– GMAB ADC demonstrated highly targeted delivery to tumor cells and durable tumor regression in preclinical model of colorectal cancer –
– Results presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024 –
HOPEWELL, NJ, USA I April 09, 2024 I Gennao Bio, a privately held genetic medicines company developing first-in-class, targeted nucleic acid therapeutics, today announced new preclinical results on the application of its non-viral, cell penetrating gene monoclonal antibody (GMAB) platform technology as an antibody-drug conjugate (ADC) for the treatment of solid tumors. The data were presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024.
Exploratory research evaluating GMAB’s ability to deliver conjugated cytotoxic payloads was conducted through Gennao’s ongoing collaboration with the laboratory of Peter M. Glazer, M.D., Ph.D., Chair of the Department of Therapeutic Radiology, Professor of Genetics and Robert E. Hunter Professor of Therapeutic Radiology at the Yale School of Medicine and co-founder of Gennao. In preclinical studies, our GMAB technology demonstrated selective delivery of payloads into tumors by targeting ENT2, a nucleoside transporter that is highly overexpressed in many tumors. ENT2 overexpression on both the plasma and nuclear membranes allows GMAB targeted therapies to internalize directly into the cytoplasm of tumor cells avoiding the endocytic pathway and traffic directly into the nucleus. In vitro studies of the GMAB ADC conjugated to exatecan, a potent topoisomerase I inhibitor, exhibited nuclear localization and activation of the DNA damage response pathway leading to tumor cell death.
“The safe targeted delivery of cytotoxic drugs continues to be a challenge for the development of new ADCs. Leveraging GMAB as an ADC represents a highly differentiated approach to the delivery of drugs exclusively to tumors while avoiding harmful impact to healthy tissue. In preclinical studies, chronic treatment of the GMAB ADC demonstrated significant tumor regression and was well tolerated, providing support for the continued investigation of this novel delivery platform as an ADC,” said Dr. Glazer.
In a preclinical study utilizing the DLD1 BRCA2 gene knockout xenograft mouse model of colorectal cancer, two aggressive systemic dosing regimens of the GMAB ADC were compared to exatecan alone and control. The GMAB ADC demonstrated durable tumor regression and a significant survival benefit compared to control and exatecan alone. Safety analyses showed no change in body weight throughout treatment and no change in blood chemistry markers indicative of no kidney or liver toxicity. Further, since ENT2 is also expressed in skeletal muscle, serum chemistry and analysis of muscle tissue sections demonstrated no indication of tissue damage to muscle.
“These preclinical results reinforce the versatility of the GMAB platform and its ability to deliver therapeutic payloads beyond genetic medicine to targeted tissue,” Chris Duke, chief executive officer of Gennao. “Additional in vivo studies are planned through our collaboration with Yale to further optimize the GMAB ADC approach. The ability to leverage a novel antigen target, combined with GMAB’s unique biology, offers the potential to create promising novel, first-in-class treatment options for individuals living with cancer.”
About Gennao Bio
Gennao Bio is a genetic medicines company developing first-in-class targeted nucleic acid therapeutics utilizing its proprietary, non-viral gene monoclonal antibody (GMAB) platform technology. GMAB is an adaptive technology that uses a novel, cell-penetrating antibody to specifically deliver nucleic acid payloads to select cells while distinctly avoiding the endocytic pathway. This next-generation delivery platform is differentiated from traditional gene delivery systems, as it can rapidly and efficiently deliver multiple types of payloads for release in the cytoplasm and nucleus, allows for repeat dosing, and employs well-established antibody manufacturing processes. Gennao Bio is developing this delivery system with an initial focus on addressing significant unmet needs in skeletal muscle diseases and oncology.
SOURCE: Gennao Bio
Post Views: 630
– GMAB ADC demonstrated highly targeted delivery to tumor cells and durable tumor regression in preclinical model of colorectal cancer –
– Results presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024 –
HOPEWELL, NJ, USA I April 09, 2024 I Gennao Bio, a privately held genetic medicines company developing first-in-class, targeted nucleic acid therapeutics, today announced new preclinical results on the application of its non-viral, cell penetrating gene monoclonal antibody (GMAB) platform technology as an antibody-drug conjugate (ADC) for the treatment of solid tumors. The data were presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024.
Exploratory research evaluating GMAB’s ability to deliver conjugated cytotoxic payloads was conducted through Gennao’s ongoing collaboration with the laboratory of Peter M. Glazer, M.D., Ph.D., Chair of the Department of Therapeutic Radiology, Professor of Genetics and Robert E. Hunter Professor of Therapeutic Radiology at the Yale School of Medicine and co-founder of Gennao. In preclinical studies, our GMAB technology demonstrated selective delivery of payloads into tumors by targeting ENT2, a nucleoside transporter that is highly overexpressed in many tumors. ENT2 overexpression on both the plasma and nuclear membranes allows GMAB targeted therapies to internalize directly into the cytoplasm of tumor cells avoiding the endocytic pathway and traffic directly into the nucleus. In vitro studies of the GMAB ADC conjugated to exatecan, a potent topoisomerase I inhibitor, exhibited nuclear localization and activation of the DNA damage response pathway leading to tumor cell death.
“The safe targeted delivery of cytotoxic drugs continues to be a challenge for the development of new ADCs. Leveraging GMAB as an ADC represents a highly differentiated approach to the delivery of drugs exclusively to tumors while avoiding harmful impact to healthy tissue. In preclinical studies, chronic treatment of the GMAB ADC demonstrated significant tumor regression and was well tolerated, providing support for the continued investigation of this novel delivery platform as an ADC,” said Dr. Glazer.
In a preclinical study utilizing the DLD1 BRCA2 gene knockout xenograft mouse model of colorectal cancer, two aggressive systemic dosing regimens of the GMAB ADC were compared to exatecan alone and control. The GMAB ADC demonstrated durable tumor regression and a significant survival benefit compared to control and exatecan alone. Safety analyses showed no change in body weight throughout treatment and no change in blood chemistry markers indicative of no kidney or liver toxicity. Further, since ENT2 is also expressed in skeletal muscle, serum chemistry and analysis of muscle tissue sections demonstrated no indication of tissue damage to muscle.
“These preclinical results reinforce the versatility of the GMAB platform and its ability to deliver therapeutic payloads beyond genetic medicine to targeted tissue,” Chris Duke, chief executive officer of Gennao. “Additional in vivo studies are planned through our collaboration with Yale to further optimize the GMAB ADC approach. The ability to leverage a novel antigen target, combined with GMAB’s unique biology, offers the potential to create promising novel, first-in-class treatment options for individuals living with cancer.”
About Gennao Bio
Gennao Bio is a genetic medicines company developing first-in-class targeted nucleic acid therapeutics utilizing its proprietary, non-viral gene monoclonal antibody (GMAB) platform technology. GMAB is an adaptive technology that uses a novel, cell-penetrating antibody to specifically deliver nucleic acid payloads to select cells while distinctly avoiding the endocytic pathway. This next-generation delivery platform is differentiated from traditional gene delivery systems, as it can rapidly and efficiently deliver multiple types of payloads for release in the cytoplasm and nucleus, allows for repeat dosing, and employs well-established antibody manufacturing processes. Gennao Bio is developing this delivery system with an initial focus on addressing significant unmet needs in skeletal muscle diseases and oncology.
SOURCE: Gennao Bio
Post Views: 630
