8-K: ALX Oncology's Evorpacept Shows Predictive Biomarker in Breast Cancer

ALX Oncology announced new clinical data showing CD47 expression predicts evorpacept activity in HER2-positive metastatic breast cancer, alongside preliminary cash estimates.

Summary

• New data from a Phase 1b/2 clinical trial evaluating ALX Oncology's investigational CD47-inhibitor evorpacept in combination with Jazz Pharmaceuticals' ZIIHERA (zanidatamab-hrii) in heavily pretreated patients with metastatic breast cancer (mBC) was announced.
• Topline findings from an exploratory analysis indicate that among patients with confirmed HER2-positive mBC, CD47 expression is predictive of evorpacept activity.
• This finding reinforces results from the ASPEN-06 clinical trial, which demonstrated CD47 expression as a predictive biomarker for response and durable benefit from evorpacept in advanced HER2-positive gastric cancer.
• Primary trial results, presented at the 2024 San Antonio Breast Cancer Symposium (SABCS), showed a 56% (5/9) confirmed objective response rate (cORR) and a median progression-free survival (mPFS) of 7.4 months in nine patients with centrally confirmed HER2-positive breast cancer who received the investigational combination, including those treated with ENHERTU.
• Preliminary unaudited estimates indicate approximately $48.3 million in cash and cash equivalents and short-term and long-term investments as of December 31, 2025.

Sentiment

Score: 7

Explanation: StockSavvy.ai views this as a moderately positive update, primarily driven by the promising clinical data and the identification of a predictive biomarker, which could enhance the drug's development pathway. The preliminary cash position provides a snapshot but is unaudited.

Positives

• CD47 expression has been identified as a predictive biomarker for evorpacept activity in HER2-positive metastatic breast cancer, which could optimize patient selection for evorpacept combinations with HER2-targeted agents.
• The evorpacept/zanidatamab combination demonstrated promising anti-tumor activity with a 56% confirmed objective response rate (cORR) and a median progression-free survival (mPFS) of 7.4 months in heavily pretreated HER2-positive mBC patients.
• The positive biomarker findings reinforce confidence in the ongoing ASPEN-09-Breast Phase 2 trial and support a CD47-dependent, HER2-driven biology for evorpacept.

Negatives

• The preliminary financial estimates for cash and investments are unaudited, subject to change, and do not present all information necessary for a complete understanding of the company's financial position.

Risks

• Forward-looking statements, including preliminary financial estimates, involve substantial risks and uncertainties.
• Actual results, performance, or achievements may be materially different from those expressed or implied by forward-looking statements due to known and unknown risks.
• These risks are described more fully in the company's filings with the Securities and Exchange Commission (SEC), including Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q.

Future Outlook

The company believes a biomarker-driven approach incorporating CD47 expression may optimize patient selection for evorpacept combinations with HER2-targeted agents. The positive data from this trial and ASPEN-06 reinforce confidence in the ongoing ASPEN-09-Breast Phase 2 trial. The full biomarker analysis from the Phase 1b/2 clinical trial has been submitted to an upcoming scientific congress for presentation.

Management Comments

• "These new findings support a CD47-dependent, HER2-driven biology for evorpacept."
• "Going forward, we believe that a biomarker-driven approach incorporating CD47 expression may optimize patient selection for evorpacept combinations with HER2-targeted agents."
• "Additionally, taken together, the data from this trial and the ASPEN-06 clinical trial reinforce our confidence in the ongoing ASPEN-09-Breast Phase 2 trial."

Industry Context

StockSavvy.ai notes that the identification of CD47 as a predictive biomarker for evorpacept activity in HER2-positive metastatic breast cancer is a significant development in precision oncology. This aligns with a broader industry trend towards personalized medicine, where patient selection based on specific biomarkers can improve treatment efficacy and reduce unnecessary exposure to therapies. The reinforcement of this biomarker finding across multiple trials (mBC and gastric cancer) strengthens the potential for evorpacept in HER2-driven cancers, positioning ALX Oncology to potentially differentiate its therapy in a competitive landscape that includes established HER2-targeted agents.

Comparison to Industry Standards

• The trial involved heavily pretreated patients, including those who had received ENHERTU, a highly effective HER2-targeted antibody-drug conjugate (ADC) from Daiichi Sankyo and AstraZeneca. Achieving a 56% cORR and 7.4 months mPFS in this refractory population suggests a meaningful clinical benefit for the evorpacept/zanidatamab combination.
• The identification of CD47 as a predictive biomarker, reinforcing findings from the ASPEN-06 trial in HER2-positive gastric cancer, suggests a consistent mechanism of action and potential for a biomarker-driven strategy, similar to how HER2 status guides treatment selection for drugs like Herceptin (trastuzumab) or Perjeta (pertuzumab).

Stakeholder Impact

• Shareholders: Positive clinical data and biomarker identification could increase investor confidence and potentially lead to share price appreciation. Preliminary cash position provides transparency on liquidity.
• Patients: The identification of a predictive biomarker could lead to more targeted and effective treatment options for heavily pretreated HER2-positive metastatic breast cancer patients.
• Medical Community: The data contributes to the understanding of CD47 inhibition and its role in HER2-driven cancers, potentially influencing future treatment guidelines and research.

Next Steps

• The full biomarker analysis from the Phase 1b/2 clinical trial has been submitted for presentation at an upcoming scientific conference.
• Continuation of the ongoing ASPEN-09-Breast Phase 2 trial.

Key Dates

Recommendation

The positive clinical data and the identification of a predictive biomarker for evorpacept are encouraging, suggesting a clearer development path and potential for improved patient outcomes. However, the financial data is preliminary and unaudited, and the company remains clinical-stage with inherent risks associated with drug development. While the clinical progress is a strong positive, a 'hold' recommendation is prudent given the early stage of the biomarker-driven approach and the need for further validation in larger trials, balancing the upside potential with ongoing development risks.

Keywords

ALX Oncology, ALXO, Evorpacept, CD47 inhibitor, Metastatic Breast Cancer, HER2-positive, Zanidatamab, ZIIHERA, Biomarker, Clinical Trial, Oncology, Biotechnology, Cancer Therapy, Drug Development, Phase 1b/2, Cash Position