- Study Demonstrates a Significant Increase in Overall Survival in Mice
- Robust Anti-tumor Response with No Toxicity Using EphA3 Antibody Drug Conjugate (ADC) and Radioimmunotherapy (RIT) Approaches
- Provides Evidence that Targeting EphA3 Expressing Tumor Stem Cells and Neovasculature is a Viable Therapeutic Strategy for Solid Tumors
BURLINGAME, Calif., Jan. 03, 2019 (GLOBE NEWSWIRE) -- Humanigen, Inc., (HGEN) (“Humanigen”), a biopharmaceutical company developing its portfolio of Humaneered® monoclonal antibodies focused on CAR-T optimization and immuno-oncology announced that new research was published in the December issue of the journal Cancers demonstrating that the EphA3 receptor, the novel target for the company’s proprietary monoclonal antibody ifabotuzumab, is an attractive tumor-specific target for glioblastoma multiforme (GBM) therapy. These results also suggest that ifabotuzumab may be therapeutically useful in the treatment of other solid tumors (available online at https://www.mdpi.com/2072-6694/10/12/519).
The research, led by Professors Bryan Day and Andrew Boyd from the Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute in Brisbane, Australia, used an anti-EphA3 antibody (IIIA4) which is the murine predecessor of the company’s Humaneered® ifabotuzumab. The research assessed the efficacy of the antibody drug conjugate (ADC) and a radioimmunotherapy (RIT) conjugate using orthotopic human GBM xenograft tumors in NOD/SCID mice. Positron emission tomography/computed tomography (PET/CT) imaging, showed that the anti-EphA3 antibody is effectively delivered across the blood-tumor barrier and accumulates specifically at the tumor site with no observed normal brain tissue uptake. Anti-tumor activity was observed in this immunocompromized mouse model, using an ADC comprising the cytotoxic drug maytansine or an RIT comprising the radioisotope Lutetium-177. Significant increases in overall survival (p=0.0007, n=6 for the ADC, p=0.0329, n=6 for the RIT) were observed for both types of conjugates.
Critically, the researchers showed previously that EphA3 is expressed most highly on glioma stem cells (GSCs), where EphA3 has a functional role in survival and self-renewal. In GBM, EphA3 expression has been shown to be significantly elevated in recurrent versus treatment-naïve disease. EphA3 has also been shown to be over-expressed in a number of human solid tumors. EphA3 antibody targeting has been shown to inhibit tumor growth by disrupting newly formed tumor microvasculature (neovasculature).
“Brain cancer sufferers have not seen meaningful increases in overall survival for decades,” stated Dr. Cameron Durrant, Chief Executive Officer of Humanigen. “By targeting the tumor stem cells, stromal cells and neovasculature, we believe ifabotuzumab has the potential to emerge as a next-generation oncology therapy.” A phase 1 clinical trial is currently underway using ifabotuzumab, the Humaneered® version of the anti-EphA3 targeting monoclonal antibody that was used in this study, in patients with recurrent GBM. This study is in part motivated by reports of the positive results of other ADC therapies in the treatment of GBM. An ADC which is in Phase 3 for GBM is in development by Abbvie and utilizes the cytotoxic agent monomethyl auristatin F (MMAF) combined with depatuxizumab. Efficacy has been demonstrated as both a single agent and in combination with temozolomide (TMZ). “Ifabotuzumab is being developed by the leading experts in the space, who played a critical role in the discovery and development of depatuxizumab,” continued Dr. Durrant.
About Humanigen, Inc.
Humanigen, Inc. is developing its portfolio of Humaneered® monoclonal antibodies to address cutting-edge CAR-T optimization and oncology treatments advancing safer, better, and more effective cancer therapies. Derived from the company’s Humaneered® platform, lenzilumab and ifabotuzumab are monoclonal antibodies with first-in-class mechanisms. Lenzilumab, which targets GM-CSF, is in development as a potential biologic therapy to make CAR-T therapy safer and more effective, as well as a potential treatment for hematologic cancers. Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3), is being explored as a potential treatment for glioblastoma multiforme (GBM) and other solid tumors, both as naked antibody and as part of an antibody-drug conjugate, as well as a backbone for a novel CAR-T construct, and a bispecific antibody platform. For more information, visit www.humanigen.com.
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