ALX Oncology Targets Key Readouts to Advance CD47, EGFR Cancer Drug Programs

Key Points

• ALX Oncology expects key data readouts in the coming months for its lead CD47 drug evorpacept and its EGFR-targeted ADC ALX2004, with management hoping both programs can advance toward later-stage, registrational trials by the end of next year.
• The company is focused on a CD47 biomarker-driven strategy, especially in HER2-positive breast cancer after ENHERTU, where it aims for ASPEN-09 results strong enough to support a potential Phase 3 study in CD47-high patients.
• ALX2004 is being positioned as a differentiated EGFR ADC, and the next clinical update later this year will mainly assess safety and doseability as the company looks for signs it can reach a therapeutic range without major EGFR-related toxicities.

ALX Oncology NASDAQ: ALXO executives said the company is focused on advancing two clinical-stage oncology programs, with upcoming data readouts expected to shape potential later-stage development plans for its lead CD47 program, evorpacept, and its EGFR-targeted antibody-drug conjugate, ALX2004.

Speaking at the Jefferies 2026 Global Healthcare Conference, Jason Lettmann, chief executive officer of ALX Oncology, said the company is coming off “a strong ASCO” and has gained momentum over the past several months. He said ALX has been working on CD47 for close to a decade and believes recent clinical findings support the company’s original approach to the target.

Lettmann said evorpacept is designed to block the “don’t eat me” signal used by cancers to evade the immune system while using an Fc active antibody to drive an “eat me” signal, leading to targeted phagocytosis against tumors. He said that approach has now been reflected in five clinical data sets.

“The other thing that’s become very clear is that CD47 is also a very strong and predictive biomarker,” Lettmann said, citing data in HER2-positive breast cancer and HER2-positive gastric cancer. He said that shift has moved the company toward what it views as a targeted oncology strategy focused on patients whose tumors overexpress CD47.

ASPEN-09 Aims to Refine CD47 Biomarker Strategy

Much of the discussion centered on ASPEN-09, a Phase 2, single-arm study in HER2-positive breast cancer patients who previously received ENHERTU. Barbara, an ALX Oncology participant in the discussion, said the post-ENHERTU setting remains an area of significant unmet need, pointing to real-world data sets showing response rates of about 15% and progression-free survival of roughly four months after ENHERTU.

Barbara said the company would like to see results in ASPEN-09 that are “well above the comparator,” adding that a response rate of about 30% and progression-free survival of about six months would create a meaningful basis for a potential future Phase 3 study.

Lettmann highlighted prior data in HER2-positive gastric cancer, where he said ALX observed a roughly 40% overall response rate difference versus control in a randomized setting. He also cited recent ESMO Breast data in which five of five patients in a combination study with zanidatamab responded, including one complete response.

“Perhaps most encouraging is the durability,” Lettmann said, pointing to duration of response of roughly 20 months and progression-free survival of more than two years in the gastric study.

Barbara said ASPEN-09 is enrolling all comers and testing retrospectively for CD47 levels in order to identify an optimal cutoff for future studies. She said ALX envisions a Phase 3 study that would enroll only CD47-high patients. The company is also working with Ventana, part of Roche Diagnostics, on a companion diagnostic.

Lettmann said ALX is guiding toward data from 80 patients around mid-year next year and expects to use those results to engage with the U.S. Food and Drug Administration about a potential Phase 3 design. He said a pivotal study could resemble ASPEN-09, evaluating evorpacept plus trastuzumab and chemotherapy against a trastuzumab-chemotherapy comparator.

ALX2004 Positioned as Differentiated EGFR ADC

The company also discussed ALX2004, its investigational EGFR-targeted antibody-drug conjugate. Lettmann said EGFR is a well-validated oncology target but remains “not yet cracked” for ADC development, with no approved EGFR ADC and limited late-stage development in the field.

He said ALX2004 uses matuzumab as its antibody epitope, which he described as distinct from other bispecifics and ADCs that often use cetuximab-based binding. Lettmann said matuzumab was originally developed by Merck Serono with the goal of avoiding on-target toxicities associated with cetuximab and panitumumab.

“By applying a different epitope, we believe we’re going to have a unique advantage there,” Lettmann said.

He also said ALX spent time optimizing the linker-payload construct and is using a Topo1 payload, a class he described as the best-established payload for ADCs. In preclinical work, Lettmann said the company did not see traditional skin-related issues or interstitial lung disease associated with the payload in non-human primate studies.

In the clinic, ALX2004 is being evaluated in a Phase 1 dose-escalation study. Lettmann said the company began dosing patients in August, starting at dose level one and escalating through two and four, with dosing now beyond four. He said ALX expects dose levels of four and above to enter the therapeutic window based on comparisons with other ADCs.

Safety Update Expected Later This Year

Barbara said the Phase 1 study is restricted to four tumor types with high EGFR expression: head and neck cancer, esophageal squamous cell cancer, non-small cell lung cancer and colorectal cancer.

Lettmann said the next update, expected later this year, will focus primarily on safety. Key questions include whether ALX2004 can be dosed into a therapeutic range without high rates of interstitial lung disease, significant diarrhea or gastrointestinal toxicity, or skin and rash toxicities associated with EGFR.

He added that signs of activity would also be important, though the current study includes relatively late-line patients across the four tumor types. Lettmann said ALX hopes to provide data from “10, 15 or more” patients and expects a mix of tumor types, with particular interest in head and neck cancer and lung cancer.

Looking ahead, Lettmann said the company’s strategy for ALX2004 is to identify the right dose and then move quickly into backfill and expansion cohorts, including settings relevant to potential Phase 3 development such as second-line head and neck cancer and second-line lung cancer.

Cash Runway Extends Into Mid-2028

Lettmann said ALX is well capitalized after raising $150 million in February and had about $170 million in cash as of the last quarter. He said that funding is expected to last well into mid-2028.

“Ideally, our internal goal is to have two programs that are ready for randomized registrational grade trials by the end of next year,” Lettmann said.

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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