- Long-lasting in vivo antibody production: DMAb levels remained stable for 72 weeks in all participants (n=24) who have reached that timepoint
- No anti-drug antibodies (ADA): no immune rejection of the DMAbs was detected across ~1,000 blood samples, unlike other gene-based antibody delivery approaches where ADA formation has been a challenge
- Well-tolerated: most common side effects were mild, temporary injection site reactions such as pain and redness; no serious adverse events (SAEs) related to study drug
- Effective target binding: expressed DMAbs successfully bound to the SARS-CoV-2 Spike protein receptor-binding domain (RBD), confirming functional activity through week 72
PLYMOUTH MEETING, PA, USA I March 13, 2025 I INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced promising interim results from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19. In the trial, 100% (24/24) of participants who have reached week 72 maintained biologically relevant levels of DMAbs, confirming the durability of in vivo antibody production. Notably, no participant developed anti-drug antibodies (ADA), a common challenge observed in other gene-based delivery platforms, such as adeno-associated virus (AAV) mediated antibody expression. Additionally, the DMAbs were well tolerated, with the most common side effects being mild, temporary injection site reactions, such as pain and redness. The trial is being led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the Perelman School of Medicine at the University of Pennsylvania.
“This study provides the first clinical proof-of-concept that DNA-encoded monoclonal antibodies can be durably and tolerably expressed in humans,” said David B. Weiner, Ph.D, Executive Vice President of The Wistar Institute and lead investigator for the study. “These findings could represent a breakthrough as they demonstrate the potential of DMAb technology to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses, making it a promising platform for a broad range of diseases. This technology has the potential to transform treatments for infectious diseases, as well as cancer and metabolic disorders by enabling long-term expression of therapeutic antibodies and other proteins.”
“One of the biggest hurdles for gene-based antibody delivery has been the immune system’s response to the vector or the antibody itself, leading to anti-drug antibodies that can limit how long a treatment will be effective,” said Pablo Tebas, M.D., a professor of Infectious Diseases at Penn. “Our DNA-based approach has demonstrated sustained antibody expression without generating ADA. And because antibodies are remaining active for longer, our approach may be a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery.”
INOVIO’s Chief Scientific Officer, Laurent Humeau, Ph.D. added: “We believe these data highlight the potential to apply our DNA Medicines technology to deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins. We’d like to thank our partners in advancing this important new technology and we look forward to working with them to complete this trial and on future research where we anticipate exploring broader applications of our technology for long-term therapeutic protein delivery.”
A manuscript describing interim results from the trial has been uploaded to Research Square for early dissemination and is under peer review by a leading scientific journal for publication. The consortium plans to present interim results from the trial at upcoming scientific conferences in 2025.
About the Phase 1 Trial
The Phase 1 trial is the first clinical study to report using synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells. Participants received an intramuscular (IM) injection of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived from AstraZeneca’s cilgavimab and tixagevimab) delivered via INOVIO’s proprietary CELLECTRA 2000 electroporation (EP) device. This delivery method temporarily increases cell permeability, which is intended to facilitate efficient DNA uptake and enable sustained antibody production.
The study is an open-label, single center, dose-escalation trial. Enrollment began in May 2022 and was completed in March 2024. The most common side effects observed were temporary local injection site reactions, such as pain and erythema, associated with the administration of the study product. There were three SAEs all of which were considered unrelated to the study product.
Now in its third year, the trial is led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the University of Pennsylvania. It is funded by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) and the Defense Advanced Research Projects Agency (DARPA).
About INOVIO’s DNA Medicines Platform
INOVIO’s DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO’s proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software that the body’s cells can download to produce specific proteins to target and fight disease. INOVIO’s proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body’s cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms.
About INOVIO
INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO’s technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com.
SOURCE: INOVIO Pharmaceuticals
Post Views: 2,471
- Long-lasting in vivo antibody production: DMAb levels remained stable for 72 weeks in all participants (n=24) who have reached that timepoint
- No anti-drug antibodies (ADA): no immune rejection of the DMAbs was detected across ~1,000 blood samples, unlike other gene-based antibody delivery approaches where ADA formation has been a challenge
- Well-tolerated: most common side effects were mild, temporary injection site reactions such as pain and redness; no serious adverse events (SAEs) related to study drug
- Effective target binding: expressed DMAbs successfully bound to the SARS-CoV-2 Spike protein receptor-binding domain (RBD), confirming functional activity through week 72
PLYMOUTH MEETING, PA, USA I March 13, 2025 I INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced promising interim results from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19. In the trial, 100% (24/24) of participants who have reached week 72 maintained biologically relevant levels of DMAbs, confirming the durability of in vivo antibody production. Notably, no participant developed anti-drug antibodies (ADA), a common challenge observed in other gene-based delivery platforms, such as adeno-associated virus (AAV) mediated antibody expression. Additionally, the DMAbs were well tolerated, with the most common side effects being mild, temporary injection site reactions, such as pain and redness. The trial is being led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the Perelman School of Medicine at the University of Pennsylvania.
“This study provides the first clinical proof-of-concept that DNA-encoded monoclonal antibodies can be durably and tolerably expressed in humans,” said David B. Weiner, Ph.D, Executive Vice President of The Wistar Institute and lead investigator for the study. “These findings could represent a breakthrough as they demonstrate the potential of DMAb technology to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses, making it a promising platform for a broad range of diseases. This technology has the potential to transform treatments for infectious diseases, as well as cancer and metabolic disorders by enabling long-term expression of therapeutic antibodies and other proteins.”
“One of the biggest hurdles for gene-based antibody delivery has been the immune system’s response to the vector or the antibody itself, leading to anti-drug antibodies that can limit how long a treatment will be effective,” said Pablo Tebas, M.D., a professor of Infectious Diseases at Penn. “Our DNA-based approach has demonstrated sustained antibody expression without generating ADA. And because antibodies are remaining active for longer, our approach may be a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery.”
INOVIO’s Chief Scientific Officer, Laurent Humeau, Ph.D. added: “We believe these data highlight the potential to apply our DNA Medicines technology to deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins. We’d like to thank our partners in advancing this important new technology and we look forward to working with them to complete this trial and on future research where we anticipate exploring broader applications of our technology for long-term therapeutic protein delivery.”
A manuscript describing interim results from the trial has been uploaded to Research Square for early dissemination and is under peer review by a leading scientific journal for publication. The consortium plans to present interim results from the trial at upcoming scientific conferences in 2025.
About the Phase 1 Trial
The Phase 1 trial is the first clinical study to report using synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells. Participants received an intramuscular (IM) injection of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived from AstraZeneca’s cilgavimab and tixagevimab) delivered via INOVIO’s proprietary CELLECTRA 2000 electroporation (EP) device. This delivery method temporarily increases cell permeability, which is intended to facilitate efficient DNA uptake and enable sustained antibody production.
The study is an open-label, single center, dose-escalation trial. Enrollment began in May 2022 and was completed in March 2024. The most common side effects observed were temporary local injection site reactions, such as pain and erythema, associated with the administration of the study product. There were three SAEs all of which were considered unrelated to the study product.
Now in its third year, the trial is led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the University of Pennsylvania. It is funded by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) and the Defense Advanced Research Projects Agency (DARPA).
About INOVIO’s DNA Medicines Platform
INOVIO’s DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO’s proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software that the body’s cells can download to produce specific proteins to target and fight disease. INOVIO’s proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body’s cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms.
About INOVIO
INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO’s technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com.
SOURCE: INOVIO Pharmaceuticals
Post Views: 2,471
