Anti-GPC-1 Antibodies for Therapeutics and Imaging

Our current objective is to target cancers with significant unmet needs, expediting market access for the company.

See GlyTherix Patent Estate and Peer Reviewed Publications.

Our patented antibody, Miltuximab, targets Glypican-1 (GPC-1), a protein overexpressed in prostate, pancreatic, bladder, glioblastoma, esophageal and other solid tumors. Currently, Miltuximab is in the clinical development phase.

First-in-Human Trial – MILGa

Preclinical studies have demonstrated that Miltuximab accurately targets prostate, pancreatic, and bladder cancer cells and is well-tolerated and highly specific in mouse models of prostate cancer. We completed a First-in-Human (FIH) trial in Australia using Miltuximab (ANZCTR registry).  This study evaluated the safety and tumor targeting of Miltuximab in patients with advanced prostate, bladder, and pancreatic cancer. Conducted at Macquarie University Hospital, the trial involved experts from the Australian Nuclear Science and Technology Organisation (ANSTO), AusPep, and Macquarie Medical Imaging we successfully enrolled and dosed 12 patients, with no drug-related adverse events reported.

Upcoming Investigator Initiated Trial

We are planning an Investigator Initiated Trial (IIT) to image patients with prostate and bladder cancers. This trial will test the tumor targeting of ⁸⁹Zr-Miltuximab and the effect of antibody mass dose (low or high). The trial will recruit 8 prostate and 8 bladder cancer patients across two sites. Data from this IIT will inform the final design of a planned Phase 1b theranostic study involving 24 patients. Selected candidates will undergo PET imaging with ⁸⁹Zr-Miltuximab before being dosed with the therapeutic version, ¹⁷⁷Lu-Miltuximab.

Schematic showing IIT trial using ⁸⁹Zr-Miltuximab:

Planned Phase-1b Trial

Data obtained from the IIT will inform a Phase 1b trial involving 24 patients with prostate and bladder cancer. This trial design includes potential expansions for both patient numbers and disease indications.

Phase 1b – Time from First to Last Patient – 10 Months

Development of Glytuzumab

Glytuzumab is the humanized version of Miltuximab, also targeting human GPC-1. The Glytuzumab program is currently in the Lead Optimization and Lead Selection stages. Several humanized leads with similar binding affinities to Miltuximab have been generated. The final Glytuzumab lead will progress from cell line development to large-scale GMP production for future clinical trials.

Total Addressable Market (Global) – Lead Indications

Global Research Collaborations

GlyTherix’s collaborations are advancing trials of cancer therapeutics and imaging, as well as building a future product pipeline. Key collaborations include:

2024-2029: The ARC Hub for Advanced Manufacture of Targeted Radiopharmaceuticals, AMTAR (University of Queensland) https://www.amtarhub.com.au/

2024-2029: ARC Training Centre for Radiochemical Technologies and Precision Radiopharmaceuticals, DART (Monash University)

2018-2023: The Centre for Advanced Imaging at the University of Queensland

2015-2018: Australian Prostate Cancer Research Centre at the Queensland University of Technology

Comparison of PSMA and GPC-1 Technologies Useful in Prostate Cancer Diagnosis and Therapy

The success of an antibody therapeutic relies on its specific expression in tumor, with limited or no expression in normal tissue. In prostate cancer, Prostate Specific Membrane Antigen (PSMA) has been targeted clinically for both imaging and therapy. Overexpressed in the prostate tumors of some individuals, it has allowed successful imaging using ⁶⁸Ga-PSMA-PET and therapy using ¹⁷⁷Lu-PSMA or ¹⁷⁷Lu-J591. However, not all patients tumors express PSMA, leaving 10-30% of patients with late stage metastatic disease who do not respond to PSMA-directed therapy.

Moreover, PSMA is not only expressed in tumor tissue, but is also expressed in a variety of normal tissues. Immunohistochemistry studies have shown PSMA to be expressed in the kidney, testis, ovary, brain, salivary gland, small intestine, lacrimal glands, colon, liver, spleen, breast, skeletal muscle and benign fractures, as well as malignancies of these tissues (Farag et al, 2020), which means that targeting PSMA using radiation leads to exposure of normal tissue to radiation and subsequent tissue damage and associated side effects.

Glypican-1 is a new tumor targeting molecule that is expressed in a variety of deadly solid tumors of high unmet need (including prostate, brain, bladder, esophageal, pancreas, mesothelioma and cervical). What makes Glypican-1 such a promising therapeutic target is its lack of expression in normal tissue (confirmed by the FIH clinical trial completed with Miltuximab). Moreover, targeting of Glypican-1 with antibody therapeutics has proven completely safe in numerous animal studies, as well as the human study of Miltuximab.

Clinically, GPC-1 is a particularly exciting target, as expression of GPC-1 has been associated with poor clinical prognosis and aggressive tumors, in several solid tumors including pancreatic, esophageal and glioblastoma. Furthermore, we have evidence to suggest potential synergy between GPC-1 directed therapy and standard of care therapies such as chemotherapy and radiotherapy.

Read more about PSMA and GPC-1 Technologies.