By Joe C. Loy, President & CEO
On September 17, Zetagen Therapeutics held our 2026 Annual Shareholders Meeting, bringing together shareholders, members of our Board of Directors, Clinical Advisors board, business leaders, and representatives of the financial community.
The annual meeting is one of the most important moments on our calendar. It gives me the opportunity to step back from the daily demands of drug development, review the progress our team has made, and remain accountable to the shareholders who have supported Zetagen’s vision.
This year’s discussion focused on the continued advancement of our preclinical and clinical-stage breast oncology platform, which is designed to bring therapy directly to the site of disease. Across our pipeline, we remain focused on a central principle: “Treating Cancer Where it Lives”.
Zetagen’s zeta-platform is built around our proprietary carriers engineered for specific anatomical environments and designed to modulate the opioid growth factor receptor (OGFR), a nuclear receptor associated with cell-growth regulation. The therapies are administered through a single intratumoral injection. By delivering therapy directly to the site of disease, our goal is to concentrate therapeutic activity within the tumor microenvironment, thereby ceasing tumor activity while minimizing unnecessary systemic exposure. The core benefit of this approach is that it is designed to avoid first-pass metabolism, reduce variability in therapeutic efficacy, limit the severe off-target toxicity associated with systemic delivery, and exert tumoricidal effects on cancer cells.
During the meeting, we reviewed progress across three breast oncology programs: ZetaMet™, our lead clinical-stage program for the treatment of breast cancer bone metastases involving lytic bone lesions; ZetaMAST™, which is being developed for unresectable, multifocal breast cancer metastases to the liver; and ZetaPrime™, which is being developed as an adjunctive treatment for primary breast cancer at the time of diagnosis.
In case you missed it, here are several key highlights.
ZetaMet is Zetagen’s lead clinical-stage drug program addressing a significant unmet need for breast cancer patients with bone metastases. Current standard-of-care treatments are primarily palliative, while ZetaMet is demonstrating promising results in ceasing tumor activity that causes skeletal destruction and promoting bone regrowth. This approach has demonstrated the potential to prevent skeletal-related events (SREs) and vertebral fractures, which are associated with shortened overall survival. Bone metastases can create severe clinical consequences and patient burden, including pain, loss of mobility, structural bone damage, fracture risk, and SREs.
ZetaMet is designed to deliver a therapeutic directly to metastatic breast cancer lesions within bone through a single intratumoral injection. This localized approach is intended to produce tumoricidal activity at the site of disease, while also addressing the destructive tumor-bone cycle. In bone, the mechanism is designed to suppress osteoclast-mediated bone degradation while also supporting osteoblast-mediated new bone formation (osteoinduction) within previously lytic lesions.
At the time of our 2025 Annual Shareholders Meeting, the Phase 2a study of ZetaMet was still ongoing, and we had access to only a subset of the data. Today, the study is complete, and Zetagen presented the results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study observations included, for every lesion treated:
These findings build on peer-reviewed publications of clinical observations from earlier compassionate-use patients, including Colleen Connor, the first patient treated with ZetaMet and the namesake of our research laboratory. The consistency we have observed from preclinical research through compassionate use and Phase 2a clinical development continues to strengthen our confidence in ZetaMet and in the broader scientific platform supporting our pipeline.
Zetagen is not a one-asset company. Our current pipeline includes three investigational breast oncology programs supported by a common scientific foundation: intratumoral administration, localized concentration control, proprietary carrier engineering, and OGFR modulation.
Zetagen’s platform is not based on a single universal carrier, because different anatomical environments create different delivery and biologic challenges. A cancerous lesion in bone is not the same as a tumor in the liver or breast tissue. Each environment requires a formulation strategy designed around where the disease occurs, how the compound is retained, and how it is released at the intended local concentration.
This is central to Zetagen’s platform strategy. The therapeutic compound is important, but so is the delivery system that enables it to reach, remain, and act at the site of disease.
ZetaMast™ is being developed for the treatment of breast cancer liver metastases, including unresectable, multifocal disease. With required nonclinical GLP studies complete, Zetagen is preparing to submit an IND to the FDA for ZetaMast by the end of 2026. Pending FDA acceptance, ZetaMast will enter a Phase 1A dose-escalation study, anticipated to begin in 1H-2027.
Because ZetaMast is designed as a fixed-dose drug, this dose escalation safety study may provide early information about therapeutic efficacy activity. Reaching this milestone would give Zetagen a second pipeline candidate generating human data and would further demonstrate how the company’s intratumoral platform can be applied beyond breast cancer bone metastases.
ZetaPrime, also known as Zeta-PBC-007, is Zetagen’s investigational program focused on primary HR-positive/HER2-negative breast cancer. It is being developed as a neoadjuvant treatment designed for intratumoral administration following diagnosis. The program uses a proprietary hydrogel-like lipid carrier specifically designed for the fatty tissue of the breast.
During the Annual Shareholders Meeting, we reviewed findings from our most recently completed ZetaPrime (3) Efficacy Study III, which showed that a single dose of ZetaPrime 3:
These findings are particularly encouraging because they suggest that an intratumoral injection of ZetaPrime at time of diagnosis may potentially be tumoricidal to the proximal breast cancer cells as well as the circulating tumor cells in the body.
Preclinical findings in oncology are often viewed with caution because many therapies that appear promising in in vivo mouse models do not produce the same results in people. Zetagen understands that history. We also believe our approach presents a different translational logic.
As our understanding of the OGFR nuclear receptor’s response to our small molecule continues to deepen, we believe the consistency observed across ZetaMet’s preclinical and clinical development provides important context for the broader Zeta-platform. Because Zetagen’s approach, utilizing the same core compound through the zeta-platform, combines a targeted biologic pathway with intratumoral administration and controlled local concentration, preclinical models may provide more meaningful insight than traditional systemic oncology models, where metabolism, systemic distribution, and off-target exposure can introduce additional variability.
This translational rationale does not replace the need for rigorous clinical research. It does, however, provide important context for why we are continuing to advance ZetaMast and ZetaPrime while moving ZetaMet towards regulatory approval.
We are equally proud of the discipline with which Zetagen has reached this point. During the first nine months of 2026, the company maintained an average monthly burn rate of approximately $310,000 while advancing three breast oncology programs and continuing to build the scientific, regulatory, manufacturing, and intellectual property foundation needed to support the platform.
Drug development requires scientific conviction, but it also requires focus, capital efficiency, and the ability to make the right decisions at the right time. Zetagen has remained lean by design, deploying capital carefully while prioritizing the milestones that we believe create the greatest scientific and shareholder value. This disciplined approach has been supported by the company’s financing progress, including an oversubscribed Series B1 financing that has helped accelerate development of the Zetagen platform.
Zetagen is also seeing strong strategic interest as we evaluate potential commercialization pathways for our therapies. These conversations remain confidential, and we look forward to sharing additional information when appropriate.
Breast cancer remains our immediate focus, but our vision extends beyond this to other cancers associated with OGFR. Our primary compound, delivered via our proprietary carriers, may have the potential to support future investigational programs in additional oncology indications, including colorectal, lung, glioblastoma, prostate, and pancreatic cancers.
We have entered Q4 with completed Phase 2a data for ZetaMet, ZetaMast moving toward a planned IND submission in late 2026, beginning a Phase 1 study in the first half of 2027 pending FDA clearance, and ZetaPrime advancing on the strength of encouraging findings from its recently completed third preclinical efficacy study.
To our shareholders, Board members, scientific collaborators, clinical partners, employees, and broader Zetagen community: thank you for your continued confidence and support. Your trust has allowed us to advance this work with urgency, discipline, and purpose.
We remain focused on “treating cancer where it lives”, creating long-term value for the shareholders who have made this work possible, and developing new therapeutic approaches for patients who need better options.
Listen to the 2026 Annual Shareholders Meeting recording HERE.
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