Zetagen Therapeutics Presents Phase 2a Results at ASCO for Investigational ZetaMet™ (Zeta BC 003) in Metastatic Breast Cancer Patients with Lytic Bone Lesions

• A single intratumoral injection resulted in no reported skeletal‑related events (SREs) or fractures
• No treatment‑emergent adverse events (AEs) or serious adverse events (SAEs)
• Cessation of tumor activity, along with reduction in pain scores, and opioid consumption
• Therapeutic effect observed in adjacent, non‑injected lesions within the treated vertebral body

AUSTIN, Texas--(BUSINESS WIRE)--Zetagen Therapeutics, a clinical‑stage biopharmaceutical company developing novel therapies for primary and metastatic breast cancer, today announced preliminary topline results from its Phase 2a clinical study evaluating ZetaMet™ (Zeta BC 003) in subjects with metastatic breast cancer (MBC) with lytic bone lesions.

In this open‑label study, no skeletal‑related events (SREs) or fractures were observed, no treatment‑emergent adverse events (AEs) or serious adverse events (SAEs) were reported, and cessation of tumor activity was noted in treated vertebral bodies. Zeta BC 003 is an investigational product that has received Breakthrough Designation from the U.S. Food and Drug Administration (FDA) and has not been approved by the FDA or any regulatory authority.

“We are encouraged by the preliminary findings from this Phase 2a study, which provide important clinical observations on the investigational use of ZetaMet™ in patients with metastatic breast cancer involving bone,” said Joe C. Loy, President & CEO of Zetagen Therapeutics. “These results also highlight a major achievement for our team, overcoming longstanding industry challenges in intratumoral administration by developing proprietary carriers which deliver compounds that demonstrate solubility and localized bio‑adhesion.”

The preliminary findings were presented by Dr. Bryan Margulies, Chief Scientific Officer, and Joe C. Loy, President & CEO, at the American Society of Clinical Oncology (ASCO) Annual Meeting on Monday, June 2, 2026. Abstract: https://doi.org/10.1200/JCO.2026.44.16_suppl.589

Study Overview
The open‑label Phase 2a study (ZGMBC; NCT05280067), conducted at the University of British Columbia, enrolled 10 subjects with a mean age of 52, representing multiple MBC subtypes:

• HR+ (n=6)
• HR+/HER2+ (n=2)
• HER2+/HR– (n=1)
• TNBC (n=1)

Five subjects had breakthrough lytic lesions despite prior bisphosphonate therapy. One subject died due to pleural edema, unrelated to study treatment. Across the 10 subjects, 11 target lesions received a single intratumoral injection of Zeta BC 003 under sedation. Four adjacent, non‑injected lesions were also evaluated.

Study Context
Historical literature reports SRE rates of approximately 53% (Parke et al., Journal Oncologist, 2018) in metastatic breast cancer with bone involvement under conventional therapy, with SREs, particularly fractures, associated with a reduction in overall survival of approximately 4.8 months (Saad et al., Journal of the National Cancer Institute, 2004).

Observed Study Findings

• No SREs or fractures reported
• Cessation of tumor activity within treated vertebral bodies
• Therapeutic spread observed to adjacent, untreated lesions within the same vertebral body
• No treatment‑emergent AEs or SAEs
• Mean bone defect volume decreased 65.4% at Day 84 (±20.5%; p=0.0003)
• Mean bone defect volume decreased 84.1% at Day 180 (±13.1%; p<0.0001)
• Pain scores (NRS) decreased by 4.16 points (p<0.05)
• Opioid use (MED) decreased 33–67% among opioid‑treated subjects
• Spinal stability (SINS) improved 18.5% (p<0.05)
• Quality of life improved:
  • PCS increased 24.2%
  • MCS increased 12.1%

While cross‑study comparisons have inherent limitations, the absence of AEs and SREs in this Phase 2a study provides supportive information for continued investigation.

These observations are also consistent with two published Expanded Access case reports (seven lesions, 2‑year follow‑up; Palma et al., Pain Management, 2023), which similarly demonstrated absence of SREs, cessation of tumor activity, neo‑trabecular bone formation, and therapeutic spread within treated vertebral bodies.

Acknowledgment of Clinical Partners
Zetagen Therapeutics acknowledges and extends its appreciation to the University of British Columbia, Nor Consult, LLC (NorCo), and Medical Medics Incorporated for their contributions to the ZetaMet™ clinical study. NorCo provided comprehensive clinical operations support, and Medical Medics delivered centralized imaging services that enabled rigorous data quality and standardized imaging assessments throughout the trial.

About ZetaMet™ (Zeta BC 003)
ZetaMet™ is designed for single intratumoral administration into lytic bone lesions associated with metastatic breast cancer. Preclinical and clinical studies suggest the potential for ZetaMet™ to cease lytic activity, reducing pain, initiating bone healing, and prevent SREs; however, ZetaMet™ has not been approved by the FDA or any regulatory authority.

About Zetagen Therapeutics
Zetagen Therapeutics is a clinical‑stage biopharmaceutical company focused on developing novel therapies for primary and metastatic breast cancer. The company’s “Zeta”‑platform is designed to address historical challenges in intratumoral delivery through our proprietary carriers and NMEs to support compound solubility and localized bio‑adhesion, with the goal of minimizing off‑target toxicity.

Forward‑Looking Statements
This press release contains certain forward-looking statements with the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company’s product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management’s current beliefs and assumptions.