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- 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, N.J.--(BUSINESS WIRE)-- 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.

~ Preclinical data show the utility of Gennao’s proprietary first-in-class monoclonal antibody 3E10-D31N (GMABD31N), a cell penetrating antibody, to non-covalently bind to and systemically deliver therapeutic levels of multiple types of nucleic acid payloads to cells in vitro and tumors in vivo ~ ~ GMABD31N combined with a RIG-I ligand 3pRNA (GMABD31N/3pRNA) efficiently targets and delivers a known RIG-I agonist to tumors in vivo and effectively prevents tumor growth in a mouse model of melanoma, comparable to anti-CTLA-4 ~ NEW HAVEN, Conn., April 10, 2021 (GLOBE NEWSWIRE) -- Gennao Bio, a privately-held genetic medicines company developing first-in-class, targeted nucleic acid therapeutics, today announced a late-breaking poster detailing preclinical results for its proprietary, non-viral gene monoclonal antibody (GMAB) nucleic acid delivery system. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2021. The GMAB technology platform, exclusively licensed from Yale University, utilizes a proprietary, cell-penetrating antibody to non-covalently bind to and deliver therapeutic levels of multiple types of nucleic acids, including synthetic RNA (ribonucleic acid) messenger RNA, small interfering RNA, deoxyribonucleic acids, antisense oligonucleotides and gene editing molecules. The preclinical data presented in the poster show the utility of the monoclonal antibody 3E10-D31N (GMABD31N) to deliver nucleic acids to cells in vitro and to tumors in vivo. This antibody, a modified version of 3E10, forms non-covalent complexes with RNAs and can mediate highly specific delivery broadly into tumors via intravenous injection by targeting the nucleoside transporter ENT2. ENT2 is highly expressed in multiple tumor types as well as skeletal and cardiac muscle. Studies completed with labeled RNAs and messenger RNAs expressing a green fluorescent protein reporter gene show tumor specific delivery and functional expression by imaging, with minimal delivery to healthy tissues. Cell culture studies show antibody-mediated delivery of a series of retinoic acid-inducible gene I (RIG-I) ligands, including hairpin RNAs and synthetic double-stranded RNA (poly(I:C)), resulting in robust RIG-I stimulation and induction of type-1 interferon signaling. Most importantly, when using a mouse B16 melanoma tumor model, substantial tumor growth suppression was observed upon intravenous injection of GMABD31N non-covalently bound to 3pRNA, an 89-nucleotide, single-stranded RNA. In this study, the tumor suppression observed was comparable to the tumor suppression that was observed using anti-CTLA-4. “The preclinical results presented today highlight the ability of GMABD31N to systemically deliver immunostimulatory RNAs in a targeted, non-invasive manner,” said 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. “This approach has the potential to offer new and significant treatment advantages over current delivery methods that are associated with systemic toxicity or rely on direct intra-tumoral injection, which is therapeutically sub-optimal, especially for metastatic disease. I look forward to working with Gennao Bio on the continued development of the GMAB platform to develop effective therapeutics for the treatment of oncology indications, as well as monogenic skeletal and cardiac muscle diseases.” The full abstract and poster presentation can be accessed on the AACR annual meeting website, , through June 21, 2021. About Gennao Bio Gennao Bio is a privately-held genetic medicines company developing first-in-class targeted nucleic acid therapeutics utilizing its proprietary gene monoclonal antibody (GMAB) platform technology. GMAB technology utilizes a novel, cell-penetrating antibody to non-covalently bind to and deliver therapeutic levels of a wide variety of nucleic acid payloads to select cells. This non-viral delivery platform offers significant advantages over traditional gene delivery systems as it can deliver multiple types of nucleic acids, allows for repeat dosing and dose optimization, and can be easily and affordably manufactured. Gennao Bio is developing this delivery system with an initial focus on oncology and monogenic skeletal muscle diseases. Investor and Media Contact: Gennao BioChris Duke732-735-0330cduke@gennaobio.com Source: Gennao Bio