asset as an EGFR-targeted ADC built with a selected EGFR antibody intended to minimize skin toxicity and improve therapeutic window, paired with a proprietary linker and a TOPO1 payload with a drug-to-antibody ratio of eight. She said non-human primate toxicology supported starting the clinical study at 1 mg/kg, and cited a 20 mg/kg dose in monkeys as the “HNSTD” in GLP studies.

She also said the ALX2004 antibody binds a different epitope than cetuximab and panitumumab, which she suggested could have implications for skin toxicity and for resistance mutations affecting binding domains of approved EGFR antibodies. Preclinical work presented by the company included linker stability claims and evidence of a bystander effect in models, as well as dose-dependent tumor suppression and regressions across multiple in vivo models.

Clinically, she said the dose-escalation trial has advanced over the last couple of quarters, with dosing every three weeks and escalation from 1 mg/kg to 2 mg/kg and then 4 mg/kg. She said the company recently entered “dose level three” and expects to report additional safety data in the second half of the year. The trial allows only four tumor types: lung cancer, head and neck cancer, colorectal cancer, and esophageal squamous cell carcinoma, described as EGFR-overexpressing tumors.

Partnering interest, but “execution first”

In a question-and-answer session, Lettmann said the strengthened balance sheet gives ALX room to execute, while the company continues discussions with potential partners. He cited the existing collaboration with Sanofi combining evorpacept with Sarclisa in multiple myeloma as an example, and said business development opportunities exist to combine evorpacept with both approved antibodies and emerging antibodies or bispecifics. For ALX2004, he said the company has seen inbound pharmaceutical interest, and characterized safety at the right dose and an efficacy signal as key upcoming inflection points.

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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